Sex differences in the association between internalizing symptoms and hair cortisol level among 10-12 year-old adolescents in China.

PubMed

Lu, Qingyun; Pan, Fada; Ren, Lingling; Xiao, Jing; Tao, Fangbiao

2018-01-01

Although numerous studies have described the relationship between HPA axis dysregulation and internalizing symptoms among adolescents, research using hair cortisol concentrations in pre- and young adolescent samples has not been reported. We investigated the association of self-reported internalizing symptoms with cortisol concertration in hair among pre- and young adolescents aged 10-12 years. Forty-six boys and 39 girls supplied a hair sample of at least 3 cm in length for an analysis of this period (3 months) cortisol excretion. Saliva cortisol reactivity to the Trier Social Stress Test for Children (TSST-C) also was assessed. The study found a positive association between ratings of depressive symptoms and cumulative levels of hair cortisol only in boys. Furthermore, higher ratings of anxiety symptoms were associated with lower hair cortisol concertration and lower saliva cortisol reactivity among girls. This study provides the first evidence for the notion that depressive symptoms in boys are associated with long-term cortisol concertration in hair, whereas anxiety symptoms in girls are associated with HPA-axis hypoactivity, when hair cortisol concentrations and saliva cortisol reactivity to acute stress are assessed concurrently.

Cortisol production rates in subjects with suspected Cushing's syndrome: assessment by stable isotope dilution methodology and comparison to other diagnostic methods.

PubMed

Samuels, M H; Brandon, D D; Isabelle, L M; Cook, D M; Graham, K E; Purnell, J Q; Loriaux, D L

2000-01-01

It can be difficult to establish the diagnosis of Cushing's Syndrome (CS) in patients with mild or nonspecific clinical and biochemical findings, because available diagnostic tests have limited predictive values. We hypothesized that measurement of 24-h cortisol production rates (CPRs) might be a more sensitive indicator of CS in such patients. We measured CPRs in 28 patients with suspected CS (but equivocal biochemical findings) and in 22 healthy control subjects, by infusing tracer amounts of deuterated cortisol, with simultaneous measurements of 24-h urine free cortisol (UFC) levels; and we frequently sampled serum cortisol levels. CPRs were calculated from the ratio of isotopic enrichment to isotopic dilution of cortisol measured by gas chromatography-negative ion chemical ionization mass spectrometry. Nine of the patients proved to have CS by surgery (CS-Yes), whereas 19 patients were determined not to have CS by biochemical testing (CS-No). Mean 24-h UFCs, nocturnal serum cortisol levels, and CPRs were higher in CS-Yes, compared with CS-No and normal subjects. However, one CS-Yes patient had a normal 24-h UFC, two had normal nocturnal serum cortisol levels, and two had normal 24-h CPRs. There was extensive overlap in all of the biochemical parameters between the CS-Yes and the CS-No groups. Thus, measurement of CPR does not seem to offer any diagnostic advantage over available tests for the diagnosis of CS. Patients with proven CS can have normal UFC levels, normal CPRs, or normal nocturnal cortisol levels, whereas patients not thought to have CS may have elevated levels of any one or more these parameters.

Cortisol Stress Response Variability in Early Adolescence Attachment, Affect and Sex

PubMed Central

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J.; Wynne-Edwards, Katherine; Wright, Joan M.; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic–pituitary–adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents. PMID:27468997

Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

PubMed

Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

2017-01-01

Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress.

PubMed

Brummelte, Susanne; Chau, Cecil M Y; Cepeda, Ivan L; Degenhardt, Amanda; Weinberg, Joanne; Synnes, Anne R; Grunau, Ruth E

2015-01-01

Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function. Differences in cortisol levels have been found in preterm infants exposed to substantial procedural stress during neonatal intensive care, compared to infants born full-term, but only a few studies investigated whether altered programming of the HPA axis persists past toddler age. Further, there is a dearth of knowledge of what may contribute to these changes in cortisol. This prospective cohort study examined the cortisol profiles in response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol, in children (n=129) born at varying levels of prematurity (24-32 weeks gestation) and at full-term (38-41 weeks gestation), at age 7 years. Further, we investigated the relationships among cortisol levels and neonatal procedural pain-related stress (controlling for multiple medical confounders), concurrent maternal factors (parenting stress, depressive and anxiety symptoms) and children's behavioral problems. For each aim we investigate acute cortisol response profiles to a cognitive challenge as well as diurnal cortisol patterns at home. We hypothesized that children born very preterm will differ in their pattern of cortisol secretion from children born full-term, possibly depended on concurrent child and maternal factors, and that exposure to neonatal pain-related stress would be associated with altered cortisol secretion in children born very preterm, possibly in a sex-dependent way. Saliva samples were collected from 7-year old children three times during a laboratory visit for assessment of cognitive and executive functions (pretest, mid-test, end-study day acute stress profile) and at four times over two consecutive non-school days at home (i.e. morning, mid-morning, afternoon and bedtime-diurnal rhythm profile). We found that cortisol profiles were similar in preterm and full-term children, albeit preterms had slightly higher cortisol at bedtime compared to full-term children. Importantly, in the preterm group, greater neonatal procedural pain-related stress (adjusted for morphine) was associated with lower cortisol levels on the study day (p=.044) and lower diurnal cortisol at home (p=.023), with effects found primarily in boys. In addition, child attention problems were negatively, and thought problems were positively, associated with the cortisol response during cognitive assessment on the study day in preterm children. Our findings suggest that neonatal pain/stress contributes to altered HPA axis function up to school-age in children born very preterm, and that sex may be an important factor. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress

PubMed Central

Brummelte, Susanne; Chau, Cecil MY; Cepeda, Ivan L.; Degenhardt, Amanda; Weinberg, Joanne; Synnes, Anne R.; Grunau, Ruth E.

2014-01-01

Summary Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function. Differences in cortisol levels have been found in preterm infants exposed to substantial procedural stress during neonatal intensive care, compared to infants born full-term, but only a few studies investigated whether altered programming of the HPA axis persists past toddler age. Further, there is a dearth of knowledge of what may contribute to these changes in cortisol. This prospective cohort study examined the cortisol profiles in response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol, in children (n=129) born at varying levels of prematurity (24–32 weeks gestation) and at full-term (38–41 weeks gestation), at age 7 years. Further, we investigated the relationships among cortisol levels and neonatal procedural pain-related stress (controlling for multiple medical confounders), concurrent maternal factors (parenting stress, depressive and anxiety symptoms) and children’s behavioral problems. For each aim we investigate acute cortisol response profiles to a cognitive challenge as well as diurnal cortisol patterns at home. We hypothesized that children born very preterm will differ in their pattern of cortisol secretion from children born full-term, possibly depended on concurrent child and maternal factors, and that exposure to neonatal pain-related stress would be associated with altered cortisol secretion in children born very preterm, possibly in a sex-dependent way. Saliva samples were collected from 7-year old children three times during a laboratory visit for assessment of cognitive and executive functions (pretest, mid-test, end - study day acute stress profile) and at four times over two consecutive non-school days at home (i.e. morning, mid-morning, afternoon and bedtime - diurnal rhythm profile). We found that cortisol profiles were similar in preterm and full-term children, albeit preterms had slightly higher cortisol at bedtime compared to full-term children. Importantly, in the preterm group, greater neonatal procedural pain-related stress (adjusted for morphine) was associated with lower cortisol levels on the study day (p=0.044) and lower diurnal cortisol at home (p=0.023), with effects found primarily in boys. In addition, child attention problems were negatively, and thought problems were positively, associated with the cortisol response during cognitive assessment on the study day in preterm children. Our findings suggest that neonatal pain/stress contributes to altered HPA axis function up to school-age in children born very preterm, and that sex may be an important factor. PMID:25313535

Relationship of 24-hour urinary free cortisol to 4-hour salivary morning and afternoon cortisol and cortisone as measured by a time-integrated oral diffusion sink.

PubMed

Kathol, R G; Poland, R E; Stokes, P E; Wade, S

1995-05-01

The relationship between salivary corticosteroids integrated over 4-hour periods and urinary free cortisol collected over 24 hours was investigated in normal controls. Twenty-one normal volunteers wore "oral diffusion sink" sampling devices in their mouths for two 4-hour periods (08:00-12:00 hours and 13:00-17:00 hours) and on the same day collected a 24-hour urine specimen. Time-integrated salivary corticosteroid concentrations were determined from the sample devices and urinary free cortisol was measured. Salivary corticosteroids were not consistently higher in the morning than in the afternoon period and did not differ between men and women. Urinary free cortisol levels were higher in women. No salivary corticosteroids measure was significantly correlated with urinary free cortisol. We conclude that time-integrated salivary corticosteroids do not reflect urinary free cortisol levels in normal controls.

Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

PubMed Central

Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

2013-01-01

Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

PubMed

Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

2001-01-01

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

STUDIES ON THE ORIGIN OF CIRCULATING 18-HYDROXYCORTISOL AND 18-OXOCORTISOL IN NORMAL HUMAN SUBJECTS.

PubMed Central

Freel, E Marie; Shakerdi, Loai A; Friel, Elaine C; Wallace, A Michael; Davies, Eleanor; Fraser, Robert; Connell, John MC

2005-01-01

18-hydroxycortisol (18-OHF) and 18-oxocortisol (18oxo-F) are derivatives of cortisol found in Primary Aldosteronism but whose origin and regulation in normal subjects is uncertain. 18-OHF can be synthesised by zona fasciculata 11-β hydroxylase; 18-oxoF can only be produced by zona glomerulosa aldosterone synthase (AS). Stably transfected cell lines expressing either CYP11B1 (11β-hydroxylase) or CYP11B2 (AS) were incubated with cortisol and other substrates over a range of concentrations. Both enzymes could synthesise 18-OHF from cortisol but only AS could synthesise 18-oxoF. AS was more efficient than 11β-hydroxylase at 18-hydroxylation. The apparent Km of AS for cortisol was estimated to be 2.6μM. In 5 patients with adrenal insufficiency maintained on hydrocortisone, urinary free cortisol and cortisone levels were high; 18-oxoF was detectable in all patients and 18-hydroxycortisol in 3. It is likely that the 18-oxygenated steroids were synthesised from circulating cortisol, either in the zona glomerulosa or at extra-adrenal sites. In 8 male volunteers, dexamethasone treatment decreased urinary excretion rates of free cortisol, cortisone, 18-OHF and 18-oxoFl, confirming dependence of 18-oxygenated steroid levels on cortisol availability. In both groups, hydrocortisone administration resulted in detectable levels of 18-OHF and raised levels of 18-oxoF. There was close correlation between 18-oxoF and cortisol excretion during hydrocortisone administration in normal subjects (r=0.86, p<0.001). These data show, for the first time, that 18-OHF and 18oxoF can be synthesised from circulating cortisol. The close correlation between 18-oxoF and cortisol suggests that 18-oxoF is normally produced by the action of aldosterone synthase utilising circulating cortisol as a substrate. Although 18OHF can be synthesized using circulating cortisol as substrate, our data suggest this is normally produced in the zona fasciculata by 11β-hydroxylase from locally available cortisol. PMID:15356073

Diagnosis and management of hypoaldosteronism without hypoadrenocorticism in an alpaca.

PubMed

Butterworth, Kelly A; Pellegrini-Masini, Alessandra M; Barton, Michelle H

2012-03-15

Primary hypoaldosteronism without concurrent hypoadrenocorticism was diagnosed in an 8-year-old female alpaca with acute onset of weakness progressing to recumbency within 6 hours after onset. Hematologic testing at admission revealed profound hyponatremia, hypochloremia, and acidemia with a normal blood potassium concentration. Further diagnostic testing, including an ACTH stimulation test, led to a diagnosis of hypoaldosteronism in conjunction with normal cortisol production. The hembra responded well to i.v. polyionic fluid therapy with sodium supplementation and was managed successfully long term with free access to saline (0.9% NaCl) solution in addition to water ad libitum. To our knowledge, this is the first reported case of hypoaldosteronism in an alpaca. Hypoaldosteronism should be considered in alpacas as a possible differential diagnosis for refractory hyponatremia or for hyponatremia in which an underlying etiology is not determined.

Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

PubMed

Lacroix, A; Bolté, E; Tremblay, J; Dupré, J; Poitras, P; Fournier, H; Garon, J; Garrel, D; Bayard, F; Taillefer, R

1992-10-01

Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.

Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

PubMed

Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

2017-04-01

Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

The Impact of Complicated Grief on Diurnal Cortisol Levels Two Years After Loss: A Population-Based Study.

PubMed

Saavedra Pérez, Heidi C; Direk, Nese; Milic, Jelena; Ikram, Mohammed Arfan; Hofman, Albert; Tiemeier, Henning

2017-05-01

Few studies have focused on the effect of complicated grief-unresolved and prolonged grief-on the neuroendocrine systems. The present study examined the association of complicated grief and normal grief with the diurnal cortisol patterns in a large population-based study. This study was set in the Rotterdam Study and comprised 2084 persons aged older than 55 years (mean [SD] age, 64.9 [5.5] years). Participants were assessed with the Complicated Grief Inventory and classified into no grief (n = 1922), normal grief (n = 131), or complicated grief (n = 31) if they experienced the loss in the past 2 years. Saliva samples were collected to measure cortisol levels. Morning cortisol and summary measures (area under the curve and the slope) were studied to account for the diurnal pattern of cortisol. Persons with depressive disorders were excluded, and analyses were additionally adjusted for depressive symptoms. Compared to normal grievers, participants with complicated grief showed lower levels of morning cortisol (11.26 vs 15.51 nmol/L; difference, -4.24; 95% confidence interval [CI] = -7.87 to -0.62; p = .022), and lower levels of overall diurnal cortisol (6.89 vs 8.98 nmol/L; difference, -2.09; 95% CI = -3.81 to -0.37; p = .017). No difference was observed in slope between both groups. Participants with complicated grief also showed lower levels of morning cortisol than the nongrievers (11.26 vs 14.71; difference, -3.46; 95% CI = -6.78 to -0.13; p = .042). In contrast, cortisol secretion patterns did not differ between persons with normal grief and nongrieving controls. Participants with complicated grief showed low levels of morning cortisol and low overall diurnal cortisol levels characteristic for a chronic stress reaction.

Effects of prenatal and postnatal parent depressive symptoms on adopted child HPA regulation: independent and moderated influences.

PubMed

Laurent, Heidemarie K; Leve, Leslie D; Neiderhiser, Jenae M; Natsuaki, Misaki N; Shaw, Daniel S; Harold, Gordon T; Reiss, David

2013-05-01

This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents' symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk.

Links between early baseline cortisol, attachment classification, and problem behaviors: A test of differential susceptibility versus diathesis-stress.

PubMed

Fong, Michelle C; Measelle, Jeffrey; Conradt, Elisabeth; Ablow, Jennifer C

2017-02-01

The purpose of the current study was to predict concurrent levels of problem behaviors from young children's baseline cortisol and attachment classification, a proxy for the quality of caregiving experienced. In a sample of 58 children living at or below the federal poverty threshold, children's baseline cortisol levels, attachment classification, and problem behaviors were assessed at 17 months of age. We hypothesized that an interaction between baseline cortisol and attachment classification would predict problem behaviors above and beyond any main effects of baseline cortisol and attachment. However, based on limited prior research, we did not predict whether or not this interaction would be more consistent with diathesis-stress or differential susceptibility models. Consistent with diathesis-stress theory, the results indicated no significant differences in problem behavior levels among children with high baseline cortisol. In contrast, children with low baseline cortisol had the highest level of problem behaviors in the context of a disorganized attachment relationship. However, in the context of a secure attachment relationship, children with low baseline cortisol looked no different, with respect to problem behavior levels, then children with high cortisol levels. These findings have substantive implications for the socioemotional development of children reared in poverty. Copyright © 2017 Elsevier Inc. All rights reserved.

Behaviour problems and cortisol levels in very-low-birth-weight children.

PubMed

Wadsby, Marie; Nelson, Nina; Ingemansson, Fredrik; Samuelsson, Stefan; Leijon, Ingemar

2014-11-01

Abstract Background. There are still diverging results concerning the behaviour of children with very-low-birth-weight (VLBW) and they have been questioned to display different levels of stress hormone than normal-birth-weight (NBW) children. Aims. This study examined behaviour and the stress hormone cortisol in children with VLBW at the ages of 7 and 9 years compared with children with NBW. Results. Fifty-one VLBW and 50 NBW children were studied with the Child Behavior Checklist. Cortisol rhythm was measured through saliva samples three times a day for 2 days. VLBW children displayed more behavioural problems than NBW children, specifically social and attention problems, although still within normal ranges. They showed lower cortisol levels both at 7 and 9 years of age. No strong association between behaviour and cortisol levels was shown. Conclusion. VLBW children display more behaviour problems compared with NBW children but both groups score are within the normal range. Down-regulation of their hypothalamic-pituitary-adrenal (HPA) function in terms of lower cortisol levels is also noted.

Steroid synthesis by primary human keratinocytes; implications for skin disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hannen, Rosalind F., E-mail: r.f.hannen@qmul.ac.uk; Michael, Anthony E.; Jaulim, Adil

2011-01-07

Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary humanmore » keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data show that PHK are capable of extra-adrenal cortisol synthesis, which could be a fundamental pathway in skin biology with implications in psoriasis and atopic dermatitis.« less

The onset of stress response in rainbow trout Oncorhynchus mykiss embryos subjected to density and handling.

PubMed

Ghaedi, Gholamreza; Falahatkar, Bahram; Yavari, Vahid; Sheibani, Mohammad T; Broujeni, Gholamreza Nikbakht

2015-04-01

The present study made an attempt to measure the cortisol content, as an indicator of stress response, in rainbow trout embryos which were exposed to different densities and handling stress (air exposure) during incubation. The three densities of experimental embryos at early development stages were considered as 2.55 embryos/cm(2) (low density), 5.10 embryos/cm(2) (normal density) and 7.65 embryos/cm(2) (high density). The cortisol content of eggs (5.09 ± 0.12 ng/g) decreased to 3.68 ± 0.14 ng/g in newly fertilized eggs. Resting level of cortisol dropped at three densities by day 18 of post fertilization. Then, cortisol increased at hatching stage to 1.16 ± 0.11, 1.20 ± 0.12 and 1.21 ± 0.14 ng/g at low, normal and high densities, respectively. There were no statistically significant differences between cortisol concentrations in three densities. The acute handling stress test (5-min out-of-water), conducted on embryos (48 h post fertilization, organogenesis and eyed stage) in three densities, revealed no differences in whole-body cortisol levels between stressed and unstressed experimental groups. At hatching stage in low-density group, level of cortisol increased but the difference with the pre-stress levels was not statistically significant. Furthermore, significant differences in cortisol levels of stressed and unstressed embryos were detected on hatching in normal and high density groups [1.20 ± 0.12 at time 0-1.49 ± 0.11 ng/g at 1 hps (hours post stress) and from 1.21 ± 0.14 at time 0 to 1.53 ± 0.10 ng/g at 3 hps, respectively]. The results showed no difference in profile of cortisol in different densities, but acute stress conducted on embryos, incubated in different densities, revealed differences in cortisol stress response at hatching between normal and high density, which lead to cortisol increase at hatching time. It indicates that the lag time in the cortisol response to stressors immediately after hatching does not occur when the siblings were stressed during the embryo stage. Results, finally, indicated that hypothalamus-pituitary-interrenal axis was active and responded to an acute stressor under normal and high density, but it is unresponsive to a stressor around hatching under low density.

Salivary Biomarkers and Training Load during Training and Competition in Paralympic Swimmers.

PubMed

Sinnott-O'Connor, Ciara; Comyns, Tom; Nevill, Alan M; Warrington, Giles

2017-11-28

Stress responses in athletes can be attributed to training and also competition, where increased physiological and psychological stress may negatively impact on performance and recovery. The aim of this study was to examine the relationship between training load and salivary biomarkers IgA, alpha-amylase (AA) and cortisol across a 16-week preparation phase and 10-day competition phase in Paralympic swimmers. Four Paralympic swimmers provided bi-weekly saliva samples during three training phases - 1) normal training, 2) intensified training and 3) taper as well as daily saliva samples in the 10 day Paralympic competition (2016 Paralympic Games). Training load (TL) was measured using session-RPE. Multi-level analysis identified a significant increase in sIgA (94.98 (27.69) μg.ml -1 ), sAA (45.78 (19.07) μg.ml -1 ) and salivary cortisol (7.92 (2.17) ng.ml) during intensified training concurrent with a 38.3% increase in TL. During taper phase, a 49.5% decrease in TL from the intensified training phase resulted in decrease in sIgA, sAA and salivary cortisol; however, all three remained higher than baseline levels. A further significant increase was observed during competition in sIgA (168.69(24.19) μg.ml -1 ), sAA (35.86(16.67) μg.ml -1 ) and salivary cortisol (10.49(1.89) ng.ml) despite a continued decrease (77.8%) in TL from taper phase. Results demonstrate performance in major competition such as Paralympic Games despite a noticeable reduction in TL induces a stress response in athletes. Due to elevated stress response observed, modifications to individual post-race recovery protocols may be required to enable athletes to maximise performance across all ten days of competition.

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

PubMed

Hammami, Muhammad M; Duaiji, Najla; Mutairi, Ghazi; Aklabi, Sabah; Qattan, Nasser; Abouzied, Mohei El-Din M; Sous, Mohamed W

2015-09-09

Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib.

Effects of Prenatal and Postnatal Parent Depressive Symptoms on Adopted Child HPA Regulation: Independent and Moderated Influences

PubMed Central

Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Harold, Gordon T.; Reiss, David

2013-01-01

This study used a prospective adoption design to investigate effects of prenatal and postnatal parent depressive symptom exposure on child hypothalamic-pituitary-adrenal (HPA) activity and associated internalizing symptoms. Birth mother prenatal symptoms and adoptive mother/father postnatal (9-month, 27-month) symptoms were assessed with the Beck Depression Inventory in a sample of 192 families as part of the Early Growth and Development adoption Study. Child morning/evening cortisol levels and child symptoms of internalizing disorders (according to mother/father report on the Child Behavior Checklist) were assessed at 54 months, and birth mother diurnal cortisol was measured at 48 months postnatal. Hierarchical linear modeling was used to test main effects and interactions of parents’ symptoms predicting child cortisol, controlling for birth mother cortisol. Prenatal exposure to birth mother symptoms predicted lower child cortisol (main effect), as did postnatal exposure to adoptive parent symptoms (interaction effects). Adoptive mother 9-month symptoms exacerbated cortisol-lowering effects of both concurrent paternal symptoms and later (27-month) maternal symptoms, and the effect of birth mother cortisol. Lower child cortisol, in turn, was associated with higher child internalizing symptoms. Implications are discussed with respect to the intergenerational transmission of depression risk. PMID:22686176

Maternal negative affect during infancy is linked to disrupted patterns of diurnal cortisol and alpha asymmetry across contexts during childhood.

PubMed

Brooker, Rebecca J; Davidson, Richard J; Goldsmith, H Hill

2016-02-01

Maternal negative affect in the early environment is believed to sensitize long-term coping capacities in children. Yet, little work has identified physiological systems associated with coping responses, which may serve as mechanisms for links between early maternal negativity and child outcomes. Using a longitudinal twin sample (N=89), we found that high levels of maternal negative affect during infancy were associated with dysregulation of diurnal cortisol and electroencephalograph (EEG) asymmetry, two physiological systems that may support active approach-oriented coping when children are 7years old. Flattened slopes of diurnal cortisol were also associated with greater numbers of concurrent overanxious behaviors in children. A mediation analysis supported the role of dysregulated diurnal cortisol as a mediator of the link between maternal negative affect in the early environment and childhood risk for anxiety problems. Copyright © 2015 Elsevier Inc. All rights reserved.

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

PubMed Central

Munoz, Miranda J.; Kumar, Raj G.; Oh, Byung-Mo; Conley, Yvette P.; Wang, Zhensheng; Failla, Michelle D.; Wagner, Amy K.

2017-01-01

Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0–6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in “younger patients” (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance. PMID:28337122

Children's biological responsivity to acute stress predicts concurrent cognitive performance.

PubMed

Roos, Leslie E; Beauchamp, Kathryn G; Giuliano, Ryan; Zalewski, Maureen; Kim, Hyoun K; Fisher, Philip A

2018-04-10

Although prior research has characterized stress system reactivity (i.e. hypothalamic-pituitary-adrenal axis, HPAA; autonomic nervous system, ANS) in children, it has yet to examine the extent to which biological reactivity predicts concurrent goal-directed behavior. Here, we employed a stressor paradigm that allowed concurrent assessment of both stress system reactivity and performance on a speeded-response task to investigate the links between biological reactivity and cognitive function under stress. We further investigated gender as a moderator given previous research suggesting that the ANS may be particularly predictive of behavior in males due to gender differences in socialization. In a sociodemographically diverse sample of young children (N = 58, M age = 5.38 yrs; 44% male), individual differences in sociodemographic covariates (age, household income), HPAA (i.e. cortisol), and ANS (i.e. respiratory sinus arrhythmia, RSA, indexing the parasympathetic branch; pre-ejection period, PEP, indexing the sympathetic branch) function were assessed as predictors of cognitive performance under stress. We hypothesized that higher income, older age, and greater cortisol reactivity would be associated with better performance overall, and flexible ANS responsivity (i.e. RSA withdrawal, PEP shortening) would be predictive of performance for males. Overall, females performed better than males. Two-group SEM analyses suggest that, for males, greater RSA withdrawal to the stressor was associated with better performance, while for females, older age, higher income, and greater cortisol reactivity were associated with better performance. Results highlight the relevance of stress system reactivity to cognitive performance under stress. Future research is needed to further elucidate for whom and in what situations biological reactivity predicts goal-directed behavior.

Indirect effect of financial strain on daily cortisol output through daily negative to positive affect index in the Coronary Artery Risk Development in Young Adults Study.

PubMed

Puterman, Eli; Haritatos, Jana; Adler, Nancy E; Sidney, Steve; Schwartz, Joseph E; Epel, Elissa S

2013-12-01

Daily affect is important to health and has been linked to cortisol. The combination of high negative affect and low positive affect may have a bigger impact on increasing HPA axis activity than either positive or negative affect alone. Financial strain may both dampen positive affect as well as increase negative affect, and thus provides an excellent context for understanding the associations between daily affect and cortisol. Using random effects mixed modeling with maximum likelihood estimation, we examined the relationship between self-reported financial strain and estimated mean daily cortisol level (latent cortisol variable), based on six salivary cortisol assessments throughout the day, and whether this relationship was mediated by greater daily negative to positive affect index measured concurrently in a sample of 776 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants. The analysis revealed that while no total direct effect existed for financial strain on cortisol, there was a significant indirect effect of high negative affect to low positive affect, linking financial strain to elevated cortisol. In this sample, the effects of financial strain on cortisol through either positive affect or negative affect alone were not significant. A combined affect index may be a more sensitive and powerful measure than either negative or positive affect alone, tapping the burden of chronic financial strain, and its effects on biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Associations between hair cortisol concentration, income, income dynamics and status incongruity in healthy middle-aged women

PubMed Central

Serwinski, Bianca; Salavecz, Gyöngyvér; Kirschbaum, Clemens; Steptoe, Andrew

2016-01-01

A body of research demonstrates that financial disadvantage is associated with general health inequalities and higher mortality rates. Most studies make use of cross-sectional analyses, although income can also be viewed as a dynamic concept. The use of endocrine-markers as proxies for health can provide information about the pathways involved in these associations. Hair cortisol analysis has been developed as a method for assessing sustained cortisol output as it provides an estimate of cumulative cortisol secretion over a prolonged time. The present study assessed income and income trajectory over a 4-year period in 164 working women (aged 26–65) in relation to hair cortisol in a longitudinal design. A negative association between hair cortisol and concurrent income was found (p = 0.025) and hair cortisol and changes in income over 4 years (p < 0.001), after adjustment for age, BMI, smoking status, hair treatment and country. Status incongruity, a mismatch between educational status and income group, was related to higher cortisol levels compared with status congruity (p = 0.009). These findings suggest that psychoneuroendocrinological pathways might partially explain the relationship between lower socio-economic status and adverse health outcomes. Future longitudinal research using hair cortisol analysis is warranted to clarify the time course of social mobility in relation to long-term cortisol, to investigate other underlying psychosocial factors implicated in these associations, and to determine the exact health implications of the neuroendocrine perturbations in individuals with limited economic resources. PMID:26923848

Associations between hair cortisol concentration, income, income dynamics and status incongruity in healthy middle-aged women.

PubMed

Serwinski, Bianca; Salavecz, Gyöngyvér; Kirschbaum, Clemens; Steptoe, Andrew

2016-05-01

A body of research demonstrates that financial disadvantage is associated with general health inequalities and higher mortality rates. Most studies make use of cross-sectional analyses, although income can also be viewed as a dynamic concept. The use of endocrine-markers as proxies for health can provide information about the pathways involved in these associations. Hair cortisol analysis has been developed as a method for assessing sustained cortisol output as it provides an estimate of cumulative cortisol secretion over a prolonged time. The present study assessed income and income trajectory over a 4-year period in 164 working women (aged 26-65) in relation to hair cortisol in a longitudinal design. A negative association between hair cortisol and concurrent income was found (p=0.025) and hair cortisol and changes in income over 4 years (p<0.001), after adjustment for age, BMI, smoking status, hair treatment and country. Status incongruity, a mismatch between educational status and income group, was related to higher cortisol levels compared with status congruity (p=0.009). These findings suggest that psychoneuroendocrinological pathways might partially explain the relationship between lower socio-economic status and adverse health outcomes. Future longitudinal research using hair cortisol analysis is warranted to clarify the time course of social mobility in relation to long-term cortisol, to investigate other underlying psychosocial factors implicated in these associations, and to determine the exact health implications of the neuroendocrine perturbations in individuals with limited economic resources. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulatory effect of Epithalon on production of melatonin and cortisol in old monkeys.

PubMed

Goncharova, N D; Khavinson, B K; Lapin, B A

2001-04-01

The effect of Epithalon on melatonin and cortisol secretion in female rhesus monkeys of various ages was evaluated by enzyme immunoassay. Epithalon stimulated evening melatonin production and normalized circadian rhythms of cortisol production in old monkeys.

Plasma and muscle cortisol measurements as indicators of meat quality and stress in pigs.

PubMed

Shaw, F D; Trout, G R; McPhee, C P

1995-01-01

Post-slaughter blood samples and muscle samples were collected from pigs slaughtered at the completion of a live-animal performance trial. There were two lines of pigs in which the halothane allele (n) was segregating. The lines were a lean line selected for rapid lean growth and an unselected fat line. There were homozygous normal (NN), homozygous halothane positive (nn) and heterozygous (Nn) genotypes in both lnes. Cortisol was measured in the plasma of the blood samples and in muscle juice obtained by high-speed centrifugation. Meat quality was assessed using pH, colour, fibre-optic probe, drip loss and cure yield measurements. Plasma cortisol concentrations in the fat line were significantly (P < 0·05) greater than thosein the lean line but concentrations did not differ significantly for the three halothane genotypes. Carcasses classified as dark, firm and dry (DFD) had significantly (P < 0·05) greater muscle cortisol concentrations than those classified as normal. Plasma and muscle cortisol concentrations of carcases classified as pale, soft and exudative (PSE) did not differ significantly from those classified as normal. Correlations between muscle cortisol and meat quality attributes were generally highly significant (r = 0·31 to r = 0·51, P < 0·001) There was a highly significant correlation (r = 0·73, P < 0·0001) between plasma and muscle cortisol concentrations.

Overnight dexamethasone suppression test: a reliable screen for Cushing's syndrome in the obese.

PubMed

Ness-Abramof, Rosane; Nabriski, Dan; Apovian, Caroline M; Niven, Mark; Weiss, Eliahu; Shapiro, Menachem S; Shenkman, Louis

2002-12-01

Reevaluation of the validity of the 1-mg overnight dexamethasone suppression test (ODST) as a screening test for Cushing's syndrome in obese patients. Eighty-six obese patients (body mass index, 30 to 53 kg/m(2)) that were referred to a general endocrine outpatient clinic for evaluation of simple obesity, diabetes mellitus, hypertension, polycystic ovary disease, or pituitary tumor. One milligram dexamethasone was administered orally at 11:00 PM, and serum cortisol levels were measured the following morning between 8:00 AM and 9:00 AM. Suppression of serum cortisol to <80 nM (3 micro g/dL) was chosen as the cut-off point for normal suppression. Patients with serum cortisol levels > or =80 nM were evaluated for Cushing's syndrome. Suppression of morning cortisol levels to <80 nM occurred in 79 of the 86 obese patients. Seven patients had serum cortisol levels higher than 80 nM; five were eventually diagnosed with Cushing's syndrome and two were considered false positive results in view of normal 24-hour free urinary cortisol and normal suppression on a low dose dexamethasone suppression test (0.5 mg of dexamethasone every 6 hours for 2 days). We found a false positive rate of 2.3% for the ODST using a cut-off serum cortisol of 80 nM. The ODST is a valid screening test for Cushing's syndrome in the obese population. The false positive rate was 2.3%, even when using a strict cut-off serum cortisol of 80 nM. Abnormal cortisol suppression in obese patients should be investigated and not be considered false positive results.

[Addison disease during pregnancy--a diagnostic dilemma. Symptoms are similar to normal pregnancy problems].

PubMed

Wålinder, Olov

The symptoms of primary adrenocortical insufficiency (Addison's disease) such as fatigue, anorexia, hypotension and hyperpigmentation are similar to those of normal pregnancy. Addison's disease is rare and the diagnosis can easily be overlooked during pregnancy. The concentration of corticosteroid-binding globulin (CBG) and cortisol in serum as well as urinary free cortisol increase 2-3 times during pregnancy. Therefore, the reference ranges for nonpregnant persons cannot be used during pregnancy. The diagnosis of Addison's disease in pregnancy should be based on analysis of p-ACTH which remains within the reference range in normal pregnancy until delivery. A case of Addison's disease diagnosed during pregnancy is presented and it illustrates the diagnostic difficulties. In patients taking oral estrogen containing contraceptives, serum levels of CBG and cortisol also increase 2-3 times, making s-cortisol values difficult to interpret. Also in these patients, analysis of p-ACTH is of value when suspecting Addison's disease.

Performance and Endocrine Responses to Differing Ratios of Concurrent Strength and Endurance Training.

PubMed

Jones, Thomas W; Howatson, Glyn; Russell, Mark; French, Duncan N

2016-03-01

The present study examined functional strength and endocrine responses to varying ratios of strength and endurance training in a concurrent training regimen. Thirty resistance trained men completed 6 weeks of 3 d·wk of (a) strength training (ST), (b) concurrent strength and endurance training ratio 3:1 (CT3), (c) concurrent strength and endurance training ratio 1:1 (CT1), or (d) no training (CON). Strength training was conducted using whole-body multijoint exercises, whereas endurance training consisted of treadmill running. Assessments of maximal strength, lower-body power, and endocrine factors were conducted pretraining and after 3 and 6 weeks. After the intervention, ST and CT3 elicited similar increases in lower-body strength; furthermore, ST resulted in greater increases than CT1 and CON (all p ≤ 0.05). All training conditions resulted in similar increases in upper-body strength after training. The ST group observed greater increases in lower-body power than all other conditions (all p ≤ 0.05). After the final training session, CT1 elicited greater increases in cortisol than ST (p = 0.008). When implemented as part of a concurrent training regimen, higher volumes of endurance training result in the inhibition of lower-body strength, whereas low volumes do not. Lower-body power was attenuated by high and low frequencies of endurance training. Higher frequencies of endurance training resulted in increased cortisol responses to training. These data suggest that if strength development is the primary focus of a training intervention, frequency of endurance training should remain low.

Measuring short-term and long-term physiological stress effects by cortisol reactivity in saliva and hair.

PubMed

van Holland, Berry J; Frings-Dresen, Monique H W; Sluiter, Judith K

2012-11-01

The aims of this study were to investigate (1) the concurrent relationship between short-term and long-term stress reactivity measured by cortisol excretion and (2) the relationship of these physiological stress effects with self-reported stress and need for recovery after work (NFR). Participants were production workers in the meat-processing industry. Short-term cortisol excretion was calculated by summing 18 saliva samples, sampled over a 3-day period. Samples were delivered by 37 participants. Twenty-nine of them also supplied one hair sample of at least 3 cm in length for an analysis of long-term (3 months) cortisol excretion. All of them filled in a short questionnaire on self-reported stress and NFR. Self-reported stress was assessed by a three-item stress screener; NFR was assessed by an 11-item scale. Short-term and long-term cortisol excretion are significantly, but moderately, associated (r = 0.41, P = 0.03). Short-term and long-term cortisol excretion correlated weakly to self-reported stress and NFR (correlations varied from -0.04 to 0.21). Short-term and long-term physiological stress excretion levels are moderately associated. Physiological stress effects assessed from saliva and hair cannot be used interchangeably with self-reported stress because they only correlate weakly. To better predict long-term cortisol excretion in workers, the predictive value of short-term cortisol excretion must be evaluated in a prognostic longitudinal study in a working population.

Maternal mood and concordant maternal and infant salivary cortisol during heel lance while in kangaroo care.

PubMed

Castral, T C; Warnock, F; Dos Santos, C B; Daré, M F; Moreira, A C; Antonini, S R R; Scochi, C G S

2015-03-01

Maternal kangaroo care (MKC) is a naturalistic intervention that alleviates neonatal pain, and mothers are assumed to play a stress regulatory role in MKC. Yet, no MKC infant pain study has examined relationship between maternal and infant stress reactivity concurrently, or whether post-partum depression and/or anxiety (PPDA) alters maternal and neonatal stress response and the regulatory effects of MKC. To examine the concordance of salivary cortisol reactivity between 42 mothers and their stable preterm infants during routine infant heel lance (HL) while in MKC and to compare salivary cortisol between groups of mothers with and without PPDA and their infants. Maternal and infant salivary cortisol samples were collected pre-HL and 20 min post-HL with two additional maternal samples at night and in the morning. Mothers and infants were allocated to with PPDA versus without PPDA study groups on the basis of maternal post-natal mental health assessment scores. Higher mothers' cortisol pre-HL was weakly associated with higher infants' salivary cortisol in response to the HL procedure. Maternal depression and/or anxiety were not associated with infants' cortisol. During HL, both groups of mothers and infants showed no change in salivary cortisol. Concordance between mother and infant salivary cortisol supports the maternal stress regulatory role in MKC. MKC may have stress regulatory benefits for mothers and their preterm infants during HL independent of PPDA. Future MKC studies that target mothers with altered mood will help to build on these findings. © 2014 European Pain Federation - EFIC®

Father Contributions to Cortisol Responses in Infancy and Toddlerhood

PubMed Central

Mills-Koonce, W. Roger; Garrett-Peters, Patricia; Barnett, Melissa; Granger, Douglas A.; Blair, Clancy; Cox, Martha J.

2015-01-01

The current study is one of the first to prospectively examine longitudinal associations between observed father caregiving behaviors and child cortisol reactivity and regulation in response to emotional arousal at 7 and 24 months of child age. Observations of father and mother caregiving behaviors and child cortisol levels in response to challenges at 7 months and 24 months were collected. Analyses were based on a subsample of children from the Family Life Project who lived with both their biological mothers and fathers and for whom there was at least partial cortisol data (7 months: n=717; 24 months n= 579). At 7 months of child age the sample was 49.0% female, 25.8% African American, and 74.2% European American. At 24 months of child age the sample was 49.9% female, 24.7% African American and 75.3% European American. Analyses across assessment points were conducted simultaneously using mixed linear modeling for repeated measures data to test for differential effects of fathering across infancy and toddlerhood. Concurrent measures of father negativity were positively associated with greater increases in child cortisol levels in response to emotion challenge at 7 months (p = .01) and with higher overall levels of cortisol at 24 months (p < .001). However, there was no evidence that father caregiving during infancy independently predicted later cortisol activity during toddlerhood. PMID:21142362

A 12-month phase 3 study of pasireotide in Cushing's disease.

PubMed

Colao, Annamaria; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Schoenherr, Ulrike; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M K

2012-03-08

Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

Salivary cortisol among American Indians with and without posttraumatic stress disorder (PTSD): gender and alcohol influences.

PubMed

Laudenslager, Mark L; Noonan, Carolyn; Jacobsen, Clemma; Goldberg, Jack; Buchwald, Dedra; Bremner, J Douglas; Vaccarino, Viola; Manson, Spero M

2009-07-01

Disruptions in hypothalamic-pituitary-adrenal regulation and immunity have been associated with posttraumatic stress disorder (PTSD). We examined the association of PTSD with diurnal rhythms in salivary cortisol in a convenience sample from a population-based study of male and female American Indians. Subjects with and without PTSD were identified from American Indians living on/near a Northern Plains reservation as part of a larger study. Over two days diurnal saliva samples were collected by staff at the University of Colorado Denver Clinical Research Center at waking, 30min after waking, before lunch, and before dinner. Generalized estimating equations linear regression models investigated the influence of PTSD on cortisol over time. The association of a lifetime diagnosis of PTSD with salivary cortisol level was assessed in subjects with complete data (PTSD: n=27; no PTSD n=32) for age, gender, and alcohol consumption in the past month. Subject mean age was 44 years, and 71% were women. When stratified by gender, women with a lifetime diagnosis of PTSD had significantly higher mean cortisol levels throughout the day than women without PTSD (p=0.01); but there was no significant association between PTSD and cortisol levels in men (p=0.36). The cortisol awakening response - the difference in cortisol levels from waking to 30min after waking - was not associated with PTSD in men or women. A lifetime diagnosis of PTSD may influence diurnal cortisol among American Indian women. These effects were independent of influences of current alcohol use/abuse. The unexpected elevation in cortisol in American Indian women with a lifetime diagnosis of PTSD may reflect acute anxiety associated with experiencing a number of novel tests in a strange location (e.g., cardiac imaging, medical, dental exams, etc.), or concurrent depression.

PAROTID FLUID CORTISOL AND CORTISONE.

DTIC Science & Technology

Concentrations of parotid fluid cortisol and cortisone, and of plasma dialyzable cortisol, were measured in normal men before and 2 hours after...of 8.5 to 17.7 micrograms/100 ml. after ACTH treatment, and to 39.4 micrograms/100 ml. after administration of the estrogen. However, parotid fluid...the increase in total plasma cortisol (which was over twice as high after administration of estrogen as of ACTH). Thus parotid fluid corticosteroids

The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

PubMed

Bruno, Oscar D; Rossi, María A; Juárez-Allen, Lea; Serra, Héctor A; Albiero, María C

2015-01-01

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p < 0.001). LNSC was 1.9 ± 1.2 nmol/l in 44 normal and 2.5 ± 1.6 in 45 obese subjects with no differences between them, but was significantly higher in 47 Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p < 0.001). Comparison of UFC/Cr and LNSC in samples obtained simultaneously showed that UFC/Cr was 12.0 ± 8.7 ng cortisol/mg creatinine in 34 normal, 12.3 ± 8.9 in 40 obese and 319.5 ± 333.4 in 35 CS subjects (p < 0.001 vs. normal and obese), whereas LNSC was 1.8 ± 1.2 nmol/l in normal, 2.6 ± 1.7 in obese and 24.6 ± 17.4 in CS patients (p < 0.001 vs. normal and obese); ROC curves showed comparable high sensitivity and specificity figures for the diagnosis of CS. We concluded that UFC/Cr test is easy to perform, readily available in routine laboratories, has high sensitivity and specificity, and offers a valuable alternative to LNSC in the study of Cushing's syndrome.

Elevated glucose levels in early puerperium, and association with high cortisol levels during parturition.

PubMed

Risberg, Anitha; Sjöquist, Mats; Wedenberg, Kaj; Larsson, Anders

2016-07-01

Background Gestational diabetes is one of the commonest metabolic problems associated with pregnancy and an accurate diagnosis is critical for the care. Research has shown that pregnant women have high levels of cortisol during the last stage of parturition. As cortisol is a diabetogenic hormone causing increased glucose levels, we wanted to study the association between cortisol and glucose levels during parturition. Materials and methods Glucose and cortisol were analyzed during parturition in 50 females divided according to slow (n = 11) and normal labors (n = 39). Blood samples were analyzed three times during the parturition and four times in the first day after delivery. Glucose levels were also measured once in each trimester. Results In the normal group, the glucose concentration increased from 6.2 (IQR 5.6-8.0) mmol/L in the latency phase to 11.6 (10.0-13.3) mmol/L at aftercare (p < 0.05). After parturition the glucose concentrations decreased gradually. There were significant Spearman rank correlations between glucose and cortisol values. Conclusions The changes associated with birth cause significant elevations of cortisol and glucose around parturition.

Salivary cortisol levels and infant temperament shape developmental trajectories in boys at risk for behavioral maladjustment.

PubMed

Pérez-Edgar, Koraly; Schmidt, Louis A; Henderson, Heather A; Schulkin, Jay; Fox, Nathan A

2008-08-01

Behavioral problems in young children can take on a variety of forms, which are linked to distinct antecedents and co-occurring markers. Internalizing difficulties in young children, for example, have been linked to individual differences in infant temperament and cortisol levels. In addition, there is growing evidence that these biobehavioral mechanisms are also shaped by gender. Four-year-old children participated in a study examining the relations between salivary cortisol and behavioral maladjustment as a function of gender and temperament. Both longitudinal (maternal report of infant temperament at 9 months) and concurrent (morning salivary cortisol at age 4) data were used to predict two forms of maladjustment: 'Withdrawal' (maternal report of internalizing behavior and laboratory observation of social reticence) and 'Acting Out' (maternal report of externalizing behavior and laboratory observation of solitary active play). High basal cortisol levels were strongly associated with Withdrawal in male participants. However, the relation was significant only in boys who exhibited high levels of negative temperament in infancy. There were no comparable findings with 'Acting Out' beyond a main effect of gender reflecting greater difficulty in boys. The data suggested that there are unique biobehavioral mechanisms shaping specific patterns of maladjustment in childhood.

Associations between circadian and stress response cortisol in children.

PubMed

Simons, Sterre S H; Cillessen, Antonius H N; de Weerth, Carolina

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (M age  = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

Stress-induced ascorbic acid depletion and cortisol production in two salmonid fishes

USGS Publications Warehouse

Wedemeyer, Gary

1969-01-01

Interrenal ascorbic acid and serum cortisol were measured in non-specificity stressed yearling coho salmon and rainbow trout.Interrenal ascorbate was markedly decreased during stress but increased to normal if adaptation occurred.Serum cortisol was elevated by non-specific stress and remained high after interrenal ascorbate had returned to initial levels.

Salivary cortisol and cortisone in the clinical setting.

PubMed

Blair, Joanne; Adaway, Jo; Keevil, Brian; Ross, Richard

2017-06-01

A resurgence of interest in salivary biomarkers has generated evidence for their value in assessing adrenal function. The advantages of salivary measurements include only free hormone is detected, samples can be collected during normal daily routines and stress-induced cortisol release is less likely to occur than during venepuncture. We review the use of salivary biomarkers to diagnose and monitor patients for conditions of cortisol excess and deficiency and discuss the value of measuring salivary cortisone versus salivary cortisol. Developments in laboratory techniques have enabled the measurement of salivary hormones with a high level of sensitivity and specificity. In states of altered cortisol binding, salivary biomarkers are more accurate measures of adrenal reserve than serum cortisol. Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations. Salivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.

[Serum cortisol level variations in thyroid diseases].

PubMed

Seck-Gassama; Ndoye, O; Mbodj, M; Akala, A; Cisse, F; Niang, M; Ndoye, R

2000-01-01

This work studies the thyroid disorders impact on adrenals glands by measuring total cortisol. Radioimmunoassays of thyroid hormones and cortisol were performed in 108 subjects, aged 20-52 years, with thyroid diseases. Our results show low cortisol values (80.35 nmol/L) in 4.77% of hyperthyroids, high values in 3.57% of hyperthyroids (1348.18 nmol/L) and 12.5% of hypothyroids (969.05 nmol/L). In hyperthyroidism, thyroid hormone stimulates the secretion of 11 ceto metabolites biologically inactive, unable to slow pituitary activity, inducing an increased production of endogene cortisol. Excessive catabolism can lead to the exhausting of overstimulated adrenal glands, and therefore to a decreased cortisol. In hypothyroidism, high cortisol results of increase cortisol half life and decrease of metabolic clearance. Control mechanisms often allow normal cortisol values. These alterations in functional activity of adrenal glands, seen in nearly 10% of these subjects, sometimes command a specific attitude in diagnosis and therapy.

Urinary Cortisol Circadian Rhythm in a Group of High-Functioning Children with Autism.

ERIC Educational Resources Information Center

Richdale, Amanda L.; Prior, Margot R.

1992-01-01

This study found no evidence for abnormal temporal placement of the basal urinary cortisol circadian rhythm in a group of 18 high-functioning children (ages 4-14) with autism. There was a tendency toward cortisol hypersecretion during the day, predominantly in autistic children who were integrated into the normal school system. (Author/JDD)

Synthesis of amino acids in weight bearing and non-weight bearing leg muscles of suspended rats

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Jaspers, S. R.

1982-01-01

The effect of hypokinesia (HYP) for 6 days on the de novo synthesis of glutamine (GLN) and glutamate (GLU), and of alanine was tested in isolated leg muscles of intact, adrenalectomized (ADX) and ADX cortisol-treated rats. The net synthesis of GLN and GLU was lower in soleus muscles of HYP animals of these three groups of rats. The synthesis of alanine was lowered by HYP in ADX animals and apparently raised by HYP in ADX cortisol-treated rats. No HYP effect was seen in the extensor digitorum longus (EDL) muscles of these animals. Although ADX lowered the synthesis of GLN and GLU in soleus muscles of control rats, while cortisol treatment restored this process to near normal, neither ADX nor cortisol treatment produced any effect in the HYP animals. However, effects of ADX and cortisol treatment on synthesis of GLN and GLU in EDL muscles and of alanine in both muscles seemed normal in HYP animals.

Urinary free cortisol in the diagnosis of Cushing's syndrome: how useful?

PubMed

Odeniyi, I A; Ifedayo, A O; Fasanmade, O A; Olufemi, A F

2013-01-01

Cushing's syndrome results from chronic exposure to excessive circulating levels of glucocorticoids. To confirm the clinical suspicion, biochemical tests are needed. These biochemical tests include the measurement of excess total endogenous cortisol secretion assessed by 24-hour urinary free cortisol (UFC), loss of the normal feedback of the hypothalamo-pituitary-adrenal axis assessed by suppressibility after dexamethasone testing, and disturbance of the normal circadian rhythm of cortisol secretion assessed by midnight serum or salivary cortisol. We searched the Medline, Pubmed, journal articles, WHO publications and reputable textbooks relating to Cushing's syndrome using publications from 1995 to 2011. UFC has been the classic screening test used to confirm hypercortisolemia as the first step in diagnostic work-up of Cushing's syndrome. Its long-term use in clinical practice has led to emergence of significant evidence regarding the utility of UFC in the diagnosis of Cushing's syndrome. UFC would have been a simple diagnostic tool to use but for the drawbacks in the sample collection, different laboratory methods of assay, not easily determined normal range. UFC use as a screening test is not strongly favoured because cortisol is not uniformly secreted during the day, and the increased prevalence of mild, preclinical or cyclic Cushing's syndrome. A very high level of UFC negates the need for other test procedures in patients with obvious symptoms and signs of Cushing's syndrome. We therefore suggest that UFC should be used with other screening tests for Cushing's syndrome to increase diagnostic yield.

Salivary cortisol among American Indians with and without posttraumatic stress disorder (PTSD): Gender and alcohol influences

PubMed Central

Laudenslager, Mark L.; Noonan, Carolyn; Jacobsen, Clemma; Goldberg, Jack; Buchwald, Dedra; Bremner, J. Douglas; Vaccarino, Viola; Manson, Spero M.

2009-01-01

Disruptions in hypothalamic-pituitary-adrenal regulation and immunity have been associated with posttraumatic stress disorder (PTSD). We examined the association of PTSD with diurnal rhythms in salivary cortisol in a convenience sample from a population-based study of male and female American Indians. Subjects with and without PTSD were identified from American Indians living on/near a Northern Plains reservation as part of a larger study. Over two days diurnal saliva samples were collected by staff at the University of Colorado Denver Clinical Research Center at waking, 30 minutes after waking, before lunch, and before dinner. Generalized estimating equations linear regression models investigated the influence of PTSD on cortisol over time. The association of a lifetime diagnosis of PTSD with salivary cortisol level was assessed in subjects with complete data (PTSD: n=27; no PTSD n=32) for age, gender, and alcohol consumption in the past month. Subject mean age was 44 years, and 71% were women. When stratified by gender, women with a lifetime diagnosis of PTSD had significantly higher mean cortisol levels throughout the day than women without PTSD (p = 0.01); but there was no significant association between PTSD and cortisol levels in men (p = 0.36). The cortisol awakening response – the difference in cortisol levels from waking to 30 minutes after waking – was not associated with PTSD in men or women. A lifetime diagnosis of PTSD may influence diurnal cortisol among American Indian women. These effects were independent of influences of current alcohol use/abuse. The unexpected elevation in cortisol in American Indian women with a lifetime diagnosis of PTSD may reflect acute anxiety associated with experiencing a number of novel tests in a strange location (e.g., cardiac imaging, medical and dental exams, etc.), or concurrent depression. PMID:19146946

Environmental enrichment of brown capuchins (Cebus apella): Behavioral and plasma and fecal cortisol measures of effectiveness

USGS Publications Warehouse

Boinski, S.; Swing, S.P.; Gross, T.S.; Davis, J.K.

1999-01-01

No consensus exists about the quantity and variety of environmental enrichment needed to achieve an acceptable level of psychological well-being among singly housed primates. Behavioral and plasma and fecal cortisol measures were used to evaluate the effectiveness of four levels of toy and foraging enrichment provided to eight wild-caught, singly housed adult male brown capuchins (Cebus apella). The 16-week-long study comprised six conditions and began with a 4-week-long preexperimental and ended with a 4-week-long postexperimental period during which the subjects were maintained at baseline enrichment levels. During the intervening 8 weeks, the subjects were randomly assigned to a sequence of four 2-week-long experimental conditions: control (baseline conditions), toy (the addition of two plastic toys to each cage), box (access to a foraging box with food treats hidden within crushed alfalfa), and box and toy (the addition of two plastic toys and access to a foraging box). Behavioral responses to changes in enrichment were rapid and extensive. Within-subject repeated-measure ANOVAs with planned post hoc contrasts identified highly significant reductions in abnormal and undesirable behaviors (and increases in normal behaviors) as the level of enrichment increased from control to toy to box to box and toy. No significant behavioral differences were found between the control and pre- and postexperimental conditions. Plasma and fecal cortisol measures revealed a different response to changing enrichment levels. Repeated-measure ANOVA models found significant changes in both these measures across the six conditions. The planned post hoc analyses, however, while finding dramatic increases in cortisol titers in both the pre- and postexperimental conditions relative to the control condition, did not distinguish cortisol responses among the four enrichment levels. Linear regressions among weekly group means in behavioral and cortisol measures (n = 16) found that plasma cortisol was significantly predicted by the proportions of both normal and abnormal behaviors; as the proportion of normal behaviors increased, the plasma cortisol measures decreased. Plasma cortisol weekly group means were also significantly and positively predicted by fecal cortisol weekly group means, but no behavioral measure significantly predicted fecal cortisol weekly group means. In sum, these findings argue strongly that access to a variety of toy and foraging enrichment positively affects behavioral and physiological responses to stress and enhances psychological well-being in singly housed brown capuchins.

Environmental enrichment of brown capuchins (Cebus apella): behavioral and plasma and fecal cortisol measures of effectiveness.

PubMed

Boinski, S; Swing, S P; Gross, T S; Davis, J K

1999-01-01

No consensus exists about the quantity and variety of environmental enrichment needed to achieve an acceptable level of psychological well-being among singly housed primates. Behavioral and plasma and fecal cortisol measures were used to evaluate the effectiveness of four levels of toy and foraging enrichment provided to eight wild-caught, singly housed adult male brown capuchins (Cebus apella). The 16-week-long study comprised six conditions and began with a 4-week-long preexperimental and ended with a 4-week-long postexperimental period during which the subjects were maintained at baseline enrichment levels. During the intervening 8 weeks, the subjects were randomly assigned to a sequence of four 2-week-long experimental conditions: control (baseline conditions), toy (the addition of two plastic toys to each cage), box (access to a foraging box with food treats hidden within crushed alfalfa), and box & toy (the addition of two plastic toys and access to a foraging box). Behavioral responses to changes in enrichment were rapid and extensive. Within-subject repeated-measure ANOVAs with planned post hoc contrasts identified highly significant reductions in abnormal and undesirable behaviors (and increases in normal behaviors) as the level of enrichment increased from control to toy to box to box & toy. No significant behavioral differences were found between the control and pre- and postexperimental conditions. Plasma and fecal cortisol measures revealed a different response to changing enrichment levels. Repeated-measure ANOVA models found significant changes in both these measures across the six conditions. The planned post hoc analyses, however, while finding dramatic increases in cortisol titers in both the pre- and postexperimental conditions relative to the control condition, did not distinguish cortisol responses among the four enrichment levels. Linear regressions among weekly group means in behavioral and cortisol measures (n=16) found that plasma cortisol was significantly predicted by the proportions of both normal and abnormal behaviors; as the proportion of normal behaviors increased, the plasma cortisol measures decreased. Plasma cortisol weekly group means were also significantly and positively predicted by fecal cortisol weekly group means, but no behavioral measure significantly predicted fecal cortisol weekly group means. In sum, these findings argue strongly that access to a variety of toy and foraging enrichment positively affects behavioral and physiological responses to stress and enhances psychological well-being in singly housed brown capuchins.

Single awakening salivary measurements provide reliable estimates of morning cortisol levels in pregnant women.

PubMed

Vlenterie, Richelle; Roeleveld, Nel; van Gelder, Marleen M H J

2016-12-01

Mood disorders during pregnancy have been associated with adverse effects on maternal as well as fetal health. Since mood, anxiety, and stress disorders are related with elevated cortisol levels, salivary cortisol may be a useful biomarker. Although multiple samples are generally recommended, a single measurement of awakening salivary cortisol could be a simpler and more cost-effective method to determine whether women have elevated morning cortisol levels during a specific period of pregnancy. Therefore, the aim of this validation study among 177 women in the PRIDE Study was to examine whether one awakening salivary cortisol measurement will suffice to classify pregnant women as having normal or elevated cortisol levels compared to awakening salivary cortisol measurements on three consecutive working days. We calculated intraclass correlation coefficients (ICC) and Cohen's kappa statistics (κ) overall as well as in sub-analyses within strata based on maternal age, level of education, net household income, pre-pregnancy BMI, parity, complications during pregnancy, caffeine consumption, gestational week of sampling, and awakening time. The mean cortisol concentrations were 8.98ng/ml (SD 5.32) for day one, 8.62ng/ml (SD 4.55) for day two, and 8.39ng/ml (SD 4.58) for day three. The overall ICC was 0.86 (95% CI 0.82-0.89) while the κ was 0.75 (95% CI 0.64-0.86). For the ICCs calculated within sub-analyses, a maximum difference of 0.11 was observed between the strata. For the κ statistics, most strata did not differ more than 0.12, except for pre-pregnancy BMI, severe nausea, and extreme fatigue with differences up to 0.22. In conclusion, one awakening salivary cortisol measurement is as reliable for the classification of pregnant women into normal and elevated morning cortisol levels as salivary cortisol measurements on three consecutive working days. Copyright © 2016 Elsevier Ltd. All rights reserved.

HPA axis response to social stress is attenuated in schizophrenia but normal in depression: evidence from a meta-analysis of existing studies.

PubMed

Ciufolini, Simone; Dazzan, Paola; Kempton, Matthew J; Pariante, Carmine; Mondelli, Valeria

2014-11-01

We conducted a meta-analysis to investigate the HPA axis response to social stress in studies that used the Trier Social Stress Test (TSST), or comparable distressing paradigms, in individuals with either depression or schizophrenia. Sample size-adjusted effect sizes (Hedge's g statistic) were calculated to estimate the HPA axis stress response to social stress. We used a meta-regression model to take into account the moderating effect of the baseline cortisol level. Participants with depression show an activation pattern to social stress similar to that of healthy controls. Despite a normal cortisol production rate, individuals with schizophrenia have lower cortisol levels than controls both in anticipation and after exposure to social stress. Participants with depression and higher cortisol levels before the task have an increased cortisol production and reached higher cortisol levels during the task. This may be explained by the presence of an impaired negative feedback. The activation pattern present in schizophrenia may explain the reduced ability to appropriately contextualize past experiences shown by individuals with psychosis in social stressful situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Salivary Cortisol Levels and Infant Temperament shape Developmental Trajectories in Boys At Risk for Behavioral Maladjustment

PubMed Central

Pérez-Edgar, Koraly; Schmidt, Louis A.; Henderson, Heather A.; Schulkin, Jay; Fox, Nathan A.

2008-01-01

SUMMARY Behavioral problems in young children can take on a variety of forms, which are linked to distinct antecedents and co-occurring markers. Internalizing difficulties in young children, for example, have been linked to individual differences in infant temperament and cortisol levels. In addition, there is growing evidence that these biobehavioral mechanisms are also shaped by gender. Four-year-old children participated in a study examining the relations between salivary cortisol and behavioral maladjustment as a function of gender and temperament. Both longitudinal (maternal report of infant temperament at 9 months) and concurrent (morning salivary cortisol at age 4) data were used to predict two forms of maladjustment: ‘Withdrawal’ (maternal report of internalizing behavior and laboratory observation of social reticence) and ‘Acting Out’ (maternal report of externalizing behavior and laboratory observation of solitary active play). High basal cortisol levels were strongly associated with Withdrawal in male participants. However, the relation was significant only in boys who exhibited high levels of negative temperament in infancy. There were no comparable findings with ‘Acting Out’ beyond a main effect of gender reflecting greater difficulty in boys. The data suggested that there are unique biobehavioral mechanisms shaping specific patterns of maladjustment in childhood. PMID:18650023

Moderating Effects of Cortisol on Neural-Cognitive Association in Cognitively Normal Elderly Subjects

PubMed Central

Lau, Way K. W.; Leung, Mei Kei; Law, Andrew C. K.; Lee, Tatia M. C.

2017-01-01

Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale—third edition (WAIS-III). Serum cortisol levels (sampled in the late morning) were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV) of the right thalamus, the gray matter volumes (GMV) of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG) in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning. PMID:28596732

[Proceeding: Production rate, metabolic clearance rate and mean plasma concentration of cortisol in hyperthyroidism (author's transl)].

PubMed

Linquette, M; Lefebvre, J; Racadot, A; Cappoen, J P

1975-01-01

The adrenocortical function was studied in 23 patients with hyperthyroidism and compared with a group of 15 normal subjects. Parameters of adrenal function were determined with 1,2(3)H-cortisol. The half-life of cortisol is significantly shortened in hyperthyroidism, as compared to normal subjects (49,5 +/- 6,6 min vs 68,3 +/- 10,5 min) and metabolic clearance rate is increased (418,5 +/- 89,5 L/24 h vs 237,5 +/- 48,5 L/24 h, for normal subjects). The production rate of cortisol, calculated from specific and cumulate activities of THE and THF is increased in hyperthyroidism expressed as mg/24 h or mg/m2/24 h (respectively : 26,7 +/- 7,8 mg/24 h vs 15,7 +/- 3 mg/24 h and 16,9 +/- 4,6 mg/m2/24 h vs 9,5 +/- 1,8 mg/m2/24 h). The mean plasma concentration, calculated as the radio (see article) is not statiscally different in hyperthyroid and normal subjects (6,8 +/- 2,1 microg/100 ml vs 7,3 +/- 1,9 microg/100 ml). 7 patients were reinvestigated after treatment of thyrotoxicosis when they were clinically and biologically in euthyroid state. All the values were normalized, without statistically significant difference from control (T 1/2 = 65,4 +/- 18 min, Metb Cl. Rate : 255 +/- 64,5 L/24 h, production rate : 15,6 +/- 1,8 mg/24 h and 9 +/- 1,4 mg/m2/24 h. mean plasma concentration : 6,8 +/- 2,8 microg/100 ml). Shortened cortisol half life, increased metabolic clearance rate and production rate, and normal mean plasma concentration have been reported in hyperthyroidism (Peterson, Copinschi, Gallagher). These changes, secondary to thyroid hormone excess, are the consequences of increased hepatic catabolism of cortisol. The activity of 11 OH steroid deshydrogenase is increased, as demonstrated by increased ratio (see article) in normal subjects (0,001 less than p less than 0,005). There is a high proportion of 17 kéto metabolites (E, DHE, THE) whose feed-back effect is weak as compared to 17 OH metabolites (F, DHF, THF). The hypothalamo-hypophyso-adrenal system is stimulated to maintain a normal plasma concentration. The fact that the mean plasma concentration is normal despite the increased production rate suggest that changes are rather due to increased catabolism than to central effect of thyroid hormones.

NMDA receptor modulation by dextromethorphan and acute stress selectively alters electroencephalographic indicators of partial report processing.

PubMed

Weckesser, Lisa J; Enge, Sören; Riedel, Philipp; Kirschbaum, Clemens; Miller, Robert

2017-10-01

Proceeding from a biophysical network model, the present study hypothesized that glutamatergic neurotransmission across the NMDA receptor (NMDAR) plays a key role in visual perception and its modulation by acute stress. To investigate these hypotheses, behavioral and electroencephalographic (EEG) indicators of partial report task processing were assessed in twenty-four healthy young men who randomly received a non-competitive NMDAR antagonist (0.8 mg/kg dextromethorphan, DXM) or a placebo, and concurrently accomplished a stress-induction (MAST) or control protocol in three consecutive sessions. Saliva samples served to quantify cortisol responses to the MAST, whereas a passive auditory oddball paradigm was implemented to verify the impact of DXM on the EEG-derived mismatch negativity component (MMN). DXM administration significantly increased MMN amplitudes but not salivary cortisol concentrations. By contrast, concurrent MAST exposure significantly reduced MMN latencies but also increased cortisol concentrations. With regard to EEG indicators, DXM administration reduced visually "evoked" (30Hz to 50Hz) and "induced" occipital gamma-band activity (70Hz to 100Hz), which was partly compensated by additional MAST exposure. However, neither the interventions nor EEG activity were significantly associated with behavioral partial report sensitivities. In summary, the present data suggest that glutamatergic neurotransmission across the NMDAR is only one among many determinants of intact visual perception. Accordingly, therapeutic doses of DXM and their inhibitory modulation by stress probably yield more pronounced electroencephalographic as compared with behavioural effects. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

PubMed Central

Torres-Farfan, Claudia; Richter, Hans G; Germain, Alfredo M; Valenzuela, Guillermo J; Campino, Carmen; Rojas-García, Pedro; Forcelledo, María Luisa; Torrealba, Fernando; Serón-Ferré, María

2004-01-01

We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[125I] iodomelatonin binding (Kd, 75.7 ± 6.9 pm; Bmax, 2.6 ± 0.4 fmol (mg protein)−1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation. PMID:14673186

The Effect of Otolith Malformation on Behavior and Cortisol Levels in Juvenile Red Drum Fish (Sciaenops ocellatus)

PubMed Central

Browning, Zoe S; Wilkes, Allison A; Moore, Erica J; Lancon, Trevor W; Clubb, Fred J

2012-01-01

Captive-raised red drum fish were observed with phenotypic abnormalities, including deformities of the spine, jaw, and cephalic region, that were consistent with vitamin C deficiency during the larval stage. In light of their visible exterior skeletal abnormalities, we suspected that the affected fish would also have abnormal otoliths. Otoliths are dense calcareous structures that function in fish hearing. We hypothesized that abnormal fish would have irregular otoliths that would alter behavior and cortisol levels as compared with those of phenotypically normal fish. The normal and abnormal fish had statistically significant differences in behavior, cortisol levels, and otolith volume and density. MicroCT assessment of abnormal fish revealed operculum abnormalities, malocclusions, and several types of otolith malformations. Therefore, the affected fish had not only an abnormal skeletal appearance but also significantly abnormal behavior and cortisol responses. PMID:23043776

Central adrenal insufficiency in young adults with Prader-Willi syndrome.

PubMed

Grugni, Graziano; Beccaria, Luciano; Corrias, Andrea; Crinò, Antonino; Cappa, Marco; De Medici, Clotilde; Di Candia, Stefania; Gargantini, Luigi; Ragusa, Letizia; Salvatoni, Alessandro; Sartorio, Alessandro; Spera, Sabrina; Andrulli, Simeone; Chiumello, Giuseppe; Mussa, Alessandro

2013-09-01

A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST). Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 μg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST. Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505). Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST. © 2013 John Wiley & Sons Ltd.

Adolescents’ Cortisol Reactivity and Subjective Distress in Response to Family Conflict: The Moderating Role of Internalizing Symptoms

PubMed Central

Spies, Lauren A.; Margolin, Gayla; Susman, Elizabeth J.; Gordis, Elana B.

2011-01-01

Purpose Internalizing symptoms have been associated with both higher and blunted cortisol responses in adolescents. Little attention has been paid to subjective experiences of distress in conjunction with internalizing symptoms in hypothalamic-pituitary-adrenal (HPA) axis responses to laboratory stressors. This report examines whether adolescents’ internalizing symptoms moderate the association between cortisol responses and distress in response to a common stressor in adolescence: family conflict. Differences are also examined between adolescents with current, past only, and no history of internalizing symptoms. Methods Adolescents (N = 70) discussed areas of conflict with their parents and subsequently reported on distress experienced during the discussion. Baseline and 5 post-stressor saliva samples were collected. Adolescents’ internalizing symptoms were assessed concurrently with the discussion and at three previous time-points. Results Internalizing symptoms moderated the association between adolescents’ reported distress and cortisol reactivity in response to family conflict. Adolescents with current and past internalizing symptoms had a blunted cortisol response, whereas adolescents with no history of internalizing symptoms showed greater cortisol reactivity when reporting greater distress. Conclusions This study expands the understanding of how current and remitted internalizing symptoms are related to adolescents’ responses to everyday family conflicts. Adolescents with current and past internalizing symptoms demonstrated a lack of correspondence between psychological and physiological stress, whereas adolescents with no history of internalizing symptoms showed the anticipated correspondence. This study has important implications for understanding the link between internalizing symptoms and adolescents’ HPA functioning in response to common social stressors. PMID:21939869

Change of salivary stress marker concentrations during pregnancy: maternal depressive status suppress changes of those levels.

PubMed

Tsubouchi, Hiroaki; Nakai, Yuichiro; Toda, Masahiro; Morimoto, Kanehisa; Chang, Yang Sil; Ushioda, Norichika; Kaku, Shoji; Nakamura, Takafumi; Kimura, Tadashi; Shimoya, Koichiro

2011-08-01

The aim of the present study was to show changes in salivary cortisol and chromogranin A/protein concentrations as stress markers during pregnancy and to clarify the effect of chronic stress on stress markers. Salivary samples were collected from 69 pregnant women during pregnancy. Salivary cortisol levels and chromogranin A/protein titers were determined. We surveyed the women's chronic stress using the Zung self-rating depression scale and General Health Questionnaire-28. Cortisol levels in the saliva of pregnant women showed biphasic change during pregnancy. Chromogranin A/protein levels in the saliva of pregnant women increased in the second and the early third trimesters and decreased to the puerperal period. Salivary cortisol concentrations of the chronic high stress group were significantly lower compared with those of the normal group. Salivary chromogranin A/protein concentrations of the chronic high stress group were also significantly lower than those of the normal group. The titration of salivary cortisol concentrations and chromogranin A/protein levels is a useful tool to determine maternal stress levels. The elevation of cortisol and chromogranin A/protein in the saliva was suppressed in the chronic high stress group during pregnancy. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Routine Support to Parents and Stressors in Everyday Domains: Associations With Negative Affect and Cortisol.

PubMed

Savla, Jyoti; Zarit, Steven H; Almeida, David M

2018-03-02

Adult children are involved a myriad of roles including providing routine (non-caregiving) support to a parent. Yet we know little about whether providing routine support to a parent is stressful and whether it has any associations with stressors in other life domains. We use daily diary data (N = 127; Study Days = 424) from the National Study of Daily Experiences to determine whether providing routine support to an older parent is associated with higher negative affect and salivary cortisol. Results confirm that providing routine support and experiencing stressors at work were independently associated with negative affect and greater cortisol output. Stress reactions were not amplified, however, on days when adult children concurrently provided support to a parent and reported work stressors. Cutting back usual activities at work or home elevated negative affect but were not associated with an upsurge of cortisol production. Findings lend support to the caregiving career framework for understanding even casual routine assistance provided to a parent. Published by Oxford University Press on behalf of The Gerontological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The interaction between parenting and children's cortisol reactivity at age 3 predicts increases in children's internalizing and externalizing symptoms at age 6.

PubMed

Barrios, Chelsey S; Bufferd, Sara J; Klein, Daniel N; Dougherty, Lea R

2017-10-01

Little is known about the role of stress reactivity in the emergence of psychopathology across early childhood. In this longitudinal study, we tested the hypothesis that child cortisol reactivity at age 3 moderates associations between early parenting and children's internalizing and externalizing symptoms from age 3 to age 6. One hundred and sixty children were assessed at age 3, and 135 children were reassessed at age 6. At age 3, we exposed children to stress-inducing laboratory tasks, during which we obtained four salivary cortisol samples, and parental hostility was assessed using an observational parent-child interaction task. At ages 3 and 6, child psychiatric symptoms were assessed using a clinical interview with parents. The results indicated that the combination of high child cortisol reactivity and high observed parental hostility at age 3 was associated with greater concurrent externalizing symptoms at age 3 and predicted increases in internalizing and externalizing symptoms from age 3 to age 6. Findings highlight that increased stress reactivity, within the context of hostile parenting, plays a role in the emergence of psychopathology from preschool to school entry.

The Interaction Between Parenting and Children’s Cortisol Reactivity at Age Three Predicts Increases in Children’s Internalizing and Externalizing Symptoms at Age Six

PubMed Central

Barrios, Chelsey S.; Bufferd, Sara J.; Klein, Daniel N.; Dougherty, Lea R.

2017-01-01

Little is known about the role of stress reactivity in the emergence of psychopathology across early childhood. In this longitudinal study, we tested the hypothesis that child cortisol reactivity at age three moderates associations between early parenting and children’s internalizing and externalizing symptoms from age three to age six. 160 children were assessed at age three and 135 children were reassessed at age six. At age three, we exposed children to stress-inducing laboratory tasks, during which we obtained four salivary cortisol samples, and parental hostility was assessed using an observational parent-child interaction task. At ages three and six, child psychiatric symptoms were assessed using a clinical interview with parents. Results indicated that the combination of high child cortisol reactivity and high observed parental hostility at age three was associated with greater concurrent externalizing symptoms at age three and predicted increases in internalizing and externalizing symptoms from age three to age six. Findings highlight that increased stress reactivity, within the context of hostile parenting, plays a role in the emergence of psychopathology from preschool to school entry. PMID:28290253

Evaluating a novel analgesic strategy for ring castration of ram lambs.

PubMed

Paull, David R; Small, Alison H; Lee, Caroline; Palladin, Pierre; Colditz, Ian G

2012-09-01

To evaluate the analgesic efficacy of the NSAIDs flunixin and meloxicam administered locally to the scrotum before ring castration. Randomised, controlled, prospective study. Forty eight single born male Merino lambs. Lambs, aged approximately 4 weeks, were allocated to four groups for castration. Groups were: sham control; castration + saline; castration + flunixin; castration + meloxicam. Drugs (5 mL) were administered subcutaneously around the circumference of the scrotum immediately before castration. Cortisol, rectal temperature, haematology and plasma haptoglobin were measured before and up to 48 hours after treatment. Behaviour recorded by video for 12 hours after treatment was classified as pain avoidance behaviours in the first hour and postural behaviours in three 4 hour intervals. Ring castration (saline group) induced a bi-phasic increase in cortisol with peaks at 90 minutes and 24 hours but no significant changes in haematology, haptoglobin or rectal temperature. Pain avoidance behaviours were increased and teat seeking decreased. Normal lying and normal standing postures were decreased and abnormal ventral lying, statue standing, abnormal standing and total abnormal postures increased. Flunixin decreased cortisol at 90 minutes (60.3 versus 117.3 nmol L(-1) ) and cortisol AUC (0-6 hours), decreased elevated leg movement (2.5 versus 5.4 events) and sum of pain avoidance behaviours (8.5 versus 16.7 events), improved time spent in normal ventral lying and decreased abnormal ventral lying and total abnormal postures compared to saline treated lambs. In a similar contrast, meloxicam caused non-significant decreases in cortisol at 90 minutes, cortisol AUC (0-6 hours) and pain avoidance behaviours, and significantly improved the postural behaviours normal ventral lying (26.7 versus 15.4%) and normal standing (13.9 versus 7.5%), and reduced abnormal standing and total abnormal postures. Physiological and behavioural responses associated with ring castration for both NSAID treatment groups were generally greater than sham controls. Locally administered NSAIDs provided partial analgesia for ring castration. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion.

PubMed

Debono, Miguel; Harrison, Robert F; Chadarevian, Rita; Gueroult, Carole; Abitbol, Jean-Louis; Newell-Price, John

2017-09-01

Adrenal incidentalomas (AIs) are found commonly on axial imaging. Around 30% exhibit autonomous cortisol secretion (ACS) associated with increased cardiovascular events and death. We hypothesized that AI/ACS patients have an abnormal cortisol rhythm that could be reversed by use of carefully timed short-acting cortisol synthesis blockade, with improvement in cardiovascular disease markers. In a phase 1/2a, prospective study (Eudract no. 2012-002586-35), we recruited six patients with AI/ACS and two control groups of six sex-, age-, and body mass index-matched individuals: (1) patients with AI and no ACS (AI/NoACS) and (2) healthy volunteers with no AI [healthy controls (HC)]. Twenty-four-hour circadian cortisol analysis was performed to determine any differences between groups and timing of intervention for cortisol lowering using the 11β-hydroxylase inhibitor metyrapone. Circadian profiles of serum interleukin-6 (IL-6) were assessed. Serum cortisol levels in group AI/ACS were significantly higher than both group AI/NoACS and group HC from 6 pm to 10 pm [area under the curve (AUC) difference: 0.81 nmol/L/h; P = 0.01] and from 10 pm to 2 am (AUC difference: 0.86 nmol/L/h; P < 0.001). In light of these findings, patients with ACS received metyrapone 500 mg at 6 pm and 250 mg at 10 pm, and cortisol rhythms were reassessed. Postintervention evening serum cortisol was lowered, similar to controls [6 pm to 10 pm (AUC difference: -0.06 nmol/L/h; P = 0.85); 10 pm to 2 am (AUC difference: 0.10 nmol/L/h; P = 0.76)]. Salivary cortisone showed analogous changes. IL-6 levels were elevated before treatment [10 pm to 2 pm (AUC difference: 0.42 pg/mL/h; P = 0.01)] and normalized post treatment. In AI/ACS, the evening and nocturnal cortisol exposure is increased. Use of timed evening doses of metyrapone resets the cortisol rhythm to normal. This unique treatment paradigm is associated with a reduction in the cardiovascular risk marker IL-6. Copyright © 2017 Endocrine Society

Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study

PubMed Central

2014-01-01

Background Lead (Pb) exposure during pregnancy may increase the risk of adverse maternal, infant, or childhood health outcomes by interfering with hypothalamic-pituitary-adrenal-axis function. We examined relationships between maternal blood or bone Pb concentrations and features of diurnal cortisol profiles in 936 pregnant women from Mexico City. Methods From 2007–11 we recruited women from hospitals/clinics affiliated with the Mexican Social Security System. Pb was measured in blood (BPb) during the second trimester and in mothers’ tibia and patella 1-month postpartum. We characterized maternal HPA-axis function using 10 timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14–35 weeks gestation). We used linear mixed models to examine the relationship between Pb biomarkers and cortisol area under the curve (AUC), awakening response (CAR), and diurnal slope. Results After adjustment for confounders, women in the highest quintile of BPb concentrations had a reduced CAR (Ratio: −13%; Confidence Interval [CI]: −24, 1, p-value for trend < 0.05) compared to women in the lowest quintile. Tibia/patella Pb concentrations were not associated with CAR, but diurnal cortisol slopes were suggestively flatter among women in the highest patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: −2, 33). BPb and bone Pb concentrations were not associated with cortisol AUC. Conclusions Concurrent blood Pb levels were associated with cortisol awakening response in these pregnant women and this might explain adverse health outcomes associated with Pb. Further research is needed to confirm these results and determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal-axis function during pregnancy. PMID:24916609

Additive effect of ketoconazole and octreotide in the treatment of severe adrenocorticotropin-dependent hypercortisolism.

PubMed

Vignati, F; Loli, P

1996-08-01

Over the last few years ketoconazole and octreotide have been employed in the treatment of pituitary-dependent or ectopic Cushing's syndrome. In four patients (two men and two women, aged 25-64 yr) with severe ACTH-dependent hypercortisolism in whom medical treatment with ketoconazole showed limited effectiveness and/or tolerability, we tried the association with octreotide. In all patients ketoconazole (200-1000 mg) induced a marked decrease in urinary free cortisol (UFC) excretion, but normalization could not be achieved. After ketoconazole discontinuation, three patients received octreotide alone (300-1500 micrograms/day, sc). This drug caused a dramatic decrease in UFC excretion, although not normalization; in all patients, escape from treatment occurred. Combined treatment was carried out for 10-180 days. Urinary cortisol excretion normalized and remained steadily within normal limits in three of four patients in whom normal UFC excretion had never been attained with both single drug regimens; in the fourth patient, UFC excretion decreased to levels lower than those achieved with ketoconazole or octreotide alone. The association with octreotide allowed a reduction in the daily dose of ketoconazole in three patients. Consistent with the steady reduction of cortisol production, a striking clinical improvement occurred in all patients after starting combined treatment. The normalization of UFC in three of four patients treated with both agents suggests that this approach may be useful in the long term treatment of severe forms of hypercortisolism of both pituitary and ectopic origin. In contrast to the limited effectiveness of each drug taken singularly at the same or higher doses, the association of the two drugs had an additive effect in the attainment of normal urinary cortisol excretion.

Compared to controls, patients with ruptured aneurysm and surgical intervention show increase in symptoms of depression and lower cognitive performance, but their objective sleep is not affected.

PubMed

Brand, Serge; Zimmerer, Stefan; Kalak, Nadeem; Planta, Sandra Von; Schwenzer-Zimmerer, Katja; Müller, Andreas Albert; Zeilhofer, Hans-Florian; Holsboer-Trachsler, Edith

2015-02-01

Patients with aneurysmal subarachnoid haemorrhage (aSAH) have impaired sleep and cognitive performance together with more difficulties in social and everyday life. Hypocortisolism has also been reported. However, a study assessing all dimensions between aSAH severity, objective and subjective sleep, cortisol secretion, cognitive performance and social and everyday life has not so far been performed. The aim of the present study was therefore two-fold: (1) to assess, in a sample of patients with aSAH, objective and subjective sleep, cognitive functioning, social skills and cortisol secretion concurrently, and (2) to compare patients on these variables with a control group. Twenty-one patients (17 females; mean age: 58.80 years) with ruptured aneurysm and surgical intervention and 21 (14 females; mean age: 58.90 years) age- and gender-matched controls took part in the study. Assessments covered objective sleep-EGG recordings, subjective sleep, salivary cortisol analysis, and psychological functioning including memory performance, mood, and emotion recognition. Compared to healthy controls, patients had lower scores for verbal memory performance and emotion recognition; they also reported more marked depressive symptoms and complained of poor sleep. However, no differences were found for objective sleep or cortisol secretion. Subjective and objective sleep, cortisol secretion and psychological functioning were unrelated. Findings indicate that patients with aSAH face psychological rather than physiological issues.

Salivary and serum cortisol levels in newborn infants.

PubMed

Forclaz, María V; Moratto, Eduardo; Pennisi, Alicia; Falco, Silvina; Olsen, Graciela; Rodríguez, Patricia; Papazian, Regina; Bergadá, Ignacio

2017-06-01

Given that serum cortisol level interpretation in newborn infants (NBIs) is hard, the objective of this study was to correlate baseline salivary and serum cortisol levels and to describe salivary cortisol levels in the first month of life. Descriptive, prospective, longitudinal, and correlational study. Term NBIs were selected from the Division of Neonatology of Hospital Nacional Profesor Alejandro Posadas in 2014. Cortisol was measured in saliva specimens while cortisol, cortisol-binding globulin, and albumin were measured in blood specimens. A linear correlation was performed to relate serum and salivary cortisol levels; Friedman test was conducted to compare cortisol levels during the first month of life, and the difference was used to analyze the performance of values equal to or lower than the first quartile. Fifty-five NBIs were studied. Serum cortisol: 7.65 (1.0-18.1 gg/dL); salivary cortisol: 35.88 (5.52-107.64 mmol/L); cortisol-binding globulin: 22.07 (16.5-33.0 gg/mL), expressed as median and range. The correlation coefficient between serum and salivary cortisol was 0.54, P = 0.001. Cortisol performance during the first month of life showed no statistically significant differences, and the difference between the second and the first specimen of values equal to or lower than the first quartile increased in 10 out of 12 patients. The measurement of cortisol in saliva reflects serum cortisol levels in normal NBIs. Some patients had low levels of cortisol at 36 hours of life and showed a trend towards a spontaneous increase during the first month of life.

Reduced nocturnal ACTH-driven cortisol secretion during critical illness

PubMed Central

Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.

2014-01-01

Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590

Acute psychosocial stress and children's memory.

PubMed

de Veld, Danielle M J; Riksen-Walraven, J Marianne; de Weerth, Carolina

2014-07-01

We investigated whether children's performance on working memory (WM) and delayed retrieval (DR) tasks decreased after stress exposure, and how physiological stress responses related to performance under stress. About 158 children (83 girls; Mage = 10.61 years, SD = 0.52) performed two WM tasks (WM forward and WM backward) and a DR memory task first during a control condition, and 1 week later during a stress challenge. Salivary alpha-amylase (sAA) and cortisol were assessed during the challenge. Only WM backward performance declined over conditions. Correlations between physiological stress responses and performance within the stress challenge were present only for WM forward and DR. For WM forward, higher cortisol responses were related to better performance. For DR, there was an inverted U-shape relation between cortisol responses and performance, as well as a cortisol × sAA interaction, with concurrent high or low responses related to optimal performance. This emphasizes the importance of including curvilinear and interaction effects when relating physiology to memory.

Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: a comparison of assays to establish hypercortisolism.

PubMed

Baid, Smita K; Sinaii, Ninet; Wade, Matt; Rubino, Domenica; Nieman, Lynnette K

2007-08-01

Although bedtime salivary cortisol measurement has been proposed as the optimal screening test for the diagnosis of Cushing's syndrome, its performance using commercially available assays has not been widely evaluated. Our objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement of salivary cortisol in obese subjects and healthy volunteers. We conducted a cross-sectional prospective study of outpatients. We studied 261 obese subjects (186 female) with at least two additional features of Cushing's syndrome and 60 healthy volunteers (30 female). Subjects provided split bedtime salivary samples for cortisol measurement by commercially available RIA and LC-MS/MS. Results were considered normal or abnormal based on the laboratory reference range. Subjects with abnormal results underwent evaluation for Cushing's syndrome. In paired samples, RIA gave a lower specificity than LC-MS/MS in obese subjects (86 vs. 94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects with at least one abnormal result, both values were abnormal in 44% (confidence interval 26-62%) of obese and 75% (confidence interval 33-96%) of healthy volunteers. In obese subjects, salivary cortisol concentrations were less than 4.0 to 643 ng/dl (<0.11-17.7 nmol/liter; normal, < or =100 ng/dl, 2.80 nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4-77.3 nmol/liter; normal, < or =170 ng/dl, 4.7 nmol/liter) by RIA. Cushing's syndrome was not diagnosed in any subject. Salivary cortisol levels should not be used as the sole test to diagnose Cushing's syndrome if laboratory-provided reference ranges are used for diagnostic interpretation.

The Short Cosyntropin Test Revisited: New Normal Reference Range Using LC-MS/MS.

PubMed

Ueland, Grethe Å; Methlie, Paal; Øksnes, Marianne; Thordarson, Hrafnkell B; Sagen, Jørn; Kellmann, Ralf; Mellgren, Gunnar; Ræder, Maria; Dahlqvist, Per; Dahl, Sandra R; Thorsby, Per M; Løvås, Kristian; Husebye, Eystein S

2018-04-01

The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges. The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays. Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile. Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively. LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.

Stress and the HPA Axis

PubMed Central

Stephens, Mary Ann C.; Wand, Gary

2012-01-01

Stress has long been suggested to be an important correlate of uncontrolled drinking and relapse. An important hormonal response system to stress—the hypothalamic–pituitary–adrenal (HPA) axis—may be involved in this process, particularly stress hormones known as glucocorticoids and primarily cortisol. The actions of this hormone system normally are tightly regulated to ensure that the body can respond quickly to stressful events and return to a normal state just as rapidly. The main determinants of HPA axis activity are genetic background, early-life environment, and current life stress. Alterations in HPA axis regulation are associated with problematic alcohol use and dependence; however, the nature of this dysregulation appears to vary with respect to stage of alcohol dependence. Much of this research has focused specifically on the role of cortisol in the risk for, development of, and relapse to chronic alcohol use. These studies found that cortisol can interact with the brain’s reward system, which may contribute to alcohol’s reinforcing effects. Cortisol also can influence a person’s cognitive processes, promoting habit-based learning, which may contribute to habit formation and risk of relapse. Finally, cortisol levels during abstinence may be useful clinical indicators of relapse vulnerability in alcohol-dependent people. PMID:23584113

Use of plasma metanephrine to aid adrenal venous sampling in combined aldosterone and cortisol over-secretion.

PubMed

Goupil, Rémi; Wolley, Martin; Ungerer, Jacobus; McWhinney, Brett; Mukai, Kuniaki; Naruse, Mitsuhide; Gordon, Richard D; Stowasser, Michael

2015-01-01

In patients with primary aldosteronism (PA) undergoing adrenal venous sampling (AVS), cortisol levels are measured to assess lateralization of aldosterone overproduction. Concomitant adrenal autonomous cortisol and aldosterone secretion therefore have the potential to confound AVS results. We describe a case where metanephrine was measured during AVS to successfully circumvent this problem. A 55-year-old hypertensive male had raised plasma aldosterone/renin ratios and PA confirmed by fludrocortisone suppression testing. Failure of plasma cortisol to suppress overnight following dexamethasone and persistently suppressed corticotrophin were consistent with adrenal hypercortisolism. On AVS, comparison of adrenal and peripheral A/F ratios (left 5.7 vs peripheral 1.0; right 1.7 vs peripheral 1.1) suggested bilateral aldosterone production, with the left gland dominant but without contralateral suppression. However, using aldosterone/metanephrine ratios (left 9.7 vs peripheral 2.4; right 1.3 vs peripheral 2.5), aldosterone production lateralized to the left with good contralateral suppression. The patient underwent left laparoscopic adrenalectomy with peri-operative glucocorticoid supplementation to prevent adrenal insufficiency. Pathological examination revealed adrenal cortical adenomas producing both cortisol and aldosterone within a background of aldosterone-producing cell clusters. Hypertension improved and cured of PA and hypercortisolism were confirmed by negative post-operative fludrocortisone suppression and overnight 1 mg dexamethasone suppression testing. Routine dexamethasone suppression testing in patients with PA permits detection of concurrent hypercortisolism which can confound AVS results and cause unilateral PA to be misdiagnosed as bilateral with patients thereby denied potentially curative surgical treatment. In such patients, measurement of plasma metanephrine during AVS may overcome this issue. Simultaneous autonomous overproduction of cortisol and aldosterone is increasingly recognised although still apparently uncommon.Because cortisol levels are used during AVS to correct for differences in dilution of adrenal with non-adrenal venous blood when assessing for lateralisation, unilateral cortisol overproduction with contralateral suppression could confound the interpretation of AVS resultsMeasuring plasma metanephrine during AVS to calculate lateralisation ratios may circumvent this problem.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Surplus dietary tryptophan reduces plasma cortisol and noradrenaline concentrations and enhances recovery after social stress in pigs.

PubMed

Koopmans, Sietse Jan; Ruis, Marko; Dekker, Ruud; van Diepen, Hans; Korte, Mechiel; Mroz, Zdzislaw

2005-07-21

Social stress occurs in intensive pig farming due to aggressive behavior. This stress may be reduced at elevated dietary levels of tryptophan (TRP). In this study, we compared the effects of high (13.2%) vs. normal (3.4%) dietary TRP to large neutral amino acid (LNAA) ratios on behavior and stress hormones in catheterized pigs ( approximately 50 kg BW), which were exposed to social stress by placing them twice into the territory of a dominant pig ( approximately 60 kg) for 15 min. Pre-stress plasma TRP concentrations were 156+/-15 vs. 53+/-6 micromol/l (p<0.01) in pigs on the high vs. normal TRP diets, respectively. Pre-stress plasma cortisol and noradrenaline concentrations were twofold (p<0.01) and 1.4-fold (p<0.05) lower but plasma adrenaline concentration was similar in pigs on the high vs. normal TRP diets, respectively. During the social confrontations, pigs on the high vs. normal TRP diets show a tendency towards reduced active avoidance behavior (3.2+/-1.1 vs. 6.7+/-1.2 min, p<0.1) but their physical activity (8.5+/-0.6 vs. 10.2+/-0.8 min) and aggressive attitude towards the dominant pig (11+/-3 vs. 7+/-2 times biting) were similar. Immediate (+5 min) post-stress plasma cortisol, noradrenaline and adrenaline responses were similar among dietary groups. After the social confrontations, the post-stress plasma cortisol, noradrenaline and adrenaline concentrations and/or curves (from +5 min to 2 h) were lower/steeper (p<0.05) in pigs on the high vs. normal TRP diets. In summary, surplus TRP in diets for pigs (1) does not significantly affect behavior when exposed to social stress, (2) reduces basal plasma cortisol and noradrenaline concentrations, (3) does not affect the immediate hormonal response to stress, and (4) reduces the long-term hormonal response to stress. In general, pigs receiving high dietary TRP were found to be less affected by stress.

Changes in 5-hydroxytryptamine and cortisol plasma levels in menopausal women after inhalation of clary sage oil.

PubMed

Lee, Kyung-Bok; Cho, Eun; Kang, Young-Sook

2014-11-01

The purpose of this study was to examine the antidepressant-like effects of clary sage oil on human beings by comparing the neurotransmitter level change in plasma. The voluntary participants were 22 menopausal women in 50's. Subjects were classified into normal and depression tendency groups using each of Korean version of Beck Depression Inventory-I (KBDI-I), KBDI-II, and Korean version of Self-rating Depression Scale. Then, the changes in neurotransmitter concentrations were compared between two groups. After inhalation of clary sage oil, cortisol levels were significantly decreased while 5-hydroxytryptamine (5-HT) concentration was significantly increased. Thyroid stimulating hormone was also reduced in all groups but not statistically significantly. The different change rate of 5-HT concentration between normal and depression tendency groups was variable according to the depression measurement inventory. When using KBDI-I and KBDI-II, 5-HT increased by 341% and 828% for the normal group and 484% and 257% for the depression tendency group, respectively. The change rate of cortisol was greater in depression tendency groups compared with normal groups, and this difference was statistically significant when using KBDI-II (31% vs. 16% reduction) and Self-rating Depression Scale inventory (36% vs. 8.3% reduction). Among three inventories, only KBDI-II differentiated normal and depression tendency groups with significantly different cortisol level. Finally, clary sage oil has antidepressant-like effect, and KBDI-II inventory may be the most sensitive and valid tool in screening for depression status or severity. Copyright © 2014 John Wiley & Sons, Ltd.

Apparent mineralocorticoid excess syndrome: report of one family with three affected children.

PubMed

Al-Harbi, Taiba; Al-Shaikh, Adnan

2012-01-01

The syndrome of apparent mineralocorticoid excess (AME) is an autosomal recessive disorder characterized by hypertension, hypokalemia, low renin, and hypoaldosteronism. It is caused by deficiency of 11β-hydroxysteroid dehydrogenase, which results in a defect of the peripheral metabolism of cortisol to cortisone. As a consequence, the serum cortisol half-life (T½) is prolonged, ACTH is suppressed, and serum cortisol concentration is normal. The hormonal diagnosis of the disorder is made by the increased ratio of urine-free cortisol to cortisone. In patients with AME, this ratio is 5-18, while in normal individuals it is <0.5. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME. We report three siblings - two female and one male - with the syndrome of apparent mineralocorticoid excess who presented with hypertension, hypokalemia, low renin, and low aldosterone levels. The finding of abnormally high ratios of 24-h urine-free cortisol to cortisone in our three patients (case 1, 8.4; case 2, 25; and case 3, 7.5) confirmed the diagnosis of apparent mineralocorticoid excess syndrome in these children. They were treated with oral potassium supplements. The addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity in all three. In this study, the genetic testing of those three siblings with the typical clinical features of AME has detected missense mutation c.662C>T (p.Arg208Cys) in exon 3 of the HSD11B2 gene in the homozygous state.

Inverse correlation between morning plasma cortisol levels and MMPI psychasthenia and depression scale scores in victims of mobbing with adjustment disorders.

PubMed

Rocco, Antonio; Martocchia, Antonio; Frugoni, Patrizia; Baldini, Rossella; Sani, Gabriele; Di Simone Di Giuseppe, Barbara; Vairano, Andrea; Girardi, Paolo; Monaco, Edoardo; Tatarelli, Roberto; Falaschi, Paolo

2007-10-01

Evidence in the literature suggests stress-related changes of hypothalamus-pituitary-adrenal (HPA) axis in mobbing. We investigated the association between HPA activity and psychological profiles in mobbing, using a multidisciplinary approach. Forty-eight victims of mobbing were evaluated by a working group of the Departments of Occupational Medicine, Psychiatry and Internal Medicine. After an informed consent, a detailed occupational history, a psychiatric interview with Minnesota Multiphasic Personality Inventory 2 (MMPI-2) administration and a blood sample (8:00 AM) for the determination of basal adrenocorticotropin (ACTH), cortisol and dehydroepiandrosterone sulphate (DHEAS) plasma levels were collected. Twenty-six patients received an overnight dexamethasone (dex) test. Mean ACTH, cortisol and DHEAS levels were within normal ranges. The dex-test response was normal, with a significant hormone suppression (ACTH p<0.001, cortisol p<0.001, DHEAS p<0.001). The correlations between basal hormones and the psychometric scales of MMPI-2 revealed that cortisol was significantly and negatively related to Psychasthenia (Pt, p=0.003) and Depression (D, p=0.006), while DHEAS showed a significant negative correlation to Hysteria (Hy, p=0.008). Basal ACTH levels were not significantly related to psychometric scales. A significant inverse correlation between morning plasma cortisol levels and psychometric parameters in victims of mobbing with adjustment disorders was observed. A larger group of patients is necessary to identify and validate a cut-off cortisol level that may become an innovative biological parameter for the diagnosis and follow-up in victims of mobbing.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes.

PubMed

Dettweiler, Ulrich; Becker, Christoph; Auestad, Bjørn H; Simon, Perikles; Kirsch, Peter

2017-04-30

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children's normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol ( p = 0.857), despite being higher in the intervention group ( p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child's diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon.

Cushing’s Disease

PubMed Central

ElShafie, Omayma; Osman, Anjum; Aamer, Fatima; Al-Mamari, Ali; Woodhouse, NJY

2012-01-01

We report five cases of Cushing’s disease where the patients were given a therapeutic trial of cabergoline. Morning serum cortisol, adrenocorticotrophic hormone (ACTH), and sleeping cortisol concentrations were significantly raised. Magnetic resonance imaging (MRI) scans revealed pituitary microadenomas in 3 patients but were normal in the others. Ectopic ACTH production was excluded in the 2 patients with normal MRI scans. All were given a therapeutic trial of cabergoline (1 mg daily). Four patients responded with a prompt fall in serum cortisol levels and had a sustained clinical and biochemical remission for 378, 44, 28 and 14 days, respectively. One patient failed to respond. In conclusion, we suggest that all patients with Cushing’s disease should undergo a therapeutic trial of cabergoline. Responders can then be prepared for surgery or, if needed, treated medically in the long term. PMID:23275847

Plasma, salivary and urinary cortisol levels following physiological and stress doses of hydrocortisone in normal volunteers.

PubMed

Jung, Caroline; Greco, Santo; Nguyen, Hanh H T; Ho, Jui T; Lewis, John G; Torpy, David J; Inder, Warrick J

2014-11-26

Glucocorticoid replacement is essential in patients with primary and secondary adrenal insufficiency, but many patients remain on higher than recommended dose regimens. There is no uniformly accepted method to monitor the dose in individual patients. We have compared cortisol concentrations in plasma, saliva and urine achieved following "physiological" and "stress" doses of hydrocortisone as potential methods for monitoring glucocorticoid replacement. Cortisol profiles were measured in plasma, saliva and urine following "physiological" (20 mg oral) or "stress" (50 mg intravenous) doses of hydrocortisone in dexamethasone-suppressed healthy subjects (8 in each group), compared to endogenous cortisol levels (12 subjects). Total plasma cortisol was measured half-hourly, and salivary cortisol and urinary cortisol:creatinine ratio were measured hourly from time 0 (between 0830 and 0900) to 5 h. Endogenous plasma corticosteroid-binding globulin (CBG) levels were measured at time 0 and 5 h, and hourly from time 0 to 5 h following administration of oral or intravenous hydrocortisone. Plasma free cortisol was calculated using Coolens' equation. Plasma, salivary and urine cortisol at 2 h after oral hydrocortisone gave a good indication of peak cortisol concentrations, which were uniformly supraphysiological. Intravenous hydrocortisone administration achieved very high 30 minute cortisol concentrations. Total plasma cortisol correlated significantly with both saliva and urine cortisol after oral and intravenous hydrocortisone (P <0.0001, correlation coefficient between 0.61 and 0.94). There was no difference in CBG levels across the sampling period. An oral dose of hydrocortisone 20 mg is supraphysiological for routine maintenance, while stress doses above 50 mg 6-hourly would rarely be necessary in managing acute illness. Salivary cortisol and urinary cortisol:creatinine ratio may provide useful alternatives to plasma cortisol measurements to monitor replacement doses in hypoadrenal patients.

[Behavior of circadian rhythm of ACTH and cortisol in 16 normal subjects after a balanced normocaloric diet and after a high protein diet (Cosinor mean method)].

PubMed

Sellini, M; Giovannini, C; Manzo, G; Barletta, C; Borboni, P

1983-01-31

In 16 normal subjects the circadian rhythm of ACTH has been studied during normal calories diet and after a 15 days period of high protein content diet (2 g/Kg body weight). The statistical study, according Cosinor method, has shown a significant increase of the mesor and of the amplitude, but has not shown any change of the ACTH and Cortisol rhythm, after hyperproteic diet. Data advise the increase of the tonic and fasic secretion of both hormones and shown the mantained acrophase. The action of the protein on the ACTH and Cortisol secretion does not seem related to mechanism like stress, neither to the probable mediation of intestinal like-ACTH messengers. On the contrary it seems related to a direct stimulus on the diencephalo-pituitary axis; it is possible that some amino-acids (tryptophan, arginine) act as a mediator, even if data concern just the effect of the over mentioned amino-acid in large doses.

Blocking Mineralocorticoid Receptors Impairs, Blocking Glucocorticoid Receptors Enhances Memory Retrieval in Humans

PubMed Central

Rimmele, Ulrike; Besedovsky, Luciana; Lange, Tanja; Born, Jan

2013-01-01

Memory retrieval is impaired at very low as well as very high cortisol levels, but not at intermediate levels. This inverted-U-shaped relationship between cortisol levels and memory retrieval may originate from different roles of the mineralocorticoid (MR) and glucocorticoid receptor (GR) that bind cortisol with distinctly different affinity. Here, we examined the role of MRs and GRs in human memory retrieval using specific receptor antagonists. In two double-blind within-subject, cross-over designed studies, young healthy men were asked to retrieve emotional and neutral texts and pictures (learnt 3 days earlier) between 0745 and 0915 hours in the morning, either after administration of 400 mg of the MR blocker spironolactone vs placebo (200 mg at 2300 hours and 200 mg at 0400 hours, Study I) or after administration of the GR blocker mifepristone vs placebo (200 mg at 2300 hours, Study II). Blockade of MRs impaired free recall of both texts and pictures particularly for emotional material. In contrast, blockade of GRs resulted in better memory retrieval for pictures, with the effect being more pronounced for neutral than emotional materials. These findings indicate indeed opposing roles of MRs and GRs in memory retrieval, with optimal retrieval at intermediate cortisol levels likely mediated by high MR but concurrently low GR activation. PMID:23303058

Blocking mineralocorticoid receptors impairs, blocking glucocorticoid receptors enhances memory retrieval in humans.

PubMed

Rimmele, Ulrike; Besedovsky, Luciana; Lange, Tanja; Born, Jan

2013-04-01

Memory retrieval is impaired at very low as well as very high cortisol levels, but not at intermediate levels. This inverted-U-shaped relationship between cortisol levels and memory retrieval may originate from different roles of the mineralocorticoid (MR) and glucocorticoid receptor (GR) that bind cortisol with distinctly different affinity. Here, we examined the role of MRs and GRs in human memory retrieval using specific receptor antagonists. In two double-blind within-subject, cross-over designed studies, young healthy men were asked to retrieve emotional and neutral texts and pictures (learnt 3 days earlier) between 0745 and 0915 hours in the morning, either after administration of 400 mg of the MR blocker spironolactone vs placebo (200 mg at 2300 hours and 200 mg at 0400 hours, Study I) or after administration of the GR blocker mifepristone vs placebo (200 mg at 2300 hours, Study II). Blockade of MRs impaired free recall of both texts and pictures particularly for emotional material. In contrast, blockade of GRs resulted in better memory retrieval for pictures, with the effect being more pronounced for neutral than emotional materials. These findings indicate indeed opposing roles of MRs and GRs in memory retrieval, with optimal retrieval at intermediate cortisol levels likely mediated by high MR but concurrently low GR activation.

Cortisol Measures Across the Weight Spectrum

PubMed Central

Schorr, Melanie; Lawson, Elizabeth A.; Dichtel, Laura E.; Klibanski, Anne

2015-01-01

Context: There are conflicting reports of increased vs decreased hypothalamic-pituitary-adrenal (HPA) activation in obesity; the most consistent finding is an inverse relationship between body mass index (BMI) and morning cortisol. In anorexia nervosa (AN), a low-BMI state, cortisol measures are elevated. Objective: This study aimed to investigate cortisol measures across the weight spectrum. Design and Setting: This was a cross-sectional study at a clinical research center. Participants: This study included 60 women, 18–45 years of age: overweight/obese (OB; N = 21); AN (N = 18); and normal-weight controls (HC; N = 21). Measures: HPA dynamics were assessed by urinary free cortisol, mean overnight serum cortisol obtained by pooled frequent sampling every 20 minutes from 2000–0800 h, 0800 h serum cortisol and cortisol-binding globulin, morning and late-night salivary cortisol, and dexamethasone-CRH testing. Body composition and bone mineral density (BMD) were assessed by dual-energy x-ray absorptiometry. Results: Cortisol measures demonstrated a U-shaped relationship with BMI, nadiring in the overweight-class I obese range, and were similarly associated with visceral adipose tissue and total fat mass. Mean cortisol levels were higher in AN than OB. There were weak negative linear relationships between lean mass and some cortisol measures. Most cortisol measures were negatively associated with postero-anterior spine and total hip BMD. Conclusions: Cortisol measures are lowest in overweight-class I obese women—lower than in lean women. With more significant obesity, cortisol levels increase, although not to as high as in AN. Therefore, extreme underweight and overweight states may activate the HPA axis, and hypercortisolemia may contribute to increased adiposity in the setting of caloric excess. Hypercortisolemia may also contribute to decreased BMD and muscle wasting in the setting of both caloric restriction and excess. PMID:26171799

The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals.

PubMed

Sang, Yu Ming; Wang, Li Jun; Mao, Hong Xian; Lou, Xue Yong; Zhu, Yi Jun

2018-06-01

This study assessed short-term memory and biochemical indicators with the levels of ghrelin, leptin, and cortisol between cognitive impairment and normal older adults with or without diabetes. We enrolled 286 older adults (aged 65-85 years) with or without diabetes from the local community. Short-term memory was assessed using pictures of common objects; cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The physiological indexes assessed were plasma levels of fasting ghrelin and leptin, ghrelin level at 2_h after breakfast, 24-h urinary cortisol value, body mass index, and plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. In both non-diabetic and diabetic subjects, short-term memory was significantly lower in the impaired cognition group (5.99 ± 2.90 in non-diabetic subjects and 4.71 ± 2.14 in diabetic subjects) than in the normal cognition group (8.14 ± 2.23 in non-diabetic subjects and 7.82 ± 3.37 in diabetic subjects). Baseline ghrelin level was significantly lower in the impaired cognition group (9.07 ± 1.13 ng/mL in non-diabetic subjects and 7.76 ± 1.34 ng/mL in diabetic subjects) than in the normal cognition group (10.94 ± 1.53 ng/mL in non-diabetic subjects and 9.93 ± 1.76 ng/mL in diabetic subjects); plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. were significantly higher in the impaired cognition group than in the normal cognition group, while no significant difference was observed in plasma levels of fasting leptin between different groups. Fasting plasma ghrelin and cortisol levels may be markers of cognitive decline and memory loss. It is possible that adjusting their levels may have a therapeutic effect, and this should be investigated in future studies.

Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants.

PubMed

Hochwald, Ori; Palegra, Gustavo; Osiovich, Horacio

2014-08-01

In this pilot study the authors demonstrate the feasibility, effectiveness and safety of the combined early treatment with hydrocortisone and dopamine for refractory hypotension in preterm newborns. Very low birth weight infants born at gestational age < 30 wk or birth weight < 1250 g in the first 48 h of life with hypotension after receiving 10-20 mL/kg bolus of normal saline, were randomized to receive concurrently with the initiation of dopamine, intravenous hydrocortisone (11 infants) or an equivalent volume of placebo (11 infants). Despite no significant clinical difference between the groups including gestational age, birth weight, prevalence of chorioamnionitis, prenatal steroid treatment, cord PH, baseline cortisol level, there was a trend towards lower incidence of bronchopulmonary dysplasia (BPD), and higher survival without BPD rate in the hydrocortisone group. In this very sick small group of infants, hydrocortisone was not associated with more adverse effects, but rather showed a trend toward association with better outcome, including survival without BPD.

Sustained remission of Cushing's disease with mitotane and pituitary irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schteingart, D.E.; Tsao, H.S.; Taylor, C.I.

1980-05-01

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly tomore » the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest.« less

Cortisol increases CXCR4 expression but does not affect CD62L and CCR7 levels on specific T cell subsets in humans.

PubMed

Besedovsky, Luciana; Linz, Barbara; Dimitrov, Stoyan; Groch, Sabine; Born, Jan; Lange, Tanja

2014-06-01

Glucocorticoids are well known to affect T cell migration, leading to a redistribution of the cells from blood to the bone marrow, accompanied by a concurrent suppression of lymph node homing. Despite numerous studies in this context, with most of them employing synthetic glucocorticoids in nonphysiological doses, the mechanisms of this redistribution are not well understood. Here, we investigated in healthy men the impact of cortisol at physiological concentrations on the expression of different migration molecules on eight T cell subpopulations in vivo and in vitro. Hydrocortisone (cortisol, 22 mg) infused during nocturnal rest when endogenous cortisol levels are low, compared with placebo, differentially reduced numbers of T cell subsets, with naive CD4(+) and CD8(+) subsets exhibiting the strongest reduction. Hydrocortisone in vivo and in vitro increased CXCR4 expression, which presumably mediates the recruitment of T cells to the bone marrow. Expression of the lymph node homing receptor CD62L on total CD3(+) and CD8(+) T cells appeared reduced following hydrocortisone infusion. However, this was due to a selective extravasation of CD62L(+) T cell subsets, as hydrocortisone affected neither CD62L expression on a subpopulation level nor CD62L expression in vitro. Corresponding results in the opposite direction were observed after blocking of endogenous cortisol synthesis by metyrapone. CCR7, another lymph node homing receptor, was also unaffected by hydrocortisone in vitro. Thus, cortisol seems to redirect T cells to the bone marrow by upregulating their CXCR4 expression, whereas its inhibiting effect on T cell homing to lymph nodes is apparently regulated independently of the expression of classical homing receptors. Copyright © 2014 the American Physiological Society.

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

PubMed Central

Feng, Xiaodi; Wood, Charles E.; Richards, Elaine; Anthony, Russell V.; Dahl, Geoffrey E.; Tao, Sha

2014-01-01

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg−1·day−1) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes. PMID:24920731

The importance of light, postural and social cues in the regulation of the plasma cortisol rhythm in man

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.

1979-01-01

A series of experiments was conducted to assess the role of photoperiodic postural and social cues in the regulation of the plasma cortisol rhythm in normal human subjects. Young healthy adult male volunteers, aged 20-25, were used as the test subjects and were selected following extensive physical and psychological examinations. The time at which peak plasma cortisol concentration occurred was calculated from harmonic curves fitted to each set of 24-hr data from each subject. The findings suggest that the plasma cortisol rhythm is not affected appreciably by the absence of postural change, whereas light and social interaction affect this rhythm profoundly.

Measurement and meaning of salivary cortisol: a focus on health and disease in children.

PubMed

Jessop, David S; Turner-Cobb, Julie M

2008-01-01

Measurement of salivary cortisol can provide important information about hypothalamic-pituitary-adrenal (HPA) axis activity under normal conditions and in response to stress. However, there are many variables relating to the measurement of cortisol in saliva which may introduce error and therefore may render difficult the comparison and interpretation of data between, and within, laboratories. This review addresses the effects of gender, age, time and location of sampling, units of measurement, assay conditions and compliance with the protocol, all of which have the potential to impact upon the precision, accuracy and reliability of salivary cortisol measurements in the literature. Some of these factors are applicable to both adults and children, but the measurement of salivary cortisol in children introduces aspects of unique variability which demand special attention. The specific focus of this review is upon the somewhat neglected area of methodological variability of salivary cortisol measurement in children. In addition to these methodological issues, the review highlights the use of salivary cortisol measurements to provide information about HPA axis dysfunction associated with psycho- and patho-physiological conditions in children. Novel applications for salivary cortisol measurements in future research into HPA axis activity in children are also discussed.

Cortisol reactivity and emotional memory after psychosocial stress in oral contraceptive users.

PubMed

Mordecai, Kristen L; Rubin, Leah H; Eatough, Erin; Sundermann, Erin; Drogos, Lauren; Savarese, Antonia; Maki, Pauline M

2017-01-02

Oral contraceptive (OC) users typically show a blunted or no cortisol response to psychosocial stress. Although most OC regimens include both an inactive (dummy) and active pill phase, studies have not systematically investigated cortisol responses during these pill phases. Further, high levels of cortisol following a stressor diminish retrieval of emotional material, but the effects of stress on memory among OC users are poorly understood. We examined the effects of a psychosocial stressor, the Trier Social Stress Test, vs. a control condition on cortisol responsivity and emotional memory retrieval in women tested either during their active (n = 18) or inactive pill phase (n = 21). In secondary analyses, we quantitatively compared OC users with normally cycling women and showed a significant lack of cortisol response during both active and inactive pill phase. Emotional recall did not differ between active and inactive pill phases. Stress differentially diminished recall of negative words compared with positive or neutral words, but cortisol levels were unrelated to memory performance. These findings indicate that OC users have distinct cortisol and memory responses to stress that are similar between the active and inactive pill phases. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cortisol, reaction time test and health among offshore shift workers.

PubMed

Harris, Anette; Waage, Siri; Ursin, Holger; Hansen, Ase Marie; Bjorvatn, Bjørn; Eriksen, Hege R

2010-10-01

The stress hormone cortisol shows a pronounced endogenous diurnal rhythm, which is affected by the sleep/wake cycle, meals and activity. Shift work and especially night work disrupts the sleep/wake cycle and causes a desynchronization of the natural biological rhythms. Therefore, different shift schedules may have different impact on performance at work and health. The purpose was to study if health, reaction time, and the cortisol rhythm were negatively affected when a group of shift workers changed their work schedule from ordinary day-night shift (fixed shift) to "swing shift". 19 healthy workers on a Norwegian oil rig participated in the study. They worked 2 weeks offshore followed by 4 weeks off work. The ordinary schedule consisted of 12-h day shift and 12-h night shift every other work period (14 days or nights=fixed shift). "Swing shift" involved 1 week of night shift, followed by 1 week of day shift during the work period. All participants worked ordinary day-night shift when baseline data were collected (questionnaires, saliva cortisol, and reaction time during work). After collection of baseline data the workers changed their work schedule to "swing shift", for every working period, and 9 months later the same data were collected. "Swing shift" did not give any negative health effects or any negative changes in reaction time during the day they shifted from night work to day work. Personnel adapted to night shift within a week regardless of schedule, but recovery from night shift took longer time. During swing shift the cortisol rhythm went back towards a normal rhythm in the second week, but it was not returned completely to normal values when they returned home for the 4 weeks off period. However, the cortisol rhythms were readapted to normal values after 1 week at home. For personnel returning home directly from 14 consecutive night shifts, cortisol adaptation was not complete after 1 week at home. We found no increase in health complaints from swing shift or reaction time in the shift from night to day work. Recovery from night shift takes longer time. Copyright © 2010 Elsevier Ltd. All rights reserved.

The cortisol level and its relationship with depression, stress and anxiety indices in chronic methamphetamine-dependent patients and normal individuals undergoing inguinal hernia surgery.

PubMed

Pirnia, Bijan; Givi, Fatemeh; Roshan, Rasool; Pirnia, Kambiz; Soleimani, Ali Akbar

2016-01-01

Stimulants addition and abuse can cause some functional and morphological changes in the normal function of glands and hormones. Methamphetamine as an addictive stimulant drug affects the Hypothalamic- pituitary-adrenal (HPA) axis and consequently makes some changes in the psychological state of the drug users. The present study aims to examine the relationship between plasma levels of cortisol with depression, stress and anxiety symptoms in chronic methamphetamine-dependent patients and normal individuals who have undergone the inguinal hernia surgery. To meet the purpose of the study, 35 chronic methamphetamine-dependent patients in the active phase of drug abuse and 35 non-users (N=70) who were homogenized regarding the demographic features were purposefully selected from among the patients referred to undergo inguinal hernia surgery since March 15 to June 9, 2015. The participants were then divided into the control and experiment group. The changes in cortisol levels in plasma were measured using Radioimmunoassay (RIA) in three-time series including 0 (upon the induction of anesthesia), 12 and 24 hours after the surgery. Further, three behavioral indices of depression, anxiety and stress were measured using the Depression Anxiety Stress Scale 21 (DASS-21) and then the data were analyzed using t-test and Pearson Correlation coefficient. The plasma level of cortisol in the chronic methamphetamine-dependent patients (experiment group) had a significant increase in 24 hours after surgery (p<0.05). This study showed that cortisol levels in chronic methamphetamine-dependent patients were significantly higher than non-dependent patients in response to alarming events such as inguinal surgery. Changes in cortisol levels were intensified due to a confrontation with the phenomenon of pain and anxiety. In addition, depression index was higher in the chronic methamphetaminedependent patients than that in the non-dependent patients. However, there was no significant relationship between the cortisol level and depression index (p=0.001). The Hypothalamic-pituitary-adrenal (HPA) axis is considered as a key structure in the addiction to simulants, the reason which can explain the faster response of the chronic methamphetamine-dependent patients to the stressors such as surgery.

Stress in School. Some Empirical Hints on the Circadian Cortisol Rhythm of Children in Outdoor and Indoor Classes

PubMed Central

Dettweiler, Ulrich; Becker, Christoph; Auestad, Bjørn H.; Simon, Perikles; Kirsch, Peter

2017-01-01

This prospective longitudinal survey compared the stress levels of students taught using an outdoor curriculum in a forest, with children in a normal school setting. We were especially interested in the effect outdoor teaching might have on the children’s normal diurnal cortisol rhythm. 48 children (mean age = 11.23; standard deviation (SD) = 0.46) were enrolled, with 37 in the intervention group (IG), and 11 in the control group (CG). The intervention consisted of one full school day per week in the forest over the school year. Stress levels were measured in cortisol with three samples of saliva per day. Furthermore, the data allowed for statistical control of physical activity (PA) values. For data analysis, we used a linear mixed-effects model (LMM) with random intercept and general correlation matrix for the within-unit residuals. The LMM yields that IG have expected greater decline of cortisol compared to CG; rate 0.069 µg/L vs. 0.0102 µg/L (log-units/2 h), p = 0.009. PA does not show a statistically significant interaction with cortisol (p = 0.857), despite being higher in the intervention group (p < 0.001). The main effect in our measures was that the IG had a steady decline of cortisol during the school day. This is in accordance with a healthy child’s diurnal rhythm, with a significant decline of cortisol from morning to noon. This effect is constant over the school year. The CG does not show this decline during either measurement day. Further research is needed to fully explain this interesting phenomenon. PMID:28468292

Hair cortisol and dehydroepiandrosterone concentrations in naturally Taenia solium infected pigs in Tanzania.

PubMed

Trevisan, Chiara; Montillo, Marta; Prandi, Alberto; Mkupasi, Ernatus M; Ngowi, Helena A; Johansen, Maria V

2017-05-15

The aim of this study was to measure hair cortisol and dehydroepiandrosterone (DHEA) concentrations in naturally Taenia solium infected and non-infected control pigs and assess the effect of an environmental change on the aforementioned parameters. Three hair patches were obtained from 13 T. solium infected and 15 non-infected controls sows, respectively corresponding to 3 time points (prior to, at and approximately two weeks after arrival at the research facility). Cortisol and DHEA were extracted using methanol and analysed by radio immune assay. Mean hair cortisol concentrations were significantly lower (p<0.001) in T. solium infected (4.7±3.0pg/mg) compared to control pigs (9.0±3.7pg/mg) prior to arrival at the research facility, however no significant difference was observed between the two groups at arrival and after approximately two weeks. Similar patterns were also observed for DHEA concentrations (infected pigs 253.9±82.3pg/mg, control pigs 387.7±116.4pg/mg) (p<0.001). Results showed that lean animals had significantly higher cortisol concentrations in both groups, infected and controls pigs, while DHEA was not significantly different between lean and normal animals. Results of this study have shown that an environmental change could have an effect on pigs' hormonal levels suggesting an undergoing adaptation process. After the pigs were kept under the same conditions, fed and watered ad libitum, no significant differences were observed between the groups, but a drop in DHEA concentrations was observed in all the pigs. Weight however had an effect on cortisol levels as lean animals had significantly higher cortisol concentrations in both groups, compared to normal pigs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

PubMed

Manenschijn, L; Quinkler, M; van Rossum, E F C

2014-04-01

The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (p<0.0001). Seven ACC patients (47%) had hair cortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients. © Georg Thieme Verlag KG Stuttgart · New York.

Corticosteroids stimulate the amphibious behavior in mudskipper: potential role of mineralocorticoid receptors in teleost fish.

PubMed

Sakamoto, Tatsuya; Mori, Chie; Minami, Shogo; Takahashi, Hideya; Abe, Tsukasa; Ojima, Daisuke; Ogoshi, Maho; Sakamoto, Hirotaka

2011-10-24

It has long been held that cortisol, a glucocorticoid in many vertebrates, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. However, 11-deoxycorticosterone (DOC) has been identified as a specific endogenous ligand for the teleostean mineralocorticoid receptor (MR). Furthermore, the expressions of MR mRNA are modest in the osmoregulatory organs, but considerably higher in the brain of most teleosts. These recent findings suggest that the mineralocorticoid system (DOC/MR) may carry out some behavioral functions in fish. To test this possibility, we examined the effects of cortisol and DOC administration in the amphibious behavior in mudskipper (Periophthalmus modestus) in vivo. It was found that mudskippers remained in the water for an increased period of time when they were immersed into 5 μM DOC or cortisol for 8h. Additionally, an exposure to 25 μM DOC for 4 to 8 h caused a decreased migratory frequency of mudskippers to the water, reflected a tendency to remain in the water. It was further observed that after 8 h of intracerebroventricular (ICV) injection with 0.3 pmol DOC or cortisol the staying period in the water increased in fish. The migratory frequency was decreased after ICV DOC injection which indicated that fishes stayed in the water. Concurrent ICV injections of cortisol with RU486 [a specific glucocorticoid-receptor (GR) antagonist] inhibited only the partial effects of cortisol. Together with no changes in the plasma DOC concentrations under terrestrial conditions, these results indicate the involvement of brain MRs as cortisol receptors in the preference for an aquatic habitat of mudskippers. Although the role of GR signaling cannot be excluded in the aquatic preference, our data further suggest that the MR may play an important role in the brain dependent behaviors of teleost fish. Copyright © 2011 Elsevier Inc. All rights reserved.

Change in parent-child conflict and the HPA-axis: Where should we be looking and for how long?

PubMed Central

Kuhlman, Kate R.; Repetti, Rena L.; Reynolds, Bridget M.; Robles, Theodore F.

2017-01-01

Objective Salivary cortisol is increasingly used as a longitudinal indicator of change in neuroendocrine regulation and as a predictor of health outcomes in youth. The purpose of this study was to describe which indices of HPA-axis functioning are sensitive to changes in parent-child conflict over a three week period and to explore the time course under which these changes can be measured. Methods Youth (n = 47; ages 8–13) completed daily diaries of their conflict with parents for 56 days. On days 17–18 and 38–39, youth contributed saliva samples upon waking, 30-minutes post-waking, afternoon, and bedtime. We assessed change in average diurnal HPA-axis functioning between day 17–18 and day 38–39 as a function of the slopes of change in parent-child conflict over 3 weeks. Results Increasing parent-child conflict was positively associated with concurrent increases in total cortisol output (AUCg), flattening of the diurnal slope, and increases in cortisol at bedtime, but not with change in the cortisol awakening response (CAR). Further, associations between parent-child conflict and both AUCg and bedtime cortisol were observed with at least 14 days of daily diary reporting, whereas any additional ratings of conflict beyond 3 days of daily diaries did not improve model fit for changes in diurnal slope. Conclusions This study demonstrates the within-subject up-regulation of the HPA-axis across three weeks in a healthy sample of youth exposed to natural increases in family conflict. In particular, cortisol at bedtime may be the HPA-axis index that is most sensitive to change over time in parent-child conflict, above and beyond conflict occurring that day. Further, when testing associations between family stressors and diurnal cortisol, the optimal schedule for assessing parent-child conflict varies for different indices of HPA-axis functioning. PMID:26963373

Parotid fluid cortisol and cortisone

PubMed Central

Katz, Fred H.; Shannon, Ira L.

1969-01-01

Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 μg/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 μg/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 μg/100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed. PMID:4305375

Multiple Salivary Cortisol Measurements Are a Useful Tool to Optimize Metyrapone Treatment in Patients with Cushing's Syndromes Treatment: Case Presentations.

PubMed

Yoshida, Kenichi; Fukuoka, Hidenori; Odake, Yukiko; Nakajima, Shinsuke; Tachibana, Mariko; Ito, Jun; Hosokawa, Yusei; Yamada, Tomoko; Miura, Hiroshi; Suematsu, Natsu; Matsumoto, Ryusaku; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Iguchi, Genzo; Ogawa, Wataru; Takahashi, Yutaka

2017-01-01

Measuring salivary cortisol is both convenient and non-invasive for patients; however, its usefulness as a marker for monitoring medical therapy has not yet been established. The aim of this study was to assess the utility of multiple salivary cortisol measurements in patients with Cushing's syndrome (CS) during medical therapy. Six patients with CS (three with cortisol-secreting adrenocortical adenoma and three with ACTH-secreting pituitary adenoma) were recruited. Samples for morning serum cortisol, urinary free cortisol (UFC), and multiple salivary cortisol levels were collected before and during metyrapone treatment. The area under the curve (AUC) and mean value (MV) of daily salivary cortisol levels were calculated. In five out of six patients, UFC were normalized; however, multiple salivary cortisol measurements revealed an impaired diurnal cortisol rhythm in these patients. To verify the usefulness of multiple salivary cortisol measurements, we performed a prospective case study of a patient in whom the excess secretion of cortisol was not controlled (UFC 211 μg/day) with 2,250 mg/day in four divided doses of metyrapone. Multiple measurements of salivary cortisol revealed that cortisol levels elevated before the next administration. Accordingly, we shortened the interval by increasing the number of administration from four to five times per day, with a slight increment of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement of diurnal pattern as well as UFC level (101 μg/day). Changes in both the MV and AUC of salivary cortisol levels were more correlated with those in UFC levels (Correlation coefficient 0.75, p  = 0.007, and 0.70, p  = 0.017) than those in the morning serum cortisol levels (0.42, p  = 0.200), indicating that multiple salivary cortisol measurements reflect more precisely the excess secretion of cortisol. Our preliminary data suggest that multiple salivary cortisol measurements can be a useful tool to visualize the diurnal cortisol rhythm and to determine the dose and timing of metyrapone during the treatment in patients with CS.

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing's syndrome.

PubMed

Giordano, Roberta; Berardelli, Rita; Karamouzis, Ioannis; D'Angelo, Valentina; Picu, Andreea; Zichi, Clizia; Fussotto, Beatrice; Manzo, Maria; Mengozzi, Giulio; Ghigo, Ezio; Arvat, Emanuela

2013-09-01

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing's syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.

The biologic effects of grounding the human body during sleep as measured by cortisol levels and subjective reporting of sleep, pain, and stress.

PubMed

Ghaly, Maurice; Teplitz, Dale

2004-10-01

Diurnal cortisol secretion levels were measured and circadian cortisol profiles were evaluated in a pilot study conducted to test the hypothesis that grounding the human body to earth during sleep will result in quantifiable changes in cortisol. It was also hypothesized that grounding the human body would result in changes in sleep, pain, and stress (anxiety, depression, irritability), as measured by subjective reporting. Twelve (12) subjects with complaints of sleep dysfunction, pain, and stress were grounded to earth during sleep for 8 weeks in their own beds using a conductive mattress pad. Saliva tests were administered to establish pregrounding baseline cortisol levels. Levels were obtained at 4-hour intervals for a 24-hour period to determine the circadian cortisol profile. Cortisol testing was repeated at week 6. Subjective symptoms of sleep dysfunction, pain, and stress were reported daily throughout the 8-week test period. Measurable improvements in diurnal cortisol profiles were observed, with cortisol levels significantly reduced during night-time sleep. Subjects' 24-hour circadian cortisol profiles showed a trend toward normalization. Subjectively reported symptoms, including sleep dysfunction, pain, and stress, were reduced or eliminated in nearly all subjects. Results indicate that grounding the human body to earth ("earthing") during sleep reduces night-time levels of cortisol and resynchronizes cortisol hormone secretion more in alignment with the natural 24-hour circadian rhythm profile. Changes were most apparent in females. Furthermore, subjective reporting indicates that grounding the human body to earth during sleep improves sleep and reduces pain and stress.

Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

PubMed

Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

2006-04-01

The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

Transformation techniques for cross-sectional and longitudinal endocrine data: application to salivary cortisol concentrations.

PubMed

Miller, Robert; Plessow, Franziska

2013-06-01

Endocrine time series often lack normality and homoscedasticity most likely due to the non-linear dynamics of their natural determinants and the immanent characteristics of the biochemical analysis tools, respectively. As a consequence, data transformation (e.g., log-transformation) is frequently applied to enable general linear model-based analyses. However, to date, data transformation techniques substantially vary across studies and the question of which is the optimum power transformation remains to be addressed. The present report aims to provide a common solution for the analysis of endocrine time series by systematically comparing different power transformations with regard to their impact on data normality and homoscedasticity. For this, a variety of power transformations of the Box-Cox family were applied to salivary cortisol data of 309 healthy participants sampled in temporal proximity to a psychosocial stressor (the Trier Social Stress Test). Whereas our analyses show that un- as well as log-transformed data are inferior in terms of meeting normality and homoscedasticity, they also provide optimum transformations for both, cross-sectional cortisol samples reflecting the distributional concentration equilibrium and longitudinal cortisol time series comprising systematically altered hormone distributions that result from simultaneously elicited pulsatile change and continuous elimination processes. Considering these dynamics of endocrine oscillations, data transformation prior to testing GLMs seems mandatory to minimize biased results. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cross reactions elicited by serum 17-OH progesterone and 11-desoxycortisol in cortisol assays.

PubMed

Brossaud, Julie; Barat, Pascal; Gualde, Dominique; Corcuff, Jean-Benoît

2009-09-01

Different pathophysiological situations such as congenital adrenal hyperplasia, adrenocortical carcinoma, metyrapone treatment, etc. elicit specificity problems with serum cortisol assay. We assayed cortisol using 2 kits and performed cross reaction studies as well as multiple regression analysis using 2 other steroids: 11-desoxycortisol and 17-OH progesterone. Analysis showed the existence of an analytical bias. Importantly, significantly different biases were demonstrated in newborns or patients taking metyrapone. Multiple regression analysis and cross reaction studies showed that 11-desoxycortisol level significantly influenced cortisol determination. Moreover, despite using the normal ranges provided by manufacturers discrepant results occurred such as 17% discordance in the diagnosis of hypocorticism in infants. We wish to raise awareness about the consequences of the (lack of) specificity of cortisol assays with regard to the evaluation of hypocorticism in infants or when "unusual" steroids may be increased.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

PubMed

Bruce, Kenneth R; Steiger, Howard; Israël, Mimi; Groleau, Patricia; Ng Ying Kin, N M K; Ouellette, Anne-Sophie; Sycz, Lindsay; Badawi, Ghislaine

2012-08-07

Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations. Copyright © 2012 Elsevier Inc. All rights reserved.

Benzodiazepine sensitivity in normal human subjects.

PubMed

Hommer, D W; Matsuo, V; Wolkowitz, O; Chrousos, G; Greenblatt, D J; Weingartner, H; Paul, S M

1986-06-01

Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.

Factitious Cushing's syndrome masquerading as Cushing's disease.

PubMed

Thynne, Tilenka; White, Graham H; Burt, Morton G

2014-03-01

Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis. © 2013 John Wiley & Sons Ltd.

Addison's Disease in Evolution: An Illustrative Case and Literature Review.

PubMed

Hinz, Laura E; Kline, Gregory A; Dias, Valerian C

2014-09-01

To present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease. We describe the clinical presentation and relevant investigations of a patient ultimately found to have Addison's disease, which is followed by a focused review of the literature. A 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, <52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, <6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made. The present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency.

Preliminary results of a pilot study investigating the potential of salivary cortisol measurements to detect occult adrenal suppression secondary to steroid nose drops.

PubMed

Patel, R S; Wallace, A M; Hinnie, J; McGarry, G W

2001-06-01

Adrenocortical suppression is a well-known risk of systemic steroids, but is thought less likely to occur with topical intranasal corticosteroids. However, the UK Committee on the Safety of Medicines (UKCSM) has expressed concern about the possibility of this complication. We assessed the prevalence of adrenal suppression in patients with rhinitis using intranasal beclomethasone and betamethasone; and the potential value of salivary cortisol as a tool for detecting this complication. Sixty-six patients (38 men: 28 women; mean age 49.6[SD 16.0] years) were prospectively screened for adrenal insufficiency using clinical assessment and salivary cortisol measurements. Abnormalities at this initial screening were confirmed with a Short Synacthen Test (SST). No patient was clinically Cushingoid. All 22 beclomethasone users had normal salivary cortisols. Eleven (25%) of 44 patients using betamethasone had subnormal salivary cortisol levels (mean morning cortisol 2.8[SD 0.9]nmol/l) suggesting adrenal suppression, which was confirmed by an impaired SST in each case. The positive predictive value of salivary cortisol measurements was 100%. Only patients with abnormal salivary cortisols had a SST, so no comment can be made about sensitivity/specificity. Topical betamethasone may produce occult adrenal insufficiency and assessment of adrenal function is recommended in these patients. Measurement of salivary cortisol is a useful, non-invasive and economical test for monitoring patients using intranasal corticosteroids.

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder).

PubMed

Hirvikoski, Tatja; Lindholm, Torun; Nordenström, Anna; Nordström, Anna-Lena; Lajic, Svetlana

2009-03-01

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n=28) with healthy controls (n=28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.

Cortisol in saliva and plasma of cattle after ACTH administration and milking.

PubMed

Negrão, J A; Porcionato, M A; de Passillé, A M; Rushen, J

2004-06-01

Interest in the measurement of salivary cortisol has increased recently because saliva can be easily collected before and after an imposed stress. This study evaluated the relationship between plasma and salivary concentrations of cortisol following ACTH administration in calves (experiment 1) and machine milking of adult cows (experiment 2). A catheter was inserted into the jugular vein of all animals 72 h before the beginning of experiments. Blood and saliva samples were collected before and after ACTH administration (0.6 IU/kg BW) in calves or before and after machine milking of cows. Using a cotton swab, each saliva sample was taken immediately following the blood sample. In general, cortisol profiles were similar in plasma and saliva and correlated in both experiments; however, plasma concentrations were significantly higher than salivary concentrations. In addition, the differences between cortisol concentrations measured in saliva and plasma within each experiment varied substantially between animals and samples. Furthermore, in experiment 2, nearly 10% of salivary samples were below limits of detection. The sharp peaks in cortisol after ACTH administration in both the plasma and saliva were reflected adrenal stimulation. In addition, increases in cortisol in response to milking in both the plasma and saliva suggest that salivary sampling is a reliable option when studying cortisol responses to normal physiological events.

The postoperative cortisol stress response following transsphenoidal pituitary surgery: a potential screening method for assessing preserved pituitary function.

PubMed

Zada, Gabriel; Tirosh, Amir; Huang, Abel P; Laws, Edward R; Woodmansee, Whitney W

2013-09-01

The ability to reliably identify patients with new hypocortisolemia acutely following pituitary surgery is critical. We aimed to quantify the postoperative cortisol stress response following selective transsphenoidal adenomectomy, as a marker for postoperative preservation of functional pituitary gland. Records of 208 patients undergoing transsphenoidal operations for pituitary lesions were reviewed. Patients with Cushing's Disease, preoperative adrenal insufficiency, and those receiving intraoperative steroids were excluded. To quantify the postoperative stress response, the ∆ cortisol index was defined as the postoperative day (POD) 1 morning cortisol minus the preoperative morning cortisol level. The incidence of new hypocortisolemia requiring glucocorticoid replacement upon hospital discharge was also recorded. Fifty-two patients met inclusion criteria. The mean preoperative, POD1, and POD2 cortisol levels were 16.5, 29.2, and 21.8 μg/dL, respectively. Morning fasting cortisol levels on POD1 ranged from 4.2 to 73.0 μg/dL. The ∆ cortisol index ranged from -19.0 to +56.2 (mean +12.7 μg/dL). Five patients (9.6%) developed new hypocortisolemia on POD 1-3 requiring glucocorticoid replacement; only one required long-term replacement. The mean ∆ cortisol in patients requiring postoperative glucocorticoids was -2.8 μg/dL, compared with +14.4 μg/dL in patients without evidence of adrenal insufficiency (p = 0.005). Of the 32 patients (61.5%) with a ∆cortisol >25 μg/dL, none developed postoperative adrenal insufficiency. The postoperative cortisol stress response, as quantified by the ∆ cortisol index, holds potential as a novel and complimentary screening method to predict preservation of normal pituitary function and acute development of new ACTH deficiency following transsphenoidal pituitary surgery.

Clinical Relationship between Cholestatic Disease and Pituitary-Dependent Hyperadrenocorticism in Dogs: A Retrospective Case Series.

PubMed

Kim, K-H; Han, S-M; Jeon, K-O; Kim, H-T; Li, Q; Ryu, M-O; Song, W-J; Park, S-C; Youn, H-Y

2017-03-01

A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. Sixty-five client-owned dogs with naturally occurring PDH. This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Salivary cortisol values in HIV-positive people.

PubMed

Barroso, Julie; Burrage, Joe; Carlson, John; Carlson, Barbara Waag

2006-01-01

Fatigue is one of the most prevalent and troubling symptoms suffered by people with HIV infection. As part of a pilot study to examine physiological and psychosocial correlates of fatigue, the authors report results from a sample of 40 HIV-positive men and women who collected three saliva samples each over the course of a day. Few in the sample exhibited the normal salivary cortisol slope (a peak in the morning and falling throughout the day). There were four groups (N = 36) based on salivary cortisol plots: a normal downward trend (n = 7), an afternoon peak (n = 15), an afternoon drop (n = 9), and an upward trend (n = 5). The data in each of these groups were then analyzed on the key variables of sex, age, depression, state/trait anxiety, fatigue severity, CD4 count, and HIV viral load; the group that had an upward trend in cortisol values had a tendency toward more depression, more state and trait anxiety, higher fatigue severity, and higher HIV viral load. However, they also trended toward higher CD4 counts than the other three groups. The need to compare additional variables over a period of time is discussed.

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

PubMed

Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma.

PubMed

Kurtulmus, Neslihan; Yarman, Sema; Azizlerli, Halil; Kapran, Yersu

2004-01-01

We report a rare case of adrenocortical carcinoma. A 26-year-old woman presented with hypokalemia and hypertension due to hyperaldosteronism. She had no signs of Cushing's syndrome. Endocrinological data showed excess of aldosterone production and nonsupressible cortisol production on 2 mg of dexamethasone. Magnetic resonance imaging showed left adrenal tumor. Transabdominal left adrenalectomy was performed and histopathological diagnosis was adrenocortical carcinoma. Her blood pressure and hypokalemia returned to normal after adrenalectomy. There is no recurrence after 36 months. We want to emphasis the importance of adrenal tests before the operation even if there are no signs of excess cortisol production.

Nitric Oxide, Inflammation, Lipid Profile, and Cortisol in Normal- and Overweight Women With Fibromyalgia.

PubMed

Rus, Alma; Molina, Francisco; Gassó, Manuela; Camacho, Maria Victoria; Peinado, Maria Ángeles; del Moral, Maria Luisa

2016-03-01

Research has identified many factors associated with fibromyalgia (FM), but findings have been inconsistent. This study aimed to investigate changes in levels of nitric oxide (NO), inflammatory markers, lipid profile, and cortisol in normal- and overweight patients with FM and controls. Since most patients with FM are overweight, we explored possible changes in these markers according to body mass index (BMI). This preliminary study was performed on serum samples of women with FM and age-matched controls, grouped according to their BMI: 12 normal-weight patients and 12 controls and 13 overweight patients and 8 controls. Ozone-based chemiluminescence assay was used to measure NO. Inflammatory mediators and cortisol were determined by immunoassay. Lipid profile was measured by a spectrophotometric procedure. Functional capacity was assessed by the fibromyalgia impact questionnaire (FIQ). Normal-weight patients showed higher levels of C-reactive protein (CRP) and apolipoprotein B compared to controls (both p < .05). CRP, apolipoprotein B, and triglycerides were higher in overweight patients versus overweight controls (all p < .05) and in overweight versus normal-weight patients (CRP p < .01; apolipoprotein B, triglycerides p < .05). The other markers were unaffected. Apolipoprotein B (r = .762; p < .05) and NO (r = -.921; p < .05) levels correlated with FIQ score in normal-weight patients. CRP level correlated with FIQ (r = .912; p < .05) in overweight patients. CRP and apolipoprotein B, biomarkers linked to cardiovascular events, may be associated with FM-related dysfunction in normal- and overweight women with FM. Their increased levels in these patients may indicate an increased risk of cardiovascular disease. © The Author(s) 2015.

Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption.

PubMed

Thom, Erling

2016-08-01

The stress hormone, cortisol, is known to affect the function and cyclic regulation of the hair follicle. When cortisol is present at high levels it has been demonstrated to reduce the synthesis and accelerate the degradation of important skin elements, namely hyaluronan and proteoglycans by approximately 40%. The following discussion outlines the relationship between stress, cortisol, and the effect on the normal function of the hair follicle. As a result of this connection, important correlations have been established in the literature to form a basis for novel, effective treatments of stress-related hair growth disorders.
Amongst various treatment methods and substances, oral supplementation with a specific bioavailable proteoglycan stands out as a promising new therapeutic treatment method.

J Drugs Dermatol. 2016;15(8):1001-1004.

Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys

PubMed Central

Newman, Jennifer L.; Perry, Jennifer L.; Carroll, Marilyn E.

2007-01-01

Environmental factors, including social interaction, can alter the effects of drugs of abuse on behavior. The present study was conducted to examine the effects of social stimuli on oral phencyclidine (PCP) self-administration by rhesus monkeys. Ten adult rhesus monkeys (M. mulatta) were housed side by side in modular cages that could be configured to provide visual, auditory, and olfactory stimuli provided by another monkey located in the other side of the paired unit. During the first experiment, monkeys self-administered PCP (0.25 mg/ml) and water under concurrent fixed ratio (FR) 16 schedules of reinforcement with either a solid or a grid (social) partition separating each pair of monkeys. In the second experiment, a PCP concentration-response relationship was determined under concurrent progressive ratio (PR) schedules of reinforcement under the solid and grid partition conditions. Under the concurrent FR 16 schedules, PCP and water self-administration was significantly higher during exposure to a cage mate through a grid partition than when a solid partition separated the monkeys. The relative reinforcing strength of PCP, as measured by PR break points, was greater during the grid partition condition compared to the solid partition condition indicated by an upward shift in the concentration-response curve. To determine whether the social stimuli provided by another monkey led to activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may have evoked the increase of PCP self-administration during the grid partition condition, a third experiment was conducted to examine cortisol levels under the two housing conditions. A modest, but nonsignificant increase in cortisol levels was found upon switching from the solid to the grid partition condition. The results suggest that social stimulation among monkeys in adjoining cages leads to enhanced reinforcing strength of PCP. PMID:17560636

Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease.

PubMed

Smans, Lisanne; Lentjes, Eef; Hermus, Ad; Zelissen, Pierre

2013-01-01

Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.

Low cortisol levels in blood from dairy cows with ketosis: a field study

PubMed Central

2010-01-01

Background An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Methods Cortisol, insulin, β-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. Results No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). Conclusions The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research. PMID:20487518

Low cortisol levels in blood from dairy cows with ketosis: a field study.

PubMed

Forslund, Kristina B; Ljungvall, Orjan A; Jones, Bernt V

2010-05-20

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants. Cortisol, insulin, beta-hydroxybutyric acid (BHBA), non esterified fatty acids (NEFA), and serum calcium were analyzed in blood serum and glucose, in whole blood, from 57 spontaneously diseased cows collected at different farms. The cows were grouped according to the disease; parturient paresis, recumbent for other reasons, mastitis, metritis, ketosis, inappetance and others. No elevated concentrations of cortisol or glucose were found in cows with metritis and mastitis but both cortisol and glucose were elevated in cows stressed by recumbency. Cows with ketonemia (BHBA > 1.5 mmol/l) did not have low concentration of glucose in blood but significantly low levels of cortisol. Some of these cows even had cortisol concentrations below the detection limit of the analysing method (< 14 nmol/l). The study gives patho-physiological support to the treatment strategies of ketosis, recommending glucocorticoids, insulin etc. However further studies of this problem are needed to understand why cows with ketosis have low levels of cortisol and normal levels of glucose. To what extent elevated cortisol and glucose levels in hypocalcemic and recumbent cows are involved in the ethiology and /or the pathogenesis of DA also will need further research.

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Adrenocortical reserves in hyperthyroidism.

PubMed

Agbaht, Kemal; Gullu, Sevim

2014-02-01

Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist. We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses. A standard-dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (ΔCor), delta DHEA-S (ΔDHEA-S) responses were evaluated. Forty-one patients [22 females, 49.5 ± 15.2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and euthyroid states. Cor(60), ΔCor, and ΔDHEA-S were lower in hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values were lower than 18 μg/dL. When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response. Regression analysis demonstrated an independent association of Cor(60) with free T3 in hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.

Cortisol intermediates and hydrocortisone responsiveness in critical neonatal disease.

PubMed

Khashana, Abdelmoneim; Saarela, Timo; Ramet, Mika; Hallman, Mikko

2017-07-01

Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock. The 48 non-responders were treated with intravenous hydrocortisone (HC) and serum cortisol concentrations were monitored a week later. The mean cortisol concentrations did not differ between the responders and non-responders: 13.6 ± 2.5 and 12.5 ± 4.5 μg/dL, respectively. Dehydroepiandrosterone (37.3 ± 19.5 versus 324.0 ± 106.3; p < 0.0001) and 17-hydroxy-pregnenolone concentrations were lower in responders than in non-responders. Dehydroepiandrosterone levels in non-responders were inversely associated with postnatal age (r = 0.50, p < 0.0001). There were no differences in 17-hydroxy-progesterone, 11-deoxy-cortisol and cortisone between the responders and non-responders. Hydrocortisone administration acutely increased blood pressure. Six non-responders who died despite HC administration had low levels of cortisol. The responders had normal serum cortisol after HC treatment. Precursors of cortisol, proximal to the 3β-hydroxysteroid dehydrogenase activity, accumulated in neonates with hypotension, responding to HC treatment.

[Cyclic Cushing's Syndrome - rare or rarely recognized].

PubMed

Kiałka, Marta; Doroszewska, Katarzyna; Mrozińska, Sandra; Milewicz, Tomasz; Stochmal, Ewa

2015-01-01

Cyclic Cushing's syndrome is a type of Cushing's disease which is characterized by alternating periods of increasing and decreasing levels of cortisol in the blood. The diagnostic criteria for cyclic Cushing's syndrome are at least three periods of hypercortisolism alternating with at least two episodes of normal levels of serum cortisol concentration. The epidemiology, signs, symptoms, pathogenesis and treatment of cyclic Cushing's syndrome have been discussed.

New approach for monitoring fish stress: A novel enzyme-functionalized label-free immunosensor system for detecting cortisol levels in fish.

PubMed

Wu, Haiyun; Ohnuki, Hitoshi; Ota, Shirei; Murata, Masataka; Yoshiura, Yasutoshi; Endo, Hideaki

2017-07-15

Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol levels in fish. As a well-known indicator of fish stress, a simple and rapid method for detecting cortisol changes especially sudden increases is desired. In this study, we describe an enzyme-functionalized label-free immunosensor system for detecting fish cortisol levels. Detection of cortisol using amperometry was achieved by immobilizing both anti-cortisol antibody (selective detection of cortisol) and glucose oxidase (signal amplification and non-toxic measurement) on an Au electrode surface with a self-assembled monolayer. This system is based on the maximum glucose oxidation output current change induced by the generation of a non-conductive antigen-antibody complex, which depends on the levels of cortisol in the sample. The immunosensor responded to cortisol levels with a linear decrease in the current in the range of 1.25-200ngml -1 (R=0.964). Since the dynamic range of the sensor can cover the normal range of plasma cortisol in fish, the samples obtained from the fish did not need to be diluted. Further, electrochemical measurement of one sample required only ~30min. The sensor system was applied to determine the cortisol levels in plasma sampled from Nile tilapia (Oreochromis niloticus), which were then compared with levels of the same samples determined using the conventional method (ELISA). Values determined using both methods were well correlated. These findings suggest that the proposed label-free immunosensor could be useful for rapid and convenient analysis of cortisol levels in fish without sample dilution. We also believe that the proposed system could be integrated in a miniaturized potentiostat for point-of-care cortisol detection and useful as a portable diagnostic in fish farms in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of an auditory stimulus on baseline cortisol concentrations in clinically normal dogs.

PubMed

Gin, T E; Puchot, M L; Cook, A K

2018-03-19

Baseline cortisol concentrations are routinely used to screen dogs for hypoadrenocorticism (HOC); this diagnosis must then be confirmed with an ACTH stimulation test. A baseline cortisol concentration less than 55 nmol/L (2 μg/dL) is highly sensitive for HOC but lacks specificity, with a false positive rate >20%. Many dogs with nonadrenal disease are therefore subjected to unnecessary additional testing. It was hypothesized that exposure to an unpleasant auditory stimulus before sample collection would improve the specificity of baseline cortisol measurements in dogs with nonadrenal disease by triggering cortisol production. Twenty-eight healthy client-owned dogs were included in the study, with a median age of 4 yr (range 2-9 yr) and a median weight of 20 kg (range 10-27 kg). Dogs were ineligible for inclusion if they had received short- or long-acting glucocorticoids within the previous 30 and 90 d, respectively. Dogs were randomly assigned to group 1 (control; no noise; n = 7), group 2 (brief noise: n = 10), or group 3 (long noise: n = 11). Each dog and owner were directed to a secluded area for approximately 15 min. Group 1 sat in relative quiet, exposed only to the background sounds of a veterinary hospital. Group 2 were exposed to the sound of a wet-dry vacuum in an adjacent hallway during the first 3 min of this period. Group 3 were exposed to random bursts of wet-dry vacuum noise during this period. At the end of the test interval, each dog was escorted to an adjacent examination room for blood collection. Samples were processed within 15 min; serum was frozen at -80°C before measurement of cortisol concentrations. Median serum cortisol concentrations and the proportion of dogs with results <55 nmol/L were similar for the 3 groups. The study hypothesis that exposure to the noise of a wet-dry vacuum cleaner would consistently drive baseline serum cortisol concentrations above 55 nmol/L in dogs with apparently normal adrenal function was therefore rejected. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of melatonin and cortisol circadian rhythms in the pathogenesis of infantile colic.

PubMed

İnce, Tolga; Akman, Hakkı; Çimrin, Dilek; Aydın, Adem

2018-03-05

Despite the high prevalence of infantile colic, the pathogenesis remains incompletely understood. Cortisol and melatonin hormones affect gastrointestinal system development in several ways, and interestingly, both cortisol and melatonin's circadian rhythms begin around the 3rd month in which infantile colic symptoms start to decrease. We hypothesized that infantile colic might associate with desynchronization of normal circadian rhythms of these hormones. In this study, we aimed to investigate the role of melatonin and cortisol in the pathogenesis of infantile colic. Patients who were diagnosed as infantile colic according to Wessel's "rule of three" were enrolled in the colic group. We measured the saliva melatonin and cortisol levels of colic group and control group infants. In both groups, the saliva samples were taken in mornings and at evenings, at the time of diagnosis and 6th month. Fifty-five infants finished the study. Melatonin circadian rhythm developed earlier in the control group than the infantile colic group in our study. We found no significant difference between the daily mean cortisol levels. However, infants with colic had flatter daily cortisol slope than controls which pointed out the probability that they had a less clearly defined cortisol rhythm than infants without colic. We found an association between melatonin levels and infantile colic. However, more research is needed to fully understand the role of hypothalamic-pituitary-adrenal axis and hormone's role on infantile colic physiopathology.

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

PubMed Central

Miller, Robert; Stalder, Tobias; Jarczok, Marc; Almeida, David M.; Badrick, Ellena; Bartels, Meike; Boomsma, Dorret I.; Coe, Christopher L.; Dekker, Marieke C. J.; Donzella, Bonny; Fischer, Joachim E.; Gunnar, Megan R.; Kumari, Meena; Lederbogen, Florian; Oldehinkel, Albertine J.; Power, Christine; Rosmalen, Judith G.; Ryff, Carol D.; Subramanian, S V; Tiemeier, Henning; Watamura, Sarah E.; Kirschbaum, Clemens

2016-01-01

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5 to 98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1 to 16 hours after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle. PMID:27448524

Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

PubMed

Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

2011-04-01

Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

Cortisol Response to Psychosocial Stress in Chinese Early Puberty Girls: Possible Role of Depressive Symptoms.

PubMed

Sun, Ying; Deng, Fang; Liu, Yang; Tao, Fang-Biao

2015-01-01

Objective. The present study aimed at investigating unique patterns of salivary cortisol reactivity and recovery in response to a social stressor among girls with early puberty and exploring possible role of depressive symptom in this association. Design. Case-control study. Patients. Fifty-six girls with early puberty and age- and body mass index- (BMI-) matched normal puberty controls (n = 56) were selected. Measurements. Salivary cortisol was measured in response to the Groningen Social Stress Test for Children. Results. Girls with early puberty had higher cortisol concentration at the end of the GSST (C3), cortisol concentration 20 min after the end of the GSST (C4), and AUC increment (AUCi) compared to non-early puberty girls. Depressive symptoms correlated with blunted HPA reactivity among girls with early puberty. Conclusion. This study demonstrated the disturbance effect of objectively examined early pubertal timing on HPA axis responses. It also suggested that stress reactivity might be blunted for individuals with depressive symptoms.

Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charbonnel, B.; Chatal, J.F.; Ozanne, P.

1981-12-01

An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. Thismore » pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland.« less

Late-night salivary cortisol measurement in the diagnosis of Cushing's syndrome.

PubMed

Carroll, Ty; Raff, Hershel; Findling, James W

2008-06-01

Making a definite diagnosis of Cushing's syndrome is a challenging problem. Unsuspected Cushing's syndrome occurs in 2-3% of patients with poorly controlled diabetes, 0.5-1% with hypertension, 6-9% with incidental adrenal masses, and 11% with unexplained osteoporosis and vertebral fractures. The increasing recognition of this syndrome highlights the need for a simple, sensitive, and specific diagnostic test. Patients with Cushing's syndrome consistently do not reach a normal nadir of cortisol secretion at night. The measurement of late-night salivary cortisol levels might, therefore, provide a new diagnostic approach for this disorder. Salivary cortisol concentrations reflect those of active free cortisol in plasma and saliva samples can easily be obtained in a nonstressful environment (e.g. at home). Late-night salivary cortisol measurement yields excellent overall diagnostic accuracy for Cushing's syndrome, with a sensitivity of 92-100% and a specificity of 93-100%. Several factors can, however, make interpretation of results difficult; these factors include disturbed sleep-wake cycles, contamination of samples (particularly by topical corticosteroids), and illnesses known to cause physiologic activation of the pituitary-adrenal axis. In this Review, we discuss the methods and value of measuring salivary cortisol for the diagnosis of Cushing's syndrome, and put forward some recommendations to maximize accuracy of results.

Pitfalls in the diagnosis and management of Cushing's syndrome.

PubMed

Bansal, Vivek; El Asmar, Nadine; Selman, Warren R; Arafah, Baha M

2015-02-01

Despite many recent advances, the management of patients with Cushing's disease continues to be challenging. Cushing's syndrome is a complex metabolic disorder that is a result of excess glucocorticoids. Excluding the exogenous causes, adrenocorticotropic hormone-secreting pituitary adenomas account for nearly 70% of all cases of Cushing's syndrome. The suspicion, diagnosis, and differential diagnosis require a logical systematic approach with attention paid to key details at each investigational step. A diagnosis of endogenous Cushing's syndrome is usually suspected in patients with clinical symptoms and confirmed by using multiple biochemical tests. Each of the biochemical tests used to establish the diagnosis has limitations that need to be considered for proper interpretation. Although some tests determine the total daily urinary excretion of cortisol, many others rely on measurements of serum cortisol at baseline and after stimulation (e.g., after corticotropin-releasing hormone) or suppression (e.g., dexamethasone) with agents that influence the hypothalamic-pituitary-adrenal axis. Other tests (e.g., measurements of late-night salivary cortisol concentration) rely on alterations in the diurnal rhythm of cortisol secretion. Because more than 90% of the cortisol in the circulation is protein bound, any alteration in the binding proteins (transcortin and albumin) will automatically influence the measured level and confound the interpretation of stimulation and suppression data, which are the basis for establishing the diagnosis of Cushing's syndrome. Although measuring late-night salivary cortisol seems to be an excellent initial test for hypercortisolism, it may be confounded by poor sampling methods and contamination. Measurements of 24-hour urinary free-cortisol excretion could be misleading in the presence of some pathological and physiological conditions. Dexamethasone suppression tests can be affected by illnesses that alter the absorption of the drug (e.g., malabsorption, celiac disease) and by the concurrent use of medications that interfere with its metabolism (e.g., inducers and inhibitors of the P450 enzyme system). In this review, the authors aim to review the pitfalls commonly encountered in the workup of patients suspected to have hypercortisolism. The optimal diagnosis and therapy for patients with Cushing's disease require the thorough and close coordination and involvement of all members of the management team.

Ionoregulatory and endocrine responses to disturbed salt and water balance in Mozambique tilapia exposed to confinement and handling stress.

PubMed

Breves, Jason P; Hirano, Tetsuya; Grau, E Gordon

2010-03-01

This study assessed the endocrine and ionoregulatory responses by tilapia (Oreochromis mossambicus) to disturbances of hydromineral balance during confinement and handling. In fresh water (FW), confinement and handling for 0.5, 1, 2 and 6h produced elevations in plasma cortisol and glucose; a reduction in plasma osmolality was observed at 6h. Elevations in plasma prolactins (PRL(177) and PRL(188)) accompanied this fall in osmolality while no effect upon growth hormone (GH) was evident; an increase in insulin-like growth-factor I (IGF-I) occurred at 0.5h. In seawater (SW), confinement and handling increased plasma osmolality and glucose between 0.5 and 6h; no effect on plasma cortisol was seen due to variable control levels. Concurrently, both PRLs were reduced in stressed fish with only transient changes in the GH/IGF-I axis. Next, the branchial expression of Na(+)/K(+)/2Cl(-) cotransporter (NKCC) and Na(+)/Cl(-) cotransporter (NCC) was characterized following confinement and handling for 6h. In SW, NKCC mRNA levels increased in stressed fish concurrently with elevated plasma osmolality and diminished gill Na(+), K(+)-ATPase activity; NCC was unchanged in stressed fish irrespective of salinity. Taken together, PRL and NKCC participate in restoring osmotic balance during acute stress while the GH/IGF-I axis displays only modest responses. Copyright 2009 Elsevier Inc. All rights reserved.

Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

PubMed

Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

2012-06-01

A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

Adrenal cortical response to stress at Three Mile Island.

PubMed

Schaeffer, M A; Baum, A

1984-01-01

The present study examined the relationship between biochemical, psychologic, and behavioral components of chronic stress associated with living near the damaged nuclear power plant at Three Mile Island (TMI). Relative to control subjects, TMI subjects had higher levels of urinary cortisol, which correlated significantly with urinary catecholamines, self-report of physical and mental symptoms, and decrements in task performance. Further, it was found that males had higher urinary cortisol levels than females at TMI, while at the control sites, levels of cortisol were comparable between males and females. Finally, no significant relationship between coping style and urinary cortisol was detected. Levels of stress response among TMI are residents, though significantly greater than control subjects, were within normal ranges and thus should be considered subclinical in intensity. Their persistence over 17 months, however, suggests some cause for concern.

Cushing's Syndrome: Screening and Diagnosis.

PubMed

Ceccato, Filippo; Boscaro, Marco

2016-09-01

Endogenous Cushing's syndrome (CS) is a rare disease, and usually characterized by hypertension, diabetes, obesity, osteoporosis, facial rounding, dorsocervical fat pad, thin skin, purple striae, hirsutism, and mood disorders. Efficient diagnostic and screening strategies lead to the diagnosis of a significantly higher number of cases of CS. As a screening test for CS, the Endocrine Society's Clinical Practice Guidelines recommend a single test with a high diagnostic accuracy, among the 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), and 24 h urinary free cortisol (UFC). In normal subjects, administering a higher than physiological dose of glucocorticoids prompts the suppression of cortisol secretion. The 1-mg DST explores this normal feedback reaction from the hypothalamic-pituitary-adrenal axis (HPA). It is a simple dynamic test, usually performed in outpatients. A morning serum cortisol level <50 nmol/L suffices to exclude CS, unless there is a strong clinical suspicion to suggest otherwise. The HPA axis reaches a nadir just after a person has fallen asleep, but its circadian rhythm is impaired in CS patients, who feature higher cortisol values at night, which are easy to measure in saliva (the LNSC assay). Saliva collection is also suitable for outpatients since cortisol is stable at room temperature and the collection device can be mailed to the laboratory for analysis. UFC levels reflect the integrated tissue exposure to free cortisol over 24 h, and thus provide a particular picture of endogenous hypercortisolism. In most cases, high UFC levels coincide with severe hypercortisolism. UFC is used not only to diagnose CS, but also to monitor its response to medical treatment. All screening tests have procedural snares: some drugs can interfere with the DST; false-positive or false-negative LNSC results may be due to an inadequate soaking of the device or to cyclic CS; and in the case of UFC it is important to ensure that patients provide complete urine collections with appropriate total volumes. Measuring cortisol with antibody-based immunoassays can also generate false-positive results due to cross-reactivity between cortisol, cortisone and other metabolites. Structurally-based assays, such as liquid chromatography with tandem mass spectrometry, only measure cortisol and have only recently become available for use in routine clinical practice. This review summarizes the recent literature on the clinical and biochemical aspects of CS diagnostics with a view to helping physicians choose the best screening test for diagnosing endogenous hypercortisolism.

Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

PubMed

Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S

2014-01-01

Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.

An exploratory study of salivary cortisol changes during chamomile extract therapy of moderate to severe generalized anxiety disorder.

PubMed

Keefe, John R; Guo, Wensheng; Li, Qing S; Amsterdam, Jay D; Mao, Jun J

2018-01-01

Dysfunctions in stress biology are hypothesized to contribute to anxiety disorders, and to be ameliorated during successful treatment, but limited clinical data exist to support this hypothesis. We evaluated whether increases in morning cortisol and the diurnal cortisol slope, markers of stress biology, are associated with clinical response to chamomile therapy among subjects with generalized anxiety disorder (GAD). Among 45 subjects with DSM-IV diagnosed GAD in an open-label clinical trial of chamomile, salivary cortisol was assessed for three days each pre- and post-treatment, at 8am, 12pm, 4pm, and 8pm. Mixed model analyses assessed whether GAD symptom change predicted the degree to which cortisol levels changed during treatment. Symptom improvement during treatment was significantly associated with pre-to-post treatment changes in cortisol. Subjects who experienced more symptomatic improvement experienced significant increases in their morning salivary cortisol (β = 0.48, p < 0.001), and a greater decrease in cortisol from morning to the rest of the day (β = 0.55, p < 0.001). In addition, at baseline a lower cortisol level (β = -0.24, p = 0.023) and a lesser decrease in cortisol after morning (β = 0.30, p = 0.003) were associated with greater symptomatic improvement. Increases in morning salivary cortisol and the diurnal cortisol slope are associated with symptom improvement in chamomile treatment of GAD. Response to treatment for GAD could partially stem from normalization of stress biology dysfunction, but further work involving establishing abnormalities within-sample, ruling out of confounds (e.g., sleep), and a placebo control is necessary to conclude an amelioration effect. NCT01072344. URL: https://clinicaltrials.gov/ct2/show/NCT01072344. Copyright © 2017. Published by Elsevier Ltd.

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study.

PubMed

Johannsson, Gudmundur; Lennernäs, Hans; Marelli, Claudio; Rockich, Kevin; Skrtic, Stanko

2016-07-01

Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure-time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5-20mg and assess intrasubject variability. Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20-55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography-tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration-time profiles. DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0-4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration-time curve (AUC)0-∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional - an important consideration when managing intercurrent illness in patients with adrenal insufficiency. © 2016 The authors.

Development of cortisol circadian rhythm in infancy.

PubMed

de Weerth, Carolina; Zijl, Robbert H; Buitelaar, Jan K

2003-08-01

Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set. Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling). The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that affect cortisol (i.e. time of sampling, feeding, etc.). Although the choice of analysis method influences the age of appearance obtained, our use of HLM shows that the infants' own variability in onset and stability of the cortisol circadian rhythm greatly contributes to the different results.

Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.

PubMed

Findling, James W; Fleseriu, Maria; Newell-Price, John; Petersenn, Stephan; Pivonello, Rosario; Kandra, Albert; Pedroncelli, Alberto M; Biller, Beverly M K

2016-11-01

Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.

Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study.

PubMed

Sandouk, Zahrae; Johnston, Philip; Bunch, Dustin; Wang, Sihe; Bena, James; Hamrahian, Amir; Kennedy, Laurence

2018-03-01

The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. To assess the frequency of variable hormonogenesis in patients presenting with CD. Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

Refining the multisystem view of the stress response: Coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict

PubMed Central

Powers, Sally I.; Granger, Douglas A.

2013-01-01

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period (“matched phase coordination”), and association between overall levels of cortisol and sAA in response to conflict (“average level coordination”). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. PMID:23684904

Industrial noise exposure and salivary cortisol in blue collar industrial workers.

PubMed

Fouladi, D Behzad; Nassiri, Parvin; Monazzam, E Mohammadreza; Farahani, Saeed; Hassanzadeh, Gholamreza; Hoseini, Mostafa

2012-01-01

Measuring non-auditory effects of noise such as stress-inducing ones have become of interest recently. Salivary cortisol has become a popular measure in stress research. So, assessing noise-induced stress via saliva cortisol evaluation can present a bright future in non-invasive exposure assessment methods. This study had 3 goals: (1) Assess and compare saliva cortisol concentrations in the morning and evening in normal work day and leisure day in industrial workers, (2) assess the relationship between industrial noise exposure and salivary cortisol concentrations, and (3) assess the possibility of using salivary cortisol as a possible marker of noise-induced stress. This study included 80 male participants working in 4 different parts (painting, assembling lines, casting, and packaging) of a household manufacturing company. Morning and evening saliva samples were collected at 7.00 am and 4.00 pm, respectively. Noise exposure levels were assessed by sound level meter and noise dosimeter. All measurements occurred in two days: One in leisure day and other in working day. Descriptive statistics, paired sample t-test, and regression analysis were used as statistical tools of this study with P < 0.05. On the leisure day, morning salivary cortisol (geometric mean [GM], 15.0; 95% CI, 12.0 to 19.0 nmol/L) was significantly higher than evening cortisol (GM, 5.2; 95% CI, 4.2 to 6.3 nmol/L) (P < 0.05). Also, on the working day, morning salivary cortisol (GM, 14.0; 95% CI, 11.25 to 18.0 nmol/L) was significantly higher than evening cortisol (GM, 8.0; 95% CI, 6.5 to 10.0 nmol/L) (P < 0.05). No significant difference was obtained for morning cortisol levels between leisure day and working day samples (P = 0.117). But, for evening cortisol concentrations, a strong significant difference was noted leisure day and working day (P < 0.001). The evening cortisol in the working day correlated significantly with noise exposure > 80 dBA. Our study revealed that industrial noise, with levels > 80 dBA, has a significant effect on salivary cortisol elevation.

The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies.

PubMed

Miller, Robert; Stalder, Tobias; Jarczok, Marc; Almeida, David M; Badrick, Ellena; Bartels, Meike; Boomsma, Dorret I; Coe, Christopher L; Dekker, Marieke C J; Donzella, Bonny; Fischer, Joachim E; Gunnar, Megan R; Kumari, Meena; Lederbogen, Florian; Power, Christine; Ryff, Carol D; Subramanian, S V; Tiemeier, Henning; Watamura, Sarah E; Kirschbaum, Clemens

2016-11-01

Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5-98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1-16h after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rectal hydrocortisone during stress in patients with adrenal insufficiency

PubMed Central

De Vroede, M; Beukering, R; Spit, M; Jansen, M

1998-01-01

OBJECTIVE—Patients with glucocorticoid deficiency need lifelong glucocorticoid replacement treatment. During acute stressful events, steroid dosage must be increased several times, which is often problematical in children. This study investigated the reliability of rectal hydrocortisone administration as an alternative to the intramuscular route.
STUDY DESIGN—Serum cortisol was assessed during stress in normal children to determine the concentration that should be achieved after rectal hydrocortisone. Subsequently, serum cortisol concentrations were measured three hours after administering a suppository containing hydrocortisone 100 mg/m2 to 57 patients with adrenocortical insufficiency. In eight patients, the time dependency of the cortisol rise after rectal administration was established.
RESULTS—In 51 previously healthy children admitted to hospital with an acute stressful condition, the mean serum cortisol concentration was 1092 nmol/l. Rectal hydrocortisone in patients with adrenocortical insufficiency resulted in a mean serum cortisol concentration of 1212 nmol/l three hours after insertion of the suppository containing hydrocortisone. In 14 of 57 children, serum cortisol was < 1000 nmol/l and in eight children it was below 600 nmol/l. One hour after administration, the mean cortisol concentration had reached 1000 nmol/l. This was sustained for more than four hours.
CONCLUSION—Rectal hydrocortisone is a safe alternative to parenteral administration in the self management of Addisonian prone conditions. However, because eight of 57 children did not achieve concentrations > 600 nmol/l, its use is recommended only after previously documenting an adequate serum cortisol concentration three hours after receiving a test dose.

 PMID:9713011

Cushing's syndrome: from physiological principles to diagnosis and clinical care

PubMed Central

Raff, Hershel; Carroll, Ty

2015-01-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic–pituitary–adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism – Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. PMID:25480800

The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children.

PubMed

Tenenbaum, Ariel; Phillip, Moshe; de Vries, Liat

2014-01-01

Few studies have addressed the role of the glucagon stimulation test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We investigated the diagnostic value of the GST in evaluating the adrenocortical response in short healthy children. The GST was performed in 190 children investigated for short stature. A peak cortisol >500 nmol/l was considered a normal response. In the 45 (23.7%) with subnormal response, a 250-μg ACTH test was done. The rate of subnormal adrenal response to GST was higher among boys (33.9 vs. 8.9%, p < 0.001) and among children ≥6 years than among younger children (32.7 vs. 18.4%, p < 0.02). Both mean basal and peak cortisol levels were higher in girls than in boys: 381 ± 165 vs. 319 ± 151 nmol/l (p = 0.003) and 741 ± 102 vs. 595 ± 208 nmol/l (p < 0.001), respectively. Peak cortisol on GST was associated with basal cortisol (r = 0.45, p < 0.001) but not with glucose nadir (r = -0.31, p = 0.67), peak GH (r = 0.069, p = 0.33) or BMI-SDS (r = -0.08, p = 0.28). Peak cortisol was >500 nmol/l in all the patients undergoing an ACTH stimulation test. Since adrenal response to GST is age- and gender-related and the false-positive rate is high, its routine performance in healthy children warrants reconsideration. © 2014 S. Karger AG, Basel.

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

PubMed

Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

Differential expression of 11β-hydroxysteroid dehydrogenase type 1 and 2 in mild and moderate/severe persistent allergic nasal mucosa and regulation of their expression by Th2 cytokines: asthma and rhinitis.

PubMed

Jun, Y J; Park, S J; Hwang, J W; Kim, T H; Jung, K J; Jung, J Y; Hwang, G H; Lee, S H; Lee, S H

2014-02-01

Glucocorticoids are used to treat allergic rhinitis, but the mechanisms by which they induce disease remission are unclear. 11β-hydroxysteroid dehydrogenase (11β-HSD) is a tissue-specific regulator of glucocorticoid responses, inducing the interconversion of inactive and active glucocorticoids. We analysed the expression and distribution patterns of 11β-HSD1, 11β-HSD2, and steroidogenic enzymes in normal and allergic nasal mucosa, and cytokine-driven regulation of their expression. The production levels of cortisol in normal, allergic nasal mucosa and in cultured epithelial cells stimulated with cytokines were also determined. The expression levels of 11β-HSD1, 11β-HSD2, steroidogenic enzymes (CYP11B1, CYP11A1), and cortisol in normal, mild, and moderate/severe persistent allergic nasal mucosa were assessed by real-time PCR, Western blot, immunohistochemistry, and ELISA. The expression levels of 11β-HSD1, 11β-HSD2, CYP11B1, CYP11A1, and cortisol were also determined in cultured nasal epithelial cell treated with IL-4, IL-5, IL-13, IL-17A, and IFN-γ. Conversion ratio of cortisone to cortisol was evaluated using siRNA technique, 11β-HSD1 inhibitor, and the measurement of 11β-HSD1 activity. The expression levels of 11β-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11β-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11β-HSD2 decreased. CYP11A1 expression level was not changed in allergic nasal mucosa or in response to stimulation with cytokines. SiRNA technique or the measurement of 11β-HSD1 activity showed that nasal epithelium activates cortisone to cortisol in a 11β-HSD-dependent manner. These results indicate that the localized anti-inflammatory effects of glucocorticoids are regulated by inflammatory cytokines, which can modulate the expression of 11β-HSD1, 11β-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids. © 2013 John Wiley & Sons Ltd.

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

PubMed Central

Ng, P; Lee, C; Lam, C; Ma, K; Fok, T; Chan, I; Wong, E

2004-01-01

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (a) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (b) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). Study design: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. Results: Basal, peak, and incremental rise in serum cortisol (ΔCort0–30) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p < 0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and ΔCort0–30) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80–0.93 and 0.81–0.89 respectively) for predicting early neonatal hypotension. Conclusions: This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants. PMID:14977894

Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis.

PubMed Central

Kenyon, C J; Fraser, R; Birnie, G G; Connell, J M; Lever, A F

1986-01-01

Isolated bovine adrenocortical cells were incubated with and without 3 ng/ml ACTH, with various concentrations (10-1000 micrograms/ml) of either cimetidine or ranitidine. Cortisol, corticosterone, and deoxycorticosterone outputs were measured. Cimetidine and ranitidine at 320 and 1000 micrograms/ml inhibited ACTH-stimulated corticosterone and cortisol synthesis and cimetidine decreased basal cortisol synthesis. The inhibitory effects of cimetidine on cortisol synthesis were approximately 10 times greater than those of ranitidine. Cimetidine (1000 micrograms/ml), but not ranitidine increased deoxycorticosterone synthesis by ACTH-stimulated cells, indicating inhibition of 11 beta-hydroxylation in the adrenal steroidogenic pathway. Although doses of cimetidine and ranitidine which produce these in vitro effects are much greater than plasma concentrations in normal clinical use, they might be important in acutely ill patients given intravenous bolus injections of cimetidine, or if either antagonist were accumulated by the adrenal to produce high intracellular concentrations. PMID:3023203

Metabolic consequences of stress during childhood and adolescence.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2012-05-01

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems. Copyright © 2012 Elsevier Inc. All rights reserved.

Diurnal salivary cortisol patterns during pregnancy and after delivery: relationship to plasma corticotrophin-releasing-hormone.

PubMed

Allolio, B; Hoffmann, J; Linton, E A; Winkelmann, W; Kusche, M; Schulte, H M

1990-08-01

The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.

Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia.

PubMed

Sarafoglou, Kyriakie; Zimmerman, Cheryl L; Gonzalez-Bolanos, Maria T; Willis, Brian A; Brundage, Richard

2015-01-01

Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated. (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters. Thirty-four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6-hour pharmacokinetic studies. Results were analyzed by noncompartmental methods to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone, and androstenedione; maximum concentration and time-to-maximum concentration for cortisol; and minimum and time-to-minimum concentration for 17-hydroxyprogesterone and androstenedione. Mean (SD) cortisol half-life and Cmax were 1.01 (0.20) hours and 24.4 (5.4) μg/dL, respectively. The AUCs for cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) μg hour/dL, 29,490 (23,539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No significant relationships existed between cortisol AUCs and the AUCs of either 17-hydroxyprogesterone (P=0.32) or androstenedione (P=0.99); nor were there differences between the change-from-baseline concentrations for cortisol with either 17-hydroxyprogesterone (P=0.80) or androstenedione (P=0.40). Cortisol simulations indicated that although four daily doses decreased 24-hour hypercortisolemia and hypocortisolemia, substantial periods of each remained. Concentration profiles of cortisol, 17-hydroxyprogesterone, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid half-life and the lack of a sustained-released product make it difficult to closely approximate normal circadian profiles.

Optimal glucocorticoid therapy.

PubMed

Debono, Miguel; Ross, Richard J

2011-01-01

The rhythmic regulation of human physiology and behaviour is controlled by a central endogenous clock located in the suprachiasmatic nucleus. Most tissues have peripheral clocks that oscillate in time with this central clock. How the central time keeper controls peripheral clocks is not established, however there is evidence to suggest that the cortisol rhythm is one important secondary messenger. Loss of the endogenous cortisol rhythm is associated with sleep disturbance, depression, and metabolic abnormalities. In adrenal insufficiency, current glucocorticoid replacement regimens cannot replace the normal circadian rhythm of cortisol, and patients have an increased mortality and impaired quality of life. We propose that reproducing circadian cortisol levels may improve quality of life in patients with adrenal insufficiency and we have been investigating the impact of circadian hydrocortisone replacement. Using Chronocort, a modified release preparation of hydrocortisone, we have demonstrated that it is possible to simulate the overnight rise in cortisol release and, in preliminary studies in patients with congenital adrenal hyperplasia, control morning androgen levels. Future studies are now required to determine whether Chronocort can improve quality of life in patients with adrenal insufficiency. Copyright © 2011 S. Karger AG, Basel.

Diurnal patterns and associations among salivary cortisol, DHEA and alpha-amylase in older adults.

PubMed

Wilcox, Rand R; Granger, Douglas A; Szanton, Sarah; Clark, Florence

2014-04-22

Cortisol and dehydroepiandrosterone (DHEA) are considered to be valuable markers of the hypothalamus-pituitary-adrenal (HPA) axis, while salivary alpha-amylase (sAA) reflects the autonomic nervous system. Past studies have found certain diurnal patterns among these biomarkers, with some studies reporting results that differ from others. Also, some past studies have found an association among these three biomarkers while other studies have not. This study investigates these patterns and associations in older adults by taking advantage of modern statistical methods for dealing with non-normality, outliers and curvature. Basic characteristics of the data are reported as well, which are relevant to understanding the nature of any patterns and associations. Boxplots were used to check on the skewness and presence of outliers, including the impact of using simple transformations for dealing with non-normality. Diurnal patterns were investigated using recent advances aimed at comparing medians. When studying associations, the initial step was to check for curvature using a non-parametric regression estimator. Based on the resulting fit, a robust regression estimator was used that is designed to deal with skewed distributions and outliers. Boxplots indicated highly skewed distributions with outliers. Simple transformations (such as taking logs) did not deal with this issue in an effective manner. Consequently, diurnal patterns were investigated using medians and found to be consistent with some previous studies but not others. A positive association between awakening cortisol levels and DHEA was found when DHEA is relatively low; otherwise no association was found. The nature of the association between cortisol and DHEA was found to change during the course of the day. Upon awakening, cortisol was found to have no association with sAA when DHEA levels are relatively low, but otherwise there is a negative association. DHEA was found to have a positive association with sAA upon awakening. Shortly after awakening and for the remainder of the day, no association was found between DHEA and sAA ignoring cortisol. For DHEA and cortisol (taken as the independent variables) versus sAA (the dependent variable), again an association is found only upon awakening. Copyright © 2014 Elsevier Inc. All rights reserved.

11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes.

PubMed

Itoi, Saori; Terao, Mika; Murota, Hiroyuki; Katayama, Ichiro

2013-10-18

The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactive cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10(-13) M cortisol, whereas 1 × 10(-5) M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol concentrations by 11β-HSD1 appears to modulate expression of inflammatory cytokines in NHEKs. Copyright © 2013 Elsevier Inc. All rights reserved.

Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder

PubMed Central

Palomar, Gloria; Ferrer, Roser; Real, Alberto; Nogueira, Mariana; Corrales, Montserrat; Casas, Miguel; Ramos-Quiroga, Josep Antoni

2015-01-01

Background: Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. Methods: Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. Results: No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). Conclusions: Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life. PMID:25782526

New diagnostic criteria of adrenal subclinical Cushing's syndrome: opinion from the Japan Endocrine Society.

PubMed

Yanase, Toshihiko; Oki, Yutaka; Katabami, Takuyuki; Otsuki, Michio; Kageyama, Kazunori; Tanaka, Tomoaki; Kawate, Hisaya; Tanabe, Makito; Doi, Masaru; Akehi, Yuko; Ichijo, Takamasa

2018-04-26

New diagnostic criteria and the treatment policy for adrenal subclinical Cushing's syndrome (SCS) are proposed on behalf of the Japan Endocrine Society. The Japanese version has been published, and the essential contents are presented in this English-language version. The current diagnostic criteria for SCS have elicited two main problems: (i) the relatively low reliability of a low range of serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone suppression test (DST); (ii) different cutoff values for serum cortisol after a 1-mg DST compared with those of other countries. Thus, new criteria are needed. In the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8 μg/dL, after a 1-mg DST are presented. Serum cortisol ≥5 μg/dL after a 1-mg DST alone is considered sufficient to judge autonomous cortisol secretion for the diagnosis of SCS, and the current criterion based on serum cortisol ≥3 μg/dL after a 1-mg DST can continue to be used. Clinical evidence suggests that serum cortisol ≥1.8-2.9 μg/dL after a 1-mg DST is not always normal, so cases who meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and nocturnal serum cortisol ≥5 μg/dL are proposed to have SCS. We suggest surgery if cases show serum cortisol ≥5 μg/dL after a 1-mg DST (or are disheartened by treatment-resistant problems) or suspicious cases of adrenal cancer according to tumor imaging.

Cortisol Response to Stress in Adults with Attention Deficit Hyperactivity Disorder.

PubMed

Corominas-Roso, Margarida; Palomar, Gloria; Ferrer, Roser; Real, Alberto; Nogueira, Mariana; Corrales, Montserrat; Casas, Miguel; Ramos-Quiroga, Josep Antoni

2015-03-17

Differences in the cortisol response have been reported between children exhibiting the inattentive and hyperactive/impulsive subtypes of attention deficit hyperactivity disorder. However, there is no such information about adults. The aim of the present study was to determine the possible differences between the combined and inattentive subtypes in the cortisol response to stress. Ninety-six adults with attention deficit hyperactivity disorder, 38 inattentive and 58 combined, without any medical or psychiatric comorbidities and 25 healthy controls were included. The Trier Social Stress Test was used to assess physiological stress responses. Clinical data and subjective stress levels, including the Perceived Stress Scale, were also recorded. No significant differences in the cortisol response to the Trier Social Stress Test were found between patients and controls. However, albeit there were no basal differences, lower cortisol levels at 15 (P=.015), 30 (P=.015), and 45 minutes (P=.045) were observed in the combined compared with the inattentive subtype after the stress induction; these differences disappeared 60 minutes after the stress. In contrast, the subjective stress responses showed significant differences between attention deficit hyperactivity disorder patients and controls (P<.001), but no differences were seen between attention deficit hyperactivity disorder subtypes. In turn, subjective stress measures, such as the Perceived Stress Scale, positively correlated with the whole cortisol stress response (P<.027). Both the combined and inattentive attention deficit hyperactivity disorder adults exhibited a normal cortisol response to stress when challenged. Nevertheless, the inattentive patients displayed a higher level of cortisol after stress compared with the combined patients. Despite the differences in the cortisol response, adults with attention deficit hyperactivity disorder reported high levels of subjective stress in their every-day life. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones.

PubMed

Vogl, Daniela; Falk, Werner; Dorner, Monika; Schölmerich, Jürgen; Straub, Rainer H

2003-02-01

In patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), low levels of adrenal steroids have been repeatedly demonstrated, but the site of alteration has not been exactly described because measurements of serum pregnenolone and 17-hydroxypregnenolone (17OHPreg) together with other adrenal steroids have never been performed. We measured serum levels of adrenal hormones such as pregnenolone, 17OHPreg, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), progesterone (P), 17-hydroxyprogesterone (17OHP), androstenedione (ASD), and cortisol in 24 healthy controls, 24 patients with RA, and 24 patients with SLE. Serum levels of pregnenolone were similar in RA and SLE patients as compared to healthy controls irrespective of prior prednisolone therapy. In all RA and SLE patients (including those with prior prednisolone treatment), serum levels of all measured hormones except pregnenolone were significantly lower as compared to controls. In RA patients without prior prednisolone treatment, serum levels of 17OHPreg, DHEA, cortisol, and ASD were similar to controls, and serum levels of P, 17OHP, and DHEAS were significantly lower as compared to controls. In SLE patients without prior prednisolone treatment, serum levels of 17OHPreg and cortisol were similar, and serum levels of P, 17OHP, ASD, DHEA, and DHEAS were significantly lower as compared to controls. The primary hormone of the adrenal steroid cascade, pregnenolone, is almost normal in RA and SLE irrespective of corticosteroid treatment. In patients with RA, we believe that there is a near normal P450scc reaction and a normal double step P450c17 reaction. In SLE patients, the P450scc reaction also seems normal but the second step of the P450c17 reaction seems to be inhibited. In both diseases, cortisol levels remain relatively stable at the expense of other adrenal hormones. This study revealed distinct changes of steroid pathways that are related to the disease entities.

Refining the multisystem view of the stress response: coordination among cortisol, alpha-amylase, and subjective stress in response to relationship conflict.

PubMed

Laurent, Heidemarie K; Powers, Sally I; Granger, Douglas A

2013-07-02

This study investigated associations among young adults' hypothalamic-pituitary-adrenal axis activity, autonomic nervous system activity, and subjective stress in response to interpersonal conflict to better characterize coordination across stress systems. Seven saliva samples were collected from 199 young adult opposite-sex couples before, during, and after they discussed an unresolved relationship conflict. Samples were later assayed for cortisol and alpha-amylase (sAA). Couples rated anticipatory stress prior to the conflict and perceived stress immediately following the task. Growth curve modeling was used to examine two possible levels of within-person coordination across physiological systems: alignment between cortisol and sAA responses throughout the sampling period ("matched phase coordination"), and association between overall levels of cortisol and sAA in response to conflict ("average level coordination"). Whereas both partners showed the former type of coordination, only women showed the latter type. Positive anticipation of the stressor predicted stronger cortisol-sAA matched phase coordination for women. Pre-task ratings related to women's sAA, and post-task ratings related to both partners' cortisol responses. Implications for a multisystem interpretation of normal and pathological responses to daily stress are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Relationship disruption stress in human infants: a validation study with experimental and control groups.

PubMed

Haley, David W

2011-09-01

The current study examined whether the psychological stress of the still-face (SF) task (i.e. stress resulting from a parent's unresponsiveness) is a valid laboratory stress paradigm for evaluating infant cortisol reactivity. Given that factors external to the experimental paradigm, such as arriving at a new place, may cause an elevation in cortisol secretion; we tested the hypothesis that infants would show a cortisol response to the SF task but not to a normal FF task (control). Saliva was collected for cortisol measurement from 6-month-old infants (n = 31) randomly assigned to either a repeated SF task or to a continuous FF task. Parent-infant dyads were videotaped. Salivary cortisol concentration was measured at baseline, 20, and 30 min after the start of the procedure. Infant salivary cortisol concentrations showed a significant increase over time for the SF task but not for the FF task. The results provide new evidence that the repeated SF task provides a psychological challenge that is due to the SF condition rather than to some non-task related factor; these results provide internal validity for the paradigm. The study offers new insight into the role of parent-infant interactions in the activation of the infant stress response system.

Cushing's syndrome: from physiological principles to diagnosis and clinical care.

PubMed

Raff, Hershel; Carroll, Ty

2015-02-01

The physiological control of cortisol synthesis in the adrenal cortex involves stimulation of adrenocorticotrophic hormone (ACTH) by hypothalamic corticotrophin-releasing hormone (CRH) and then stimulation of the adrenal by ACTH. The control loop of the hypothalamic-pituitary-adrenal (HPA) axis is closed by negative feedback of cortisol on the hypothalamus and pituitary. Understanding this system is required to master the diagnosis, differential diagnosis and treatment of endogenous hypercortisolism--Cushing's syndrome. Endogenous Cushing's syndrome is caused either by excess ACTH secretion or by autonomous cortisol release from the adrenal cortex. Diagnosis of cortisol excess exploits three physiological principles: failure to achieve the normal nadir in the cortisol diurnal rhythm, loss of sensitivity of ACTH-secreting tumours to cortisol negative feedback, and increased excretion of free cortisol in the urine. Differentiating a pituitary source of excess ACTH (Cushing's disease) from an ectopic source is accomplished by imaging the pituitary and sampling for ACTH in the venous drainage of the pituitary. With surgical removal of ACTH or cortisol-secreting tumours, secondary adrenal insufficiency ensues because of the prior suppression of the HPA axis by glucocorticoid negative feedback. Medical therapy is targeted to the anatomical location of the dysregulated component of the HPA axis. Future research will focus on new diagnostics and treatments of Cushing's syndrome. These are elegant examples of translational research: understanding basic physiology informs the development of new approaches to diagnosis and treatment. Appreciating pathophysiology generates new areas for inquiry of basic physiological and biochemical mechanisms. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Getting better, but not well: A 1.5 year follow-up of cognitive performance and cortisol levels in clinical and non-Clinical burnout.

PubMed

Oosterholt, Bart G; Maes, Joseph H R; Van der Linden, Dimitri; Verbraak, Marc J P M; Kompier, Michiel A J

2016-05-01

The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of bedrest on circadian rhythms of plasma renin, aldosterone, and cortisol

NASA Technical Reports Server (NTRS)

Chavarri, M.; Ganguly, A.; Luetscher, J. A.; Zager, P. G.

1977-01-01

Previous studies of normal men after 5 d of bedrest showed that circulatory instability on head-up tilt or standing is preceded by increased plasma renin activity (PRA) at bedrest. In the present study, the circadian rhythms of PRA, aldosterone, and cortisol have been observed in five normal men on a constant diet. In ambulatory controls, PRA and aldosterone increased normally after standing. On the third morning of bedrest, PRA was higher than before, and at noon, PRA was higher than in standing controls. The nocturnal peaks of PRA resulting from episodic renin secretion during sleep were higher after bedrest. Plasma aldosterone was also increased by bedrest. The findings are compatible with the theory that intermittent beta-adrenergic nerve activity during sleep is increased after bedrest, but other factors, such as loss of body sodium and a lower plasma volume, may also be involved.

Effects of a transdermal lidocaine patch on indicators of postoperative pain in dogs undergoing midline ovariohysterectomy.

PubMed

Merema, Danielle K; Schoenrock, Emily K; Le Boedec, Kevin; McMichael, Maureen A

2017-05-15

OBJECTIVE To determine the effects of a transdermal lidocaine patch (TLP) on indicators of postoperative pain in healthy dogs following ovariohysterectomy. DESIGN Randomized, blinded controlled trial. ANIMALS 40 healthy shelter-owned female dogs admitted to a student surgery program for ovariohysterectomy. PROCEDURES Dogs were randomly assigned to receive after ovariohysterectomy a 5-cm-wide strip of TLP applied topically on both sides of the incision, for the full length of the incision and a wound dressing (n = 19) or a placebo patch (nonmedicated wound dressing; 21). All dogs underwent midline ovariohysterectomy. Immediately afterward, dogs received 2 IM morphine injections, carprofen (SC, q 12 h for 2 days), and the assigned patch (left in place for 18 hours). Postoperative comfort was evaluated by use of the short form of the Glasgow Composite Measures Pain Scale and serum cortisol concentrations measured prior to premedication and 1, 2, 4, 6, 8, 10, and 18 hours after surgery. RESULTS No significant difference in pain scores or serum cortisol concentrations was identified between dogs that received the TLP and dogs that received a placebo patch after ovariohysterectomy. CONCLUSIONS AND CLINICAL RELEVANCE The TLP provided no additional analgesic benefit to dogs treated concurrently with recommended doses of morphine and carprofen following ovariohysterectomy. Additional studies are needed to investigate whether similar results might be achieved in dogs treated concurrently with other analgesics. (J Am Vet Med Assoc 2017;250:1140-1147).

Achieving a physiological cortisol profile with once-daily dual-release hydrocortisone: a pharmacokinetic study

PubMed Central

Lennernäs, Hans; Marelli, Claudio; Rockich, Kevin; Skrtic, Stanko

2016-01-01

Objective Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy was developed to provide a cortisol exposure−time profile that closely resembles the physiological cortisol profile. This study aimed to characterize single-dose pharmacokinetics (PK) of DR-HC 5–20mg and assess intrasubject variability. Methods Thirty-one healthy Japanese or non-Hispanic Caucasian volunteers aged 20−55 years participated in this randomized, open-label, PK study. Single doses of DR-HC 5, 15 (3×5), and 20mg were administered orally after an overnight fast and suppression of endogenous cortisol secretion. After estimating the endogenous cortisol profile, PK of DR-HC over 24h were evaluated to assess dose proportionality and impact of ethnicity. Plasma cortisol concentrations were analyzed using liquid chromatography−tandem mass spectrometry. PK parameters were calculated from individual cortisol concentration−time profiles. Results DR-HC 20mg provided higher than endogenous cortisol plasma concentrations 0−4h post-dose but similar concentrations later in the profile. Cortisol concentrations and PK exposure parameters increased with increasing doses. Mean maximal serum concentration (Cmax) was 82.0 and 178.1ng/mL, while mean area under the concentration−time curve (AUC)0−∞ was 562.8 and 1180.8h×ng/mL with DR-HC 5 and 20mg respectively. Within-subject PK variability was low (<15%) for DR-HC 20mg. All exposure PK parameters were less than dose proportional (slope <1). PK differences between ethnicities were explained by body weight differences. Conclusions DR-HC replacement resembles the daily normal cortisol profile. Within-subject day-to-day PK variability was low, underpinning the safety of DR-HC for replacement therapy. DR-HC PK were less than dose proportional – an important consideration when managing intercurrent illness in patients with adrenal insufficiency. PMID:27129362

Role of cortisol in the pathogenesis of deficient counterregulation after antecedent hypoglycemia in normal humans.

PubMed Central

Davis, S N; Shavers, C; Costa, F; Mosqueda-Garcia, R

1996-01-01

The aim of this study was to determine the role of increased plasma cortisol levels in the pathogenesis of hypoglycemia-associated autonomic failure. Experiments were carried out on 16 lean, healthy, overnight fasted male subjects. One group (n = 8) underwent two separate, 2-d randomized experiments separated by at least 2 mo. On day 1 insulin was infused at a rate of 1.5 mU/kg per min and 2 h clamped hypoglycemia (53 +/- 2 mg/dl) or euglycemia (93 +/- 3 mg/dl) was obtained during morning and afternoon. The next morning subjects underwent a 2-h hyperinsulinemic (1.5 mU/kg per min) hypoglycemic (53 +/- 2 mg/dl) clamp study. In the other group (n = 8), day 1 consisted of morning and afternoon 2-h clamped hyperinsulinemic euglycemia with cortisol infused to stimulate levels of plasma cortisol occurring during clamped hypoglycemia (53 mg/dl). The next morning (day 2) subjects underwent a 2-h hyperinsulinemic hypoglycemic clamp identical to the first group. Despite equivalent day 2 plasma glucose and insulin levels, steady state epinephrine, norepinephrine, pancreatic polypeptide, glucagon, ACTH and muscle sympathetic nerve activity (MSNA) values were significantly (R < 0.01) blunted after day 1 cortisol infusion compared to antecedent euglycemia. Compared to day 1 cortisol, antecedent hypoglycemia produced similar blunted day 2 responses of epinephrine, norepinephrine, pancreatic polypeptide and MSNA compared to day 1 cortisol. Antecedent hypoglycemia, however, produced a more pronounced blunting of plasma glucagon, ACTH, and hepatic glucose production compared to day 1 cortisol. We conclude that in healthy overnight fasted men (a) antecedent physiologic increases of plasma cortisol can significantly blunt epinephrine, norepinephrine, glucagon, and MSNA responses to subsequent hypoglycemia and (b) these data suggest that increased plasma cortisol is the mechanism responsible for antecedent hypoglycemia causing hypoglycemia associated autonomic failure. PMID:8698859

Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in adolescents with schizotypal personality disorder.

PubMed

Weinstein, D D; Diforio, D; Schiffman, J; Walker, E; Bonsall, R

1999-04-01

A relationship between schizotypal personality disorder and schizophrenia has been documented in behavioral genetic studies, and there are similarities in the cognitive deficits and brain abnormalities associated with these disorders. Adolescents with schizotypal personality disorder are of particular interest because the postpubertal period is a critical one for the development of a DSM axis I disorder. It is likely that some schizotypal adolescents will remain stable over time, some will improve, and a subgroup will develop schizophrenia. This study tested the hypotheses that, like schizophrenic patients, schizotypal adolescents manifest an elevated rate of minor physical and dermatoglyphic anomalies, both of which suggest prenatal neurodevelopmental abnormalities. Cortisol release is also of interest because of evidence that the hypothalamic-pituitary-adrenal axis may influence the behavioral expression of vulnerability to schizophrenia. Minor physical anomalies, dermatoglyphic asymmetries, and salivary cortisol levels were measured in three groups of adolescents: 20 with schizotypal personality disorder, 20 with other personality disorders, and 26 with no disorder. Assessments began at noon, and four saliva samples were obtained at hourly intervals. The schizotypal personality disorder group showed more minor physical anomalies and dermatoglyphic asymmetries than the normal comparison group and higher cortisol levels than both of the other groups. Group differences in cortisol level were most pronounced at the beginning of the evaluation. Cortisol level and age were positively correlated. The findings support the assumption that schizotypal personality disorder is associated with perturbations in fetal neurodevelopment and, under some circumstances, a heightened cortisol response.

Anticipatory cortisol, testosterone and psychological responses to judo competition in young men.

PubMed

Salvador, A; Suay, F; González-Bono, E; Serrano, M A

2003-04-01

This study compares the anticipatory hormonal and psychological responses of 17 male judo players to an official competition with the data obtained during eight resting sessions carried out at the same time of day, throughout an entire sports season. Testosterone (T) and cortisol (C) levels were determined 1 h and 30 min before competition, and mood, anxiety and expectancies were also evaluated. C levels and anxiety scores were concurrently higher before the contest than in resting conditions; however, non-significant correlations between them were found. The anticipatory T response was not significant for the whole group. However, one group of subjects did display T increases, higher C levels, and higher motivation to win scores than the other group. Furthermore, this group also obtained a better outcome. Thus, this hormonal pattern and its relationships with psychological variables suggest an adaptive psychobiological response to a competition. Results are discussed in the context that neuroendocrine response to competition is associated with cognitive appraisal.

Stress and puberty-related hormone reactivity, negative emotionality, and parent--adolescent relationships.

PubMed

Marceau, Kristine; Dorn, Lorah D; Susman, Elizabeth J

2012-08-01

Hormone reactivity to stressors and hormones that rapidly change at puberty are hypothesized to influence moods, which may in turn affect parent-child relationship quality. The present study investigated whether reactivity of testosterone, DHEA, and cortisol in a clinic setting (venipuncture paradigm) predicted negative emotionality and family problems at Time 1 (0 months), Time 2 (6 months), and Time 3 (12 months) in a sample of 56 boys (M = 12.72, SD = 1.32 years) and 52 girls (M = 11.99, SD = 1.55 years). Reactivity of each hormone, negative emotionality, and family problems were measured at each of three laboratory visits. Testosterone reactivity at the first assessment predicted family problems one year later. DHEA stress reactivity was related to concurrent negative emotionality at six and 12 months. Cortisol reactivity did not predict negative emotionality or family problems. Reactivity of different hormones that change at puberty may play an important role in adolescent moods and family processes during puberty. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differences in cortisol response affect the distinction of observed reactive and proactive aggression in children with aggressive behaviour disorders.

PubMed

Kempes, M; de Vries, H; Matthys, W; van Engeland, H; van Hooff, J

2008-01-01

Various researchers distinguished two categories of aggressive behaviour, namely reactive and proactive aggression. Reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is behaviour that anticipates a reward. In the present study, including both a sample of disruptive behaviour disordered (DBD) and normal control (NC) children, we observed reactive and proactive aggressive behaviour during an experimental dyadic play session. DBD children showed more observed reactive and proactive aggression. Subsequently, we investigated whether the observed measures correlated with parent-rated measures of reactive and proactive aggression in. We distinguished in both NC and DBD children a subgroup showing a rise in cortisol level, i.e. responders, and a subgroup who did not show a rise in cortisol, i.e. non-responders. Results suggest that differences in the cortisol response affects the correspondence between observed and parent-rated reactive and proactive aggression since only DBD non-responders showed the expected correlations.

A stochastic differential equation model of diurnal cortisol patterns

NASA Technical Reports Server (NTRS)

Brown, E. N.; Meehan, P. M.; Dempster, A. P.

2001-01-01

Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems.

Melatonin and cortisol assessment of circadian shifts in astronauts before flight

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Putcha, L.; Chen, Y. M.; Baker, E.

1995-01-01

Melatonin and cortisol were measured in saliva and urine samples to assess the effectiveness of a 7-day protocol combining bright-light exposure with sleep shifting in eliciting a 12-hr phase-shift delay in eight U.S. Space Shuttle astronauts before launch. Baseline acrophases for 15 control subjects with normal sleep-wake cycles were as follows: cortisol (saliva) at 0700 (0730 in urine); melatonin (saliva) at 0130 (6-hydroxymelatonin sulfate at 0230 in urine). Acrophases of the astronaut group fell within 2.5 hr of these values before the treatment protocols were begun. During the bright-light and sleep-shifting treatments, both absolute melatonin production and melatonin rhythmicity were diminished during the first 3 treatment days; total daily cortisol levels remained constant throughout the treatment. By the fourth to sixth day of the 7-day protocol, seven of the eight crew members showed phase delays in all four measures that fell within 2 hr of the expected 11- to 12-hr shift. Although cortisol and melatonin rhythms each corresponded with the phase shift, the rhythms in these two hormones did not correspond with each other during the transition.

Lower stress-reactive cortisol in female veterans associated with military status but not PTSD.

PubMed

Pierce, Meghan E; Pritchard, Laurel M

2016-09-01

Female veterans are a growing yet understudied population. Currently, 14.6% of all troops deployed to Afghanistan and Iraq are female. Military service is associated with an increased risk for trauma exposure and subsequent development of posttraumatic stress disorder (PTSD). Dysregulation of the hypothalamic-pituitary-adrenal axis is frequently associated with PTSD. Few studies have examined females diagnosed with PTSD and only one study, to our knowledge, has examined HPA-axis dysregulation in female veterans. This study examined salivary cortisol in 52 female veterans and civilians both with and without PTSD. We collected saliva samples at bedtime and awakening, as well as in response to the Trier social stress test (TSST). We found that female veterans had blunted cortisol concentrations at all time points during the TSST compared to female civilians, regardless of PTSD status. Even though all groups showed the expected diurnal decline in cortisol, the difference between awakening and bedtime samples were significant only in civilians without PTSD. The results of our study suggest that stressors specific to the military may lead to lower than normal cortisol, which may not be associated with the expressions of PTSD.

Melatonin and cortisol assessment of circadian shifts in astronauts before flight.

PubMed

Whitson, P A; Putcha, L; Chen, Y M; Baker, E

1995-04-01

Melatonin and cortisol were measured in saliva and urine samples to assess the effectiveness of a 7-day protocol combining bright-light exposure with sleep shifting in eliciting a 12-hr phase-shift delay in eight U.S. Space Shuttle astronauts before launch. Baseline acrophases for 15 control subjects with normal sleep-wake cycles were as follows: cortisol (saliva) at 0700 (0730 in urine); melatonin (saliva) at 0130 (6-hydroxymelatonin sulfate at 0230 in urine). Acrophases of the astronaut group fell within 2.5 hr of these values before the treatment protocols were begun. During the bright-light and sleep-shifting treatments, both absolute melatonin production and melatonin rhythmicity were diminished during the first 3 treatment days; total daily cortisol levels remained constant throughout the treatment. By the fourth to sixth day of the 7-day protocol, seven of the eight crew members showed phase delays in all four measures that fell within 2 hr of the expected 11- to 12-hr shift. Although cortisol and melatonin rhythms each corresponded with the phase shift, the rhythms in these two hormones did not correspond with each other during the transition.

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

PubMed

Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

2015-01-01

To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Itoi, Saori; Terao, Mika, E-mail: mterao@derma.med.osaka-u.ac.jp; Murota, Hiroyuki

Highlights: •We investigate the role of 11β-HSD1 in skin inflammation. •Various stimuli increase expression of 11β-HSD1 in keratinocytes. •11β-HSD1 knockdown by siRNA decreases cortisol levels in media. •11β-HSD1 knockdown abrogates the response to pro-inflammatory cytokines. •Low-dose versus high-dose cortisol has opposing effects on keratinocyte inflammation. -- Abstract: The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme. The enzyme that catalyzes the intracellular conversion of hormonally-inactivemore » cortisone into active cortisol is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is expressed in normal human epidermal keratinocytes (NHEKs) and negatively regulates proliferation of NHEKs. In this study, we investigated the role of 11β-HSD1 in skin inflammation. Expression of 11β-HSD1 was induced by UV-B irradiation and in response to the pro-inflammatory cytokines, IL-1β and TNFα. Increased cortisol concentrations in culture media also increased in response to these stimuli. To investigate the function of increased 11β-HSD1 in response to pro-inflammatory cytokines, we knocked down 11β-HSD1 by transfecting siRNA. Production of IL-6 and IL-8 in response to IL-1β or TNFα stimulation was attenuated in NHEKs transfected with si11β-HSD1 compared with control cells. In addition, IL-1β-induced IL-6 production was enhanced in cultures containing 1 × 10{sup −13} M cortisol, whereas 1 × 10{sup −5} M cortisol attenuated production of IL-6. Thus, cortisol showed immunostimulatory and immunosuppressive activities depending on its concentration. Our results indicate that 11β-HSD1 expression is increased by various stimuli. Thus, regulation of cytosolic cortisol concentrations by 11β-HSD1 appears to modulate expression of inflammatory cytokines in NHEKs.« less

Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: Associations with birthweight and gestation at delivery.

PubMed

Stirrat, Laura I; O'Reilly, James R; Barr, Sarah M; Andrew, Ruth; Riley, Simon C; Howie, Alexander F; Bowman, Maria; Smith, Roger; Lewis, John G; Denison, Fiona C; Forbes, Shareen; Seckl, Jonathan R; Walker, Brian R; Norman, Jane E; Reynolds, Rebecca M

2016-01-01

The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism.

PubMed

Feldman, E C; Bruyette, D S; Nelson, R W; Farver, T B

1990-07-01

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of adrenal function by measurement of salivary steroids in response to corticotrophin in patients infected with human immunodeficiency virus.

PubMed

Cardoso, Estela; Persi, Gabriel; González, Natalia; Tumilasci, Omar; Arregger, Alejandro; Burgos, Myriam; Rodríguez, Viviana; Molina, Ana; Contreras, Liliana N

2007-04-01

Adrenal insufficiency has been reported among critically ill HIV-infected patients. This is the first study that attempts to detect subclinical hypoadrenal states in non-critical HIV patients through salivary steroids in response to intramuscular low-dose ACTH injection. We studied 21 ambulatory adult HIV-infected patients without specific clinical signs or symptoms of adrenal insufficiency. Normal salivary flow-rate and salivary alpha-amylase activity confirmed adequate salivary gland function. Salivary cortisol (SAF) and salivary aldosterone (SAL) were obtained at baseline and 30 min after the injection of 25 microg of ACTH in the deltoid muscle (LDT(s)). Assessment of salivary steroids after stimulation with 250 microg of intramuscular ACTH (HDT(s)) was performed on those who hyporesponded to LDT(s). Basal blood samples were drawn for steroids, renin and ACTH measurements. At baseline SAF and SAL correlated significantly (p=0.0001) with basal serum cortisol and aldosterone (r=0.70 and 0.91, respectively). Plasma ACTH and renin concentrations were within the normal range in all patients. Eight of the twenty-one HIV(+) patients were LDT(s) hyporesponders in either SAF (n:1) or SAL (n:7). LDT(s) repeated in six cases after a year reconfirmed the impairment of aldosterone secretion. LDT(s) hyporesponders had normal steroid responses to HDT(s). LDT(s) is a simple, safe, well-accepted and non-invasive approach to assess adrenal function in HIV-infected ambulatory patients. It revealed subnormal cortisol (5%) and aldosterone responses (33%) when HDT(s) results were normal.

Chronic administration of ellagic acid improved the cognition in middle-aged overweight men.

PubMed

Liu, Ying; Yu, Shuyi; Wang, Fen; Yu, Haitao; Li, Xueli; Dong, Wanru; Lin, Ruichao; Liu, Qingshan

2018-03-01

This study aimed to investigate if ellagic acid has beneficial effects on cognitive deficits in middle-aged overweight individuals and to propose a possible mechanism. A total of 150 middle-aged male participants, including 76 normal-weight and 74 overweight men, aged between 45 to 55 years, were recruited for this study. Both normal-weight and overweight participants were administered either 50 mg ellagic acid or placebo cellulose daily for 12 weeks. Blood lipids, peripheral brain-derived neurotrophic factor (BDNF), and saliva cortisol were assessed on the last day of the procedure to investigate the effects induced by ellagic acid. The results revealed that ellagic acid treatment improved the levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3% decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5% decline in low-density lipoprotein. Additionally, ellagic acid increased plasma BDNF by 21.2% in the overweight group and showed no effects on normal-weight participants. Moreover, the increased saliva cortisol level in overweight individuals was inhibited by 22.7% in a 12-week ellagic acid treatment. Also, compared with placebo, overweight individuals who consumed ellagic acid showed enhanced cognitive function as measured by the Wechsler Adult Intelligence Scale-Revised and the Montreal Cognitive Assessment. To the best of our knowledge, this is the first report showing that ellagic acid prevents cognitive deficits through normalization of lipid metabolism, increase in plasma BDNF level, and reduction of saliva cortisol concentration. These results indicate that ellagic acid has a potential to restore cognitive performance related to mild age-related declines.

Analysis of serum corticosteroid-induced alkaline phosphatase isoenzyme in dogs with hepatobiliary diseases.

PubMed

Kojima, K; Ohno, K; Kanemoto, H; Goto-Koshino, Y; Fukushima, K; Tsujimoto, H

2017-05-01

To reveal the relationship between canine corticosteroid-induced alkaline phosphatase isoenzyme activity and hepatobiliary diseases. Retrospective analysis of the relationship between serum corticosteroid-induced alkaline phosphatase activity and diagnosis, serum cortisol concentration and alanine transferase activity in dogs with hepatobiliary diseases. Dogs with a history of glucocorticoid administration were excluded. Seventy-two dogs with hepatobiliary diseases were analysed. The serum corticosteroid-induced alkaline phosphatase concentration was increased in dogs with hepatobiliary diseases. There was no correlation between serum cortisol concentration and serum corticosteroid-induced alkaline phosphatase percentage or activity. Dogs with hepatobiliary disease can exhibit high serum alkaline phosphatase activity even if the dogs have not been administrated glucocorticoids and the serum cortisol concentration is normal. © 2017 British Small Animal Veterinary Association.

Serum cortisol and thyroxine concentrations as predictors of death in critically ill puppies with parvoviral diarrhea.

PubMed

Schoeman, Johan P; Goddard, Amelia; Herrtage, Michael E

2007-11-15

To evaluate the role of adrenal and thyroid hormones in the prediction of death in a population of critically ill puppies with parvoviral diarrhea by measuring serial daily serum concentrations of cortisol and thyroxine. Prospective case-control study. 57 critically ill puppies with parvoviral diarrhea admitted to the hospital and 17 clinically normal control puppies. Basal serum cortisol and thyroxine concentrations were measured for each dog with parvoviral diarrhea at admission (prior to treatment) and daily until death, euthanasia, or discharge. Median time between admission and death was 48 hours (ie, on day 3). Median serum cortisol concentration on day 1 (admission) in all dogs with parvoviral diarrhea (248 nmol/L) was significantly higher than in control dogs (77 nmol/L). No significant difference was found in the day 1 median serum cortisol concentration of 11 dogs that died (302 nmol/L) and 46 dogs that survived (238 nmol/L). A significantly higher median serum cortisol concentration was, however, found in nonsurvivor group dogs, compared with survivor group dogs, on days 2 and 3. Median serum thyroxine concentration on day 1 in dogs with parvoviral diarrhea was significantly lower than in control dogs (8.12 nmol/L vs 35 nmol/L, respectively). Median serum thyroxine concentration of nonsurvivor group dogs (4.4 nmol/L) was significantly lower than that of survivor group dogs (9.2 nmol/L) at admission and became even lower on days 2 and 3. High serum cortisol and low serum thyroxine concentrations at 24 and 48 hours after admission were associated with death in dogs with parvoviral diarrhea.

Androgen Responses to ACTH Infusion among Individual Women with Polycystic Ovary Syndrome

PubMed Central

Maas, Kevin H.; Chuan, Sandy; Harrison, Evan; Cook-Andersen, Heidi; Duleba, Antoni J; Chang, R. Jeffrey

2016-01-01

Objective To compare androgen responses during ACTH infusion among women with PCOS and normal women. Design Cross-sectional study. Setting Research center at an academic medical center. Participants Women with PCOS (n=13) and normal controls (n=15). Interventions Blood samples were obtained frequently during a 6-hour dose-response ACTH infusion. Main Outcome Measures Comparison of basal and stimulated levels of 17-OHP, androgens, and cortisol during ACTH infusion with those following hCG injection within individual subjects. Results In women with PCOS increased 17-OHP, A4, and DHEA responses during ACTH infusion were comparable to those observed in normal controls. The magnitude of responses was highly variable among PCOS women. Within individual women with PCOS adrenal responses to ACTH and ovarian responses to hCG were significantly correlated. Cortisol responses to ACTH were similar in PCOS and normal controls. Conclusion Within individual women with PCOS, enhanced androgen responses to ACTH are accompanied by comparable androgen responsiveness to hCG. These findings suggest that dysregulated steroidogenesis leading to hyperandrogenemia in this disorder is likely present in both adrenal and ovarian tissues. PMID:27473350

A longitudinal analysis of circulating stress-related proteins and chronic ethanol self-administration in cynomolgus macaques

PubMed Central

Helms, Christa M.; Messaoudi, Ilhem; Jeng, Sophia; Freeman, Willard M.; Vrana, Kent E.; Grant, Kathleen A.

2011-01-01

Background Alcoholics have alterations in endocrine and immune function and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods Plasma proteins (n = 60; Luminex) and hormones (adrenocorticotropic hormone, ACTH; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n = 10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4 months and after 12 months of 22-h daily concurrent access to ethanol and water. Results Significant changes were observed in ACTH, cortisol and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, eight proteins were elevated and nine showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusion Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity. PMID:22141444

Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.

PubMed

Srithunyarat, Thanikul; Hagman, Ragnvi; Höglund, Odd V; Stridsberg, Mats; Olsson, Ulf; Hanson, Jeanette; Nonthakotr, Chalermkwan; Lagerstedt, Anne-Sofie; Pettersson, Ann

2017-03-21

Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis. Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups. Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs. Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed. However, because of the large degree of overlap with normal values, our results suggest that plasma CST concentrations have a limited potential as a clinically useful biomarker for pain-induced stress.

Sleep-wake cycle effects on sleep stages, and plasma cortisol and growth secretions

NASA Technical Reports Server (NTRS)

1971-01-01

Studies were made of the effects of various stimuli on sleep stages and of secretion of a number of different hormones during sleep in human subjects. Among the stimuli were vestibular stimulation, the action of L-Dopa, and a three-hour sleep-wake cycle. Hormones observed included plasma cortisol, growth hormone, dehydroisoandrosterone, and luteinizing hormone. Relationships between sleep onset, the presence of Cushing's syndrome or sleep disorders, and ultradian rhythmicity, and hormone secretion were investigated. Sleep patterns and hormone secretion in normal subjects were also studied.

Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis.

PubMed

Crofford, L J; Kalogeras, K T; Mastorakos, G; Magiakou, M A; Wells, J; Kanik, K S; Gold, P W; Chrousos, G P; Wilder, R L

1997-04-01

Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed, untreated RA patients early in the course of their disease and five age-, gender-, and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h time-integrated plasma ACTH, plasma cortisol levels, and urinary free cortisol excretion that were not significantly different from control subjects, in spite of their disease activity. However, an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P < 0.05). There was pronounced circadian variation of plasma Il-6 levels. In the RA patients, we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol, with elevated levels of IL-6 before the elevations of ACTH and cortisol by 1 and 2 h, respectively. In the same patients, we detected a negative effect of cortisol upon IL-6 exerted with a delay of 5 h. The data presented here suggest that although endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall activity of the hypothalamic-pituitary-adrenal axis remains normal and apparently is insufficient to inhibit ongoing inflammation in early untreated RA patients.

Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance

PubMed Central

Shamim, W; Yousufuddin, M; Francis, D; Gualdiero, P; Honour, J; Anker, S; Coats, A

2001-01-01

OBJECTIVE—To evaluate urinary glucocorticoid excretion profiles in a cohort of recently diagnosed young hypertensive patients.
METHODS—After excluding patients with secondary causes, 60 individuals with premature hypertension were recruited (diagnosed by ambulatory blood pressure monitoring before the age of 36 years). In addition, 30 older hypertensive controls (age of onset > 36 years, "middle aged hypertensive controls"), and 30 normal controls (age matched to the young hypertensive group) were studied. All provided 24 hour urine collections for mass spectrometry for total cortisol metabolites and total androgen metabolites by gas chromatography.
RESULTS—Among male patients, those with premature hypertension had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) µg/day) than age matched normal controls (7270 (1788) µg/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) µg/day; p = 0.002). A similar increase was seen among the female patients, although the absolute concentrations were lower. There was no significant difference between middle aged hypertensive patients and normal controls. Urinary total androgen excretion profiles in female patients also showed an unusual increase in the premature hypertension group (2958 (1672) µg/day) compared with the other groups (middle aged hypertensive controls, 1373 (748) µg/day, p = 0.0003; normal controls, 1687 (636) µg/day, p = 0.002). In all subjects, serum sodium and creatinine concentrations were within the normal range; serum potassium concentrations were found to be low before the start of treatment.
CONCLUSIONS—Individuals presenting with premature hypertension have an abnormally high excretion of glucocorticoid metabolites in the urine. While the mechanism remains uncertain, these findings are compatible with partial resistance of the glucocorticoid receptors, with a compensatory increase in cortisol and androgen metabolites. The mineralocorticoid effects of the latter (sodium and water retention) may contribute to an abnormally high blood pressure and may have implications for targeted selection of first line treatment in young hypertensive patients.


Keywords: premature hypertension; glucocorticoid resistance; cortisol metabolites; glucocorticoid receptor resistance PMID:11454825

The acute salivary ghrelin response to a psychosocial stress is enhanced in symptomatic patients with bulimia nervosa: a pilot study.

PubMed

Monteleone, Palmiero; Tortorella, Alfonso; Scognamiglio, Pasquale; Serino, Ismene; Monteleone, Alessio Maria; Maj, Mario

2012-01-01

Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour. Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures. No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification. Copyright © 2012 S. Karger AG, Basel.

When endocrinology and democracy collide: emotions, cortisol and voting at national elections.

PubMed

Waismel-Manor, Israel; Ifergane, Gal; Cohen, Hagit

2011-11-01

Faced with stressful experiences, such as uncertainty or novelty, the adrenal glands secrete glucocorticoid hormones to help us cope with stress. Since many decision-making situations are stressful, there is reason to believe that voting is a stressful event. In this study, we asked voters in Israel's national election (N=113) to report on their general affective state immediately before entering the polling place using the Positive Affect Negative Affect Schedule (PANAS) and to provide us with a saliva sample through which we could evaluate their cortisol levels. Compared to a second sample of voters who reported their affective state on election night (N=70), we found that voters at the ballot box had higher positive and negative affect. Moreover, our voters at the polling place exhibited cortisol levels that were significantly higher than their own normal levels obtained on a similar day, and significantly higher than those of a second control group sampled the day after the elections (N=6). Our data demonstrate that elections are exciting, yet stressful events, and it is this stress, among other factors, that elevates the cortisol levels of voters. Since elevated cortisol has been found to affect memory consolidation, impair memory retrieval and lead to risk-seeking behavior, we discuss how these outcomes of elevated cortisol levels may affect voting in general and the field of electoral studies in particular. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

Cushing's syndrome: aftermath of the cure.

PubMed

Pivonello, Rosario; De Martino, Maria Cristina; De Leo, Monica; Tauchmanovà, Libuse; Faggiano, Antongiulio; Lombardi, Gaetano; Colao, Annamaria

2007-11-01

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure.

Parenting predicts Strange Situation cortisol reactivity among children adopted internationally.

PubMed

DePasquale, Carrie E; Raby, K Lee; Hoye, Julie; Dozier, Mary

2018-03-01

The functioning of the hypothalamic pituitary adrenal (HPA) axis can be altered by adverse early experiences. Recent studies indicate that children who were adopted internationally after experiencing early institutional rearing and unstable caregiving exhibit blunted HPA reactivity to stressful situations. The present study examined whether caregiving experiences post-adoption further modulate children's HPA responses to stress. Parental sensitivity during naturalistic parent-child play interactions was assessed for 66 children (M age = 17.3 months, SD = 4.6) within a year of being adopted internationally. Approximately 8 months later, children's salivary cortisol levels were measured immediately before as well as 15 and 30 min after a series of brief separations from the mother in an unfamiliar laboratory setting. Latent growth curve modeling indicated that experiencing more parental sensitivity predicted increased cortisol reactivity to the stressor. Although half the families received an intervention designed to improve parental sensitivity, the intervention did not significantly alter children's cortisol outcomes. These findings suggest that post-adoption parental sensitivity may help normalize the HPA response to stress among children adopted internationally. Copyright © 2018 Elsevier Ltd. All rights reserved.

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

NASA Technical Reports Server (NTRS)

Zeitzer, J. M.; Ayas, N. T.; Shea, S. A.; Brown, R.; Czeisler, C. A.

2000-01-01

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

PubMed

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.

Effects of Pre-Experience of Social Exclusion on Hypothalamus-Pituitary-Adrenal Axis and Catecholaminergic Responsiveness to Public Speaking Stress

PubMed Central

Weik, Ulrike; Kuepper, Yvonne; Hennig, Juergen; Deinzer, Renate

2013-01-01

Backround Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Methods Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Results Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. Conclusions We replicated our previous study result of a supressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective. PMID:23573255

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

PubMed

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

Effect of administration of corticotropin-releasing hormone and glucocorticoid on arginine vasopressin response to osmotic stimulus in normal subjects and patients with hypocorticotropinism without overt diabetes insipidus.

PubMed

Yamada, K; Tamura, Y; Yoshida, S

1989-08-01

We examined the effect of CRH administration on the response of plasma arginine vasopressin (AVP) induced by an osmotic stimulus in six normal subjects and five patients with hypocorticotropinism without overt diabetes insipidus (four patients with Sheehan's syndrome and one with idiopathic pituitary dwarfism with ACTH deficiency). Hypertonic saline infusion (855 mmol/L saline solutions at a rate of 205 mumol/kg.min for 10 min) increased plasma AVP 5.7-fold (P less than 0.01) in normal subjects and 2.4-fold (P less than 0.05) in the patients. CRH administration significantly augmented the plasma AVP response to the osmotic stimulus in the normal subjects, but not in the patients with hypocorticotropinism. CRH administration alone did not influence plasma AVP. These findings suggest that a central CRH-related mechanism(s) was at least partly involved in the augmentation of AVP release. Based on the relatively low plasma AVP response to the osmotic stimulus in patients and their lower plasma AVP levels and higher plasma osmolality under basal conditions, we suggest that patients with hypocorticotropinism have partial diabetes insipidus, in which impairment of central CRH action might be, at least in part, involved. The response of plasma AVP to the osmotic stimulus was attenuated significantly when the patients were given cortisol. Since basal PRA, plasma aldosterone, plasma osmolality, hematocrit, body weight, mean blood pressure, and heart rate were similar with and without cortisol administration, this effect of cortisol may have been due to central suppression of the AVP response to the osmotic stimulus.

High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing.

PubMed

Friedman, T C; Ghods, D E; Shahinian, H K; Zachery, L; Shayesteh, N; Seasholtz, S; Zuckerbraun, E; Lee, M L; McCutcheon, I E

2010-11-01

Many Endocrinologists believe that a single determination of eucortisolism or a single demonstration of appropriate suppression to dexamethasone excluded Cushing's syndrome, except in what was previously thought to be the rare patient with episodic or periodic Cushing's syndrome. We hypothesize that episodic Cushing's syndrome is relatively common and a single test assessing hypercortisolism may not be sufficient to accurately rule out or diagnose Cushing's syndrome and retrospectively examined the number of normal and abnormal tests assessing hypercortisolism performed on multiple occasions in 66 patients found to have mild and/or episodic Cushing's syndrome compared to a similar group of 54 patients evaluated for, but determined not to have Cushing's syndrome. We found that 65 of the 66 patients with Cushing's syndrome had at least one normal test of cortisol status and most patients had several normal tests. The probability of having Cushing's syndrome when one test was negative was 92% for 23:00 h salivary cortisol, 88% for 24-h UFC, 86% for 24-h 17OHS, and 54% for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing's syndrome and no single test was effective in conclusively diagnosing or excluding the condition. Rather, the paradigm for the diagnosis should be a careful history and physical examination and in those patients in whom mild Cushing's syndrome/disease is strongly suspected, multiple tests assessing hypercortisolism should be performed on subsequent occasions, especially when the patient is experiencing signs and symptoms of short-term hypercortisolism. © Georg Thieme Verlag KG Stuttgart · New York.

An 8-Year Longitudinal Study of Overreaching in 114 Elite Female Chinese Wrestlers

PubMed Central

Tian, Ye; He, Zihong; Zhao, Jiexiu; Tao, Dalang; Xu, Kuiyuan; Midgley, Adrian; McNaughton, Lars

2015-01-01

Context: Successful training involves structured overload but must avoid the combination of excessive overload and inadequate recovery. Objective: The aim of this study was to determine the incidence of functional overreaching (FOR), nonfunctional overreaching (NFOR), and overtraining syndrome in elite female wrestlers during their normal training and competition schedules and to explore the utility of blood markers for the early detection of overreaching. Classification of FOR, NFOR, and overtraining syndrome was based on the European Congress of Sports Medicine position statement. Design: Case series. Setting: China Institute of Sport Science. Patients or Other Participants: Over an 8-year period, 114 wrestlers from the women's Asian wrestling team were monitored to help identify if and when they experienced FOR, NFOR, or overtraining syndrome. Main Outcome Measure(s): Creatine kinase, hemoglobin, testosterone, and cortisol were measured throughout the period to identify whether wrestlers were outside the reference intervals (constructed from normal recovery data) during periods of overreaching and not overreaching. Results: Among the 114 athletes, there were 13 (3.6%) instances of FOR, 23 (6.4%) instances of NFOR, and 2 (0.6%) instances of overtraining syndrome. The diagnostic sensitivity for FOR was 38%, 15%, 45%, and 18% for creatine kinase, hemoglobin, testosterone, and cortisol, respectively. The diagnostic sensitivity for NFOR was 29%, 33%, 26%, and 35% for creatine kinase, hemoglobin, testosterone, and cortisol, respectively. Specificity was 79%, 88%, 90%, and 82% for creatine kinase, hemoglobin, testosterone, and cortisol, respectively. Post hoc analysis showed no mean differences in creatine kinase (F = 0.5, P = .47), hemoglobin (F = 3.8, P = .052), testosterone (F = 0.2, P = .62), or cortisol (F = 0.04, P = .85) between monitoring periods when wrestlers were and were not diagnosed with FOR and NFOR. Conclusions: Coaches and sports scientists should not use single blood variables as markers of overreaching in elite female wrestlers. PMID:25329348

Prolonged weightlessness effect on postflight plasma thyroid hormones

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C.; Driscoll, T. B.

1977-01-01

Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

Childhood poverty and health: cumulative risk exposure and stress dysregulation.

PubMed

Evans, Gary W; Kim, Pilyoung

2007-11-01

A massive literature documents the inverse association between poverty or low socioeconomic status and health, but little is known about the mechanisms underlying this robust relation. We examined longitudinal relations between duration of poverty exposure since birth, cumulative risk exposure, and physiological stress in two hundred seven 13-year-olds. Chronic stress was assessed by basal blood pressure and overnight cortisol levels; stress regulation was assessed by cardiovascular reactivity to a standard acute stressor and recovery after exposure to this stressor. Cumulative risk exposure was measured by multiple physical (e.g., substandard housing) and social (e.g., family turmoil) risk factors. The greater the number of years spent living in poverty, the more elevated was overnight cortisol and the more dysregulated was the cardiovascular response (i.e., muted reactivity). Cardiovascular recovery was not affected by duration of poverty exposure. Unlike the duration of poverty exposure, concurrent poverty (i.e., during adolescence) did not affect these physiological stress outcomes. The effects of childhood poverty on stress dysregulation are largely explained by cumulative risk exposure accompanying childhood poverty.

Metabolic effects of cortisol, ACTH, adrenalin and insulin in the marsupial sugar glider, Petaurus breviceps.

PubMed

Bradley, A J; Stoddart, D M

1990-11-01

The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals but contrast with the pattern described for two macropodid marsupials, the red kangaroo Macropus rufus and the quokka Setonix brachyurus.

[Influence, in normal subjects, of an isocaloric hyperprotein diet on cortisol, ACTH, GH and PRL response to lysine-8-vasopressin].

PubMed

Giovannini, C; Sellini, M; Manzo, G; Barletta, C; Scavo, D

1981-12-30

The Lysin-8-Vasopressin test has been experimented in ten healthy subjects during normocaloric balanced diet and after hyperproteic-normocaloric diet. The levels of ACTH, Cortisol and GH are significantly more elevated after hyperproteic-normocaloric diet than in basal conditions. The levels of Prolactin do not show any remarkable change. These results can indicate the increased reactivity of the diencephalon-hypophysis-adrenal axis and of the hormones connected with the mechanisms of homeostasis and stress, probably correlated to more disposable proteic material and to the metabolic effects which follow.

Validation of Autonomic and Endocrine Reactivity to a Laboratory Stressor in Young Children

PubMed Central

Roos, Leslie E.; Giuliano, Ryan J.; Beauchamp, Kathryn G.; Gunnar, Megan; Amidon, Brigette; Fisher, Philip A.

2017-01-01

The validation of laboratory paradigms that reliably induce a stress response [including hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activation], is critical for understanding how children’s stress-response systems support emotional and cognitive function. Early childhood research to date is markedly limited, given the difficulty in establishing paradigms that reliably induce a cortisol response. Furthermore, research to date has not included a control condition or examined concurrent ANS reactivity. We addressed these limitations by characterizing the extent to which a modified matching task stressor paradigm induces HPA and ANS activation, beyond a closely matched control condition. Modifications include an unfamiliar and unfriendly assessor to increase the stressful nature of the task. Results validate the matching task as a laboratory stressor, with significant differences in HPA and ANS responsivity between conditions. The Stressor group exhibited a cortisol increase post-stressor, while the Control group was stable over time. Children in both conditions exhibited reduced parasympathetic activity to the first-half of the task, but in the second-half, only children in the Stressor condition, who were experiencing exaggerated signals of failure, exhibited further parasympathetic decline. The Stressor condition induced higher sympathetic activity (versus Control) throughout the task, with exaggerated second-half differences. Within the Stressor condition, responsivity was convergent across systems, with greater cortisol reactivity correlated with the magnitude of parasympathetic withdrawal and sympathetic engagement. Future research employing the matching task will facilitate understanding the role of HPA and ANS function in development. PMID:28024268

The burden of online friends: the effects of giving up Facebook on stress and well-being.

PubMed

Vanman, Eric J; Baker, Rosemary; Tobin, Stephanie J

2018-01-01

People occasionally choose to cut themselves off from their online social network by taking extended breaks from Facebook. This study investigated whether abstaining from Facebook reduces stress but also reduces subjective well-being because of the resulting social disconnection. Participants (138 active Facebook users) were assigned to either a condition in which they were instructed to give up Facebook for 5 days or continue to use Facebook as normal. Perceived stress and well-being, as well as salivary cortisol, were measured before and after the test period. Relative to those in the Facebook Normal condition, those in the No Facebook condition experienced lower levels of cortisol and life satisfaction. Our results suggest that the typical Facebook user may occasionally find the large amount of social information available to be taxing, and Facebook vacations could ameliorate this stress-at least in the short term.

Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

PubMed

Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

2003-09-01

Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

Endocrine stress responses and risk of type 2 diabetes mellitus.

PubMed

Siddiqui, Azaz; Madhu, S V; Sharma, S B; Desai, N G

2015-08-13

This study was carried to ascertain whether stress responses are associated with abnormalities in glucose tolerance, insulin sensitivity and pancreatic beta cell function and risk of type 2 Diabetes Mellitus. Salivary cortisol, a marker of hypothalamic-pituitary-adrenal (HPA) axis and salivary α-amylase, a marker of sympathetic nervous system (SNS) were compared in 125 subjects of newly detected diabetes mellitus (NDDM) and normal glucose tolerance (NGT) subjects who were diagnosed on the basis of oral glucose tolerance test (OGTT). Assessment of stress in them was done through stress scales - presumptive stressful life events scale (PSLES), perceived stress scale (PSS) and sense of coherence (SOC) and correlated with these and other stress response markers. Significantly higher 10 pm salivary cortisol and post dexamethasone salivary cortisol were found in NDDM subjects as compared to NGT. 10 pm salivary cortisol correlated significantly with fasting plasma glucose (FPG), 2 h plasma glucose (2h PG) and glycated hemoglobin (HbA1c) while post dex salivary cortisol correlated with 2h PG, HbA1c and salivary α-amylase with 2h PG. Stepwise logistic regression analysis showed that body mass index (OR: 1.840), SOC (OR: 0.688) and 10 pm salivary cortisol (OR: 1.427) were the strongest predictors of NDDM. The results of the present study indicate that NDDM subjects display significantly higher chronic stress and stress responses when compared to subjects with NGT. Chronic stress and endocrine stress responses are significantly associated with glucose intolerance, insulin resistance and diabetes mellitus.

Allostasis model facilitates understanding race differences in the diurnal cortisol rhythm

PubMed Central

Skinner, Martie L.; Shirtcliff, Elizabeth A.; Haggerty, Kevin P.; Coe, Christopher L.; Catalano, Richard F.

2012-01-01

The concept of allostasis suggests that greater cumulative stress burden can influence stress-responsive physiology. Dysregulation of allostatic mediators, including the hypothalamic-pituitary-adrenal (HPA) axis, is thought to precede many other signs of age-related pathology as the persistent burden of stressors accumulates over the individual's lifespan. We predicted that even in young adulthood, HPA regulation would differ between Blacks and Whites reflecting, in part, higher rates of stressor exposure and greater potential for stressors to “get under the skin”. We examined whether stressor exposure, including experiences with racism and discrimination, explained race differences in waking cortisol and the diurnal rhythm. We also examined whether HPA functioning was associated with mental health outcomes previously linked to cortisol. Salivary cortisol was assayed in 275 young adults (127 Blacks, 148 Whites, 19 to 22 years old), four times a day across 3 days. Hierarchical linear models revealed flatter slopes for Blacks, reflecting significantly lower waking and higher bedtime cortisol levels compared to Whites. Associations of HPA functioning with stressors were typically more robust for Whites such that more stress exposure created an HPA profile that resembled that of Black young adults. For Blacks, greater stressor exposure did not further impact HPA functioning, or, when significant, was often associated with higher cortisol levels. Across both races, flatter slopes generally indicated greater HPA dysregulation and were associated with poor mental health outcomes. These differential effects were more robust for Whites. These findings support an allostatic model in which social contextual factors influence normal biorhythms, even as early as young adulthood. PMID:22018088

Hypercorticism blunts circadian variations of osteocalcin regardless of nutritional status.

PubMed

Vergély, N; Lafage-Proust, M-H; Caillot-Augusseau, A; Millot, L; Lang, F; Estour, B

2002-02-01

Anorexia nervosa (AN) and Cushing's syndrome (CS) are both responsible for osteoporosis. The mechanisms leading to osteoporosis in AN include hypogonadism, nutritional depletion, and in some cases hypercorticism. Osteocalcin circulating level is a serum marker of osteoblastic activity that follows a circadian rhythm (OCR). Serum osteocalcin is decreased in both CS and AN and can be increased with treatment. In this study we analyzed the influence of combined cortisol and nutritional status on osteocalcin levels and its circadian rhythm in these two different models of hypercorticism, one nutritionally replete (CS) and one nutritionally deplete (AN), and we evaluated the effects of their treatment (surgical cure and weight gain, respectively). Before treatment, osteocalcin levels were lower in CS (n = 16) and AN (n = 42) than in controls and in the AN patient subgroup with hypercorticism (n = 13) compared to those without (n = 29). OCR was absent in CS and in AN patients with hypercorticism, whereas their circadian cortisol cycle was maintained. In CS, successful surgical treatment increased osteocalcin levels (n = 5) and restored OCR. In AN, weight gain (n = 13) induced a significant decrease in cortisol levels in hypercortisolic AN patients, and restored normal osteocalcin levels and OCR. In conclusion, we found that hypercorticism was associated with a decrease in osteocalcin levels in nutritionally replete or deplete patients and that OCR was more affected by cortisol levels than by cortisol cycle.

Characterization of estrogens, testosterone, and cortisol in normal bottlenose dolphin (Tursiops truncatus) pregnancy.

PubMed

Steinman, Karen J; Robeck, Todd R; O'Brien, Justine K

2016-01-15

The goal of this study was to describe profiles of serum estrogens, testosterone and cortisol during normal pregnancy in bottlenose dolphins. Predominant estrogens in all categories of dolphin sera pools during estrus and pregnancy (EARLY: Days 0-120; MID: Days 121-240; LATE: Days 241 to parturition; Day 0=day of conception) were estrone/estrone conjugates (E1-C) and estriol (E3). Serum samples collected throughout 101 normal pregnancies were analyzed for E1-C, E3, testosterone (T) and cortisol (CORT). E1-C was higher (P<0.05) during LATE compared to EARLY and MID, and higher (P<0.05) in nulliparous than multiparous females. E1-C concentrations were also inversely associated with maternal age (P=0.05). E3 was higher (P<0.05) in EARLY than MID and LATE, and higher overall for nulliparous than multiparous females, but concentrations were similar among gestational stages when parity was excluded from analyses. Analysis by indexed month post-conception (IMPC) demonstrated that E1-C increased from IMPC 9 and peaked at IMPC 11. E3 was significantly elevated during IMPC 1, decreased until IMPC 6 and peaked at IMPC 11. T increased (P<0.05) at IMPC 3 and continued to increase throughout gestation (P<0.05). CORT was higher (P<0.05) during LATE compared to EARLY and MID (P<0.05), peaked during IMPC 12, and was not affected by parity. Hormone profiles were not influenced by fetal sex. Copyright © 2015 Elsevier Inc. All rights reserved.

Characterization and longitudinal monitoring of serum androgens and glucocorticoids during normal pregnancy in the killer whale (Orcinus orca).

PubMed

Robeck, Todd R; Steinman, Karen J; O'Brien, Justine K

2017-06-01

The secretory patterns of testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA), cortisol (C), and corticosterone (Co) were characterized throughout 28 normal pregnancies until two-months post-partum in eleven killer whales. Effects of fetal sex, dam parity or age, and season were evaluated across either day post-conception (DPC), stage of pregnancy (PRE, EARLY, MID, LATE, POST) or indexed month post-conception (IMPC) using a mixed model linear regression with animal ID and pregnancy number as the random variables. Across DPC, DHEA, A4 and T concentrations were affected (P<0.05) by season, with highest concentrations during spring (DHEA, A4, & T) and summer (A4) as compared to the fall. A significant effect of parity on androgen production was observed only for DHEA, with multiparous females having higher (P=0.01) concentrations than nulliparous females. All three androgens significantly increased with each successive pregnancy stage and IMPC with peak concentrations occurring during IMPC 10 (DHEA), 13 (A4) and 14 (T), respectively. Cortisol was affected by season (P=0.03) with highest concentrations being detected during the months of fall, while Co was only affected by parity (P=0.003) with significant increases observed for primiparous females as compared to nulliparous females. Cortisol and Co concentrations peaked (P<0.05) during IMPC 17 (i.e., the month prior to parturition). The C to Co ratio during pregnancy was 7.4 to 1, indicating that cortisol is the major circulating glucocorticoid studied to date in pregnant killer whales. The significant increase in concentrations of maternal androgens throughout pregnancy, which were unrelated to fetal sex, indicates that they play an important role during killer whale fetal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical and Genetic Heterogeneity, Overlap with Other Tumor Syndromes, and Atypical Glucocorticoid Hormone Secretion in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Compared with Other Adrenocortical Tumors

PubMed Central

Hsiao, Hui-Pin; Kirschner, Lawrence S.; Bourdeau, Isabelle; Keil, Margaret F.; Boikos, Sosipatros A.; Verma, Somya; Robinson-White, Audrey J.; Nesterova, Maria; Lacroix, André; Stratakis, Constantine A.

2009-01-01

Objective: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is often associated with subclinical cortisol secretion or atypical Cushing’s syndrome (CS). We characterized a large series of patients of AIMAH and compared them with patients with other adrenocortical tumors. Design and Patients: We recruited 82 subjects with: 1) AIMAH (n = 16); 2) adrenocortical cortisol-producing adenoma with CS (n = 15); 3) aldosterone-producing adenoma (n = 19); and 4) single adenomas with clinically nonsignificant cortisol secretion (n = 32). Methods: Urinary free cortisol (UFC) and 17-hydroxycorticosteroid (17OHS) were collected at baseline and during dexamethasone testing; aberrant receptor responses was also sought by clinical testing and confirmed molecularly. Peripheral and/or tumor DNA was sequenced for candidate genes. Results: AIMAH patients had the highest 17OHS excretion, even when UFCs were within or close to the normal range. Aberrant receptor expression was highly prevalent. Histology showed at least two subtypes of AIMAH. For three patients with AIMAH, there was family history of CS; germline mutations were identified in three other patients in the genes for menin (one), fumarate hydratase (one), and adenomatosis polyposis coli (APC) (one); a PDE11A gene variant was found in another. One patient had a GNAS mutation in adrenal nodules only. There were no mutations in any of the tested genes in the patients of the other groups. Conclusions: AIMAH is a clinically and genetically heterogeneous disorder that can be associated with various genetic defects and aberrant hormone receptors. It is frequently associated with atypical CS and increased 17OHS; UFCs and other measures of adrenocortical activity can be misleadingly normal. PMID:19509103

Terrestrial predator alarm vocalizations are a valid monitor of stress in captive brown capuchins (Cebus apella)

USGS Publications Warehouse

Boinski, S.; Gross, T.S.; Davis, J.K.

1999-01-01

The vocal behavior of captive animals is increasingly exploited as an index of well-being. Here we show that the terrestrial predator alarm (TPA) vocalization, a robust and acoustically distinctive anti-predation vocal response present in many mammal and bird species, offers useful information on the relative well-being and stress levels of captive animals. In a 16-week experiment evaluating the effects of varying levels of physical environmental enrichment (control < toys < foraging box < foraging box and toys) in the cages of eight singly housed adult male brown capuchins, we quantified the 1) emission rate of TPAs, 2) proportions of normal and abnormal behavior sample intervals, and 3) fecal and plasma cortisol levels. Variation in TPA emission across the experimental conditions was significant. We found significant reductions in the mean TPA production rate by the group in the enriched (toys, foraging box, and foraging box and toys) compared to the control condition; pre-and post-experimental conditions, however, did not differ from the control condition. Mean TPA production by the group was also significantly positively correlated to mean group levels of fecal cortisol and proportion of abnormal behavior sample intervals, and significantly negatively correlated to the average proportion of normal behavior sample intervals in the group. Based on group means, plasma cortisol levels were positively, but not significantly, related to increasing TPA rate. At the level of the responses of an individual subject, however, the covariation between the vocal and non-vocal behavioral measures and the cortisol assays seldom attained significance. Nevertheless, the direction of the relationships among these parameters within individual subjects typically mirrored those correlations based on group means. At both the group mean and individual levels, our results are consistent with the.

Unilateral Adrenalectomy as a First-Line Treatment of Cushing's Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia.

PubMed

Debillon, Emmanuelle; Velayoudom-Cephise, Fritz-Line; Salenave, Sylvie; Caron, Philippe; Chaffanjon, Philippe; Wagner, Tristan; Massoutier, Maximilien; Lambert, Benoit; Benoit, Marine; Young, Jacques; Tabarin, Antoine; Chabre, Olivier

2015-12-01

Bilateral adrenalectomy is the reference treatment for Cushing's syndrome (CS) related to primary bilateral macronodular adrenal hyperplasia (PBMAH). It is, however, responsible for definitive adrenal insufficiency. The objective of the study was to evaluate the clinical interest of unilateral adrenalectomy (UA) of the larger gland for the treatment of CS related to PBMAH. This was a retrospective study in four tertiary French centers including all 15 patients with PBMAH and CS who underwent UA of the larger gland between 2001 and 2015. Urinary free cortisol, plasma cortisol, ACTH, body mass index, blood pressure, plasma glucose, and lipids were registered pre- and postoperatively and on follow-up. Median follow-up was 60 months (interquartile range 39-105), including 8 of 15 patients followed up for at least 5 years. A normal or low urinary free cortisol was obtained in 15 of 15 patients (100%) postoperatively. Six patients (40%) became adrenal insufficient, of whom three of six recovered a quantitatively normal cortisol secretion on follow-up. Decrease of both body mass index and blood pressure were observed at 1 year, and decrease of blood pressure was persistent 5 years postoperatively. Diabetes was cured in four of six patients. Two patients experienced a recurrence of hypercortisolism, and one was treated with mitotane, whereas the other underwent a second adrenal surgery 9 years after initial UA. UA induced remission of hypercortisolism in all patients, with sustained significant clinical improvement. The rates of both definitive adrenal insufficiency and 5-year recurrence were low. UA appears an interesting alternative to bilateral adrenalectomy as a first-line treatment in PBMAH responsible for overt CS.

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder.

PubMed

Markianos, Manolis; Tripodianakis, John; Sarantidis, Democritos; Hatzimanolis, John

2007-08-01

Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder.

[Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

PubMed

Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

2008-09-01

Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But he still had obvious hirsutism. No side effect of DEX was found. PGRS may present with pseudo-precocious puberty and galactorrhea. The aim of treatment in glucocorticoid resistance is to suppress the excessive secretion of ACTH and the increased production of adrenal androgens. The administration of synthetic GC with minimal intrinsic mineralocorticoid activity, such as DEX, provides a rational treatment for PGRS. Long-term DEX treatment should be individualized and carefully titrated based on the clinical manifestations and biochemical profile in order to control the clinical manifestations of the disease.

Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

PubMed

Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

2004-08-01

Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at acute treatment but showed a gradual rise reflecting the stress imposed on the animals. The rise in cortisol levels was visualized to potentiate the cardiovascular and metabolic changes. The effects on insulin and thyroxin were similar to those of testosterone level showing normal or stimulatory effect with acute treatment followed by decreased levels of hormones with chronic treatment.

[CHALLENGES IN THE DIAGNOSIS OF CUSHING'S SYNDROME IN THE MODERN ERA].

PubMed

Saiegh, Leonard; Sheikh-Ahmad, Mohammad; Reut, Maria; Jubran, Yousef; Shechner, Carmela

2015-12-01

Cushing's syndrome results from prolonged and excessive exposure to medically prescribed corticosteroids, or from excess endogenous cortisol secretion. When endogenous cortisol secretion is suspected, several screening tests are conducted in order to confirm or to rule out the diagnosis. In recent years, as the cut-off point of cortisol concentration on the 1 mg overnight dexamethasone suppression test was lowered, the prevalence of Cushing's syndrome has increased, and more cases of mild syndromes, with negative results on one or more screening tests, have increasingly been reported. In this paper, we will describe the various screening tests used for Cushing's syndrome, and will discuss their degree of sensitivity in the diagnosis of mild cases. We conclude that, in cases of mild syndromes, the sensitivity of some tests appears to be notably lower than has been reported. Until recently, the major challenge has been to distinguish between pseudo-Cushing's states and Cushing's syndrome. Today, however, the challenge has become to avoid misdiagnosis of mild cases, presenting with normal results on some screening tests. The sensitivity of urinary free cortisol seems to be lower than previously reported. Therefore, we recommend not to rely solely on this test in ruling out Cushing's syndrome.

Cushing's syndrome due to ectopic production of corticotropin-releasing hormone in an infant with ganglioneuroblastoma.

PubMed

Zangeneh, Farhad; Young, William F; Lloyd, Ricardo V; Chiang, Myra; Kurczynski, Elizabeth; Zangeneh, Fereydoun

2003-01-01

To report the first recognized case of Cushing's syndrome due to a corticotropin-releasing hormone (CRH)-secreting ganglioneuroblastoma, which was found in an 18-month-old boy with hypertensive encephalopathy. The clinical, biochemical, and immunohistochemical characteristics of this rare syndrome are described, and the relevant literature is reviewed. An 18-month-old boy with a history of recent weight gain was admitted because of sudden onset of right fixed esotropia and left facial palsy after episodes of emesis. Magnetic resonance imaging showed old left frontal lobe and right hypothalamic infarcts. The patient had generalized obesity, decelerated linear growth, hypertrichosis, hypertension (144/103 mm Hg), hypokalemia, and proteinuria. The 24-hour urinary excretion of free cortisol, catecholamines, and metanephrines was increased. The serum cortisol concentration after a 1-mg overnight dexamethasone suppression test (DST) was 53.7 mg/dL (normal, <5). The serum adrenocorticotropic hormone (ACTH) concentration was 7 pg/mL (normal, 10 to 60), and the CRH level was 439 pg/mL (normal, 24 to 40). An overnight high-dose DST (8 mg) failed to suppress serum cortisol; however, both cortisol and ACTH were responsive to ovine CRH stimulation. Despite discordant dynamic endocrine testing and negative somatostatin receptor scintigraphy, computed tomography showed a right 3.6- by 3.0-cm extra-adrenal retroperitoneal mass with central calcification extending 7 cm cephalocaudally. The patient underwent exploratory laparotomy, followed by chemotherapy. Findings on light microscopic and immunohistochemical examination of the retroperitoneal mass were consistent with a ganglioneuroblastoma that expressed CRH, pro-opiomelanocortin, and ACTH. The evaluation of Cushing's syndrome is one of the most complex endocrine challenges. In this case, it was due to ectopic production of CRH by a ganglioneuroblastoma. Because most CRH-producing tumors also secrete ACTH, the ectopic production may represent a paracrine phenomenon in addition to an endocrine phenomenon. The ectopic CRH may also indirectly provoke pituitary ACTH secretion. This dual mechanism may explain the resistance of the tumor to feedback inhibition and a CRH-stimulation response indistinguishable from that observed in pituitary-dependent Cushing's syndrome.

Depressive disorder as possible risk factor of osteoporosis.

PubMed

Vrkljan, M; Thaller, V; Lovricević, I; Gaćina, P; Resetić, J; Bekić, M; Sonicki, Z

2001-12-01

Hypothalamo-pituitary-adrenal (HPA) axis is a very complicated control system playing an important role in stress reaction, where glucocorticoids suppress the autonomic (vegetative), endocrine, immunologic and psychic responses to stressful stimuli. We described the marked clinical, physiological, and biochemical connection between osteoporosis and major depressive disorder (MDD). Both conditions are associated with a hyperactive HPA axis and LC/NE system, and hence with increased CRH, cortisol, and catecholamine secretion. There are numerous states or diseases associated with osteoporosis and we were looking for a hypercorticism value as a one of these. Some recent studies demonstrated that earlier history of MDD was associated with marked osteoporosis. In MDD there are two well-documented biochemical abnormalities: hypercortisolism and its resistance to dexamethasone suppression. The present study included 31 MDD patients (19 males and 12 females, mean age 37 +/- 1.3, age range 29-41 years), and 17 healthy male volunteers (mean age 39 +/- 1.6, age range 34-45 years). In each of our patients 24-hour urinary free cortisol, serum cortisol level at 8 a.m. and 5 p.m., cortisol in dexamethasone suppression test and bone mineral density were measured. We have, therefore, analyzed a group of young men and women with normal menstrual cycles, who were without signs of osteoporosis in the beginning, and who received anti-depressive therapy for many years. Analysis showed that increased levels of cortisol and the occurrence of osteoporosis, that developed as the result of elevated cortisol level. For our workshop we used nonparametric rang-correlation with Spearman's rho = -0.805, with statistic significant at the 0.01 level (2-tailed). Patients under long-term history of depression could develop a very stronger type of osteoporosis i.e. it is before known that the patients with untreated Cushing syndrome developed hard osteoporosis.

Sleep quality but not sleep quantity effects on cortisol responses to acute psychosocial stress

PubMed Central

Bassett, Sarah M.; Lupis, Sarah B.; Gianferante, Danielle; Rohleder, Nicolas; Wolf, Jutta M.

2016-01-01

Given the well-documented deleterious health effects, poor sleep has become a serious public health concern and increasing efforts are directed towards understanding underlying pathways. One potential mechanism may be stress and its biological correlates; however, studies investigating the effects of poor sleep on a body’s capacity to deal with challenges are lacking. The current study thus aimed at testing the effects of sleep quality and sleep quantity on cortisol responses to acute psychosocial stress. A total of 73 college-aged adults (44 females) were investigated. Self-reported sleep behavior was assessed via the Pittsburgh Sleep Quality Index and salivary cortisol responses to the Trier Social Stress Test (TSST) were measured. In terms of sleep quality, we found a significant three-way interaction, such that relative to bad sleep quality, men who reported fairly good or very good sleep quality showed blunted or exaggerated cortisol responses, respectively, while women’s stress responses were less dependent on their self-reported sleep quality. Contrarily, average sleep duration did not appear to impact cortisol stress responses. Lastly, participants who reported daytime dysfunctions (i.e., having trouble staying awake or keeping up enthusiasm) also showed a trend to blunted cortisol stress responses compared to participants who did not experience these types of daytime dysfunctions. Overall, the current study suggests gender-specific stress reactivity dysfunctions as one mechanism linking poor sleep with detrimental physical health outcomes. Furthermore, the observed differential sleep effects may indicate that while the body may be unable to maintain normal HPA functioning in an acute psychosocial stress situation after falling prey to low sleep quality, it may retain capacities to deal with challenges during extended times of sleep deprivation. PMID:26414625

Serum cortisol concentration with exploratory cut-off values do not predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery.

PubMed

Verweij, E J; Hogenbirk, Karin; Roest, Arno A W; van Brempt, Ronald; Hazekamp, Mark G; de Jonge, Evert

2012-10-01

Low cardiac output syndrome is common after paediatric cardiac surgery. Previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. This study was set up to test the hypothesis that the effects of hydrocortisone on haemodynamics in children with low cardiac output syndrome depend on the presence of (relative) adrenal insufficiency. A retrospective study was done on paediatric patients who received hydrocortisone when diagnosed with resistant low cardiac output syndrome after paediatric cardiac surgery in the period from 1 November 2005 to 31 December 2008. We studied the difference in effects of treatment with hydrocortisone administration between patients with adrenal insufficiency defined as an exploratory cut-off value of total cortisol of <100 nmol/l and patients with a serum total cortisol of ≥ 100 nmol/l. A total of 62 of patients were enrolled, meeting the inclusion criteria for low cardiac output syndrome. Thirty-two patients were assigned to Group 1 (<100 nmol/l) and 30 were assigned to Group 2 (≥ 100 nmol/l). Haemodynamics improved after hydrocortisone administration, with an increase in blood pressure, a decrease in administered vasopressors and inotropic drugs, an increase in urine production and a decrease in plasma lactate concentrations. The effects of treatment with hydrocortisone in children with low cardiac output after cardiac surgery was similar in patients with a low baseline serum cortisol concentration and those with normal baseline cortisol levels. A cortisol value using an exploratory cut-off value of 100 nmol/l for adrenal insufficiency should not be used as a criterion to treat these patients with hydrocortisone.

Sleep quality but not sleep quantity effects on cortisol responses to acute psychosocial stress.

PubMed

Bassett, Sarah M; Lupis, Sarah B; Gianferante, Danielle; Rohleder, Nicolas; Wolf, Jutta M

2015-01-01

Given the well-documented deleterious health effects, poor sleep has become a serious public health concern and increasing efforts are directed toward understanding underlying pathways. One potential mechanism may be stress and its biological correlates; however, studies investigating the effects of poor sleep on a body's capacity to deal with challenges are lacking. The current study thus aimed at testing the effects of sleep quality and quantity on cortisol responses to acute psychosocial stress. A total of 73 college-aged adults (44 females) were investigated. Self-reported sleep behavior was assessed via the Pittsburgh Sleep Quality Index and salivary cortisol responses to the Trier Social Stress Test were measured. In terms of sleep quality, we found a significant three-way interaction, such that relative to bad sleep quality, men who reported fairly good or very good sleep quality showed blunted or exaggerated cortisol responses, respectively, while women's stress responses were less dependent on their self-reported sleep quality. Contrarily, average sleep duration did not appear to impact cortisol stress responses. Lastly, participants who reported daytime dysfunctions (i.e. having trouble staying awake or keeping up enthusiasm) also showed a trend to blunted cortisol stress responses compared to participants who did not experience these types of daytime dysfunctions. Overall, the current study suggests gender-specific stress reactivity dysfunctions as one mechanism linking poor sleep with detrimental physical health outcomes. Furthermore, the observed differential sleep effects may indicate that while the body may be unable to maintain normal hypothalamic-pituitary-adrenal functioning in an acute psychosocial stress situation after falling prey to low sleep quality, it may retain capacities to deal with challenges during extended times of sleep deprivation.

37 CFR 1.989 - Merger of concurrent reexamination proceedings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Merger of concurrent... November 29, 1999 Concurrent Proceedings Involving Same Patent in Inter Partes Reexamination § 1.989 Merger... suspend one of the two proceedings. Where merger is ordered, the merged examination will normally result...

Fluconazole in the treatment of Cushing's disease

PubMed Central

Christie-David, Darshika; Gunton, Jenny E

2016-01-01

Summary Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its in vivo efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76 mmol/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552 nmol/l with an inappropriate ACTH of 9.3 pmol/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150 nmol/mmol with failure to suppress after 48 h of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200 nmol/day. Metyrapone was commenced at 750 mg tds. Ketoconazole was later added at 400 mg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200 mg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400 mg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged in vivo efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease. Learning points Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-β-hydroxylase and 17-α-hydroxylase, though its availability is limited in many countries.Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.Fluconazole represents a suitable alternative for the medical management of Cushing's disease and proved an effective addition to metyrapone in the management of this case. PMID:26858837

Working hours, sleep, salivary cortisol, fatigue and neuro-behavior during Mars analog mission: five crews study.

PubMed

Rai, Balwant; Foing, Bernard H; Kaur, Jasdeep

2012-05-16

The buoyancy of humans in exploring extreme space environments has been established during missions to the moon. Long duration missions like mission to Mars however, requires humans to adapt to systemic and complex environments beyond the human body's capacity. Astronauts will encounter both physiological and psychological extremes during this trip. Very few studies are conducted on effect of long duration work and sleepiness on cognitive performance. So, this study was planned to find out effects of leadership responsibility, sleepiness and long duration working hours on cognitive performance. The 30 members (leadership: normal; 10:20) were selected from MDRS crews (Mars Desert Research Station, USA). Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated during first day, mid and end day of mission. The leadership group did not show any signs of reduced test performance, even in elevated fatigue and sleepiness. The leadership group had faster reaction times on end of mission as compared to first and after 7 day of mission. Salivary cortisol levels were significantly higher in leadership group as compared to normal group. The results suggest that long duration work and sleepiness does not affect the cognitive performance of crew member. Further study is required while taking into account all factors and large sample size to prove this fact. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mechanisms underlying the comorbidity between depressive and addictive disorders in adolescents: interactions between stress and HPA activity.

PubMed

Rao, Uma; Hammen, Constance L; Poland, Russell E

2009-03-01

Depression may be a precursor to substance use disorder in some youngsters, and substance abuse might complicate the subsequent course of depression. This study examined whether hypothalamic-pituitary-adrenal (HPA) activity and stressful life experiences are related to the development of substance use disorder in depressed and nondepressed adolescents, and whether substance use disorder predicts a worsening course of depression. Urinary-free cortisol was measured for 3 nights in 151 adolescents with no prior history of substance use disorder (55 depressed, 48 at high risk for depression, and 48 normal subjects). Information was obtained on recent stressful life experiences. The participants were followed for up to 5 years to assess the onset of substance use disorder, course of depression, and stressful experiences. The relationships among depression, cortisol as a measure of HPA activity, stressful experiences, and substance use disorder were examined. Elevated cortisol was associated with onset of substance use disorder. Stressful life experiences moderated this relationship. Cortisol and stress accounted for the effects of a history or risk of depression on the development of substance use disorder. Substance use disorder was associated with higher frequency of subsequent depressive episodes. Higher cortisol prior to the onset of substance use disorder may indicate vulnerability to substance use disorder. Stressful experiences increase the risk for substance use disorder in such vulnerable youth. The high prevalence of substance use disorders in depressed individuals may be explained, in part, by high levels of stress and increased HPA activity.

Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight.

PubMed

Chao, Ariana M; Jastreboff, Ania M; White, Marney A; Grilo, Carlos M; Sinha, Rajita

2017-04-01

To examine whether baseline chronic stress, morning cortisol, and other appetite-related hormones (leptin, ghrelin, and insulin) predict future weight gain and food cravings in a naturalistic, longitudinal, 6-month follow-up study. A prospective community cohort of 339 adults (age 29.1 ± 9.0 years; BMI = 26.7 ± 5.4 kg/m 2 ; 56.9% female; 70.2% white) completed assessments at baseline and 6-month follow-up. Fasting blood draws were used to assess cortisol and other appetite-related hormone levels at baseline. At baseline and follow-up, body weight was measured, and the Cumulative Adversity Interview and Food Craving Inventory were administered. Data were analyzed using linear mixed models adjusting for demographic and clinical covariates. Over the 6-month period, 49.9% of the sample gained weight. Food cravings and chronic stress decreased over 6 months (Ps < 0.05). However, after adjusting for covariates, individuals with higher baseline total ghrelin had significantly higher food cravings at 6 months (P = 0.04). Furthermore, higher cortisol, insulin, and chronic stress were each predictive of greater future weight gain (Ps < 0.05). These results suggest that ghrelin plays a role in increased food cravings and reward-driven eating behaviors. Studies are needed that examine the utility of stress reduction methods for normalizing disrupted cortisol responses and preventing future weight gain. © 2017 The Obesity Society.

Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight

PubMed Central

Chao, Ariana M.; Jastreboff, Ania M.; White, Marney A.; Grilo, Carlos M.; Sinha, Rajita

2017-01-01

Objective To examine whether baseline chronic stress, morning cortisol, and other appetite-related hormones (leptin, ghrelin, and insulin) predict future weight gain and food cravings in a naturalistic longitudinal 6-month follow-up study. Methods A prospective community cohort of three hundred and thirty-nine adults (age=29.1± 9.0 years; BMI=26.7±5.4 kg/m2; 56.9% female; 70.2% White) completed assessments at baseline and 6-month follow-up. Fasting blood draws were used to assess cortisol and other appetite-related hormones levels at baseline. At baseline and follow-up, body weight was measured and the Cumulative Adversity Interview and Food Craving Inventory were administered. Data were analyzed using linear mixed models adjusting for demographic and clinical covariates. Results Over the 6-month period, 49.9% of the sample gained weight. Food cravings and chronic stress decreased over 6 months (ps<0.05). However, after adjusting for covariates, individuals with higher baseline total ghrelin had significantly higher food cravings at 6 months (p=0.04). Furthermore, higher cortisol, insulin, and chronic stress were each predictive of greater future weight gain (ps<0.05). Conclusions These results suggest that ghrelin plays a role in increased food cravings and reward-driven eating behaviors. Studies are needed that examine the utility of stress reduction methods for normalizing disrupted cortisol responses and preventing future weight gain. PMID:28349668

[Hormonal axes in obesity: cause or effect?].

PubMed

Lordelo, Roberta A; Mancini, Marcio C; Cercato, Cíntia; Halpern, Alfredo

2007-02-01

Several endocrine changes have been described in the obesity state. The corticotropic axis is hyperresponsive and there is enhancement of hormonal clearance, but cortisol levels are within the normal range. It is important to characterize a pseudo-Cushing in obesity. Leptin seems to be a permissive hormone for the beginning of puberty. In adults, gonadotropines are normal, and hyperandrogenism and hyperestrogenism are found. In women, insulin resistance has a central role in polycystic ovarian syndrome (POS), which is associated to ovarian hyperandrogenemia. In obese subjects, growth hormone (GH) is generally low and IGF1 is normal. Thyroid function is commonly normal in obese subjects.

Stereotactic Radiosurgery for Cushing Disease: Results of an International, Multicenter Study.

PubMed

Mehta, Gautam U; Ding, Dale; Patibandla, Mohana Rao; Kano, Hideyuki; Sisterson, Nathaniel; Su, Yan-Hua; Krsek, Michal; Nabeel, Ahmed M; El-Shehaby, Amr; Kareem, Khaled A; Martinez-Moreno, Nuria; Mathieu, David; McShane, Brendan; Blas, Kevin; Kondziolka, Douglas; Grills, Inga; Lee, John Y; Martinez-Alvarez, Roberto; Reda, Wael A; Liscak, Roman; Lee, Cheng-Chia; Lunsford, L Dade; Vance, Mary Lee; Sheehan, Jason P

2017-11-01

Cushing disease (CD) due to adrenocorticotropic hormone-secreting pituitary tumors can be a management challenge. To better understand the outcomes of stereotactic radiosurgery (SRS) for CD and define its role in management. International, multicenter, retrospective cohort analysis. Ten medical centers participating in the International Gamma Knife Research Foundation. Patients with CD with >6 months endocrine follow-up. SRS using Gamma Knife radiosurgery. The primary outcome was control of hypercortisolism (defined as normalization of free urinary cortisol). Radiologic response and adverse radiation effects (AREs) were recorded. In total, 278 patients met inclusion criteria, with a mean follow-up of 5.6 years (0.5 to 20.5 years). Twenty-two patients received SRS as a primary treatment of CD. Mean margin dose was 23.7 Gy. Cumulative initial control of hypercortisolism was 80% at 10 years. Mean time to cortisol normalization was 14.5 months. Recurrences occurred in 18% with initial cortisol normalization. Overall, the rate of durable control of hypercortisolism was 64% at 10 years and 68% among patients who received SRS as a primary treatment. AREs included hypopituitarism (25%) and cranial neuropathy (3%). Visual deficits were related to treatment of tumor within the suprasellar cistern (P = 0.01), whereas both visual (P < 0.0001) and nonvisual cranial neuropathy (P = 0.02) were related to prior pituitary irradiation. SRS for CD is well tolerated and frequently results in control of hypercortisolism. However, recurrences can occur. SRS should be considered for patients with persistent hypercortisolism after pituitary surgery and as a primary treatment in those unfit for surgery. Long-term endocrine follow-up is essential after SRS. Copyright © 2017 Endocrine Society

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis.

PubMed

Lichtenstein, Gary R; Travis, Simon; Danese, Silvio; D'Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J

2015-09-01

Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9 mg, 6 mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9 mg or placebo for 4 weeks, then open-label budesonide MMX 9 mg for 4 weeks]; and one open-label study [budesonide MMX 9 mg for 8 weeks] were pooled. Patients randomised to budesonide MMX 9 mg [n = 288], 6 mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9 mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Budesonide MMX 9 mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Budesonide MMX for the Induction of Remission of Mild to Moderate Ulcerative Colitis: A Pooled Safety Analysis

PubMed Central

Travis, Simon; Danese, Silvio; D’Haens, Geert; Moro, Luigi; Jones, Richard; Huang, Michael; Ballard, E. David; Bagin, Robert; Hardiman, Yun; Collazo, Raul; Sandborn, William J.

2015-01-01

Background and aims: Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined. Methods: Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled. Results: Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects. Conclusions: Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis. PMID:26094251

Suppressed pituitary ACTH response after ACTH treatment of infantile spasms.

PubMed

Ross, D L

1986-01-01

Suppression of an adrenocorticotropic hormone (ACTH) response to insulin hypoglycemia has been reported in ACTH-treated adults. There are no guidelines for withdrawal of ACTH treatment in children. After observing suppressed morning cortisol in several children, insulin tolerance tests were performed in five children within 48 hours after tapered withdrawal of ACTH treatment for myoclonic seizures. ACTH response, as determined by cortisol and beta-endorphin radioimmunoassay, was adequate in four of the children. One child showed low basal levels and minimal elevation during hypoglycemia for both beta-endorphin (0 to 3 pg/ml) and cortisol (3.6 to 4.4 micrograms/dL) on initial testing, but normal responses six weeks later. Measurement of beta-endorphin response supported a central basis for suppression in the child, who had had an adrenal hemorrhage during gram-negative sepsis while on ACTH. ACTH release is transiently suppressed in some children after exogenous ACTH treatment. Tapered withdrawal and stress coverage is recommended.

The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review.

PubMed

van Dalfsen, Jens H; Markus, C Rob

2018-06-01

Inadequate sleep is highly prevalent and known to decline both physical- and mental health. Literature suggests that altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis might underlie this association. This assumption is mainly based on changes in basal neuroendocrine activity and it is of equal importance to elucidate whether sleep may also influence HPA stress responsiveness. The present review provides a complete outline of recent human studies that have investigated how different aspects of sleep influence cortisol reactivity to laboratory stress. From the available data it can be concluded that both objective and subjective decrements in sleep quality potentiate the stress reactivity of the HPA axis. On the contrary, normal variations in sleep duration do not seem to influence cortisol stress responsiveness whereas excessive daytime sleepiness is associated with a blunting of the cortisol response. Given its well-established health consequences, sensitization of the HPA axis might well be a crucial component linking inadequate sleep to stress-related pathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of adrenal function in patients with tuberculosis.

PubMed

Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

2018-07-01

Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal insufficiency in TB cases attending chest department at a tertiary care hospital was significantly high but comparable in both pulmonary and extra-pulmonary type of TB. Females in general and particularly those with extra-pulmonary TB were observed to be at increased risk of adrenal insufficiency. The low dose ACTH stimulation test was able to identify cases with adrenal insufficiency which had normal basal serum cortisol levels. Screening all TB cases for adrenal insufficiency by measuring both morning basal serum cortisol levels and low dose ACTH stimulation test can help identify cases at risk of fatal adrenal crisis and institute timely management, thus improving disease prognosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Phaeochromocytoma with hypercortisolism and hypercalcaemia.

PubMed

Edafe, Ovie; Webster, Jonathan; Fernando, Malee; Vinayagam, Ragu; Balasubramanian, Sabapathy P

2015-10-07

We report a case of phaeochromocytoma associated with hypercortisolism and hypercalcaemia in a 62-year-old man. The patient presented to clinic, with a 3-year history of exertional headaches, and a 4-month history of increasing fatigue, sweating and palpitations, loss of appetite and weight, and sleepiness. He did not have a medical, family or social history that could account for these symptoms. 24 h urinary catecholamines, plasma metanephrines, 24 h urinary cortisol and adjusted serum calcium, were elevated. Overnight low-dose dexamethasone suppression test did not suppress morning plasma cortisol. Serum intact parathyroid hormone and parathyroid hormone-related peptide were low, and adrenocorticotropic hormone was normal. The patient was treated with intravenous 0.9% sodium chloride and disodium pamidronate to control hypercalcaemia. CT showed a 10 cm left adrenal mass. Following inpatient treatment with phenoxybenzamine, he underwent a left adrenectomy and histology confirmed a phaeochromocytoma. Postoperatively, he required long-term steroids for contralateral adrenal suppression. Adjusted serum calcium returned to normal postoperatively. 2015 BMJ Publishing Group Ltd.

β-Amyloid, APOE and BDNF Genotype, and Depressive and Anxiety Symptoms in Cognitively Normal Older Women and Men.

PubMed

Holmes, Sophie E; Esterlis, Irina; Mazure, Carolyn M; Lim, Yen Ying; Ames, David; Rainey-Smith, Stephanie; Martins, Ralph N; Salvado, Olivier; Dore, Vincent; Villemagne, Victor L; Rowe, Christopher C; Laws, Simon M; Masters, Colin L; Maruff, Paul; Pietrzak, Robert H

2016-12-01

To examine how β-amyloid (Aβ), APOE and BDNF genotypes, and cortisol relate to depressive and anxiety symptoms in cognitively normal older women and men. Cross-sectional data were analyzed from 423 older adults from the Australian Imaging Biomarkers and Lifestyle study. Analyses of covariance evaluated associations between Aβ, APOE and BDNF genotype, and cortisol in relation to severity of depressive and anxiety symptoms. Among Aβ+ older adults, APOE ε4 carriage was associated with greater severity of anxiety symptoms (d = 0.55); and in the full sample, APOE ε4 carriage was linked to greater severity of depressive (d = 0.26) and anxiety (d = 0.21) symptoms. Among Aβ+ women, ε4 carriers reported greater anxiety symptoms than non-ε4 carriers (d = 0.83), and female BDNF rs6265 Val66 Met allele carriers reported greater depressive symptoms (d = 0.29). Sex moderated the relationship between Aβ, APOE genotype, and BDNF genotype in predicting severity of anxiety and depressive symptoms in cognitively normal older adults. Copyright © 2016 American Association for Geriatric Psychiatry. All rights reserved.

Influence of dominance status on adrenal activity and ovarian cyclicity status in captive African elephants.

PubMed

Proctor, Christine M; Freeman, Elizabeth W; Brown, Janine L

2010-01-01

The North American African (Loxodonta africana) elephant population is not self-sustaining, in part because of a high rate of abnormal ovarian activity. About 12% of adult females exhibit irregular cycles and 31% do not cycle at all. Our earlier work revealed a relationship between dominance status and ovarian acyclicity, with dominant females being more likely to not cycle normally. One theory is that dominant females may be expending more energy to maintaining peace within the captive herd than for supporting reproduction. The goal of this study was to determine if there was a relationship among dominance status, serum cortisol concentrations, and ovarian acyclicity. We hypothesized that adrenal glucocorticoid activity would be increased in dominant, noncycling elephants as compared with subdominant individuals. Blood samples were collected weekly over a 2-year period in 81 females of known dominance and cyclicity status, and analyzed for cortisol. Based on a path analysis model (Reticular Action Model Or Near Approximation [RAMONA]), noncycling, dominant African elephant females did not have higher mean serum cortisol concentrations, or exhibit more variability (i.e., coefficient of variation, standard deviation) in cortisol secretion. This study suggests that alterations in adrenal activity are not related to dominance status nor contribute directly to acyclicity in captive African elephants.

Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease.

PubMed

Pistollato, Francesca; Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

2016-07-01

Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. © 2016 American Society for Nutrition.

Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

PubMed Central

Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

2012-01-01

Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

Associations between Sleep, Cortisol Regulation, and Diet: Possible Implications for the Risk of Alzheimer Disease12

PubMed Central

Sumalla Cano, Sandra; Elio, Iñaki; Masias Vergara, Manuel; Giampieri, Francesca; Battino, Maurizio

2016-01-01

Accumulation of proteinaceous amyloid β plaques and tau oligomers may occur several years before the onset of Alzheimer disease (AD). Under normal circumstances, misfolded proteins get cleared by proteasome degradation, autophagy, and the recently discovered brain glymphatic system, an astroglial-mediated interstitial fluid bulk flow. It has been shown that the activity of the glymphatic system is higher during sleep and disengaged or low during wakefulness. As a consequence, poor sleep quality, which is associated with dementia, might negatively affect glymphatic system activity, thus contributing to amyloid accumulation. The diet is another important factor to consider in the regulation of this complex network. Diets characterized by high intakes of refined sugars, salt, animal-derived proteins and fats and by low intakes of fruit and vegetables are associated with a higher risk of AD and can perturb the circadian modulation of cortisol secretion, which is associated with poor sleep quality. For this reason, diets and nutritional interventions aimed at restoring cortisol concentrations may ease sleep disorders and may facilitate brain clearance, consequentially reducing the risk of cognitive impairment and dementia. Here, we describe the associations that exist between sleep, cortisol regulation, and diet and their possible implications for the risk of cognitive impairment and AD. PMID:27422503

Effect of a concurrent auditory task on visual search performance in a driving-related image-flicker task.

PubMed

Richard, Christian M; Wright, Richard D; Ee, Cheryl; Prime, Steven L; Shimizu, Yujiro; Vavrik, John

2002-01-01

The effect of a concurrent auditory task on visual search was investigated using an image-flicker technique. Participants were undergraduate university students with normal or corrected-to-normal vision who searched for changes in images of driving scenes that involved either driving-related (e.g., traffic light) or driving-unrelated (e.g., mailbox) scene elements. The results indicated that response times were significantly slower if the search was accompanied by a concurrent auditory task. In addition, slower overall responses to scenes involving driving-unrelated changes suggest that the underlying process affected by the concurrent auditory task is strategic in nature. These results were interpreted in terms of their implications for using a cellular telephone while driving. Actual or potential applications of this research include the development of safer in-vehicle communication devices.

Dynamics of postoperative serum cortisol after transsphenoidal surgery for Cushing's disease: implications for immediate reoperation and remission.

PubMed

Mayberg, Marc; Reintjes, Stephen; Patel, Anika; Moloney, Kelley; Mercado, Jennifer; Carlson, Alex; Scanlan, James; Broyles, Frances

2017-12-22

OBJECTIVE Successful transsphenoidal surgery for adrenocorticotropin hormone (ACTH)-producing pituitary tumors is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate reoperation. However, little is known about the detailed temporal course of changes in serum cortisol in the immediate postoperative period, and the relationship of postoperative cortisol dynamics to remission and late recurrence. METHODS A single-center retrospective cohort analysis was performed for all patients undergoing pituitary surgery from 2007 through 2015. Standardized diagnostic and treatment algorithms were applied to all patients with potential Cushing's disease (CD), including microsurgical transsphenoidal adenomectomy (TSA) by a single surgeon. All patients had serum cortisol levels drawn at 6-hour intervals for 72 hours after surgery, and were offered reoperation within 3 days for normal or supranormal postoperative cortisol levels. Primary outcomes were 6-month remission and late recurrence; secondary outcomes were persistent postoperative hypocortisolism and surgical morbidity. Discriminatory levels of postoperative serum cortisol for predicting remission were calculated at various intervals after surgery using receiver operating characteristic (ROC) curves. RESULTS Among 89 patients diagnosed with CD, 81 underwent initial TSA for a potentially curable lesion; 23 patients (25.8%) underwent an immediate second TSA. For the entire cohort, 6-month remission was achieved in 77.8% and late recurrences occurred in 9.5%, at a mean of 43.5 months. Compared with patients with a single surgery, those with an immediate second TSA had similar rates of remission (78.3% vs 77.6%) and late recurrence (5.6% vs 11.1%). The rate of hypocortisolism for patients with 2 surgeries (12/23, 52.2%) was significantly greater than that for patients with single surgeries (13/58, 22.4%; p < 0.001). There was no difference in the incidence of CSF leaks between the first and second operations. Remission was achieved in 58 (92.1%) of 64 patients who completed the 2-surgery protocol. The temporal course of postoperative serum cortisol levels among patients varied considerably, with subnormal nadir levels < 2 μg/dl occurring between 12 hours and 66 hours. Patients achieving remission had significantly lower mean serum cortisol levels at every time point after surgery (p < 0.01). By ROC curve analysis, nadir cortisol levels < 2.1 μg/dl were predictive of 6-month remission for the entire cohort over 3 days (positive predictive value [PPV] = 94%); discriminating cortisol levels for predicting remission on postoperative day (POD) 2 were < 5.4 μg/dl (PPV = 97%), although patients with remission after postoperative cortisol levels of 2-5 μg/dl had a significantly higher rate of late recurrence. CONCLUSIONS There is substantial variation in the temporal course of serum cortisol levels over the first 72 hours after TSA for CD, with nadir levels predictive for remission occurring as late as POD 3. Although a cortisol level of 2.1 μg/dl at any point was an accurate predictor of 6-month remission, levels less than 5.4 μg/dl on POD 2 were reasonably accurate. These data may enable decisions regarding the efficacy of an immediate second surgical procedure performed during the same hospitalization; immediate reoperation is associated with excellent remission rates and low recurrence rates in patients otherwise unlikely to achieve remission, but carries a higher risk of permanent hypocortisolism.

Cure of Psoriasis and Arthritis when Addison's Disease Was Detected

PubMed Central

Lind, Marcus

2010-01-01

Introduction Corticoid therapy is well-known to improve the symptoms of psoriasis. Addison's disease is an autoimmune disease which leads to a loss of cortisol production in the adrenal glands. This case report describes a patient with wide-spread psoriasis for 34 years who was cured when Addison's disease was detected and substitution to reach normal biological cortisol levels was introduced. Case Report A 59-year-old man was diagnosed with Addison's disease. He had been tired for several years and had had difficulties in continuing his work. His brother had Addison's disease and recommended him to make a screen for the disease. Synacthen test diagnosed Addison's disease with a clear deficiency of cortisol production. After substitution with hydrocortisone the patient's constitution improved rapidly and he felt no longer tired during work. At the same time, all skin lesions of psoriasis disappeared as well as aches in several joints, both symptoms having been present for a couple of decades. Previously, salves of cortisol had been used to reduce the symptoms of psoriasis, but now, 1–2 years later, after the treatment of Addison's disease, no symptoms in the skin or joints have reoccurred. Conclusions This report illustrates that Addison's disease, although a rare condition, should be kept in mind before treatment of psoriasis is started. Especially if other symptoms such as fatigue are present, a screening test of serum cortisol in the morning should be liberally made. The report also illustrates a need of examining corticoid levels in patients with psoriasis compared to the general population. PMID:21103194

Cure of Psoriasis and Arthritis when Addison's Disease Was Detected.

PubMed

Lind, Marcus

2010-06-01

INTRODUCTION: Corticoid therapy is well-known to improve the symptoms of psoriasis. Addison's disease is an autoimmune disease which leads to a loss of cortisol production in the adrenal glands. This case report describes a patient with wide-spread psoriasis for 34 years who was cured when Addison's disease was detected and substitution to reach normal biological cortisol levels was introduced. CASE REPORT: A 59-year-old man was diagnosed with Addison's disease. He had been tired for several years and had had difficulties in continuing his work. His brother had Addison's disease and recommended him to make a screen for the disease. Synacthen test diagnosed Addison's disease with a clear deficiency of cortisol production. After substitution with hydrocortisone the patient's constitution improved rapidly and he felt no longer tired during work. At the same time, all skin lesions of psoriasis disappeared as well as aches in several joints, both symptoms having been present for a couple of decades. Previously, salves of cortisol had been used to reduce the symptoms of psoriasis, but now, 1-2 years later, after the treatment of Addison's disease, no symptoms in the skin or joints have reoccurred. CONCLUSIONS: This report illustrates that Addison's disease, although a rare condition, should be kept in mind before treatment of psoriasis is started. Especially if other symptoms such as fatigue are present, a screening test of serum cortisol in the morning should be liberally made. The report also illustrates a need of examining corticoid levels in patients with psoriasis compared to the general population.

Levels of salivary stress markers in patients with anxiety about halitosis.

PubMed

Fukui, Makoto; Hinode, Daisuke; Yokoyama, Masaaki; Yoshioka, Masami; Kataoka, Kosuke; Ito, Hiro-O

2010-11-01

To investigate the relationship between salivary stress markers and mental stress states in patients complaining of oral malodour. The utility of the salivary stress markers in assessment of mental conditions of those patients was also investigated. The study population included 74 patients, aged 20-59 years, who complained of oral malodour and were referred to the Breath Odor Clinic at Tokushima University Hospital. Patients were classified into two groups, genuine halitosis (GH) and psychosomatic halitosis (PH), according to the results of organoleptic rating measurement. All patients were subjected to examination by the Cornell Medical Index (CMI) Health Questionnaire. Resting saliva was collected and levels of salivary IgA, cortisol and chromogranin A were determined by ELISA. Twenty-three volunteers not complaining of halitosis were included as the control group. Kruskal-Wallis test and Mann-Whitney's U-test were used for statistical analysis. A significant increase was observed in the concentrations of salivary cortisol in the PH group as compared with GH and control groups (p<0.05). Concentrations of IgA and chromogranin A in saliva were not significantly different among the three groups. In addition, higher salivary cortisol concentrations were found in CMI scale III and IV (tendency towards neurosis) than in scale I and II (normal) (p<0.05). Since salivary cortisol reflects a status of chronic stress condition, psychosomatic halitosis might be closely related to this state of chronic stress. Determination of cortisol levels in saliva may provide useful information for evaluating the mental status of patients complaining of halitosis. Copyright © 2010 Elsevier Ltd. All rights reserved.

Long-term follow-up on Cushing disease patient after transsphenoidal surgery.

PubMed

Jeong, Insook; Oh, Moonyeon; Kim, Ja Hye; Cho, Ja Hyang; Choi, Jin-Ho; Yoo, Han-Wook

2014-09-01

Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH) production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.

Hypercortisolemia is associated with severity of bone loss and depression in hypothalamic amenorrhea and anorexia nervosa.

PubMed

Lawson, Elizabeth A; Donoho, Daniel; Miller, Karen K; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B; Klibanski, Anne

2009-12-01

Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing's disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA. Our objective was to investigate whether hypercortisolemia is associated with bone loss and mood disturbance in women with HA and AN. We conducted a cross-sectional study in a clinical research center. We studied 52 women [21 healthy controls (HC), 13 normal-weight women with functional HA, and 18 amenorrheic women with AN]. Serum samples were measured every 20 min for 12 h overnight and pooled for average cortisol levels. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered. BMD was lower in AN and HA than HC at all sites and lower in AN than HA at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored higher than HC. Cortisol levels were highest in AN, intermediate in HA, and lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol levels were positively associated with HAM-A and HAM-D scores and negatively associated with BMD. Hypercortisolemia is a potential mediator of bone loss and mood disturbance in these disorders.

[Changes in index-F and index-delta 4P in normal pregnancy, labor and the puerperium].

PubMed

Kamada, T

1984-04-01

Index-F and index-delta 4P (cortisol and progesterone which are not bound to corticosteroid-binding globulin (CBG) in the umbilical cord vein and the maternal blood were determined during pregnancy, at delivery and puerperium. Index-F and index-delta 4P were calculated as the total cortisol or total progesterone X% unbound to CBG divided by 100. The level of index-F showed a gradual rise during pregnancy, and in late pregnancy reached about 1.5 times as high as that of non-pregnant women, whereas the total cortisol level was about 3.3 times. Near delivery, index-F was almost completely stable, but at delivery, it increased suddenly in proportion to the rise in the total cortisol level. This rise is probably due to stress. In the umbilical cord vein blood, the level of index-F was 1.5 times higher than that in the maternal plasma before delivery; however the total cortisol level was lower than that of the maternal plasma. The levels of both index-delta 4P and total progesterone showed a gradual increase during pregnancy in parallel, and each value in late pregnancy was about 4.5 to 4.9 times that of early pregnant women. At or near delivery, the level of index-delta 4P was almost stable and no decrease occurred. In the umbilical cord vein plasma, the levels of index-delta 4P and total progesterone were extremely high. However, the meaning of these results isn't clear.

Nicotine as a Factor in Stress Responsiveness Among Detoxified Alcoholics

PubMed Central

Gilbertson, Rebecca; Frye, Reginald F.; Nixon, Sara Jo

2011-01-01

Aims: The effect of transdermal nicotine on stress reactivity was investigated in currently smoking, detoxified, substance-dependent individuals (65% alcohol dependent, n = 51; 31 male) following a psychosocial stressor. Methods: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either active transdermal nicotine (low or high dose) or placebo. Six hours following nicotine administration, subjects performed a laboratory psychosocial stressor consisting of two 4-min public-speaking sessions. Results: Consistent with prior reports, substance-dependent individuals displayed a blunted stress response. However, a review of the cortisol distribution data encouraged additional analyses. Notably, a significant minority of the substance-dependent individuals (33%) demonstrated elevated poststress cortisol levels. This group of responders was more likely to be alcohol dependent and to have received the high dose of nicotine [χ2(2) = 32, P < 0.0001], [χ2(2) = 18.66, P < 0.0001]. Differences in salivary cortisol responses between responders and nonresponders could not be accounted for by the length of sobriety, nicotine withdrawal levels, anxiety or depressive symptomatology at the time of the psychosocial stressor. Conclusion: These results suggest that nicotine administration may support a normalization of the salivary cortisol response following psychosocial stress in subgroups of substance-dependent individuals, particularly those who are alcohol dependent. Given the association between blunted cortisol levels and relapse, and the complex actions of nicotine at central and peripheral sites, these findings support the systematic study of factors including nicotine, which may influence stress reactivity and the recovery process in alcohol-dependent individuals. PMID:21045074

Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

PubMed Central

Ben-Zvi, Amos; Vernon, Suzanne D.; Broderick, Gordon

2009-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning. PMID:19165314

Reciprocal relationship between acute stress and acute fatigue in everyday life in a sample of university students.

PubMed

Doerr, Johanna M; Ditzen, Beate; Strahler, Jana; Linnemann, Alexandra; Ziemek, Jannis; Skoluda, Nadine; Hoppmann, Christiane A; Nater, Urs M

2015-09-01

We investigated whether stress may influence fatigue, or vice versa, as well as factors mediating this relationship. Fifty healthy participants (31 females, 23.6±3.2 years) completed up to 5 momentary assessments of stress and fatigue during 5 days of preparation for their final examinations (exam condition) and 5 days of a regular semester week (control condition). Sleep quality was measured by self-report at awakening. A sub-group of participants (n=25) also collected saliva samples. Fatigue was associated with concurrent stress, stress reported at the previous measurement point, and previous-day stress. However, momentary stress was also predicted by concurrent fatigue, fatigue at the previous time point, and previous-day fatigue. Sleep quality mediated the association between stress and next-day fatigue. Cortisol and alpha-amylase did not mediate the stress-fatigue relationship. In conclusion, there is a reciprocal stress-fatigue relationship. Both prevention and intervention programs should comprehensively cover how stress and fatigue might influence one another. Copyright © 2015 Elsevier B.V. All rights reserved.

Neonatal hydrocortisone therapy does not have a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal axis.

PubMed

Takayanagi, Toshimitsu; Matsuo, Koji; Egashira, Tomoko; Mizukami, Tomoko

2015-05-01

This study investigated whether providing extremely low birthweight (ELBW) infants with a large amount of hydrocortisone had a serious suppressive effect on the later function of the hypothalamus-pituitary-adrenal (HPA) axis. We evaluated the function of the HPA axis in 58 ELBW infants receiving 9.0 ± 7.2 mg/kg of intravenous and 68.1 ± 34.1 mg/kg of oral hydrocortisone using a human corticotropin-releasing hormone stimulation test. The mean age at investigation was 12.0 ± 5.2 months. The response was judged to be normal when the maximum to minimum ratio of the plasma adrenocorticotropic hormone (ACTH) concentration was >2, the peak value of the serum cortisol concentration was >552 nmol/L, or the increment was >193 nmol/L than baseline concentration. Of the 58 infants studied, 51 (88%) displayed a normal response to both the ACTH and cortisol secretion and seven infants (12%) who were judged to be poor responders exhibited a peak cortisol value of >386 nmol/L without any episode of adrenal insufficiency. Providing ELBW infants with a daily low dose of long-term hydrocortisone therapy should not lead to a serious suppressive effect on the later function of the HPA axis, regardless of the administration method. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury.

PubMed

Dong, Tingting; Zhi, Liang; Bhayana, Brijesh; Wu, Mei X

2016-08-25

Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to a closed head mild TBI (mTBI) by a standard controlled cortical impact, along with or without treatment of sphingosine 1-phosphate (S1P) or rolipram, after which the brain tissue of the impact site was evaluated for cell morphology via histology, inflammation by qRT-PCR and T cell staining, and cell death with Caspase-3 and TUNEL staining. Circulating lymphocytes were quantified by flow cytometry, and plasma hydrocortisone was analyzed by LC-MS/MS. To investigate the mechanism whereby cortisol lowered the number of peripheral T cells, T cell egress was tracked in lymph nodes by intravital confocal microscopy after hydrocortisone administration. We detected a decreased number of circulating lymphocytes, in particular, T cells soon after mTBI, which was inversely correlated with a transient and robust increase of plasma cortisol. The transient lymphocytopenia might be caused by cortisol in part via a blockade of lymphocyte egress as demonstrated by the ability of cortisol to inhibit T cell egress from the secondary lymphoid tissues. Moreover, exogenous hydrocortisone severely suppressed periphery lymphocytes in uninjured mice, whereas administering an egress-promoting agent S1P normalized circulating T cells in mTBI mice and increased T cells in the injured brain. Likewise, rolipram, a cAMP phosphodiesterase inhibitor, was also able to elevate cAMP levels in T cells in the presence of hydrocortisone in vitro and abrogate the action of cortisol in mTBI mice. The investigation demonstrated that the number of circulating T cells in the early phase of TBI was positively correlated with T cell infiltration and inflammatory responses as well as cell death at the cerebral cortex and hippocampus beneath the impact site. Decreases in intracellular cAMP might be part of the mechanism behind cortisol-mediated blockade of T cell egress. The study argues strongly for a protective role of cortisol-induced immune suppression in the early stage of TBI.

Health impact of fasting in Saudi Arabia during Ramadan: association with disturbed circadian rhythm and metabolic and sleeping patterns.

PubMed

Ajabnoor, Ghada M; Bahijri, Suhad; Borai, Anwar; Abdulkhaliq, Altaf A; Al-Aama, Jumana Y; Chrousos, George P

2014-01-01

Muslims go through strict Ramadan fasting from dawn till sunset for one month yearly. These practices are associated with disturbed feeding and sleep patterns. We recently demonstrated that, during Ramadan, circadian cortisol rhythm of Saudis is abolished, exposing these subjects to continuously increased cortisol levels. Secretory patterns of other hormones and metabolic parameters associated with cortisol, and insulin resistance, might be affected during Ramadan. Ramadan practitioners (18 males, 5 females; mean age ±SEM = 23.16±1.2 years) were evaluated before and two weeks into Ramadan. Blood was collected for measurements of endocrine and metabolic parameters at 9 am (±1 hour) and again twelve hours later. In Ramadan, glucose concentration was kept within normal range, with a significant increase in the morning. Mean morning concentration of leptin was significantly higher than pre-Ramadan values (p = 0.001), in contrast to that of adiponectin, which was significantly lower (p<0.001). These changes were associated with increased insulin resistance in morning and evening. Concentrations of hsCRP were lower during Ramadan than those during regular living conditions, however, normal circadian fluctuation was abolished (p = 0.49). Even though means of liver enzymes, total bilirubin, total protein and albumin were all decreased during Ramadan, statistically lower means were only noted for GGT, total protein, and albumin (p = 0.018, 0.002 and 0.001 respectively). Saudi Ramadan practitioners have altered adipokine patterns, typical of insulin resistance. The noted decreases of hsCRP, liver enzymes, total protein, and albumin, are most likely a result of fasting, while loss of circadian rhythmicity of hsCRP is probably due to loss of circadian cortisol rhythm. Modern Ramadan practices in Saudi Arabia, which are associated with evening hypercortisolism, are also characterized by altered adipokines patterns, and an abolished hsCRP circadian rhythm, all likely to increase cardiometabolic risk.

Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.

PubMed

Mussi, Chiara; Angelini, Carlo; Crippa, Stefano; Caprotti, Roberto; Fumagalli, Luca; Motta, Vittorio; Uggeri, Franco

2003-12-01

in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. 40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients. increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days. it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.

Breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure

USDA-ARS?s Scientific Manuscript database

Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it’s normally decreasing. To extend these fi...

Ketoconazole treatment in Cushing's syndrome: experience in 34 patients.

PubMed

Sonino, N; Boscaro, M; Paoletta, A; Mantero, F; Ziliotto, D

1991-10-01

Ketoconazole treatment of Cushing's syndrome has been reported in single cases and a few small groups of 5-8 patients. We report our experience in 34 patients. Clinical study, with pretreatment and post-treatment evaluations. Out of 67 patients with Cushing's syndrome admitted during the last 6 years, 34 (28 females/six males; age range 14-67 years) received ketoconazole as a palliative treatment due to severe clinical conditions or management of the disease while awaiting results of definitive therapy. Urinary cortisol, plasma cortisol and ACTH, and routine chemistry were measured every week for 4 weeks, and then once a month. Comparing the last values (mean +/- SEM) during treatment with baseline, urinary cortisol decreased from 1296 +/- 176 to 270 +/- 69 nmol/d (n = 34; P less than 0.001); plasma cortisol decreased from 672 +/- 31 to 549 +/- 35 nmol/l (n = 34; P less than 0.001). For patients with pituitary-dependent Cushing's syndrome, urinary cortisol decreased from 1073 +/- 126 to 200 +/- 21 nmol/d (n = 28; P less than 0.001) while plasma ACTH changed from 12.5 +/- 1.3 to 11.3 +/- 0.8 pmol/l (n = 26; not significant). Twelve patients were treated for more than 6 months, and those with pituitary-dependent disease all received pituitary radiation therapy, except the two who eventually escaped pharmacological control. One additional patient with adrenal carcinoma and one with ectopic ACTH syndrome showed lack of control of urinary cortisol levels. Ketoconazole was withdrawn within the first week in two patients for allergic reaction and acute liver toxicity. Other side-effects included: asymptomatic liver function abnormalities in three patients; gastrointestinal symptoms in four; worsening of gynaecomastia in one. Rapid clinical improvement was observed together with the normalization of urinary cortisol levels, with regression of symptoms such as diabetes mellitus, hypertension, hypokalaemia, and restoration of well being. These data confirm that ketoconazole is valuable in the management of hypercortisolism, provided that patients are closely watched to exclude those who may develop liver toxicity and to prevent the occurrence of adrenal insufficiency.

Salivary cortisol levels, but not salivary α-amylase levels, are elevated in patients with rheumatoid arthritis irrespective of depression.

PubMed

Kim, Hyoun-Ah; Jeon, Ja-Young; Koh, Bo-Ram; Park, Sat-Byul; Suh, Chang-Hee

2016-02-01

Stress is recognized as an important factor in the etiology of rheumatoid arthritis (RA). Therefore, we explored multiple aspects of stress in RA patients. Salivary cortisol and α-amylase levels were measured as markers of the hypothalamic-pituitary-adrenal axis activity and sympatho-adrenomedullary system activity, respectively. Depression was assessed by the Beck Depression Inventory (BDI) and short-term analysis of the heart rate variability (HRV) was performed to evaluate the autonomic nervous system. The salivary cortisol levels of the RA patients were significantly higher than those of the normal controls (NC; 0.12 ± 0.162 μg/dL vs. 0.068 ± 0.052 μg/dL, P = 0.006). There was no difference in salivary α-amylase levels between the RA and the NC. The BDI levels of the RA patients were significantly higher than the NC (13.7 ± 8.9 vs. 6.4 ± 6.9, P < 0.001). Depression was more prevalent in RA patients than in the NC. The salivary cortisol levels were still significantly higher in the RA than the NC after controlling BDI by logistic regression analysis (P = 0.002). There was no significant difference in the HRV of RA patients and the NC. The evaluation of relationship between stress measures and disease activity markers of RA revealed that only BDI was positively correlated with the visual analogue pain scale. Salivary cortisol levels and the BDI of RA patients were higher than those of the NC, and elevated salivary cortisol levels were independent of depression. However, the level of stress may not be correlated with disease activity in RA. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Salivary cortisol: a possible biomarker in evaluating stress and effects of interventions in young foster children?

PubMed

van Andel, Hans W H; Jansen, Lucres M C; Grietens, Hans; Knorth, Erik J; van der Gaag, Rutger Jan

2014-01-01

Young foster children undergo an early separation from their caregiver(s) and often experience severe stress before placement. However, a considerable part of the children do not show apparent signs of distress, making it difficult for the foster carer to be aware of the amount of stress in their foster child. Potential evidence for using salivary cortisol levels as a dimension to evaluate the amount of stress in young foster children is reviewed. Moreover, the applicability of salivary cortisol in the evaluation of stress-reducing interventions for young foster children is discussed. A systematic review was performed using the databases Medline, Psychinfo, Embase, Ebscohost, and Academic Search Premier. Nine studies were traced in which salivary cortisol was used to measure stress in children placed in family foster care or in adoptive families. Stress in general but also neglect, early loss of a caregiver, a younger age at first placement, and a higher number of placements were associated with an altered hypothalamic-pituitary-adrenal (HPA) axis function in foster children. Moreover, four studies on the effect of stress-reducing interventions on HPA-axis functioning of young foster children were found. These studies suggest that caregiver-based interventions can actually help to normalize the HPA-axis function in foster children, and that such changes co-occur with improved behavioral functioning. Although the results from the papers discussed in this review suggest that diurnal cortisol with a wake up and a bedtime measurement may be a relevant tool to evaluate stress in young foster children, this cannot yet be concluded from the present studies, because statistical data from the studies on foster care and adoption in this review were not robust and researchers used different methods to collect the salivary cortisol. Still, it is noteworthy that all studies did find the same pattern of reduced levels in relation to chronic stress (caused by maltreatment and neglect of the child).

The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression

PubMed Central

Komori, Teruhisa

2015-01-01

Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS) may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI) included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal levels and circadian rhythm of salivary cortisol. PMID:26266022

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

PubMed

Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

2018-06-01

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs

NASA Technical Reports Server (NTRS)

O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

1993-01-01

The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.

Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

PubMed

Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

2009-01-01

Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to <50 nM (1.8 microg/dL) after dexamethasone administration was chosen as the cut-off point for normal suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

Hydrocortisone accelerates the decay of iconic memory traces: on the modulation of executive and stimulus-driven constituents of sensory information maintenance.

PubMed

Miller, Robert; Weckesser, Lisa J; Smolka, Michael N; Kirschbaum, Clemens; Plessow, Franziska

2015-03-01

A substantial amount of research documents the impact of glucocorticoids on higher-order cognitive functioning. By contrast, surprisingly little is known about the susceptibility of basic sensory processes to glucocorticoid exposure given that the glucocorticoid receptor density in the human visual cortex exceeds those observed in prefrontal and most hippocampal brain regions. As executive tasks also rely on these sensory processes, the present study investigates the impact of glucocorticoid exposure on different performance parameters characterizing the maintenance and transfer of sensory information from iconic memory (IM; the sensory buffer of the visual system) to working memory (WM). Using a crossover factorial design, we administered one out of three doses of hydrocortisone (0.06, 0.12, or 0.24mg/kg bodyweight) and a placebo to 18 healthy young men. Thereafter participants performed a partial report task, which was used to assess their individual ability to process sensory information. Blood samples were concurrently drawn to determine free and total cortisol concentrations. The compiled pharmacokinetic and psychophysical data demonstrates that free cortisol specifically accelerated the decay of sensory information (r=0.46) without significantly affecting the selective information transfer from IM to WM or the capacity limit of WM. Specifically, nonparametric regression revealed a sigmoid dose-response relationship between free cortisol levels during the testing period and the IM decay rates. Our findings highlight that glucocorticoid exposure may not only impact on the recruitment of top-down control for an active maintenance of sensory information, but alter their passive (stimulus-driven) maintenance thereby changing the availability of information prior to subsequent executive processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Multifaceted Mineralocorticoid Receptor

PubMed Central

Gomez-Sanchez, Elise; Gomez-Sanchez, Celso E.

2015-01-01

The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non-genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β-HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β-HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β-HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect. PMID:24944027

Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: A case series analysis.

PubMed

Ranganathan, Prerna; Kumar, Raj G; Davis, Kendra; McCullough, Emily H; Berga, Sarah L; Wagner, Amy K

2016-01-01

To describe hormone profiles for pre-/post-menopausal women, to monitor time to resumption of menstruation among pre-menopausal women and to describe cortisol associated LH suppression and phasic variation in other sex hormones over timeMethods and procedures: This study determined amenorrhea duration and characterized acute (days 0-7) and chronic (months 1-6) gonadotropins [luteinizing hormone and follicle stimulating hormone (LH, FSH)], sex hormones (progesterone, estradiol) and stress hormone (cortisol) profiles. Women were pre-menopausal (n = 3) or post-menopausal (n = 3). Among pre-menopausal women, menstrual cycle resolution and phase association (luteal/follicular) was monitored using self-report monthly reproductive history questionnaires. This study compared post-TBI hormone profiles, stratified by menopausal status, to hormone levels from seven controls and described 6- and 12-month outcomes for these women. Consistent with functional hypothalamic amenorrhea (FHA), menstruation resumption among pre-menopausal women occurred when serum cortisol normalized to luteal phase control levels. For post-menopausal women, serum cortisol reductions corresponded with resolution of suppressed LH levels. The stress of TBI results in anovulation and central hypothalamic-pituitary-ovarian (HPG) axis suppression. Future work will examine acute/chronic consequences of post-TBI hypercortisolemia and associated HPG suppression, the temporal association of HPG suppression with other neuroendocrine adaptations and how HPG suppression impacts multidimensional recovery for women with TBI.

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

PubMed Central

Lew, Kim H.; Ludwig, Elizabeth A.; Milad, Mark A.; Donovan, Kathleen; Middleton, Elliott; Ferry, James J.; Jusko, William J.

2014-01-01

The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response. PMID:8222483

Concurrent and discriminant validity of the Star Excursion Balance Test for military personnel with lateral ankle sprain.

PubMed

Bastien, Maude; Moffet, Hélène; Bouyer, Laurent; Perron, Marc; Hébert, Luc J; Leblond, Jean

2014-02-01

The Star Excursion Balance Test (SEBT) has frequently been used to measure motor control and residual functional deficits at different stages of recovery from lateral ankle sprain (LAS) in various populations. However, the validity of the measure used to characterize performance--the maximal reach distance (MRD) measured by visual estimation--is still unknown. To evaluate the concurrent validity of the MRD in the SEBT estimated visually vs the MRD measured with a 3D motion-capture system and evaluate and compare the discriminant validity of 2 MRD-normalization methods (by height or by lower-limb length) in participants with or without LAS (n = 10 per group). There is a high concurrent validity and a good degree of accuracy between the visual estimation measurement and the MRD gold-standard measurement for both groups and under all conditions. The Cohen d ratios between groups and MANOVA products were higher when computed from MRD data normalized by height. The results support the concurrent validity of visual estimation of the MRD and the use of the SEBT to evaluate motor control. Moreover, normalization of MRD data by height appears to increase the discriminant validity of this test.

Fluctuating serotonergic function in premenstrual dysphoric disorder and premenstrual syndrome: findings from neuroendocrine challenge tests.

PubMed

Inoue, Y; Terao, T; Iwata, N; Okamoto, K; Kojima, H; Okamoto, T; Yoshimura, R; Nakamura, J

2007-02-01

Premenstrual dysphoric disorder (PMDD) has been assumed to be a subtype of premenstrual syndrome (PMS) with depressive symptoms, such as depressive mood, tension, anxiety, and mood liability during luteal phase. At present, no conclusion has been established about serotonergic function in PMDD. The purpose of this study was to investigate the serotonergic function of PMDD subjects in comparison to PMS without PMDD subjects and normal controls via neuroendocrine challenge tests. Twenty-four women (seven with PMDD, eight with PMS without PMDD, and nine normal controls) were tested on three occasions (follicular phase, early luteal phase, and late luteal phase) receiving paroxetine 20 mg orally as a serotonergic probe at 8:00 A: .M: . Plasma ACTH and cortisol were measured prior to the administration and every hour for 6 h thereafter. As a whole, there were significant differences in serotonergic function measured by ACTH and cortisol responses to paroxetine challenge across these three groups. PMDD subjects showed higher serotonergic function in follicular phase but lower serotonergic function in luteal phase, compared with women with PMS without PMDD and normal controls. The present findings suggest that PMDD women have fluctuating serotonergic function across their menstrual cycles and that the pattern may be different from PMS without PMDD.

Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.

PubMed

Rydzewska, Marta; Krawczuk-Rybak, Maryna; Zajkowska, Adrianna; Jurczuk, Natalia; Polnik, Dariusz; Szalecki, Mieczysław; Moszczyńska, Elżbieta; Savage, Martin O; Bossowski, Artur

2017-04-01

Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.

Serum brain-derived neurotrophic factor (BDNF) across pregnancy and postpartum: Associations with race, depressive symptoms, and low birth weight.

PubMed

Christian, Lisa M; Mitchell, Amanda M; Gillespie, Shannon L; Palettas, Marilly

2016-12-01

Brain-derived neurotrophic factor (BDNF) is implicated as a causal factor in major depression and is critical to placental development during pregnancy. Longitudinal data on BDNF across the perinatal period are lacking. These data are of interest given the potential implications for maternal mood and fetal growth, particularly among Black women who show ∼2-fold greater risk for delivering low birth weight infants. Serum BDNF, serum cortisol, and depressive symptoms (per CES-D) were assessed during each trimester and 4-11 weeks postpartum among 139 women (77 Black, 62 White). Low birth weight (<2500g) was determined via medical record. Serum BDNF declined considerably from 1st through 3rd trimesters (ps≤0.008) and subsequently increased at postpartum (p<0.001). Black women exhibited significantly higher serum BDNF during the 1st trimester, 2nd trimester, and postpartum (ps≤0.032) as well as lower serum cortisol during the 2nd and 3rd trimester (ps≤0.01). Higher serum cortisol was concurrently associated with lower serum BDNF in the 2nd trimester only (p<0.05). Controlling for race, serum BDNF at both the 2nd and 3rd trimester was negatively associated with 3rd trimester depressive symptoms (ps≤0.02). In addition, women delivering low versus healthy weight infants showed significantly lower serum BDNF in the 3rd trimester (p=0.004). Women delivering low versus healthy weight infants did not differ in depressive symptoms at any time point during pregnancy (ps≥0.34). Serum BDNF declines considerably across pregnancy in Black and White women, with overall higher levels in Blacks. Lower serum BDNF in late pregnancy corresponds with higher depressive symptoms and risk for low birth weight in Black and White women. However, the predictive value of serum BDNF in pregnancy is specific to within-race comparisons. Potential links between racial differences in serum BDNF and differential pregnancy-related cortisol adaptation require further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disorganized Steroidogenesis in Adrenocortical Carcinoma, a Case Study.

PubMed

Uchida, Toyoyoshi; Nishimoto, Koshiro; Fukumura, Yuki; Asahina, Miki; Goto, Hiromasa; Kawano, Yui; Shimizu, Fumitaka; Tsujimura, Akira; Seki, Tsugio; Mukai, Kuniaki; Kabe, Yasuaki; Suematsu, Makoto; Gomez-Sanchez, Celso E; Yao, Takashi; Horie, Shigeo; Watada, Hirotaka

2017-03-01

Most adrenocortical carcinomas (ACCs) produce excessive amounts of steroid hormones including aldosterone, cortisol, and steroid precursors. However, aldosterone- and cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary aldosteronism and subclinical Cushing's syndrome. Removal of the tumor cured both conditions. In order to examine the expression patterns of the steroidogenic enzymes responsible for adrenocortical hormone production, 10 tumor portions were immunohistochemically analyzed for aldosterone synthase (CYP11B2), 11β-hydroxylase (CYP11B1, cortisol-synthesizing enzyme), 3β-hydroxysteroid dehydrogenase (3βHSD, upstream enzyme for both CYP11B2 and CYP11B1), and 17α-hydroxylase/C17-20 lyase (CYP17, upstream enzyme for CYP11B1, but not for CYP11B1). CYP11B2, CYP11B1, and 3βHSD were expressed sporadically, and their expression patterns varied significantly among the different tumor portions examined. The expression of these enzymes was random and not associated with each other. CYP17 was expressed throughout the tumor, even in CYP11B2-positive cells. Small tumor cell populations were aldosterone- or cortisol-producing cells, as judged by 3βHSD coinciding with either CYP11B2 or CYP11B1, respectively. These results suggest that the tumor produced limited amounts of aldosterone and cortisol due to the lack of the coordinated expression of steroidogenic enzymes, which led to mild clinical expression in this case. We delineated the expression patterns of steroidogenic enzymes in ACC. The coordinated expression of steroidogenic enzymes in normal and adenoma cells was disturbed in ACC cells, resulting in the inefficient production of steroid hormones in relation to the large tumor volume.

How stressful are 105 days of isolation? Sleep EEG patterns and tonic cortisol in healthy volunteers simulating manned flight to Mars.

PubMed

Gemignani, Angelo; Piarulli, Andrea; Menicucci, Danilo; Laurino, Marco; Rota, Giuseppina; Mastorci, Francesca; Gushin, Vadim; Shevchenko, Olga; Garbella, Erika; Pingitore, Alessandro; Sebastiani, Laura; Bergamasco, Massimo; L'Abbate, Antonio; Allegrini, Paolo; Bedini, Remo

2014-08-01

Spaceflights "environment" negatively affects sleep and its functions. Among the different causes promoting sleep alterations, such as circadian rhythms disruption and microgravity, stress is of great interest also for earth-based sleep medicine. This study aims to evaluate the relationships between stress related to social/environmental confinement and sleep in six healthy volunteers involved in the simulation of human flight to Mars (MARS500). Volunteers were sealed in a spaceship simulator for 105 days and studied at 5 specific time-points of the simulation period. Sleep EEG, urinary cortisol (24 h preceding sleep EEG recording) and subjectively perceived stress levels were collected. Cognitive abilities and emotional state were evaluated before and after the simulation. Sleep EEG parameters in the time (latency, duration) and frequency (power and hemispheric lateralization) domains were evaluated. Neither cognitive and emotional functions alterations nor abnormal stress levels were found. Higher cortisol levels were associated to: (i) decrease of sleep duration, increase of arousals, and shortening of REM latency; (ii) reduction of delta power and enhancement of sigma and beta in NREM N3; and (iii) left lateralization of delta activity (NREM and REM) and right lateralization of beta activity (NREM). Stressful conditions, even with cortisol fluctuations in the normal range, alter sleep structure and sleep EEG spectral content, mirroring pathological conditions such as primary insomnia or insomnia associated to depression. Correlations between cortisol fluctuations and sleep changes suggest a covert risk for developing allostatic load, and thus the need to develop ad-hoc countermeasures for preventing sleep alterations in long lasting manned space missions. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

PubMed

Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Direction of post-prandial ghrelin response associated with cortisol response, perceived stress and anxiety, and self-reported coping and hunger in obese women.

PubMed

Sarker, Marjana R; Franks, Susan; Caffrey, James

2013-11-15

The neurobiological mechanisms modulating stress may share common pathways with appetite regulation and consequent obesity. The orexigenic hormone, ghrelin may moderate anxiety and stress-related eating behavior. This study was designed to investigate humoral (ghrelin, cortisol) and psychological/behavioral characteristics (subjective hunger, anxiety, and stress; eating behavior; coping ability) among obese subjects in a fasting state and after eating a standard meal. Subjects included 18 obese but otherwise healthy adult women. Subjects were divided into two groups based on the relative direction of ghrelin response to a standard meal. A meal mediated suppression in serum ghrelin (post/pre<.94) was defined as a normal ghrelin response (NG) (n=9) and failure to suppress (post/pre>1.0) was designated as faulty ghrelin response (FG) (n=9). Ghrelin and cortisol responses were correlated, r(18)=0.558, p=.016. FG subjects had lower ratings of coping ability [t(2,16)=2.437, p=.027 and higher ratings of hunger cues in the expected direction [t(2,16)=-2.061, p=.056] compared to NG subjects. Meal mediated declines in subjective hunger were observed for both NG [t(1,8)=4.141, p=.003] and FG [t(1,8)=2.718, p=.026]. NG also showed declines in subjective anxiety [t(1,8)=2.977, p=.018], subjective stress [t(1,8)=2.321, p=.049], and cortisol [t(1,8)=4.214, p=.003]. In conclusion, changes in ghrelin, cortisol and selected psychological and behavioral indices are closely associated with one another suggesting that ghrelin may influence stress related eating and thus, the consequent observed relationship among stress, mood and obesity. Copyright © 2013 Elsevier B.V. All rights reserved.

Hypercortisolemia Is Associated with Severity of Bone Loss and Depression in Hypothalamic Amenorrhea and Anorexia Nervosa

PubMed Central

Lawson, Elizabeth A.; Donoho, Daniel; Miller, Karen K.; Misra, Madhusmita; Meenaghan, Erinne; Lydecker, Janet; Wexler, Tamara; Herzog, David B.; Klibanski, Anne

2009-01-01

Context: Anorexia nervosa (AN) and functional hypothalamic amenorrhea (HA) are associated with low bone density, anxiety, and depression. Women with AN and HA have elevated cortisol levels. Significant hypercortisolemia, as in Cushing’s disease, causes bone loss. It is unknown whether anxiety and depression and/or cortisol dysregulation contribute to low bone density in AN or HA. Objective: Our objective was to investigate whether hypercortisolemia is associated with bone loss and mood disturbance in women with HA and AN. Design and Setting: We conducted a cross-sectional study in a clinical research center. Participants: We studied 52 women [21 healthy controls (HC), 13 normal-weight women with functional HA, and 18 amenorrheic women with AN]. Outcome Measures: Serum samples were measured every 20 min for 12 h overnight and pooled for average cortisol levels. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry (DXA) at anteroposterior and lateral spine and hip. Hamilton Rating Scales for Anxiety (HAM-A) and Depression (HAM-D) were administered. Results: BMD was lower in AN and HA than HC at all sites and lower in AN than HA at the spine. On the HAM-D and HAM-A, AN scored higher than HA, and HA scored higher than HC. Cortisol levels were highest in AN, intermediate in HA, and lowest in HC. HAM-A and HAM-D scores were associated with decreased BMD. Cortisol levels were positively associated with HAM-A and HAM-D scores and negatively associated with BMD. Conclusions: Hypercortisolemia is a potential mediator of bone loss and mood disturbance in these disorders. PMID:19837921

Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

2001-09-01

To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

Association of aldosterone and cortisol with cardiovascular risk factors in prehypertension stage.

PubMed

Syed, Sadiqa Badar; Qureshi, Masood Anwar

2012-01-01

Background. The Pakistani population has higher incidence of cardiovascular (CV) diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN). A variety of associated HTN stressors is also reported. The study plans to understand the variables associated with initiation of HTN in this population. Objective. To find plasma aldosterone and cortisol relationship with some CV risk factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium) in different stages of HTN particularly prehypertension. Subjects and Methods. The study conducted on 276 subjects (25-60 years), classified into prehypertensive (n = 55), HTN stage-1 (n = 70) and II (n = 76) according to 7th JNC report and compared with normotensive controls (n = 75). The anthropometric profiles (height, weight, waist circumference, Body Mass index) and BP recorded. Serum cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood glucose, Na(+) and K(+), using standard laboratory techniques, were determined in fasting blood samples. Results. Subjects were mostly overweight and obese (80%, 90%, and 76% in pre-HTN, stage-I and II versus 69% in controls). The aldosterone level (ng/dl) was in higher normal range (9.17-12.41) and significantly correlated to BMI (0.587) in controls, and to TC (0.726) and LDL (0.620) in pre-HTN stage-I. The cortisol level was positively correlated (P < 0.01) to BMI (0.538), Na(+) (0.690) and K(+) (0.578) in control, and to BMI (0.628) and WC (0.679) in pre-HTN group, showing its association with BMI > 25. Conclusion. Pre-HTN stage among Pakistani population with successive increase in various risk factors of HTN in relation to aldosterone and cortisol has been identified. Interaction of the risk factors with endogenous levels of these hormones may initiate stages of HTN.

Association of Aldosterone and Cortisol with Cardiovascular Risk Factors in Prehypertension Stage

PubMed Central

Syed, Sadiqa Badar; Qureshi, Masood Anwar

2012-01-01

Background. The Pakistani population has higher incidence of cardiovascular (CV) diseases at younger ages, due to undiagnosed, uncontrolled hypertension (HTN). A variety of associated HTN stressors is also reported. The study plans to understand the variables associated with initiation of HTN in this population. Objective. To find plasma aldosterone and cortisol relationship with some CV risk factors (obesity, dyslipidemia, hyperglycemia, sodium and potassium) in different stages of HTN particularly prehypertension. Subjects and Methods. The study conducted on 276 subjects (25–60 years), classified into prehypertensive (n = 55), HTN stage-1 (n = 70) and II (n = 76) according to 7th JNC report and compared with normotensive controls (n = 75). The anthropometric profiles (height, weight, waist circumference, Body Mass index) and BP recorded. Serum cortisol, aldosterone, total cholesterol, Low density lipoproteins, blood glucose, Na+ and K+, using standard laboratory techniques, were determined in fasting blood samples. Results. Subjects were mostly overweight and obese (80%, 90%, and 76% in pre-HTN, stage-I and II versus 69% in controls). The aldosterone level (ng/dl) was in higher normal range (9.17–12.41) and significantly correlated to BMI (0.587) in controls, and to TC (0.726) and LDL (0.620) in pre-HTN stage-I. The cortisol level was positively correlated (P < 0.01) to BMI (0.538), Na+ (0.690) and K+ (0.578) in control, and to BMI (0.628) and WC (0.679) in pre-HTN group, showing its association with BMI > 25. Conclusion. Pre-HTN stage among Pakistani population with successive increase in various risk factors of HTN in relation to aldosterone and cortisol has been identified. Interaction of the risk factors with endogenous levels of these hormones may initiate stages of HTN. PMID:22957211

Body temperature, behavior, and plasma cortisol changes induced by chronic infusion of Staphylococcus aureus in goats.

PubMed

Mphahlele, Noko R; Fuller, Andrea; Roth, Joachim; Kamerman, Peter R

2004-10-01

Most experimentally induced fevers are acute, usually lasting approximately 6-12 h, and thus do not mimic chronic natural fevers, which can extend over several days or more. To produce a model of chronic natural fever, we infused eight goats (Capra hircus) intravenously with 2 ml of 2 x 10(11) cell walls of Staphylococcus aureus (S. aureus) for 6 days using osmotic infusion pumps (10 microl/h) while measuring changes in body temperature, behavior, and plasma cortisol concentration. Seven control animals were infused with sterile saline. Abdominal temperature-sensitive data loggers and osmotic infusion pumps were implanted under halothane anesthesia. To compare our new model with existing models of experimental fever, we also administered 2-ml bolus intravenous injections of 2 x 10(11) S. aureus cell walls, 0.1 microg/kg lipopolysaccharide (Escherichia coli, serotype 0111:B4), and sterile saline in random order to six other goats. Bolus injection of lipopolysaccharide and S. aureus induced typical acute phase responses, characterized by fevers lasting approximately 6 h, sickness behavior, and increased plasma cortisol concentration. Infusion of S. aureus evoked prolonged fevers, which lasted for approximately 3 days, starting on day 4 of infusion (ANOVA, P < 0.05), and did not disrupt the normal circadian rhythm of body temperature. However, pyrogen infusion did not cause plasma cortisol concentration to rise (ANOVA, P > 0.05) or the expression of sickness behavior. In conclusion, infusion of S. aureus produced a fever response resembling that of sustained natural fevers but did not elicit the cortisol and behavioral responses that often are described clinically and during short-term experimental fevers.

Developing Physiologic Stress Profiles for School-Age Children Who Stutter

ERIC Educational Resources Information Center

Ortega, Aishah Y.; Ambrose, Nicoline G.

2011-01-01

Purpose: Physiologic reactivity profiles were generated for 9 school-age children with a history of stuttering. Utilizing salivary sampling, stress biomarkers cortisol and alpha-amylase were measured in response to normal daily stressors. Children with a history of stuttering were characterized as high or low autonomic reactors when compared to…

Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

NASA Astrophysics Data System (ADS)

D'Orsogna, Maria; Chou, Tom; Kim, Lae

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

Aldosterone and Mineralocorticoid Receptors-Physiology and Pathophysiology.

PubMed

Funder, John W

2017-05-11

Aldosterone is a uniquely terrestrial hormone, first appearing in lungfish, which have both gills and lungs. Mineralocorticoid receptors (MRs), on the other hand, evolved much earlier, and are found in cartilaginous and bony fish, presumptive ligand cortisol. MRs have equivalent high affinity for aldosterone, progesterone, and cortisol; in epithelia, despite much higher cortisol circulating levels, aldosterone selectively activates MRs by co-expression of the enzyme 11β-hydroxysteroid dehydrogenase, Type 11. In tissues in which the enzyme is not expressed, MRs are overwhelmingly occupied but not activated by cortisol, which normally thus acts as an MR antagonist; in tissue damage, however, cortisol mimics aldosterone and acts as an MR agonist. The risk profile for primary aldosteronism (PA) is much higher than that in age-, sex-, and blood pressure-matched essential hypertensives. High levels of aldosterone per se are not the problem: in chronic sodium deficiency, as seen in the monsoon season in the highlands of New Guinea, plasma aldosterone levels are extraordinarily high, but cause neither hypertension nor cardiovascular damage. Such damage occurs when aldosterone levels are out of the normal feedback control, and are inappropriately elevated for the salt status of the individual (or experimental animal). The question thus remains of how excess salt can synergize with elevated aldosterone levels to produce deleterious cardiovascular effects. One possible mechanism is through the agency of the elusive ouabain-like factors (OLFs). Such factors are secreted from the adrenal in response to ACTH (adrenalocortical tropic hormone), to angiotensin via AT2R, and-the polar opposite of aldosterone-to sodium loading. They act on blood vessels to cause vasoconstriction and thus elevate blood pressure to dump excess sodium through pressure natriuresis. Their levels are chronically elevated in PA in response to the continually elevated sodium status, and they thus act to constrict coronary and systemic arteries. In the context of the elevated blood volume and total body sodium in a PA patient, this raises blood pressure and acts as the proximate cause of cardiovascular damage. If this is the case, it would appear to offer new insights into therapy for PA. One would be the use of digibindin, or its more recent successors as antagonists of OLFs acting on Na/K ATPase at the vessel wall. A second would be to routinely combine a low dose MR antagonist, an ENaC inhibitor, and sodium restriction as first-line therapy for bilateral aldosterone overproduction. Finally, for unilateral cases post-surgery, there is good reason to include low-dose MRs in drug therapy if required, given the ability of cortisol in damaged blood vessels to mimic aldosterone vasoconstrictor action.

Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol.

PubMed

Randolph, J F; Miller, C L; Cummings, J F; Lothrop, C D

1990-01-01

Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.

Association between neuroendocrinological parameters and learning and memory functions in adolescent anorexia nervosa before and after weight recovery.

PubMed

Buehren, Katharina; Konrad, Kerstin; Schaefer, Kerstin; Kratzsch, Juergen; Kahraman-Lanzerath, Berak; Lente, Christina; Herpertz-Dahlmann, Beate

2011-06-01

A growing body of evidence indicates that hormones play an important role in learning and memory functions as well as in mood modulation. During the acute stage of anorexia nervosa (AN), weight loss has a significant effect on serum levels of estrogen, thyroid hormones, and cortisol. Furthermore deficits in learning and memory functions are evident in patients with eating disorders during emaciation. Hormonal and neuropsychological alterations at least partly remit during weight restoration. We investigated the association between learning and memory functions as well as mood and neuroendocrinological parameters before and after weight gain in adolescent AN. Twenty-eight female subjects with AN, diagnosed according to DSM-IV, were examined before and after weight recovery. Both investigations took place while the patients were receiving hospital treatment, and the results were compared to a control group consisting of 18 age- and IQ-matched normal-weight female adolescents also tested twice within 4 months. Verbal memory and learning were assessed by a German paper-pencil-test (LGT). We performed correlation calculations between neuropsychological functions and depressive symptoms and estrogen, cortisol and free triiodothyronine (fT₃) in the plasma at both time points. Compared to normal controls adolescents with AN performed worse in one subtest of the LGT which requires the verbal reproduction of figural material across both time points. Verbal learning was positively correlated with estrogen levels after weight recovery. Depressive symptoms of AN patients significantly decreased during weight rehabilitation and correlated negatively with fT₃ at T₁. We did not find a relationship between cortisol levels and neuropsychological functions. We observed subtle memory impairments and depressive symptoms in subjects with adolescent AN associated with starvation-induced estrogen and triiodothyronine deficits, respectively. Normalization of body weight and resuming of menses is needed to restore learning and memory functions as well as to alleviate depressive symptoms.

Immediate effects of reiki on heart rate variability, cortisol levels, and body temperature in health care professionals with burnout.

PubMed

Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel; Fernández-de-las-Peñas, Cesar; García-Lafuente, Francisca; García-Royo, Carmen; Tomás-Rojas, Inmaculada

2011-10-01

Burnout is a work-related mental health impairment comprising three dimensions: emotional exhaustion, depersonalization, and reduced personal accomplishment. Reiki aims to help replenish and rebalance the body's energetic system, thus stimulating the healing process. The objective of this placebo-controlled, repeated measures, crossover, single-blind, randomized trial was to analyze the immediate effects of Reiki on heart rate variability (HRV), body temperature, and salivary flow rate and cortisol level in health care professionals with burnout syndrome (BS). Participants included 21 health care professionals with BS, who were asked to complete two visits to the laboratory with a 1-week interval between sessions. They were randomly assigned the order in which they would receive a Reiki session applied by an experienced therapist and a placebo treatment applied by a therapist with no knowledge of Reiki, who mimicked the Reiki treatment. Temperature, Holter ECG recordings (standard deviation of the normal-to-normal interval [SDNN], square root of mean squared differences of successive NN intervals [RMSSD], HRV index, low frequency component [LF], and high frequency component [HF]), salivary flow rate and cortisol levels were measured at baseline and postintervention by an assessor blinded to allocation group. SDNN and body temperature were significantly higher after the Reiki treatment than after the placebo. LF was significantly lower after the Reiki treatment. The decrease in the LF domain was associated with the increase in body temperature. These results suggest that Reiki has an effect on the parasympathetic nervous system when applied to health care professionals with BS.

Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci.

PubMed

Mathes, Rachel L; Burdette, Erin L; Moore, Phillip A; Myrna, Kathern E

2012-03-01

To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. © 2011 American College of Veterinary Ophthalmologists.

Suppression of HPA-axis activity by haloperidol after experimentally induced heat stress.

PubMed

Hennig, J; Rzepka, U; Mai, B; Netter, P

1995-07-01

1. Healthy male volunteers were exposed to either a heat condition (52 degrees C) or normal temperature (28 degrees C) receiving a single oral dose of 3 mg haloperidol or placebo in a double-blind design. 2. Ratings on aversiveness as well as on intensity of ambient temperature and saliva samples for determination of cortisol were sampled at defined intervals. Body core temperature and sweat loss were measured continuously throughout the three hour experiment. 3. Results indicate increased levels of cortisol after exposure to heat but not after a pretreatment with haloperidol. 4. The findings of this study suggest that D2-receptors of tuberoinfundibular neurons are blocked by haloperidol which suppresses the dopamine mediated release of vasopressin induced by dehydration and the subsequent stimulation of CRH.

Adrenocortical responses of the Apollo 17 crew members

NASA Technical Reports Server (NTRS)

Leach, C. S.; Rambaut, P. C.; Johnson, P. C.

1974-01-01

Changes in adrenal activity of the three Apollo 17 crew members were studied during the 12.55-day mission and during selected post-recovery days. Aldosterone excretion was normal early and elevated later in the mission, probably causing a loss in total body exchangeable potassium. There was decreased 17-hydroxycorticosteroid excretion only during the early mission days for the two moon landers and throughout the mission for the other astronaut. Cortisol excretion was elevated on physically stressful mission days. At recovery, plasma ACTH was elevated without a similar increase in plasma cortisol. Angiotensin I activity was elevated at recovery in only one crewman. This crewman was the only one with a decreased extracellular fluid volume. These results indicate that the mission and its activities affect adrenal function of the crewmen.

Hypothalamic-Pituitary-Adrenal Axis Function in Children with Attention-Deficit Hyperactivity Disorder.

ERIC Educational Resources Information Center

Kaneko, Motohisa; And Others

1993-01-01

This study with 30 children showing attention deficit hyperactivity disorder (ADHD) found a normal diurnal saliva cortisol rhythm in only 43.3 percent of the subjects and a dexamethasone suppression in 46.7 percent, with both these abnormalities more frequent in the severely than the mildly hyperactive group. Results suggest abnormalities in…

Normal Physiological Values for Conscious Pigs Used in Biomedical Research

DTIC Science & Technology

1989-05-01

6. Cardiovascular and Pulmonary Functions........... 18 TABLE 7. Bioenergetics..................................... 19 TABLE 8. Renal Function...procedure developed in our laboratory. Plasma concentrations of aldosterone, cortisol, total T3, total T4, free T4, insulin and glucagon were...pulmonary vascular resistance , alveolar ventilation, alveolar ventilation/perfusion ratio, arterial 02 transport, tissue 02 extraction ratio, pulmonary

Detection of endogenous cortisol in equine tears and blood at rest and after simulated stress.

PubMed

Monk, Caroline S; Hart, Kelsey A; Berghaus, Roy D; Norton, Natalie A; Moore, Phillip A; Myrna, Kathern E

2014-07-01

To determine whether cortisol is present in equine tears at rest and during simulated stress and compare tear cortisol to serum free and total cortisol. Fourteen healthy adult horses were included. Paired tear total cortisol and serum total and free cortisol concentrations were measured with ELISA, chemiluminescent immunoassay, and ultrafiltration methodology, respectively, in 10 horses at rest once daily for five consecutive days. In an additional four horses, paired tear and serum samples were collected for cortisol measurement before and after adrenocorticotropic hormone (ACTH) stimulation (cosyntropin, 1 μg/kg IV). Cortisol was detectable in equine tears at rest. Following ACTH stimulation, tear cortisol increased significantly from baseline at 60-120 min (P ≤ 0.001). Serum total and free cortisol also increased significantly at 30-180 min after ACTH stimulation (P ≤ 0.001). Both serum and tear cortisol returned to baseline concentrations by 360 min. Changes in tear cortisol were similarly associated with changes in serum total and free cortisol, although high tear cortisol concentrations suggest a portion of tear cortisol may be protein-bound. Cortisol is present in equine tears and increases in concert with serum cortisol following ACTH stimulation. Further study is needed to determine whether endogenous cortisol in tears contributes to ocular pathology. © 2013 American College of Veterinary Ophthalmologists.

Salivary cortisol reactivity in preschoolers is associated with hair cortisol and behavioral problems.

PubMed

Kao, Katie; Doan, Stacey N; St John, Ashley M; Meyer, Jerrold S; Tarullo, Amanda R

2018-01-01

The interplay between children's cortisol reactivity to challenge and cumulative cortisol exposure is not well understood. Examining the role of cortisol reactivity in early childhood may elucidate biological mechanisms that contribute to children's chronic physiological stress and behavioral dysregulation. In a sample of 65 preschool-aged children, we examined the relation between children's salivary cortisol reactivity to challenging tasks and their hair cortisol concentration (HCC). While both are biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis, salivary cortisol reactivity reflects an acute cortisol response to a stressor and HCC reflects cumulative cortisol exposure. In addition, we examined the relations of these stress biomarkers with internalizing and externalizing problems. Salivary cortisol reactivity was associated with higher HCC and with increased externalizing behaviors. Child HCC also was positively correlated with parent HCC. Results highlight the contributions of salivary cortisol reactivity to children's cumulative cortisol exposure, which may add to their biological risk for health problems later. The observed association between externalizing problems and salivary cortisol reactivity indicates concordances between dysregulated behavioral reactions and dysregulated cortisol responses to challenges. The finding that salivary cortisol reactivity to challenge in early childhood plays a role in children's cumulative cortisol exposure and behavioral development suggests pathways through which cortisol reactivity may influence long-term physical and mental health.

Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish.

PubMed

Faught, Erin; Best, Carol; Vijayan, Mathilakath M

2016-02-01

Abnormal embryo cortisol level causes developmental defects and poor survival in zebrafish (Danio rerio). However, no study has demonstrated that maternal stress leads to higher embryo cortisol content in zebrafish. We tested the hypothesis that maternal stress-associated elevation in cortisol levels increases embryo cortisol content in this asynchronous breeder. Zebrafish mothers were fed cortisol-spiked food for 5 days, to mimic maternal stress, followed by daily breeding for 10 days to monitor temporal embryo cortisol content. Cortisol treatment increased mean embryo yield, but the daily fecundity was variable among the groups. Embryo cortisol content was variable in both groups over a 10-day period. A transient elevation in cortisol levels was observed in the embryos from cortisol-fed mothers only on day 3, but not on subsequent days. We tested whether excess cortisol stimulates 11βHSD2 expression in ovarian follicles as a means to regulate embryo cortisol deposition. Cortisol treatment in vitro increased 11β HSD2 levels sevenfold, and this expression was regulated by actinomycin D and cycloheximide suggesting tight regulation of cortisol levels in the ovarian follicles. We hypothesize that cortisol-induced upregulation of 11βHSD2 activity in the ovarian follicles is a mechanism restricting excess cortisol incorporation into the eggs during maternal stress.

Outcome of Microscopic Transsphenoidal Surgery in Cushing Disease: A Case Series of 96 Patients.

PubMed

Shirvani, Manochehr; Motiei-Langroudi, Rouzbeh; Sadeghian, Homa

2016-03-01

To analyze the results of transsphenoidal surgery in patients with Cushing disease and outcome. Retrospective analysis of the records of 96 patients with Cushing disease from 1997 to 2012. There were 73 females and 23 males, with a mean follow-up of 44 months (range, 3-13 years). The sex ratio was significantly different in children and teenagers versus adults. Magnetic resonance imaging showed microadenoma, macroadenoma, and no adenoma in 66, 18, and 12 patients, respectively. There was no surgical mortality. Early remission (normal 24-hour urinary free cortisol and basal serum cortisol <5 μg/dL) was achieved in 94.8%. Regression analysis showed that only tumor size, cavernous sinus extension, and tumor consistency influenced remission. Recurrence was seen in 21.9%. Regression analysis showed that age, preoperative basal cortisol levels, and follow-up duration influenced recurrence. Correlation analysis showed that there was a significant negative correlation between patient age and the follow-up period. After detection of recurrence, 17 patients underwent repeat transsphenoidal surgery that resulted in remission in 12 patients (70.6%). The other 5 patients were referred for gamma knife radiosurgery or bilateral adrenalectomy. Transsphenoidal surgery is a safe and highly efficient procedure in the treatment of Cushing disease. Macroadenomas, cavernous sinus invasion, and harder tumor consistencies, however, are associated with lower remission rates (higher disease persistence) and younger age, higher preoperative cortisol levels, and longer follow-up periods are associated with higher recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Golden, Sherita Hill; Sánchez, Brisa N; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V; Seeman, Teresa; Wand, Gary S

2013-11-01

Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Concerns Regarding Hair Cortisol as a Biomarker of Chronic Stress in Exercise and Sport Science

PubMed Central

Gerber, Markus; Brand, Serge; Lindwall, Magnus; Elliot, Catherine; Kalak, Nadeem; Herrmann, Christian; Pühse, Uwe; Jonsdottir, Ingibjörg H.

2012-01-01

Hair cortisol has the potential to fill the methodological void of long-term cortisol assessment while becoming a widely accepted measure in biopsychology. This review critically examines the applicability and relevance of hair cortisol measurement specifically within the field of exercise and sport science. Current measures of the HPA axis only cover a brief time period, whereas hair cortisol is a unique, non-invasive means to capture long- term cortisol secretion. Studies have shown that individuals who have elevated cortisol secretion (e.g. due to diseases associated with a disturbed activation of the HPA axis or exposure to stressful life events) reveal increased hair cortisol. By contrast, only weak correlations exist between hair cortisol and perceived stress, and the direction of the relationship between hair cortisol levels and mental disorders is unclear. Acute exercise, however, results in increased levels of cortisol that eventually is reflected in higher levels of cortisol in hair samples and studies have shown that exercise intensity is related to hair cortisol level. Thus, elevated hair cortisol levels found among regular exercisers are not necessarily pathological. Thus, one should practice caution when associating athletes’ elevated hair cortisol with poor mental health or disease. Hair cortisol analysis can contribute to a more complete understanding of how long-term cortisol elevation mediates stress-related effects on the health and performance of recreational exercisers and elite athletes. Nevertheless, it is crucial for exercise and sport scientists to consider whether their research questions can be adequately addressed, given that regular intense exercise results in substantially augmented hair cortisol levels. Key points Hair cortisol is a unique, non-invasive and painless means to capture long-term cortisol secretion. Individuals expected to have elevated cortisol secretion (e.g. due to trauma) have increased hair cortisol. Preliminary evidence shows that exercisers have higher hair cortisol levels as well. Hair cortisol analysis can contribute to a more complete understanding of how long-term cortisol secretion mediates stress-related effects on health and performance. There is a great dearth of knowledge about the relationship between sport, exercise and hair cortisol. PMID:24150065

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

PubMed Central

Orlander, Philip R.

2011-01-01

Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

Chronic Stress in the Mother-Infant Dyad: Maternal Hair Cortisol, Infant Salivary Cortisol and Interactional Synchrony

PubMed Central

Tarullo, Amanda R.; St. John, Ashley Moore; Meyer, Jerrold S.

2017-01-01

Stress physiology is shaped by early experience, with enduring effects on health. The relation of chronic maternal physiological stress, as indexed by hair cortisol, to infants' stress systems and to mother-infant interaction quality has not been established. We examined maternal hair and salivary cortisol, six-month-old infants' salivary cortisol, and mother-infant interaction in 121 mother-infant dyads. High maternal hair cortisol was related to higher infant average salivary cortisol concentration. Maternal hair cortisol and bedtime salivary cortisol were both uniquely related to infant bedtime salivary cortisol. Mothers with higher hair cortisol were more intrusive and had lower positive engagement synchrony with their infants. Maternal intrusiveness moderated the association of maternal hair cortisol and infant salivary cortisol, such that maternal hair and infant average salivary cortisol were related only when mothers were more intrusive. Maternal chronic physiological stress may upregulate infants' developing stress systems, particularly in the context of lower mother-infant interaction quality. PMID:28391126

Chronic stress in the mother-infant dyad: Maternal hair cortisol, infant salivary cortisol and interactional synchrony.

PubMed

Tarullo, Amanda R; St John, Ashley Moore; Meyer, Jerrold S

2017-05-01

Stress physiology is shaped by early experience, with enduring effects on health. The relation of chronic maternal physiological stress, as indexed by hair cortisol, to infants' stress systems and to mother-infant interaction quality has not been established. We examined maternal hair and salivary cortisol, six-month-old infants' salivary cortisol, and mother-infant interaction in 121 mother-infant dyads. High maternal hair cortisol was related to higher infant average salivary cortisol concentration. Maternal hair cortisol and bedtime salivary cortisol were both uniquely related to infant bedtime salivary cortisol. Mothers with higher hair cortisol were more intrusive and had lower positive engagement synchrony with their infants. Maternal intrusiveness moderated the association of maternal hair cortisol and infant salivary cortisol, such that maternal hair and infant average salivary cortisol were related only when mothers were more intrusive. Maternal chronic physiological stress may upregulate infants' developing stress systems, particularly in the context of lower mother-infant interaction quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Social Stress Increases Cortisol and Hampers Attention in Adolescents with Excess Weight

PubMed Central

Verdejo-Garcia, Antonio; Moreno-Padilla, Maria; Garcia-Rios, M. Carmen; Lopez-Torrecillas, Francisca; Delgado-Rico, Elena; Schmidt-Rio-Valle, Jacqueline; Fernandez-Serrano, Maria J.

2015-01-01

Objective To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition. Design and Methods We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making). Results Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups. Conclusion Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills. PMID:25898204

Effects of routine handling and tagging procedures on physiological stress responses in juvenile chinook salmon

USGS Publications Warehouse

Sharpe, C.S.; Thompson, D.A.; Blankenship, H.L.; Schreck, C.B.

1998-01-01

Juvenile chinook salmon Oncorhynchus tshawytscha were subjected to handling and tagging protocols typical of normal hatchery operations and monitored for their physiological response to stress. Treatments included coded-wire-tagging, counting, ventral fin clipping, adipose fin clipping, and a procedure simulating a pond split. Treatment fish were also subjected to a standardized stress challenge (1 h confinement) to evaluate their ability to deal with disturbances subsequent to a handling or tagging procedure. Circulating levels of cortisol and glucose were used as indicators of stress. Each of the treatments elicited very similar responses among treatment groups. Cortisol increased from resting levels of about 20 ng/mL to about 90 ng/mL by 1 h poststress and returned to near resting levels by 8 h poststress. Glucose levels increased from 50 mg/dL to about 80 mg/dL by 1 h poststress and remained elevated for much of the experiment. The cortisol and glucose responses to the confinement stress did not differ over time or among treatments. However, the confinement stress results do suggest a small but significant cumulative response, indicating small residual effects of the original handling protocols. No deaths were noted among treatment groups.

Decreased lymphocytes and increased risk for infection are common in endogenous pediatric Cushing syndrome.

PubMed

Tatsi, Christina; Boden, Rebecca; Sinaii, Ninet; Keil, Meg; Lyssikatos, Charalampos; Belyavskaya, Elena; Rosenzweig, Sergio D; Stratakis, Constantine A; Lodish, Maya B

2018-02-01

BackgroundHypercortisolemia results in changes of the immune system and elevated infection risk, but data on the WBC changes in pediatric Cushing syndrome (CS) are not known. We describe the changes of the WBC lineages in pediatric endogenous hypercortisolemia, their associations with the markers of disease severity, and the presence of infections.MethodsWe identified 197 children with endogenous CS. Clinical and biochemical data were recorded. Sixty-six children with similar age and gender, and normocortisolemia served as controls.ResultsThe absolute lymphocyte count of CS patients was significantly lower than that of controls, while the total WBC and the absolute neutrophil counts were significantly higher. These changes correlated with several markers of CS severity and improved after resolution of hypercortisolemia. Infections were identified in 35 patients (17.8%), and their presence correlated to elevated serum morning cortisol, midnight cortisol, and urinary free cortisol levels, as well as with the decrease in absolute lymphocyte count.ConclusionsChildren with endogenous CS have abnormal WBC counts, which correlate with the severity of CS, and normalize after cure. Infections are common in this population; clinicians should be aware of this complication of CS and have low threshold in diagnosis and treating infections in CS.

Overnight Social Isolation in Pigs Decreases Salivary Cortisol but Does Not Impair Spatial Learning and Memory or Performance in a Decision-Making Task.

PubMed

van der Staay, F Josef; Schoonderwoerd, Annelieke J; Stadhouders, Bo; Nordquist, Rebecca E

2015-01-01

Pigs in modern farming practice may be exposed to a number of stressors, including social stressors such as mixing or isolation. This may potentially affect both cognitive abilities and stress physiology of the animals. We tested the hypothesis that overnight social isolation in pigs impairs performance in a cognitive holeboard (HB) task (Experiment 1) and the Pig Gambling Task (PGT) (Experiment 2), a decision-making task inspired by the Iowa Gambling Task. In addition, we tested the effect of overnight social isolation on salivary cortisol levels. A within-subjects approach was used in which performance in the two behavioral tasks and cortisol levels were first determined during normal social housing, followed by performance and cortisol levels after experiencing stress induced by overnight social isolation. A total of 19 female pigs with a birth weight closest to their respective litter average was selected from 10 different litters and placed in two pens after weaning. Following habituation, pigs were trained in the HB task, starting at 10 weeks of age. Then, the pigs were isolated overnight, five individuals per night, at 15, 16, and 17 weeks of age. Between these three isolations, social housing and training in the HB continued. Starting 6 weeks after the end of the HB experiment, at approximately 23 weeks of age, the pigs were trained in the PGT. The effects of overnight social isolation on performance in this task were assessed once, when the pigs were 25 weeks old. Salivary cortisol was measured from samples collected 15 min after the start of isolation and at the end of the isolation period and compared to baseline values collected before the start of social isolation. Our results did not confirm the hypothesis that isolation impaired HB performance and decision-making in the PGT. Unexpectedly, overnight social isolation decreased cortisol levels below baseline values, an effect that was not associated with changes in performance of the behavioral tasks. We hypothesized that the housing and testing conditions may have prepared the animals to cope efficiently with stress.

Overnight Social Isolation in Pigs Decreases Salivary Cortisol but Does Not Impair Spatial Learning and Memory or Performance in a Decision-Making Task

PubMed Central

van der Staay, F. Josef; Schoonderwoerd, Annelieke J.; Stadhouders, Bo; Nordquist, Rebecca E.

2016-01-01

Pigs in modern farming practice may be exposed to a number of stressors, including social stressors such as mixing or isolation. This may potentially affect both cognitive abilities and stress physiology of the animals. We tested the hypothesis that overnight social isolation in pigs impairs performance in a cognitive holeboard (HB) task (Experiment 1) and the Pig Gambling Task (PGT) (Experiment 2), a decision-making task inspired by the Iowa Gambling Task. In addition, we tested the effect of overnight social isolation on salivary cortisol levels. A within-subjects approach was used in which performance in the two behavioral tasks and cortisol levels were first determined during normal social housing, followed by performance and cortisol levels after experiencing stress induced by overnight social isolation. A total of 19 female pigs with a birth weight closest to their respective litter average was selected from 10 different litters and placed in two pens after weaning. Following habituation, pigs were trained in the HB task, starting at 10 weeks of age. Then, the pigs were isolated overnight, five individuals per night, at 15, 16, and 17 weeks of age. Between these three isolations, social housing and training in the HB continued. Starting 6 weeks after the end of the HB experiment, at approximately 23 weeks of age, the pigs were trained in the PGT. The effects of overnight social isolation on performance in this task were assessed once, when the pigs were 25 weeks old. Salivary cortisol was measured from samples collected 15 min after the start of isolation and at the end of the isolation period and compared to baseline values collected before the start of social isolation. Our results did not confirm the hypothesis that isolation impaired HB performance and decision-making in the PGT. Unexpectedly, overnight social isolation decreased cortisol levels below baseline values, an effect that was not associated with changes in performance of the behavioral tasks. We hypothesized that the housing and testing conditions may have prepared the animals to cope efficiently with stress. PMID:26793715

Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

PubMed Central

Nesan, Dinushan; Vijayan, Mathilakath M.

2016-01-01

In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals.

PubMed

van Ockenburg, S L; Schenk, H M; van der Veen, A; van Rossum, E F C; Kema, I P; Rosmalen, J G M

2016-11-01

Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. Ten healthy individuals collected 24-h urine samples for 63 consecutive days and provided a hair sample at the end of the study period. 24-h urinary creatinine levels in every urine sample were determined to assess completeness of the samples. Cortisol levels in 24-h urine samples and in hair were measured with liquid chromatography tandem mass spectrometry. The correlations between urinary cortisol and hair cortisol were calculated using Kendall's tau. We found a nonsignificant moderate correlation between average urinary cortisol secretion and average hair cortisol concentration r т =0.422, p=0.089. Hair cortisol concentration correlates low to moderately with 24-h urinary cortisol concentration over a period of 63days. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

PubMed

Stomby, A; Simonyte, K; Mellberg, C; Ryberg, M; Stimson, R H; Larsson, C; Lindahl, B; Andrew, R; Walker, B R; Olsson, T

2015-05-01

Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied. Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

PubMed Central

Rao, Guruprasad; Murthy, K. Dilip; Bhat, P. Gopalakrishna

2007-01-01

The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC) housed in home cage and left in the laboratory; restrained rats (with three subgroups) subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC) having their restrainers kept in the laboratory; restrained pyramid rats (RP) being kept in the pyramid; and restrained square box rats (RS) in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA) and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH) levels, erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats. PMID:17342239

Long-term treatment of Cushing's disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial.

PubMed

Petersenn, S; Salgado, L R; Schopohl, J; Portocarrero-Ortiz, L; Arnaldi, G; Lacroix, A; Scaroni, C; Ravichandran, S; Kandra, A; Biller, B M K

2017-07-01

Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein. Sixteen patients received 5 years of pasireotide treatment. Among these, median (95% confidence interval) percentage change from baseline in mean urinary free cortisol was -82.6% (-89.0, -41.9) and -81.8% (-89.8, -67.4) at months 12 and 60. Eleven patients had mean urinary free cortisol ≤ upper limit of normal at month 60. Improvements in clinical signs were sustained during long-term treatment. The safety profile of pasireotide at 5 years was similar to that reported after 12 months. Fifteen of 16 patients experienced a hyperglycaemia-related adverse event; glycated haemoglobin levels were stable between months 6 and 60. Adverse events related to hyperglycaemia, bradycardia, gallbladder/biliary tract, and liver safety were most likely to first occur by month 6; adverse event severity did not tend to worsen over time. This represents the longest prospective trial of a medical therapy for Cushing's disease to date. A subset of patients treated with pasireotide maintained biochemical and clinical improvements for 5 years, with no new safety signals emerging. These data support the use of pasireotide as an effective long-term therapy for some patients with Cushing's disease.

Hormonal profile impact on female sexual function in young women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Craina, Marius; Pater, Liana; Pater, Flavius

2014-12-01

Female sexual function is dependent, in physiological milieu upon hormonal impulses: estradiol, testosterone, cortisol, progesterone, prolactin and TSH. Out study tries to appreciate the impact of testosterone, estradiol and prolactin, the major hormones involved in the sexual response, on the normal sexual function. This parameter is approximated by the value of the total FSFI score, a validated international structured interview.

Influence of bacterial kidney disease on smoltification in salmonids: Is it a case of double jeopardy?

USGS Publications Warehouse

Mesa, M.G.; Maule, A.G.; Poe, T.P.; Schreck, C.B.

1999-01-01

We investigated the effects of a chronic, progressive infection with Renibacterium salmoninarum (Rs), the causative agent of bacterial kidney disease (BKD), on selected aspects of smoltification in yearling juvenile spring chinook salmon (Oncorhynchus tshawytscha). After experimentally infecting fish with Rs using an immersion challenge, we sampled them every two weeks to monitor changes in gill Na+, K+-ATPase (ATPase), cortisol, infection level, mortality, growth, and other stress-related physiological factors during the normal time of parr-smolt transformation in fresh water (i.e., from winter to spring). A progressively worsening infection with Rs did not alter the normal changes in gill ATPase and condition factor associated with smoltification in juvenile chinook salmon. The infection did, however, lead to elevated levels of plasma cortisol and lactate and depressed levels of plasma glucose, indicating that the disease is stressful during the later stages. A dramatic proliferation of BKD was associated with maximal responses of indicators of smoltification, suggesting that the process of smoltification itself can trigger outbreaks of disease. Our results suggest mechanisms that probably influence the reported inability of Rs-infected fish to successfully adapt to sea water.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

Observations on cardiovascular and neuroendocrine disturbance in the Guillain-Barré syndrome

PubMed Central

Davies, A. G.; Dingle, H. R.

1972-01-01

Cardiovascular disturbances were found to be a common feature of patients with the Guillian-Barré syndrome who were severely paralysed, requiring assisted ventilation. Glycosuria was noted in association with these disturbances, and in five patients investigated we found impaired glucose tolerance tests at the height of the paralysis. Catecholamine and 17-hydroxycorticosteroid urinary excretions were found to be high in four patients investigated when the neuropathy was most severe, and in one patient plasma cortisol levels were high with loss of diurnal variation. With recovery from paralysis cardiovascular disturbances became less marked, catecholamine and 17-hydroxycorticosteroid urinary excretions reverted to normal, glucose tolerance improved but remained abnormal in three patients during the period of observation. It is suggested that increased levels of catecholamines and cortisol contributed to the development of impaired glucose tolerance and cardiovascular disturbances. PMID:4113954

Patterns of Adolescent Regulatory Responses during Family Conflict and Mental Health Trajectories

PubMed Central

Koss, Kalsea J.; Cummings, E. Mark; Davies, Patrick T.; Cicchetti, Dante

2016-01-01

Four distinct patterns of adolescents’ behavioral, emotional, and physiological responses to family conflict were identified during mother-father-adolescent (M=13.08 years) interactions. Most youth displayed adaptively-regulated patterns comprised of low overt and subjective distress. Under-controlled adolescents exhibited elevated observable and subjective anger. Over-controlled adolescents were withdrawn and reported heightened subjective distress. Physiologically reactive adolescents had elevated cortisol coupled with low overt and subjective distress. Regulation patterns were associated with unique mental health trajectories. Under-controlled adolescents had elevated conduct and peer problems whereas over-controlled adolescents had higher anxiety and depressive symptoms. Physiologically reactive adolescents had low concurrent, but increasing levels of depressive, anxiety, and peer problem symptoms. Findings underscore the importance of examining organizations of regulatory strategies in contributing to adolescent mental health. PMID:28498540

Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

PubMed

Plihal, W; Born, J

1999-09-09

Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.

PubMed

Heather, Natasha L; Jefferies, Craig; Hofman, Paul L; Derraik, José G B; Brennan, Christine; Kelly, Patrick; Hamill, James K M; Jones, Rhys G; Rowe, Deborah L; Cutfield, Wayne S

2012-02-01

We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

The importance of salivary cortisol in the diagnosis of adrenal insufficiency in cirrhosis.

PubMed

Araz, Filiz; Soydaş, Barış; Özer, Birol; Serin, Ender

2016-05-01

Reports on adrenal insufficiency (AI) are unexpectedly high in cirrhosis, and the diagnosis of this condition remains a challenge. We aimed to define the prevalence rate of AI in stable cirrhotic patients and determine the correlations of free cortisol and salivary cortisol with total cortisol. Between January 2011 and September 2011, 110 consecutive cirrhotic patients without any infection or hemodynamic instability were enrolled. Baseline total and salivary cortisol levels were measured. The free cortisol level was calculated according to the Coolens' formula. Post-stimulation total and salivary cortisol levels were measured, and the free cortisol level was recalculated. The mean age of the patients was 62.1±11.4 years. There were 54 males (49.1%). The mean Child-Turcotte-Pugh (CTP) score was 7.2±2.3. Twenty-two (20%) patients were at the CTP-C level. AI was present in 23 (20.9%) and 17 (15.5%) of all patients according to the total and free cortisol criteria, respectively. For basal and stimulated levels, salivary cortisol rather than total cortisol correlates well with free cortisol. The diagnosis of AI on the basis of total cortisol measurement overestimates the prevalence of AI in cirrhosis. Salivary cortisol, which correlates well with free cortisol, is a promising alternative for the diagnosis of AI in cirrhotic patients.

Validity of the Eating Attitudes Test and the Eating Disorders Inventory in Bulimia Nervosa.

ERIC Educational Resources Information Center

Gross, Janet; And Others

1986-01-01

Assessed criterion and concurrent validity of the Eating Attitudes Test and the Eating Disorder Inventory in 82 women with bulimia nervosa. Both tests demonstrated criterion validity by discriminating bulimia nervosa subjects from normals. Only weak support was found for concurrent validity within bulimia subjects. Recommends combination of…

Development of an LC-MS/MS method for the determination of endogenous cortisol in hair using (13)C3-labeled cortisol as surrogate analyte.

PubMed

Binz, Tina M; Braun, Ueli; Baumgartner, Markus R; Kraemer, Thomas

2016-10-15

Hair cortisol levels are increasingly applied as a measure for stress in humans and mammals. Cortisol is an endogenous compound and is always present within the hair matrix. Therefore, "cortisol-free hair matrix" is a critical point for any analytical method to accurately quantify especially low cortisol levels. The aim of this project was to modify current methods used for hair cortisol analysis to more accurately determine low endogenous cortisol concentrations in hair. For that purpose, (13)C3-labeled cortisol, which is not naturally present in hair (above 13C natural abundance levels), was used for calibration and comparative validation applying cortisol versus (13)C3-labeled cortisol. Cortisol was extracted from 20mg hair (standard sample amount) applying an optimized single step extraction protocol. An LC-MS/MS method was developed for the quantitative analysis of cortisol using either cortisol or (13)C3-cortisol as calibrators and D7-cortisone as internal standard (IS). The two methods (cortisol/(13)C3-labeled cortisol) were validated in a concentration range up to 500pg/mg and showed good linearity for both analytes (cortisol: R(2)=0.9995; (13)C3-cortisol R(2)=0.9992). Slight differences were observed for limit of detection (LOD) (0.2pg/mg/0.1pg/mg) and limit of quantification (LOQ) (1pg/mg/0.5pg/mg). Precision was good with a maximum deviation of 8.8% and 10% for cortisol and (13)C3-cortisol respectively. Accuracy and matrix effects were good for both analytes except for the quality control (QC) low cortisol. QC low (2.5pg/mg) showed matrix effects (126.5%, RSD 35.5%) and accuracy showed a deviation of 26% when using cortisol to spike. These effects are likely to be caused by the unknown amount of endogenous cortisol in the different hair samples used to determine validation parameters like matrix effect, LOQ and accuracy. No matrix effects were observed for the high QC (400pg/mg) samples. Recovery was good with 92.7%/87.3% (RSD 9.9%/6.2%) for QC low and 102.3%/82.1% (RSD 5.8%/11.4%) for QC high. After successful validation the applicability of the method could be proven. The study shows that the method is especially useful for determining low endogenous cortisol concentrations as they occur in cow hair for example. Copyright © 2016 Elsevier B.V. All rights reserved.

A combination of high stress-induced tense and energetic arousal compensates for impairing effects of stress on memory retrieval in men.

PubMed

Boehringer, Andreas; Schwabe, Lars; Schachinger, Hartmut

2010-09-01

Stress can both impair and enhance memory retrieval. Glucocorticoids mediate impairing effects of stress on memory retrieval. Little is known, however, about factors that facilitate post-stress memory performance. Here, we asked whether stress-induced arousal mediates facilitative stress effects on memory retrieval. Two arousal dimensions were separated: tense arousal, which is characterized by feelings ranging from tension and anxiety to calmness and quietness, and energetic arousal, which is associated with feelings ranging from energy and vigor to states of fatigue and tiredness. Fifty-one men (mean age +/- SEM: 24.57 +/- 0.61 years) learned emotional and neutral words. Memory for these words was tested 165 min later, after participants were exposed to a psychosocial stress or a non-arousing control condition. Changes in heart rate, self-reported (energetic and tense) arousal, and saliva cortisol in response to the stress/control condition were measured. Overall, stress impaired memory retrieval. However, stressed participants with large increases in both tense and energetic arousal performed comparably to controls. Neither salivary cortisol level nor autonomic arousal predicted memory performance after controlling for changes in energetic and tense arousal. The present data indicate that stress-induced concurrent changes in tense and energetic arousal can compensate for impairing effects of stress on memory retrieval. This finding could help to explain some of the discrepancies in the literature on stress and memory.

Effect of hypothyroidism on insulin sensitivity and glucose tolerance in dogs.

PubMed

Hofer-Inteeworn, Natalie; Panciera, David L; Monroe, William E; Saker, Korinn E; Davies, Rebecca Hegstad; Refsal, Kent R; Kemnitz, Joseph W

2012-04-01

To determine the effects of hypothyroidism on insulin sensitivity, glucose tolerance, and concentrations of hormones counter-regulatory to insulin in dogs. 8 anestrous mixed-breed bitches with experimentally induced hypothyroidism and 8 euthyroid control dogs. The insulin-modified frequently sampled IV glucose tolerance test and minimal model analysis were used to determine basal plasma insulin and glucose concentrations, acute insulin response to glucose, insulin sensitivity, glucose effectiveness, and disposition index. Growth hormone response was assessed by stimulation and suppression tests. Additionally, basal serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations and urine cortisol-to-creatinine concentration ratios were measured and dual energy x-ray absorptiometry was performed to evaluate body composition. Insulin sensitivity was lower in the hypothyroid group than in the euthyroid group, whereas acute insulin response to glucose was higher. Glucose effectiveness and disposition index were not different between groups. Basal serum GH and IGF-1 concentrations as well as abdominal fat content were high in hypothyroid dogs, but urine cortisol-to-creatinine concentration ratios were unchanged. Hypothyroidism appeared to negatively affect glucose homeostasis by inducing insulin resistance, but overall glucose tolerance was maintained by increased insulin secretion in hypothyroid dogs. Possible factors affecting insulin sensitivity are high serum GH and IGF-1 concentrations and an increase in abdominal fat. In dogs with diseases involving impaired insulin secretion such as diabetes mellitus, concurrent hypothyroidism can have important clinical implications.

ACTH and Cortisol Response to Dex/CRH Testing in Women with and without Premenstrual Dysphoria during GnRH Agonist-Induced Hypogonadism and Ovarian Steroid Replacement

PubMed Central

Lee, Ellen E.; Nieman, Lynnette K.; Martinez, Pedro E.; Harsh, Veronica L.; Rubinow, David R.

2012-01-01

Context: During conditions of ovarian suppression, women with premenstrual dysphoria (PMD) experience abnormal behavioral responses to physiological levels of ovarian steroids. Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation frequently accompanies depression, and ovarian steroids regulate HPA axis responsivity, the role of HPA axis dysregulation in PMD is not known. We hypothesized that women with PMD would show abnormalities of HPA axis function analogous to those reported in depressive illness, and that ovarian steroids would differentially regulate HPA axis function in women with PMD compared with asymptomatic controls (AC). Objective: Our objective was to characterize the HPA axis response to physiological levels of estradiol and progesterone in women with PMD and AC. Design and Setting: We conducted an open-label trial of the GnRH agonist depot Lupron with ovarian steroid replacement administered in a double-blind crossover design in an outpatient clinic. Participants: Forty-three women (18 with prospectively confirmed PMD and 25 AC) participated. Interventions: Women received Lupron for 6 months. After 3 months of hypogonadism, women received 5 wk each of estradiol (100-μg patch daily) or progesterone (suppositories 200 mg twice daily). During each condition, combined dexamethasone-suppression/CRH-stimulation tests and 24-h urinary free cortisol levels were performed. Main Outcome Measures: Plasma cortisol and ACTH levels were evaluated. Results: HPA axis function was similar in PMD compared with AC. In all, progesterone significantly increased the secretion of cortisol compared with estradiol [area under the curve (t74 = 3.1; P < 0.01)] and urinary free cortisol (t74 = 3.2; P < 0.01) and ACTH compared with hypogonadism [area under the curve (t74 = 2.4; P < 0.05)]. Conclusions: HPA axis regulation is normal in PMD, suggesting that the pathophysiology of PMD differs from major depression. As observed previously, progesterone but not estradiol up-regulates HPA axis function in women. PMID:22466349

Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood.

PubMed

Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R

2016-12-01

This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.

Addison disease presenting with acute neurologic deterioration: a rare presentation yields new lessons from old observations in primary adrenal failure.

PubMed

Myers, Kenneth A; Kline, Gregory A

2010-01-01

To report a rare case of Addison disease presenting with acute neurologic deterioration, and to discuss previous reports and illustrative clinical lessons drawn from the case. We detail the clinical presentation and sequence of events leading to diagnosis of Addison disease in a 20-year-old man whose initial symptoms were those of acute neurologic deterioration. A 20-year-old man presented with acute, rapid neurologic deterioration. The patient required intubation, but his condition responded very well to mannitol and dexamethasone. Head computed tomography showed a fourth ventricle reduced in size and basal cistern effacement, changes consistent with mild cerebral edema. Primary adrenal insufficiency was diagnosed after a low morning cortisol concentration prompted a corticotropin-stimulation test and serum aldosterone measurement (undetectable). The diagnosis was almost missed because of suspected confounders of dexamethasone and etomidate use. Subsequently, the patient tested positive for anti-21- hydroxylase antibodies. Cerebral edema rarely occurs with Addison disease and is most likely secondary to hyponatremia. Diagnosis in such cases may be complicated by resuscitative therapies; however, low cortisol levels should always be thoroughly investigated. This patient's presentation was also unique in that he maintained a normal electrolyte profile despite hypoaldosteronism, a phenomenon that may be explained by enhanced mineralocorticoid activity of exogenous cortisol. The diagnosis of primary adrenal insufficiency may not be suspected in the absence of classic hyperpigmentation and hyperkalemia, but should remain in the differential diagnosis of acute confusion. While the use of dexamethasone and etomidate in initial resuscitation can transiently suppress adrenal function, any unusually low cortisol level merits thorough investigation.

Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone.

PubMed

Wong, M L; Kling, M A; Munson, P J; Listwak, S; Licinio, J; Prolo, P; Karp, B; McCutcheon, I E; Geracioti, T D; DeBellis, M D; Rice, K C; Goldstein, D S; Veldhuis, J D; Chrousos, G P; Oldfield, E H; McCann, S M; Gold, P W

2000-01-04

Both stress-system activation and melancholic depression are characterized by fear, constricted affect, stereotyped thinking, and similar changes in autonomic and neuroendocrine function. Because norepinephrine (NE) and corticotropin-releasing hormone (CRH) can produce these physiological and behavioral changes, we measured the cerebrospinal fluid (CSF) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression. Plasma adrenocorticotropic hormone (ACTH) and cortisol levels were obtained every 30 min. Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock. Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls. Despite their hypercortisolism, depressed patients had normal levels of plasma ACTH and CSF CRH. However, plasma ACTH and CSF CRH levels in depressed patients were inappropriately high, considering the degree of their hypercortisolism. In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls, patients with depression showed no statistical relationship between these parameters. These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder. These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism. We postulate that alpha-noradrenergic blockade, CRH antagonists, and treatment with antiglucocorticoids may act at different loci, alone or in combination, in the treatment of major depression with melancholic features.

Stress in African catfish (Clarias gariepinus) following overland transportation.

PubMed

Manuel, Remy; Boerrigter, Jeroen; Roques, Jonathan; van der Heul, Jan; van den Bos, Ruud; Flik, Gert; van de Vis, Hans

2014-02-01

Of the many stressors in aquaculture, transportation of fish has remained poorly studied. The objective of this study was therefore to assess the effects of a (simulated) commercial transportation on stress physiology of market-size African catfish (Clarias gariepinus). Catfish weighing approximately 1.25 kg were returned to the farm after 3 h of truck-transportation, and stress-related parameters were measured for up to 72 h following return. Recovery from transportation was assessed through blood samples measuring plasma cortisol, glucose and non-esterified fatty acids (NEFA) and gill histology. Also, the number of skin lesions was compared before and after transport. Pre-transport handling and sorting elevated plasma cortisol levels compared to unhandled animals (before fasting). Plasma cortisol levels were further increased due to transportation. In control fish, plasma cortisol levels returned to baseline values within 6 h, whereas it took 48 h to reach baseline values in transported catfish. Plasma glucose and NEFA levels remained stable and were similar across all groups. Transported catfish did not, on average, have more skin lesions than the handling group, but the number of skin lesions had increased compared to unhandled animals. The macroscopic condition of the gills was similar in control, transported and unhandled catfish; however, light microscopy and immunohistochemistry revealed atypical morphology and chloride cell migration normally associated with adverse water conditions. From our data, we conclude that transportation may be considered a strong stressor to catfish that may add to other stressors and thus inflict upon the welfare of the fish.

Variation in the ovine cortisol response to systemic bacterial endotoxin challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

You Qiumei; Karrow, Niel A.; Cao Honghe

Bi-directional communication between the neuroendocrine and immune systems is designed, in part, to maintain or restore homeostasis during physiological stress. Exposure to endotoxin during Gram-negative bacterial infection for example, elicits the release of pro-inflammatory cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal glucocorticoids subsequently down regulates the host inflammatory response, minimizing potential tissue damage. Sequence and epigenetic variants in genes involved in regulating the neuroendocrine and immune systems are likely to contribute to individual differences in the HPAA response, and this may influence the host anti-inflammatory response to toxin exposure and susceptibility to inflammatory disease. In thismore » study, high (HCR) and low (LCR) cortisol responders were selected from a normal population of 110 female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that contribute to variation in the cortisol response phenotype. This phenotype was stable over several years in the HCR and LCR animals, and did not appear to be attributed to differences in expression of hepatic immune-related genes or systemic pro-inflammatory cytokine concentrations. Mechanistic studies using corticotrophin-releasing factor (0.5 {mu}g/kg body weight), arginine vasopressin (0.5 {mu}g/kg), and adrenocorticotropic hormone (0.5 {mu}g/kg) administered iv demonstrated that variation in this phenotype is largely determined by signalling within the HPAA. Future studies will use this ovine HCR/LCR model to investigate potential genetic and epigenetic variants that may contribute to variation in cortisol responsiveness to bacterial endotoxin.« less

Physiological responses to treadmill exercise and ambient temperature in normal and malignant hyperthermia susceptible pigs.

PubMed Central

D'Allaire, S; DeRoth, L

1986-01-01

Ten susceptible and ten resistant pigs to malignant hyperthermia were used to observe the effects of exercise and ambient temperature on selected physiological parameters. Pigs were submitted to a ten minute exercise on a treadmill operating at a speed of 1.8 km/h and inclined to 11 degrees. Exercise in the first group was at an ambient temperature of 14 degrees C, and in the second at 29 degrees C. The right carotid artery was previously cannulated for blood pressure measurements and for repeated blood sampling during exercise. Arterial pressure, heart rate, rectal and cutaneous temperatures were recorded. Levels of cortisol, creatine kinase and its isoenzymes were measured. At 14 degrees C, exercise caused some physiological adjustments in susceptible animals; heart rate, skin temperature and cortisol levels increased (P less than 0.05). In resistant pigs, only the heart rate was elevated significantly following exertional stress at 14 degrees C. Exercise at 29 degrees C produced severe stress and marked physiological changes: heart rate, rectal and skin temperatures and cortisol levels increased significantly in both susceptible and resistant swine. At 29 degrees C, susceptible pigs also had higher levels of serum cortisol, total creatine kinase and MM isoenzyme (P less than 0.05) compared to resistant pigs. The results indicate that, following exertional or thermal stress, susceptible pigs undergo more extensive physiological changes than do resistant pigs. Similar levels of stress prior to slaughter may trigger physiological changes which in the susceptible pigs would likely result in pale, soft exudative myopathy. PMID:3742362

Cortisol Levels and Longitudinal Cortisol Change as Predictors of Anxiety in Adolescents

ERIC Educational Resources Information Center

Schiefelbein, Virginia L.; Susman, Elizabeth J.

2006-01-01

Although previous research has suggested cortisol-emotion relationships, little is known regarding the effect of anxiety type on cortisol levels or relationships between anxiety and longitudinal cortisol change in adolescents. The authors examine the differential relationship of cortisol levels with generalized and social anxiety and relationships…

Does cortisol influence core executive functions? A meta-analysis of acute cortisol administration effects on working memory, inhibition, and set-shifting.

PubMed

Shields, Grant S; Bonner, Joseph C; Moons, Wesley G

2015-08-01

The hormone cortisol is often believed to play a pivotal role in the effects of stress on human cognition. This meta-analysis is an attempt to determine the effects of acute cortisol administration on core executive functions. Drawing on both rodent and stress literatures, we hypothesized that acute cortisol administration would impair working memory and set-shifting but enhance inhibition. Additionally, because cortisol is thought to exert different nongenomic (rapid) and genomic (slow) effects, we further hypothesized that the effects of cortisol would differ as a function of the delay between cortisol administration and cognitive testing. Although the overall analyses were nonsignificant, after separating the rapid, nongenomic effects of cortisol from the slower, genomic effects of cortisol, the rapid effects of cortisol enhanced response inhibition, g+ = 0.113, p=.016, but impaired working memory, g+ = -0.315, p=.008, although these effects reversed over time. Contrary to our hypotheses, there was no effect of cortisol administration on set-shifting. Thus, although we did not find support for the idea that increases in cortisol influence set-shifting, we found that acute increases in cortisol exert differential effects on working memory and inhibition over time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cortisol level

MedlinePlus

... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

Catalytic distillation process

DOEpatents

Smith, Jr., Lawrence A.

1982-01-01

A method for conducting chemical reactions and fractionation of the reaction mixture comprising feeding reactants to a distillation column reactor into a feed zone and concurrently contacting the reactants with a fixed bed catalytic packing to concurrently carry out the reaction and fractionate the reaction mixture. For example, a method for preparing methyl tertiary butyl ether in high purity from a mixed feed stream of isobutene and normal butene comprising feeding the mixed feed stream to a distillation column reactor into a feed zone at the lower end of a distillation reaction zone, and methanol into the upper end of said distillation reaction zone, which is packed with a properly supported cationic ion exchange resin, contacting the C.sub.4 feed and methanol with the catalytic distillation packing to react methanol and isobutene, and concurrently fractionating the ether from the column below the catalytic zone and removing normal butene overhead above the catalytic zone.

Catalytic distillation process

DOEpatents

Smith, L.A. Jr.

1982-06-22

A method is described for conducting chemical reactions and fractionation of the reaction mixture comprising feeding reactants to a distillation column reactor into a feed zone and concurrently contacting the reactants with a fixed bed catalytic packing to concurrently carry out the reaction and fractionate the reaction mixture. For example, a method for preparing methyl tertiary butyl ether in high purity from a mixed feed stream of isobutene and normal butene comprising feeding the mixed feed stream to a distillation column reactor into a feed zone at the lower end of a distillation reaction zone, and methanol into the upper end of said distillation reaction zone, which is packed with a properly supported cationic ion exchange resin, contacting the C[sub 4] feed and methanol with the catalytic distillation packing to react methanol and isobutene, and concurrently fractionating the ether from the column below the catalytic zone and removing normal butene overhead above the catalytic zone.

Whole-body cortisol response of zebrafish to acute net handling stress

USGS Publications Warehouse

Ramsay, J.M.; Feist, G.W.; Varga, Z.M.; Westerfield, M.; Kent, M.L.; Schreck, C.B.

2009-01-01

Zebrafish, Danio rerio, are frequently handled during husbandry and experimental procedures in the laboratory, yet little is known about the physiological responses to such stressors. We measured the whole-body cortisol levels of adult zebrafish subjected to net stress and air exposure at intervals over a 24 h period; cortisol recovered to near control levels by about 1 h post-net-stress (PNS). We then measured cortisol at frequent intervals over a 1 h period. Cortisol levels were more than 2-fold higher in net stressed fish at 3 min PNS and continued to increase peaking at 15 min PNS, when cortisol levels were 6-fold greater than the control cortisol. Mean cortisol declined from 15 to 60 min PNS, and at 60 min, net-stressed cortisol was similar to control cortisol. Because the age of fish differed between studies, we examined resting cortisol levels of fish of different ages (3, 7, 13, and 19 months). The resting cortisol values among tanks with the same age fish differed significantly but there was no clear effect of age. Our study is the first to report the response and recovery of cortisol after net handling for laboratory-reared zebrafish. ?? 2009 Elsevier B.V.

Salivary cortisol differs with age and sex and shows inverse associations with WHR in Swedish women: a cross-sectional study.

PubMed

Larsson, Charlotte A; Gullberg, Bo; Råstam, Lennart; Lindblad, Ulf

2009-06-21

Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population. In 2001-2004, 1811 men and women (30-75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses. Morning and Delta-cortisol (morning - evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Delta-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0-2.2, p = 0.058) for morning cortisol and 1.9 (1.3-2.8) for Delta-cortisol. All findings for Delta-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003). In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Delta-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.

Work/non-workday differences in mother, child, and mother-child morning cortisol in a sample of working mothers and their children.

PubMed

Hibel, Leah C; Trumbell, Jill M; Mercado, Evelyn

2014-01-01

Mothers have been shown to have higher morning cortisol on days they go to work compared to non-workdays; however, it is unknown how maternal workday associates with child morning cortisol or the attunement of mother-child morning cortisol. This study examined the presence and stability of morning cortisol levels and slopes (i.e., cortisol awakening response or CAR) in a sample of 2-4year old children in out-of-home child care with working mothers. In addition, we examined the differential contributions of maternal workday on mother-child attunement in morning cortisol. Mother and child morning cortisol was sampled twice a day (awakening and 30min later) across four consecutive days (2 non-workdays; 2 workdays) among 47 working mothers and their young children. Mothers also reported on compliance with sampling procedures and provided demographic information. While children exhibited stability in cortisol levels, children's CARs were variable, with children's non-work CARs not predictive of work CARs. Similarly, a significant morning rise in cortisol was only found on workdays, not non-workdays. Overall, mothers had higher cortisol levels and steeper CARs than their children. Further, maternal workday moderated the attunement of mother-child morning cortisol, such that mothers and children had concordant cortisol levels on non-workdays, but discordant cortisol levels on workdays. Morning cortisol may be more variable in pre-school aged children than adults but may be similarly responsive to the social environment. Further, workday mornings may be a time of reduced mother-child cortisol attunement. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.

PubMed

Yu, Kenny; Roncaroli, Federico; Kearney, Tara; Ewins, David; Beeharry, Deepa; Naylor, Thomas; Ray, David; Bhalla, Rajiv; Gnanalingham, Kanna

2018-05-01

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

Adult attachment style and cortisol responses across the day in older adults

PubMed Central

Kidd, Tara; Hamer, Mark; Steptoe, Andrew

2013-01-01

The association between cortisol and adult attachment style, an important indicator of social relationships, has been relatively unexplored. Previous research has examined adult attachment and acute cortisol responses to stress in the laboratory, but less is known about cortisol levels in everyday life. The present study examined adult romantic attachment style and cortisol responses across the day. Salivary cortisol was collected at six time points during the course of the day in 1,807 healthy men and women from a subsample of the Whitehall II cohort. Significant associations were found between attachment on cortisol across the day and slope of cortisol decline. The lowest cortisol output was associated with fearful attachment, with preoccupied attachment having the highest levels and a flatter cortisol profile. The results tentatively support the proposition that attachment style may contribute to HPA dysregulation. PMID:23808770

Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: Data from two preliminary studies

PubMed Central

Gaffey, Allison E.; Wirth, Michelle M.; Hoks, Roxanne M.; Jahn, Allison L.; Abercrombie, Heather C.

2014-01-01

Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants’ cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 hours. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 hours. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications: (1) when given a controlled dose of hydrocortisone, cortisol levels may increase more dramatically in women taking HBC vs. women not on HBC or men; and (2) in studies manipulating cortisol levels, women on hormonal contraceptives should be investigated as a separate group. PMID:24773147

Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies.

PubMed

Gaffey, Allison E; Wirth, Michelle M; Hoks, Roxanne M; Jahn, Allison L; Abercrombie, Heather C

2014-07-01

Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants' cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 h. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 h. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications: (1) when given a controlled dose of hydrocortisone, cortisol levels may increase more dramatically in women taking HBC versus women not on HBC or men; and (2) in studies manipulating cortisol levels, women on hormonal contraceptives should be investigated as a separate group.

The detection of cortisol in human sweat: implications for measurement of cortisol in hair.

PubMed

Russell, Evan; Koren, Gideon; Rieder, Michael; Van Uum, Stan H M

2014-02-01

Hair cortisol analysis has been shown to be an effective measure of chronic stress. Cortisol is assumed to incorporate into hair via serum, sebum, and sweat sources; however, the extent to which sweat contributes to hair cortisol content is unknown. Sweat and saliva samples were collected from 17 subjects after a period of intensive exercise and analyzed by salivary enzyme-linked immunosorbent assay (ELISA). Subsequently, an in vitro test on exposure of hair to hydrocortisone was conducted. Residual hair samples were immersed in a 50-ng/mL hydrocortisone solution for periods lasting 15 minutes to 24 hours, followed by a wash or no-wash condition. Hair cortisol content was determined using our modified protocol for a salivary ELISA. Postexercise control sweat cortisol concentrations ranged from 8.16 to 141.7 ng/mL and correlated significantly with the log-transformed time of day. Sweat cortisol levels significantly correlated with salivary cortisol concentrations. In vitro hair exposure to a 50-ng/mL hydrocortisone solution (mimicking sweat) for 60 minutes or more resulted in significantly increased hair cortisol concentrations. Washing with isopropanol did not affect immersion-increased hair cortisol concentrations. Human sweat contains cortisol in concentrations comparable with salivary cortisol levels. This study suggests that perfuse sweating after intense exercise may increase cortisol concentrations detected in hair. This increase likely cannot be effectively decreased with conventional washing procedures and should be considered carefully in studies using hair cortisol as a biomarker of chronic stress.

Effect of Age on F[subscript 0] Difference Limen and Concurrent Vowel Identification

ERIC Educational Resources Information Center

Vongpaisal, Tara; Pichora-Fuller, Margaret Kathleen

2007-01-01

Purpose: To investigate the effect of age on voice fundamental frequency (F[subscript 0]) difference limen (DL) and identification of concurrently presented vowels. Method: Fifteen younger and 15 older adults with normal audiometric thresholds in the speech range participated in 2 experiments. In Experiment 1, F[subscript 0] DLs were measured for…

Endocrine Drugs in Aircrew

DTIC Science & Technology

2001-06-01

cells (ICA) present the case, the primary goal of diet therapy is simply in their serum at the time of diagnosis, and some caloric reduction to achieve...transplantation caloric intake and weight gain, and suppresses rejection, pemphigus, and immune hematologic inflammation and the immune system.10 Cortisol...hypoglycemic normal.24𔃼 5 agents is still accompanied by the risk of hypo - glycemia and of the micro- and macrovascular Secondary adrenal

[The efficacy and safety of budesonide inhalation suspension via transnasal nebulization compared with oral corticosteroids in chronic rhinosinusitis with nasal polyps].

PubMed

Lou, Hongfei; Wang, Chengshuo; Zhang, Luo

2015-05-01

To evaluate the efficacy and safety of a short course of nebulized budesonide via transnasal inhalation in chronic rhinosinusitis with nasal polyps. Fifty patients with severe eosinophilic nasal polyps were randomized devided into study group (n = 25) and control group (n = 25). The study group received budesonide inhalation suspension (1 mg twice daily) via transnasal nebulization for one week and the control group received oral prednisone (24 mg QD). Visual analogue scales (VAS) of nasal symptoms, endoscopic polyp scores (kennedy scores) and morning serum cortisol concentrations were assessed in both groups pre- and post-treatment. Operation time and surgical field bleeding were evaluated. Four subjects dropped out in control group. Budesonide transnasal nebulization caused a significant improvement in all nasal symptoms especially nasal obstruction (baseline: 8.25 ± 0.53; after treatment: 4.97 ± 0.97, P < 0.01) and reduced polyp size significantly (baseline: 4.64 ± 0.63; after treatment: 3.40 ± 0.76, P < 0.01) compared to pre-treatment. The patients treated with oral prednisone, however, showed more obvious improvement in nasal symptoms and polyp size, shorter operation time and better surgical field than budesonide group. Additionally, the morning serum cortisol concentration was mildly decreased after one week treatment in budesonide group [baseline (17.18 ± 2.83) μg/dl, after treatment (16.24 ± 2.93) μg/dl, P > 0.05], but all values were still located in normal range (normal range: 5-25 μg/dl). Conversely, the morning serum cortisol concentration in oral prednisone group was lower than normal limit [baseline (18.19 ± 2.81) μg/dl, after treatment (2.26 ± 0.70) μg/dl, P < 0.01]. Twice daily budesonide transnasal nebulization is an effective and safe treatment as evidenced by significant improvements in nasal symptoms and reduction in polyp size, coupled with an absence of hypothalamic-pituitary-adrenal axis suppression, which is safer than the systemic corticosteroids. Budesonide transnasal nebulization offers a viable treatment option for CRSwNP before operation.

Comparison of vegetable shortening and cocoa butter as vehicles for cortisol manipulation in Salmo trutta.

PubMed

Birnie-Gauvin, K; Peiman, K S; Larsen, M H; Aarestrup, K; Gilmour, K M; Cooke, S J

2018-01-01

This study demonstrates that vegetable shortening and cocoa butter are two effective vehicles for intraperitoneal cortisol implants in juvenile teleosts, specifically brown trout Salmo trutta, residing in north temperate freshwater environments. Each vehicle showed a different pattern of cortisol elevation. Vegetable shortening was found to be a more suitable vehicle for long-term cortisol elevation [elevated at 3, 6 and 9 days post treatment (dpt)], while cocoa butter may be better suited for short-term cortisol elevation (only elevated at 3 dpt). Additionally, plasma cortisol levels were higher with cortisol-vegetable shortening than with cortisol-cocoa butter implants. Plasma glucose levels were elevated 6 and 9 dpt for fishes injected with cortisol-vegetable shortening, but did not change relative to controls and shams in cortisol-cocoa butter fishes. In conclusion, vegetable shortening and cocoa butter are both viable techniques for cortisol manipulation in fishes in temperate climates, providing researchers with different options depending on study objectives. © 2017 The Fisheries Society of the British Isles.

Salivary Cortisone Reflects Cortisol Exposure Under Physiological Conditions and After Hydrocortisone.

PubMed

Debono, Miguel; Harrison, Robert F; Whitaker, Martin J; Eckland, David; Arlt, Wiebke; Keevil, Brian G; Ross, Richard J

2016-04-01

In this study we tested the use of salivary cortisol and cortisone as alternatives to serum cortisol. Salivary cortisol is often undetectable and contaminated by hydrocortisone. Salivary cortisone strongly reflects serum cortisol.

Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates.

PubMed

Tsilchorozidou, Tasoula; Honour, John W; Conway, Gerard S

2003-12-01

Androgen excess in women with polycystic ovary syndrome (PCOS) may be ovarian and/or adrenal in origin, and one proposed contributing mechanism is altered cortisol metabolism. Increased peripheral metabolism of cortisol may occur by enhanced inactivation of cortisol by 5alpha-reductase (5alpha-R) or impaired reactivation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) resulting in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess. We have tested whether any enzyme dysregulation was related to circulating insulin or androgen concentrations in women with PCOS and have sought to clarify their relationship with obesity. First, to avoid obesity-related effects on cortisol metabolism, 18 lean women with PCOS were compared with 19 lean controls who were closely matched for body mass index (BMI). Second, the impact of obesity was studied in a cross-section of 42 PCOS women of a broad range of BMI. We measured 24-h urinary excretion of steroid metabolites by gas chromatography/mass spectrometry and fasting metabolic and hormone profiles. Urinary excretion of androgens [androsterone (P = 0.003), etiocholanolone (P = 0.02), and C19 steroid sulfates (P = 0.009)], cortisone metabolites [tetrahydrocortisone (THE) (P = 0.02), alpha-cortolone (P < 0.001), beta-cortol + beta-cortolone (P < 0.001), cortolones (P < 0.001), and E metabolites (P < 0.001)], and TCM (P = 0.002) were raised in lean PCOS subjects when compared with controls. A significantly higher 5alpha-tetrahydrocortisol (5alpha-THF)/5beta-THF ratio (P = 0.04) and a significantly lower alpha-THF + THF + alpha-cortol/THE + cortolones ratio (P = 0.01) were found in lean PCOS women compared with lean controls, indicating both enhanced 5alpha-R and reduced 11beta-HSD1 activities. A decreased THE/cortolones ratio (P = 0.03) was also found in lean PCOS women compared with lean controls, indicating increased 20 alpha/beta-HSD activity. In the group of 42 PCOS subjects, measures of 5alpha/5beta reduction were positively correlated with the homeostasis model insulin resistance index (HOMA-R): alpha-THF/THF and HOMA-R (r = 0.34; P = 0.03), androsterone/etiocholanolone and HOMA-R (r = 0.32; P = 0.04), and total 5alpha /total 5beta and HOMA-R (r = 0.37; P = 0.02). A positive correlation was also found between measures of 5alpha-R and BMI (r = 0.37; P = 0.02). No correlation was found between measures of 11beta-HSD1 activity and indices of insulin sensitivity or BMI. We have demonstrated that there is an increased production rate of cortisol and androgens as measured in vivo in lean PCOS women. Insulin seems to enhance 5alpha reduction of steroids in PCOS but was not associated with the elevated cortisol production rate. The changes in 5alpha-R, 11beta-HSD1, and 20alpha/beta-HSD enzyme activities observed in PCOS may contribute to the increased production rates of cortisol and androgens, supporting the concept of a widespread dysregulation of steroid metabolism. This dysregulation does not seem to be the primary cause of PCOS because no correlation was found between serum androgen levels or urinary excretion of androgens with measurements of either 5alpha-R or 11beta-HSD1 activities.

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.

PubMed

Rousseau, Elise; Joubert, Michael; Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves

2015-01-01

Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range. Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.

Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency

PubMed Central

Trzepla, Géraldine; Parienti, Jean Jacques; Freret, Thomas; Vanthygem, Marie Christine; Desailloud, Rachel; Lefebvre, Hervé; Coquerel, Antoine; Reznik, Yves

2015-01-01

Background Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated. Methods Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients’ cortisol AUC in the control range. Results Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients’ cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement. Conclusions Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients. PMID:26317782

Relationship of salivary and plasma cortisol levels in preterm infants: results of a prospective observational study and systematic review of the literature.

PubMed

Maas, Christoph; Ringwald, Christine; Weber, Karin; Engel, Corinna; Poets, Christian F; Binder, Gerhard; Bassler, Dirk

2014-01-01

(1) To investigate the relationship of salivary and plasma cortisol levels in preterm infants with a focus on the usability of salivary cortisol in diagnostic work-up of infants at risk of adrenal insufficiency. (2) To perform a systematic review addressing this question. Clinical study: We conducted a prospective observational single-center study in preterm infants. We analyzed plasma and saliva cortisol concentrations by enzyme immunoassay. Correlation analysis was used to determine the relation between salivary and plasma cortisol levels and the agreement of the measurement methods was analyzed according to Bland-Altman. Systematic review: A systematic literature search (PubMed and Embase) on the relationship of salivary and plasma cortisol levels in neonates was performed in November 2012. Clinical study: We enrolled 58 preterm infants (median (interquartile range) gestational age at birth was 31.4 (28.1-32.7) weeks, birth weight 1,340 (974-1,745) g, respectively). Correlation analyses revealed a relationship of plasma cortisol and salivary cortisol levels. Rank correlation coefficient was 0.6. Estimating plasma cortisol levels based on measured salivary cortisol levels showed poor agreement of the two methods for determining plasma cortisol levels (direct and via salivary cortisol). Sensitivity and specificity of salivary cortisol for the detection of adrenal insufficiency were 0.66 and 0.62, respectively. Systematic review: Six studies in preterm infants and term neonates depicting the correlation of salivary and plasma cortisol were identified with a range of saliva-plasma correlation coefficients from 0.44 to 0.83. Substitution of plasma cortisol by salivary cortisol determination cannot be recommended in preterm infants because of unsatisfactory agreement between methods.

Maternal salivary cortisone to cortisol ratio in late pregnancy: An improved method for predicting offspring birth weight.

PubMed

Wilson, Meredith; Thayer, Zaneta

2017-04-01

Overexposure to maternal cortisol in utero has been associated with lower birth weight of offspring. In order to regulate fetal exposure to this hormone, placental expression of 11-β-hydroxysteroid dehydrogenase-2, an enzyme that converts active cortisol to inactive cortisone, increases across pregnancy. Because of this increase in 11-βHSD2 activity, measuring maternal cortisol in isolation may not reflect actual fetal exposure to the hormone. Previous work by Hellgren et al. (2016) has shown that maternal serum cortisone:cortisol ratio was a better predictor of offspring birth weight than cortisol measured in isolation. This paper sought to replicate these results when examining maternal salivary cortisone:cortisol ratio. Data come from 55 pregnant women from Auckland, New Zealand. Cortisol and cortisone were measured in saliva samples collected at waking and prior to going to sleep on two consecutive weekdays between 34 and 36 weeks of gestation. We found that salivary cortisol and cortisone followed the expected diurnal rhythm and that cortisone was higher than cortisol at both times of day. Maternal bedtime cortisone:cortisol ratio was significantly and inversely related to offspring birth weight. However, waking and bedtime cortisol, as well as waking cortisone:cortisol ratio, were unrelated to birth weight. These results show that maternal salivary cortisone:cortisol ratio, like serum cortisone:cortisol ratio, is a more sensitive biomarker for predicting infant birth weight than cortisol measured in isolation. This ratio could be a valuable, minimally-invasive measurement for future studies interested in understanding the relationship between maternal HPA-axis function and offspring birth weight. Copyright © 2017 Elsevier Ltd. All rights reserved.

The low single nucleotide polymorphism heritability of plasma and saliva cortisol levels.

PubMed

Neumann, Alexander; Direk, Nese; Crawford, Andrew A; Mirza, Saira; Adams, Hieab; Bolton, Jennifer; Hayward, Caroline; Strachan, David P; Payne, Erin K; Smith, Jennifer A; Milaneschi, Yuri; Penninx, Brenda; Hottenga, Jouke J; de Geus, Eco; Oldehinkel, Albertine J; van der Most, Peter J; de Rijke, Yolanda; Walker, Brian R; Tiemeier, Henning

2017-11-01

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

In utero cortisol and testosterone exposure and fear reactivity in infancy.

PubMed

Bergman, Kristin; Glover, Vivette; Sarkar, Pampa; Abbott, Dave H; O'Connor, Thomas G

2010-03-01

Fetal programming is emerging as a major conceptual model for understanding developmental origins of health and disease, including behavioral outcomes. As part of a larger study of prenatal stress and child development, we examined the association between prenatal hormone exposure and fear reactivity, a temperament dimension that is a predictor of long-term behavioral adjustment. Amniotic fluid was collected from a sample of women undergoing clinically indicated amniocentesis for later analysis of cortisol and testosterone. Children with normal birth outcomes were recalled for follow-up assessment at 17 months, at which time we administered an observational assessment of temperament (lab-TAB; n=108). Information on pregnancy and obstetric outcome was included as covariates. Results indicated that there was a significant association between prenatal testosterone and observed fear reactivity in boys (r(53)=0.34, p=0.01); no significant effect was found in girls (r(54)=-0.07, ns); the effect remained when obstetric, psychosocial, and parental anxiety were controlled for. There was not a significant association between fetal cortisol exposure and fear reactivity. The prediction from in utero testosterone exposure to fear reactivity in boys extends prior research on prenatal testosterone and may represent an association with a general predisposition to greater arousal and reactivity. Copyright 2010 Elsevier Inc. All rights reserved.

In utero cortisol and testosterone exposure and fear reactivity in infancy

PubMed Central

Bergman, Kristin; Glover, Vivette; Sarkar, Pampa; Abbott, Dave; O'Connor, Thomas G

2010-01-01

Fetal programming is emerging as a major conceptual model for understanding developmental origins of health and disease, including behavioral outcomes. As part of a larger study of prenatal stress and child development, we examined the association between prenatal hormone exposure and fear reactivity, a temperament dimension that is a predictor of long-term behavioral adjustment. Amniotic fluid was collected from a sample of women undergoing clinically indicated amniocentesis for later analysis of cortisol and testosterone. Children with normal birth outcomes were recalled for follow-up assessment at 17 months, at which time we administered an observational assessment of temperament (lab-TAB; n=108). Information on pregnancy and obstetric outcome was included as covariates. Results indicated that there was a significant association between prenatal testosterone and observed fear reactivity in boys (r(53)=0.34, p=0.01); no significant effect was found in girls (r(54)=-.07, ns); the effect remained when obstetric, psychosocial, and parental anxiety were controlled for. There was not a significant association between fetal cortisol exposure and fear reactivity. The prediction from in utero testosterone exposure to fear reactivity in boys extends prior research on prenatal testosterone, and may represent an association with a general predisposition to greater arousal and reactivity. PMID:20060000

Maternal prenatal cortisol and infant cognitive development: moderation by infant-mother attachment.

PubMed

Bergman, Kristin; Sarkar, Pampa; Glover, Vivette; O'Connor, Thomas G

2010-06-01

Experimental animal studies suggest that early glucocorticoid exposure may have lasting effects on the neurodevelopment of the offspring; animal studies also suggest that this effect may be eliminated by positive postnatal rearing. The relevance of these findings to humans is not known. We prospectively followed 125 mothers and their normally developing children from pregnancy through 17 months postnatal. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infants were assessed at an average age of 17 months with the Bayley Scales of Infant Development, and ratings of infant-mother attachment classification were made from the standard Ainsworth Strange Situation assessment. Prenatal cortisol exposure, indexed by amniotic fluid levels, negatively predicted cognitive ability in the infant, independent of prenatal, obstetric, and socioeconomic factors. This association was moderated by child-mother attachment: in children with an insecure attachment, the correlation was [r(54) = -.47, p < .001]; in contrast, the association was nonexistent in children who had a secure attachment [r(70) = -.05, ns]. These findings mimic experimental animal findings and provide the first direct human evidence that increased cortisol in utero is associated with impaired cognitive development, and that its impact is dependent on the quality of the mother-infant relationship. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man.

PubMed

Touitou, Y; Benoit, O; Foret, J; Aguirre, A; Bogdan, A; Clodoré, M; Touitou, C

1992-03-01

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma patterns of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00-23.00) male students (22.5 +/- 1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux; other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.

Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors

PubMed Central

Wan, Cynthia; Couture-Lalande, Marie-Ève; Narain, Tasha A.; Lebel, Sophie; Bielajew, Catherine

2016-01-01

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes. PMID:27023572

Salivary Alpha-Amylase Reactivity in Breast Cancer Survivors.

PubMed

Wan, Cynthia; Couture-Lalande, Marie-Ève; Narain, Tasha A; Lebel, Sophie; Bielajew, Catherine

2016-03-23

The two main components of the stress system are the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes. While cortisol has been commonly used as a biomarker of HPA functioning, much less attention has been paid to the role of the SAM in this context. Studies have shown that long-term breast cancer survivors display abnormal reactive cortisol patterns, suggesting a dysregulation of their HPA axis. To fully understand the integrity of the stress response in this population, this paper explored the diurnal and acute alpha-amylase profiles of 22 breast cancer survivors and 26 women with no history of cancer. Results revealed that breast cancer survivors displayed identical but elevated patterns of alpha-amylase concentrations in both diurnal and acute profiles relative to that of healthy women, F (1, 39) = 17.95, p < 0.001 and F (1, 37) = 7.29, p = 0.010, respectively. The average area under the curve for the diurnal and reactive profiles was 631.54 ± 66.94 SEM and 1238.78 ± 111.84 SEM, respectively. This is in sharp contrast to their cortisol results, which showed normal diurnal and blunted acute patterns. The complexity of the stress system necessitates further investigation to understand the synergistic relationship of the HPA and SAM axes.

Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects.

PubMed

Liu, Shuai; Wang, Yinyan; Xu, Kaibin; Ping, Fan; Li, Fang; Wang, Renzhi; Cheng, Xin

2018-01-01

Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD) owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG PET), between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

Interrenal dysfunction in fish from contaminated sites: In vivo and in vitro assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hontela, A.

1998-01-01

Cortisol, synthesized in the interrenal cells of teleost head kidney, has a major role in the physiologic response to physical and chemical stressors. Plasma levels of cortisol increase in physiologically competent fish acutely exposed to stressors such as cadmium or mercury. The effects of chronic low level exposures are less well understood. The author has diagnosed an endocrine impairment characterized by a reduced capacity to elevate plasma cortisol levels in response to an acute standardized capture stress in yellow perch (Perca flavescens) and in northern pike (Esox lucius) sampled at sites contaminated by mixtures of pollutants (heavy metals, polycyclic aromaticmore » hydrocarbons, and polychlorinated biphenyls), by heavy metals, or by bleached kraft mill effluent. The studies with fish, as well as with amphibians at contaminated sites, demonstrated that low level chronic exposures impair secretion of corticosteroids. The author has developed new tests for assessment of the functional integrity of teleost and amphibian interrenal tissue using an adrenocorticotropic hormone (ACTH) challenge, in vivo and in vitro. The reduced ability to respond to ACTH indicates that the normal neuroendocrine response to stressors may be disrupted and that the ability to cope with biotic and abiotic stressors in the environment may be significantly reduced in the impaired animals.« less

Affective states and adaptation to parabolic flights

NASA Astrophysics Data System (ADS)

Collado, Aurélie; Langlet, Cécile; Tzanova, Tzvetomira; Hainaut, Jean-Philippe; Monfort, Vincent; Bolmont, Benoît

2017-05-01

This exploratory study investigates (i) inter-individual variations of affective states before a parabolic flight (i.e., PF) on the basis of quality of adaptation to physical demands, and (ii) intra-individual variations of affective states during a PF. Mood-states, state-anxiety and salivary cortisol were assessed in two groups with a different quality of adaptation (an Adaptive Group, i.e., AG, and a Maladaptive Group, i.e., MG) before and during a PF. Before PF, MG scored higher on mood states (Anger-Hostility, Fatigue-Inertia) than AG. During the flight, while AG seemed to present "normal" affective responses to the demanding environment (e.g., increase in salivary cortisol), MG presented increases in mood states such as Confusion-Bewilderment or Tension-Anxiety. The findings suggest that the psychological states of MG could have disturbed their ability to integrate sensory information from an unusual environment, which led to difficulties in coping with the physical demands of PF.

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

PubMed

Skjöldebrand Sparre, L; Kollind, M; Carlström, K

2002-01-01

To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO. Copyright 2002 S. Karger AG, Basel

Effect of housing rats within a pyramid on stress parameters.

PubMed

Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

2003-11-01

The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.

Cortisol and 3,4-Methylenedioxymethamphetamine: Neurohormonal Aspects of Bioenergetic Stress in Ecstasy Users

PubMed Central

Parrott, A.C.

2009-01-01

Aims 3,4-Methylenedioxymethamphetamine (MDMA) can affect both neurotransmitter and neurohormonal activity. This review will debate the role of the metabolic activation hormone cortisol for the psychobiological effects of ecstasy/MDMA. Methods The empirical literature on cortisol release following acute MDMA administration and cortisol functioning in drug-free recreational ecstasy/MDMA users will be reviewed. This will be followed by an overview of cortisol as a bioenergetic stress neurohormone, and a debate on how it could be modulating the acute and chronic psychobiological effects of MDMA. Results Cortisol release is increased by stimulatory factors, including physical activity, thermal stress and stimulant drugs. In laboratory studies MDMA leads to an acute cortisol increase of around 150% in sedentary humans. In MDMA-using dance clubbers, the cortisol levels are increased by around 800%, possibly due to the combined factors of stimulant drug, physical exertion and psychosocial stimulation. Regular ecstasy/MDMA users also demonstrate changes in baseline cortisol levels and cortisol reactivity, with compromised hypothalamic-pituitary-adrenal activity. Nonpharmacological research has shown how cortisol is important for psychological aspects such as memory, cognition, sleep, impulsivity, depression and neuronal damage. These same functions are often impaired in recreational ecstasy/MDMA users, and cortisol may be an important modulatory co-factor. Conclusions The energizing hormone cortisol is involved in the psychobiology of MDMA, probably via its effects on energy metabolism. Acute cortisol release may potentiate the stimulating effects of MDMA in dance clubbers. Chronically, cortisol may contribute to the variance in functional and structural consequences of repeated ecstasy usage. PMID:19893332

A systematic review of the effects of mindfulness interventions on cortisol.

PubMed

O'Leary, Karen; O'Neill, Siobhan; Dockray, Samantha

2016-09-01

Cortisol is increasingly included in examinations of mindfulness intervention effects as an indicator of efficacy; however, the association of cortisol and mindfulness has yet to be rigorously evaluated. A systematic review of six studies examining mindfulness intervention effects on cortisol was conducted. Inconsistent results were found for mindfulness effects on cortisol. Significant changes in cortisol levels were observed in within-participants studies but not observed in randomised controlled trial designs. Mindfulness may influence cortisol, but findings are inconclusive. Mindfulness pathways and methodological differences influence variations in mindfulness effects. Robust protocols are needed to adequately examine mindfulness effects on cortisol. © The Author(s) 2015.

Reduced Cortisol Metabolism during Critical Illness

PubMed Central

Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

2015-01-01

BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian Fund for Scientific Research and others; ClinicalTrials.gov numbers, NCT00512122 and NCT00115479; and Current Controlled Trials numbers, ISRCTN49433936, ISRCTN49306926, and ISRCTN08083905.) PMID:23506003

Normal cortisol response to cold pressor test, but lower free thyroxine, after recovery from undernutrition.

PubMed

Martins, Vinicius J B; Neves, Andrea P O; Garcia, Márcia C; Spadari, Regina C; Clemente, Ana Paula G; de Albuquerque, Maria P; Hoffman, Daniel J; Sawaya, Ana L

2016-01-14

Undernutrition is a stressor with long-term consequences, and the effect of nutritional recovery on cortisol and thyroid hormone status is unknown. To investigate basal thyroid hormones and the cortisol response to a cold pressor test in children recovered from undernutrition, a cross-sectional study was undertaken on children (6-16 years) separated into four groups: control (n 41), stunted (n 31), underweight (n 27) and recovered (n 31). Salivary cortisol was collected over the course of 10 h: upon awakening, before and after an unpleasant and a pleasant stimulus. Cortisol upon awakening was highest in the stunted and lowest in the underweight groups: control=5·05 (95% CI 3·71, 6·89) nmol/l, stunted=6·62 (95% CI 3·97, 11·02) nmol/l, underweight=2·51 (95% CI 1·75, 3·63) nmol/l and recovered=3·46 (95% CI 2·46, 4·90) nmol/l (P=0·005). Girls had higher cortisol concentrations upon awakening compared with boys (P=0·021). The undernourished groups showed an elevated cortisol response both to the unpleasant stimulus and at the last measurement (16.00 hours) compared with that of the recovered group: AUC, control=2·07 (95% CI 1·69, 2·45) nmol/l×30 min, stunted=2·48 (95% CI 1·91, 3·06) nmol/l×30 min, underweight=2·52 (95% CI 2·07, 2·97) nmol/l×30 min, recovered=1·68 (95% CI 1·26, 2·11) nmol/l×30 min (P=0·042); and control=2·03 (95% CI 1·75, 2·39) nmol/l×30 min, stunted=2·51 (95% CI 1·97, 3·19) nmol/l×30 min, underweight=2·61 (95% CI 2·16, 3·16) nmol/l×30 min, recovered=1·70 (95% CI 1·42, 2·03) nmol/l×30 min (P=0·009). Lower free thyroxine (T4) was found in the recovered and stunted groups: control=1·28 (95% CI 1·18, 1·39) pmol/l, stunted=0·98 (95% CI 0·87, 1·10) pmol/l, underweight=1·10 (95% CI 1·01, 1·21) pmol/l and recovered=0·90 (95% CI 0·83, 0·99) pmol/l (P<0·001). Multivariate analysis showed a lower cortisol concentration along 10 h (06.00-16.00 hours) in the recovered compared with the other groups (P=0·017), and similar concentrations between the recovered and control group. In conclusion, the children with recovery in weight and height had a cortisol stress response similar to control but a lower basal free T4. Longitudinal studies are warranted to determine the extent of these endocrine changes after recovery of undernutrition and in adulthood.

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures

PubMed Central

Short, Sarah J.; Stalder, Tobias; Marceau, Kristine P.; Entringer, Sonja; Moog, Nora K.; Shirtcliff, Elizabeth A.; Wadhwa, Pathik D.; Buss, Claudia

2016-01-01

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean ± SD age: 34 ± 8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30 min, at bedtime) and the average of 4 weekly 24-hr urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: 1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and 2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r = 0.61, p = 0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-hr UFC and HCC did not reach statistical significance (r = 0.30, p = 0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r = 0.84, p < 0.001), followed by 24-hr UFC (week-to-week: r’s between 0.59 and 0.68, ps < 0.05) and then integrated salivary cortisol concentrations (week-to-week: r’s between 0.38 and 0.61, p’s between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period. PMID:27235635

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures.

PubMed

Short, Sarah J; Stalder, Tobias; Marceau, Kristine; Entringer, Sonja; Moog, Nora K; Shirtcliff, Elizabeth A; Wadhwa, Pathik D; Buss, Claudia

2016-09-01

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean±SD age: 34±8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30min, at bedtime) and the average of 4 weekly 24-h urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: (1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and (2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r=0.61, p=0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-h UFC and HCC did not reach statistical significance (r=0.30, p=0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r=0.84, p<0.001), followed by 24-h UFC (week-to-week: r's between 0.59 and 0.68, ps<0.05) and then integrated salivary cortisol concentrations (week-to-week: r's between 0.38 and 0.61, p's between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship of Sleep Quantity and Quality with 24-Hour Urinary Catecholamines and Salivary Awakening Cortisol in Healthy Middle-Aged Adults

PubMed Central

Zhang, Jihui; Ma, Ronald C.W.; Kong, Alice P.S.; So, Wing Yee; Li, Albert M.; Lam, Sui Ping; Li, Shirley Xin; Yu, Mandy W.M.; Ho, Chung Shun; Chan, Michael H.M.; Zhang, Bin; Wing, Yun Kwok

2011-01-01

Objectives: a. Explore the stability in sleep/wake patterns of middle-aged adults over a 3-year follow-up period. b. Explore the relationship between objectively measured sleep indices, urinary catecholamines, and salivary cortisol. Design: Naturalistic follow-up for sleep/wake patterns (n = 114) by 2-week sleep log and cross-sectional design for objective sleep assessments and hormonal measures (n = 96) at follow-up period nearly 3 years after baseline measurements. Setting: Community Participants: Healthy middle-aged adults Interventions: N/A Measurements and Results: There were high correlations between baseline and follow-up period (2.6 ± 0.5 years) on sleep/wake patterns (r = 0.6–0.79) as measured by 2-week sleep log. For wave 2 cross-sectional study, objective poor sleepers (3-day actigraphy sleep efficiency < 85%) had a higher 24-h urinary norepinephrine (NE) level (205.7 ± 105 nmol/d vs 162.1 ± 55.6 nmol/d, P = 0.03) and a nearly significantly higher 24-h urinary epinephrine (E) level (P = 0.12) than good sleepers. There were no differences in 3-day mean salivary awakening cortisol and 24-h urinary catecholamines (NE and E) between short and normal/long sleepers. Linear regression results, however, showed that shorter time in bed and actual sleep time, longer sleep onset latency, and lower sleep efficiency were correlated with higher 24-h urinary E and NE (all P < 0.05) but not salivary cortisol. The effect of poor sleep quality on 24-h urinary catecholamines was stronger in males than females. Conclusions: Increased sympathetic activity as measured by 24-h urinary catecholamines might play a critical role in the pathogenesis mediating the relationship of insufficient sleep (quantity and quality) with subsequent cardiovascular and metabolic complications. Salivary awakening cortisol was not associated with sleep quantity and quality in healthy middle-aged adults. Citation: Zhang J; Ma RCW; Kong APS; So WY; Li AM; Lam SP; Li SX; Yu MWM; Ho CS; Chan MHM; Zhang B; Wing YK. Relationship of sleep quantity and quality with 24-hour urinary catecholamines and salivary awakening cortisol in healthy middle-aged adults. SLEEP 2011;34(2):225-233. PMID:21286244

Direct immune-detection of cortisol by chemiresistor graphene oxide sensor.

PubMed

Kim, Yo-Han; Lee, Kyungmin; Jung, Hunsang; Kang, Hee Kyung; Jo, Jihoon; Park, In-Kyu; Lee, Hyun Ho

2017-12-15

In this study, a biosensor to detect a stress biomarker of cortisol using cortisol monoclonal antibody (c-Mab) covalently immobilized on reduced graphene oxide (rGO) channel as electrical sensing element was demonstrated. Highly specific immune-recognition between the c-Mab and the cortisol was identified and characterized on a basis of resistance change at the rGO channel based chemiresistor sensor achieving the limit of detection of 10pg/mL (27.6 pM). In addition, cortisol concentrations of real human salivary sample and buffer solution of rat adrenal gland acute slices, which could secret the cortisol induced by adrenocorticotropic hormone (ACTH), were directly measured by the chemiresistor corresponding to the specific sensing of the cortisol. The rGO chemiresistor could selectively measure the cortisol levels in spite of diverse neuroendocrine's existence. The potential perspective of this study can be a protocol of new cortisol sensor development, which will be applicable to point-of-care testing (POCT) targeted for salivary cortisol, in vitro psychobiological study on cortisol induction, and implantable sensor chip in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of cortisol and sirtuin1 during the response to stress of hypothalamic circadian system and food intake-related peptides in rainbow trout, Oncorhynchus mykiss.

PubMed

Naderi, Fatemeh; Hernández-Pérez, Juan; Chivite, Mauro; Soengas, José L; Míguez, Jesús M; López-Patiño, Marcos A

2018-05-08

Stress is conditioning animal welfare by negatively affecting a wide range of physiological and behavioral functions. This may be applied to circadian physiology and food intake. Cortisol, the stress-related hormone, may mediate such effect of stress, but other indirect mediators might be considered, such as sirtuin1. Then, either the independent modulatory effect or the existence of any interaction between mediators may be responsible. The circadian system is the main modulator of several integrative mechanisms at both central and peripheral levels that are rhythmically presented, thus influencing different processes such as food intake. In this way, food intake is controlled by the circadian system, as demonstrated by the persistence of such rhythms of food intake in the absence of environmental external cues. Our study aimed to evaluate the daily profile of hypothalamic mRNA abundance of circadian clock genes (clock1a, bmal1, per1 and rev-erbβ-like), and food intake regulators (crf, pomc-a1, cart, and npy) in rainbow trout (Oncorhynchus mykiss), the impact of stress on such rhythms, and the involvement of cortisol and sirtuin1 as mediators. Four cohorts of trout were subjected to 1) normal stocking density (control group), 2) high stocking density for 72 hours (stress group), 3) normal stocking density and implanted with mifepristone, a glucocorticoid receptors antagonist, and 4) mifepristone administered and stressed for 72 hours. Fish from each group were sampled every 4-h along the 24-h LD cycle, and cortisol, glucose and lactate plasma levels were evaluated. Hypothalamic mRNA abundance of clock genes, food intake regulators, glucocorticoid receptors and sirtuin1 were qPCR assayed. Our results reveal the impact of stress on most of the genes assayed, but different mechanisms appear to be involved. The rhythm of clock genes displayed decreased amplitude and averaged levels in stressed trout, with no changes of the acrophase being observed. This effect was not prevented by mifepristone. On the contrary, the effect of stress on the daily profile of crf, pomc-a1, and npy was totally prevented by mifepristone administration. Accordingly, cortisol appears to mainly mediate the effect of stress on food intake regulators through binding to specific glucocorticoid receptors within trout hypothalamus, whereas sirtuin1 is apparently mediating such effects on the circadian system in the same brain region. Further research must be performed to clarify those mechanisms through which stress influences food intake and the circadian oscillator within the same brain region, hypothalamus, in rainbow trout, and the interaction among them all.

Successful measurement of the mismatch negativity despite a concurrent movie soundtrack: reduced amplitude but normal component morphology.

PubMed

Moreau, Patricia; Jolicœur, Pierre; Lidji, Pascale; Peretz, Isabelle

2013-12-01

To examine the mechanisms responsible for the reduction of the mismatch negativity (MMN) ERP component observed in response to pitch changes when the soundtrack of a movie is presented while recording the MMN. In three experiments we measured the MMN to tones that differed in pitch from a repeated standard tone presented with a silent subtitled movie, with the soundtrack played forward or backward, or with soundtracks set at different intensity levels. MMN amplitude was reduced when the soundtrack was presented either forward or backward compared to the silent subtitled movie. With the soundtrack, MMN amplitude increased proportionally to the increments in the sound-to-noise intensity ratio. MMN was reduced in amplitude but had normal morphology with a concurrent soundtrack, most likely because of basic acoustical interference from the soundtrack with MMN-critical tones rather than from attentional effects. A normal MMN can be recorded with a concurrent movie soundtrack, but signal amplitudes need to be set with caution to ensure a sufficiently high sound-to-noise ratio between MMN stimuli and the soundtrack. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The impact of cortisol in steatotic and non-steatotic liver surgery.

PubMed

Cornide-Petronio, María Eugenia; Bujaldon, Esther; Mendes-Braz, Mariana; Avalos de León, Cindy G; Jiménez-Castro, Mónica B; Álvarez-Mercado, Ana I; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

2017-10-01

The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

MATERNAL SELF-REPORTED DEPRESSIVE SYMPTOMS AND MATERNAL CORTISOL LEVELS INTERACT TO PREDICT INFANT CORTISOL LEVELS.

PubMed

Khoury, Jennifer E; Gonzalez, Andrea; Levitan, Robert; Masellis, Mario; Basile, Vincenzo; Atkinson, Leslie

2016-01-01

Three basic findings have emerged from research on maternal depressive symptoms and offspring hypothalamic-pituitary-adrenal functioning: (a) Mothers' depressive symptoms are positively associated with their offsprings' cortisol stress response, (b) numerous individual and interpersonal maternal characteristics moderate this association, and (c) maternal and infant cortisol levels are highly correlated. In combination, these findings have suggested that maternal cortisol levels may moderate the relation between maternal depressive symptoms and infant cortisol responsivity; the current study assessed this hypothesis. Participants were 297 mother-infant dyads who were recruited from the community. Maternal depressive symptoms were assessed via self-report. Dyads participated in two differentially stressful infant challenges when infants were 16 and 17 months old. Mother and infant salivary cortisol was collected before and after challenges. Results indicate that maternal cortisol levels moderated associations between maternal depressive symptoms and infant cortisol levels across both challenges. Infants showed higher cortisol levels if their mothers had both higher depressive symptoms and higher cortisol levels, as compared to infants of mothers with higher depressive symptoms and lower cortisol, and to infants of mothers with lower depressive symptoms and either higher or lower cortisol levels. We discuss findings in relation to environmental and biological factors that may contribute to the intergenerational transmission of depressive symptoms. © 2016 Michigan Association for Infant Mental Health.

Interaction of attentional and motor control processes in handwriting.

PubMed

Brown, T L; Donnenwirth, E E

1990-01-01

The interaction between attentional capacity, motor control processes, and strategic adaptations to changing task demands was investigated in handwriting, a continuous (rather than discrete) skilled performance. Twenty-four subjects completed 12 two-minute handwriting samples under instructions stressing speeded handwriting, normal handwriting, or highly legible handwriting. For half of the writing samples, a concurrent auditory monitoring task was imposed. Subjects copied either familiar (English) or unfamiliar (Latin) passages. Writing speed, legibility ratings, errors in writing and in the secondary auditory task, and a derived measure of the average number of characters held in short-term memory during each sample ("planning unit size") were the dependent variables. The results indicated that the ability to adapt to instructions stressing speed or legibility was substantially constrained by the concurrent listening task and by text familiarity. Interactions between instructions, task concurrence, and text familiarity in the legibility ratings, combined with further analyses of planning unit size, indicated that information throughput from temporary storage mechanisms to motor processes mediated the loss of flexibility effect. Overall, the results suggest that strategic adaptations of a skilled performance to changing task circumstances are sensitive to concurrent attentional demands and that departures from "normal" or "modal" performance require attention.

Hair Cortisol in the Evaluation of Cushing Syndrome

PubMed Central

Hodes, Aaron; Lodish, Maya B.; Tirosh, Amit; Meyer, Jerrold; Belyavskaya, Elena; Lyssikatos, Charalampos; Rosenberg, Kendra; Demidowich, Andrew; Swan, Jeremy; Jonas, Nichole; Stratakis, Constantine A.; Zilbermint, Mihail

2017-01-01

Purpose Hair cortisol evaluation has been used to help detect patients with suspected Cushing Syndrome. Our goal was to correlate segmental hair cortisol with biochemical testing in patients with Cushing syndrome and controls. This study was a prospective analysis of hair cortisol in confirmed Cushing syndrome cases over 16 months. Methods Thirty six subjects (26.5±18.9 years, 75% female, and 75% Caucasian) were analyzed by diurnal serum cortisol, 24 h urinary free cortisol corrected for body surface area (UFC/BSA), and 24 h urinary 17-hydroxysteroids corrected for creatinine (17OHS/Cr). Thirty patients were diagnosed with Cushing syndrome, and six were defined as controls. 3-cm hair samples nearest to the scalp, cut into 1-cm segments (proximal, medial, and distal), were analyzed for cortisol by enzyme immunoassay and measured as pmol cortisol/g dry hair. Hair cortisol levels were compared with laboratory testing done within previous 2 months of the evaluation. Results Proximal hair cortisol was higher in Cushing syndrome patients (266.6 ± 738.4 pmol/g) than control patients (38.9 ± 25.3 pmol/g) (p = 0.003). Proximal hair cortisol was highest of all segments in 25/36 (69%) patients. Among all subjects, proximal hair cortisol was strongly correlated with UFC/BSA (r=0.5, p=0.005), midnight serum cortisol (r=0.4, p=0.03), and 17OHS/Cr, which trended towards significance (r=0.3, p=0.06). Conclusions Among the three examined hair segments, proximal hair contained the highest cortisol levels and correlated the most with the initial biochemical tests for Cushing syndrome in our study. Further studies are needed to validate proximal hair cortisol in the diagnostic workup for Cushing syndrome. PMID:28194652

The role of anxiety in cortisol stress response and cortisol recovery in boys with oppositional defiant disorder/conduct disorder.

PubMed

Schoorl, Jantiene; Rijn, Sophie van; Wied, Minet de; van Goozen, Stephanie; Swaab, Hanna

2016-11-01

Children with antisocial and aggressive behaviors have been found to show abnormal neurobiological responses to stress, specifically impaired cortisol stress reactivity. The role of individual characteristics, such as comorbid anxiety, in the stress response is far less studied. Furthermore, this study extended previous studies in that not only baseline and reactivity to a psychosocial stressor were examined, but also recovery from a stressor. These three phases of cortisol could be impacted differentially in boys with oppositional defiant disorder/conduct disorder (ODD/CD) with (+ANX) and without anxiety (-ANX). The results revealed that cortisol patterns in response to psychosocial stress were different for boys with ODD/CD+ANX (n=32), ODD/CD-ANX (n=22) and non-clinical controls (NC) (n=34), with age range of 7.8-12.9 years. The ODD/CD-ANX group showed lower overall cortisol levels than the NC group. When considering the three phases of cortisol separately, the ODD/CD-ANX group had lower baseline cortisol levels relative to the other groups, whereas the ODD/CD+ANX showed an impaired cortisol recovery response. Within those with ODD/CD, callous-unemotional traits were predictive of high baseline cortisol levels. Also, anxiety predicted high baseline and recovery cortisol levels, whereas a high number of CD symptoms predicted reduced cortisol stress reactivity. These results clearly indicate that comorbid anxiety is an important factor in explaining differences in stress response profiles in boys with ODD/CD; although boys with CD/ODD are generally characterized by an impaired cortisol stress response, we found that those with comorbid anxiety showed impaired cortisol recovery, whereas those without anxiety showed reduced baseline cortisol levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hair cortisol in the evaluation of Cushing syndrome.

PubMed

Hodes, Aaron; Lodish, Maya B; Tirosh, Amit; Meyer, Jerrold; Belyavskaya, Elena; Lyssikatos, Charalampos; Rosenberg, Kendra; Demidowich, Andrew; Swan, Jeremy; Jonas, Nichole; Stratakis, Constantine A; Zilbermint, Mihail

2017-04-01

Hair cortisol evaluation has been used to help detect patients with suspected Cushing syndrome. Our goal was to correlate segmental hair cortisol with biochemical testing in patients with Cushing syndrome and controls. This study was a prospective analysis of hair cortisol in confirmed Cushing syndrome cases over 16 months. Thirty-six subjects (26.5 ± 18.9 years, 75% female, and 75% Caucasian) were analyzed by diurnal serum cortisol, 24 h urinary free cortisol corrected for body surface area (UFC/BSA), and 24 h urinary 17-hydroxysteroids corrected for creatinine (17OHS/Cr). Thirty patients were diagnosed with Cushing syndrome, and six were defined as controls. 3-cm hair samples nearest to the scalp, cut into 1-cm segments (proximal, medial, and distal), were analyzed for cortisol by enzyme immunoassay and measured as pmol cortisol/g dry hair. Hair cortisol levels were compared with laboratory testing done within previous 2 months of the evaluation. Proximal hair cortisol was higher in Cushing syndrome patients (266.6 ± 738.4 pmol/g) than control patients (38.9 ± 25.3 pmol/g) (p = 0.003). Proximal hair cortisol was highest of all segments in 25/36 (69%) patients. Among all subjects, proximal hair cortisol was strongly correlated with UFC/BSA (r = 0.5, p = 0.005), midnight serum cortisol (r = 0.4, p = 0.03), and 17OHS/Cr, which trended towards significance (r = 0.3, p = 0.06). Among the three examined hair segments, proximal hair contained the highest cortisol levels and correlated the most with the initial biochemical tests for Cushing syndrome in our study. Further studies are needed to validate proximal hair cortisol in the diagnostic workup for Cushing syndrome.

Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations.

PubMed

Grass, Juliane; Kirschbaum, Clemens; Miller, Robert; Gao, Wei; Steudte-Schmiedgen, Susann; Stalder, Tobias

2015-03-01

Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative marker of long-term systemic cortisol secretion. However, contrary to this assumption, some recent observations have raised the possibility that HCC may be subject to acute influences, potentially related to cortisol incorporation from sweat. Here, we provide a first detailed in vivo investigation of this possibility comprising two independent experimental studies: study I (N=42) used a treadmill challenge to induce sweating together with systemic cortisol reactivity while in study II (N=52) a sauna bathing challenge induced sweating without systemic cortisol changes. In both studies, repeated assessments of HCC, salivary cortisol, cortisol in sweat and individuals' sweating rate (single assessment) were conducted on the experimental day and at a next-day follow-up. Results across the two studies consistently revealed that HCC were not altered by the acute interventions. Further, HCC were found to be unrelated to acute salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of examination. In line with previous data, cortisol levels in sweat were strongly related to total salivary cortisol output across the examined periods. The present results oppose recent case report data by showing that single sweat-inducing interventions do not result in acute changes in HCC. Our data also tentatively speak against the notion that cortisol in sweat may be a dominant source of HCC. Further, our findings also indicate that HCC are not subject to diurnal variation. This research provides further support for hair cortisol analysis as a marker of integrated long-term systemic cortisol secretion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression.

PubMed

Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M; Essex, Marilyn J

2014-09-01

Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determination of cortisol in human plasma by thin-layer chromatography and fluorescence derivatization with isonicotinic acid hydrazide.

PubMed

Fenske, Martin

2008-01-01

The present work describes a specific and rapid determination of cortisol in human plasma. The method includes liquid-liquid extraction of plasma samples, thin-layer chromatography (TLC) of ethanolic extracts on aluminium foil-backed silica gel 60 TLC plates, derivatization of cortisol with isonicotinic acid hydrazide, and densitometric measurement of the fluorescence intensity of cortisol hydrazone. The fluorescence was linearly related to cortisol amounts; the correlation coefficients of standard curve plots were r>0.99. The coefficient of variation ranged between 2.8-7.9% (20 ng, within-assay/between assay variation) and 1.6-6.8% (80 ng, within-assay/between assay variation). The recovery of cortisol from plasma spiked with 21-deoxycortisol was 85%+/-4%. Cortisol concentration in the plasma was 66+/-32 ng/mL (mean+/-standard deviation, n=24). The advantage of this method is its simplicity to separate cortisol from other steroids by TLC, its specificity (formation of cortisol hydrazone), and the rapid quantitation of cortisol by densitometry.

The relationship of subepidermal moisture and early stage pressure injury by visual skin assessment.

PubMed

Kim, Chul-Gyu; Park, Seungmi; Ko, Ji Woon; Jo, Sungho

2018-05-08

The purpose of this study was to examine the relationship of subepidermal moisture and early stage pressure injury by visual skin assessment in elderly Korean. Twenty-nine elderly participated at a particular nursing home. Data were collected for 12 weeks by one wound care nurse. Visual skin assessment and subepidermal moisture value were measured at both buttocks, both ischia, both trochanters, sacrum, and coccyx of each subject once a week. Subepidermal moisture value of stage 1 pressure injury was significantly higher than that of no injury and blanching erythema. After adjustment with covariates, odds ratios of blanching erythema to normal skin and stage 1 pressure injury to blanching erythema/normal skin were statistically significant (p < 0.05). Odds ratio of blanching erythema to normal skin was 1.003 (p = .047) by 1-week prior subepidermal moisture value, and that of concurrent subepidermal moisture value was 1.004 (p = .011). Odds ratio of stage 1 pressure injury to normal skin/blanching erythema was 1.003 (p = .005) by 1-week prior subepidermal moisture value, and that for concurrent subepidermal moisture value was 1.007 (p = .030). Subepidermal moisture was associated with concurrent and future (1 week later) skin damage at both trochanters. Subepidermal moisture would be used to predict early skin damage in clinical nursing field for the effective pressure injury prevention. Copyright © 2018. Published by Elsevier Ltd.

Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

PubMed

Storr, Helen L; Plowman, P Nicholas; Carroll, Paul V; François, Inge; Krassas, Gerasimos E; Afshar, Farhad; Besser, G Michael; Grossman, Ashley B; Savage, Martin O

2003-01-01

Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH secretion and preservation of other anterior pituitary function.

Cortisol extraction through human skin by reverse iontophoresis.

PubMed

Ventura, Stephanie A; Heikenfeld, Jason; Brooks, Tiffany; Esfandiari, Leyla; Boyce, Steven; Park, Yoonjee; Kasting, Gerald B

2017-04-01

Continuous monitoring of cortisol at the surface of the skin would advance the diagnosis and treatment of cortisol-related diseases, or of elevated cortisol levels related to stress in otherwise healthy populations. Reliable and accurate detection of cortisol at the skin surface remains a limiting factor in real-time monitoring of cortisol. To address this limitation, cortisol extraction through excised human skin by reverse iontophoresis was studied in vitro in side-by-side diffusion cells using a radiolabeled probe. The skin was subjected to four direct current regimens (0, 28, 56, 113μAcm -2 ) with the anode in the donor chamber and the cumulative cortisol concentrations recorded in the receiver chamber. The 56 and 113μAcm -2 regimens significantly increased transport of 3 H-cortisol through the skin, and current density correlated directly with transcutaneous transport of 3 H-cortisol. The threshold of detection of electroosmotic versus passive diffusion of cortisol through the skin was between 28 and 56μAcm -2 . The results of this study are significant in examining how lipophilic analytes found in the bloodstream respond to reverse iontophoresis across the skin. In addition, a device integration technique is presented which illustrates how continuous cortisol extraction and sensing could potentially be achieved in a conventional wearable format. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurement of salivary cortisol level for the diagnosis of critical illness-related corticosteroid insufficiency in children.

PubMed

Gunnala, Vishal; Guo, Rong; Minutti, Carla; Durazo-Arvizu, Ramon; Laporte, Cynthia; Mathews, Herbert; Kliethermis, Stephanie; Bhatia, Rahul

2015-05-01

To compare serum total, serum free and salivary cortisol in critically ill children. Prospective observational cohort study. Tertiary pediatric critical care unit at Ronald McDonald Children's Hospital at Loyola University Medical Center. We enrolled 59 patients (4 weeks to 18 years of age) between January 2012 and May 2013. Thirty-four patients were included in the salivary to serum free cortisol correlational analysis. Blood and saliva samples were obtained simultaneously within 24 hours of admission between the hours of 6 AM and 12 PM. Salivary cortisol was tested by liquid chromatography/tandem mass spectrometry, serum free cortisol by liquid chromatography/tandem mass spectrometry followed by equilibrium dialysis, and serum total cortisol by liquid chromatography/tandem mass spectrometry. Salivary and serum free cortisol values from 34 patients had a correlation coefficient (r) of 0.87 (95% CI, 0.75-0.93; p < 0.0001). The total serum and salivary cortisol values had a correlation coefficient (r) of 0.67 (95% CI, 0.42-0.81; p < 0.0001). The total serum and serum free cortisol values had a correlation coefficient (r) of 0.83 (95% CI, 0.69-0.91; p < 0.0001). Serum free and salivary cortisol values correlate in critically ill children. Salivary cortisol can be used as a surrogate for serum free cortisol in critically ill pediatric patients. Salivary cortisol is a cost-effective and less invasive measure of bioavailable cortisol and offers an alternate and accurate method for assessing critical illness-related corticosteroid insufficiency in children.

Development of the cortisol circadian rhythm in the light of stress early in life.

PubMed

Simons, Sterre S H; Beijers, Roseriet; Cillessen, Antonius H N; de Weerth, Carolina

2015-12-01

The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of maternal cortisol treatment on offspring size, responses to stress, and anxiety-related behavior in wild largemouth bass (Micropterus salmoides).

PubMed

Redfern, Julia C; Cooke, Steven J; Lennox, Robert J; Nannini, Michael A; Wahl, David H; Gilmour, Kathleen M

2017-10-15

Cortisol, the main glucocorticoid stress hormone in teleost fish, is of interest as a mediator of maternal stress on offspring characteristics because it plays an organizational role during early development. The present study tested the hypothesis that maternal exposure to cortisol treatment prior to spawn affects offspring phenotype using wild largemouth bass (Micropterus salmoides). Baseline and stress-induced cortisol concentrations, body size (i.e. length and mass), and behavior (i.e. anxiety, exploration, boldness, and aggression) were assessed at different offspring life-stages and compared between offspring of control and cortisol-treated females. Cortisol administration did not affect spawning success or timing, nor were whole-body cortisol concentrations different between embryos from cortisol-treated and control females. However, maternal cortisol treatment had significant effects on offspring stress responsiveness, mass, and behavior. Compared to offspring of control females, offspring of cortisol-treated females exhibited larger mass right after hatch, and young-of-the-year mounted an attenuated cortisol response to an acute stressor, and exhibited less thigmotaxic anxiety, exploratory behavior, boldness and aggression. Thus, offspring phenotype was affected by elevated maternal cortisol levels despite the absence of a significant increase in embryo cortisol concentrations, suggesting that a mechanism other than the direct deposition of cortisol into eggs mediates effects on offspring. The results of the present raise questions about the mechanisms through which maternal stress influences offspring behavior and physiology, as well as the impacts of such phenotypic changes on offspring fitness. Copyright © 2017 Elsevier Inc. All rights reserved.

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

PubMed Central

Jarcho, Michael R.; Slavich, George M.; Tylova-Stein, Hana; Wolkowitz, Owen M.; Burke, Heather M.

2013-01-01

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5 mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease. PMID:23410758

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

PubMed

Berardelli, R; Karamouzis, I; D'Angelo, V; Fussotto, B; Minetto, M A; Ghigo, E; Giordano, R; Arvat, E

2016-05-01

Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study.

PubMed

Blom, Dirk J; Djedjos, C Stephen; Monsalvo, Maria Laura; Bridges, Ian; Wasserman, Scott M; Scott, Rob; Roth, Eli

2015-09-25

Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. To determine the effects of evolocumab on vitamin E and steroid hormone levels. After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01516879. © 2015 American Heart Association, Inc.

Short-term impact of a stress management and health promotion program on perceived stress, parental stress, health locus of control, and cortisol levels in parents of children and adolescents with diabetes type 1: a pilot randomized controlled trial.

PubMed

Tsiouli, Eleni; Pavlopoulos, Vassilis; Alexopoulos, Evangelos C; Chrousos, George; Darviri, Christina

2014-01-01

Parents of children and adolescents with diabetes type 1 (DT1) usually experience high stress levels, as they have to cope with multiple demands in their everyday life. Different complex interventions have been implemented, which sometimes have led to opposite results. The purpose of this study was to assess stress levels in parents of children and adolescents with DT1 and to evaluate the effectiveness of a stress management program (progressive muscle relaxation combined with diaphragmatic breathing) in reducing perceived and parenting stress, increasing internal locus of control, promoting healthy lifestyle, and normalizing cortisol levels. Randomized controlled trial. A total of 44 parents were randomly assigned to the intervention group (performing relaxation for eight weeks, n = 19) and control group (n = 25). Pre-post measurements included cortisol levels, lifestyle characteristics, perceived stress, perception of health, and parenting stress. A statistically significant decrease in perceived stress (from 27.21 to 19.00, P = .001), as well as in parenting stress (from 85.79 to 73.68, P = .003), was observed in the intervention group. A statistically significant difference was found in perceived stress between the two groups after the intervention (Dmean = 6.64, P = .010). No significant difference was revealed between or within the groups in cortisol levels. Significant improvement was reported by the subjects of the intervention group in various lifestyle parameters. Relaxation techniques seem to have a positive impact on stress and on various lifestyle factors in parents of children and adolescents with DT1. Future research on long-term benefits of an intervention program comprising of various relaxation schemes is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

[Evaluation of a chronic fatigue in patients with moderate-to-severe chronic heart failure].

PubMed

Jasiukeviciene, Lina; Vasiliauskas, Donatas; Kavoliūniene, Ausra; Marcinkeviciene, Jolanta; Grybauskiene, Regina; Grizas, Vytautas; Tumyniene, Vida

2008-01-01

To evaluate the chronic fatigue and its relation to the function of hypothalamus-pituitary-adrenal axis in patients with New York Heart Association (NYHA) functional class III-IV chronic heart failure. A total of 170 patients with NYHA functional class III-IV chronic heart failure completed MFI-20L, DUFS, and DEFS questionnaires assessing chronic fatigue and underwent echocardiography. Blood cortisol concentration was assessed at 8:00 am and 3:00 pm, and plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) concentration was measured at 8:00 am. Neurohumoral investigations were repeated before cardiopulmonary exercise test and after it. The results of all questionnaires showed that 100% of patients with NYHA functional class III-IV heart failure complained of chronic fatigue. The level of overall fatigue was 54.5+/-31.5 points; physical fatigue - 56.8+/-24.6 points. Blood cortisol concentration at 8:00 am was normal (410.1+/-175.1 mmol/L) in majority of patients. Decreased concentration was only in four patients (122.4+/-15.5 mmol/L); one of these patients underwent heart transplantation. In the afternoon, blood cortisol concentration was insufficiently decreased (355.6+/-160.3 mmol/L); reaction to a physical stress was attenuated (Delta 92.9 mmol/L). Plasma NT-proBNP concentration was 2188.9+/-1852.2 pg/L; reaction to a physical stress was diminished (Delta 490.3 pg/L). All patients with NYHA class III-IV heart failure complained of daily chronic fatigue. Insufficiently decreased blood cortisol concentration in the afternoon showed that in the presence of chronic fatigue in long-term cardiovascular organic disease, disorder of a hypothalamus-pituitary-adrenal axis is involved.

MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing's syndrome during pregnancy: solved and unsolved questions.

PubMed

Brue, Thierry; Amodru, Vincent; Castinetti, Frederic

2018-06-01

With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained. © 2018 European Society of Endocrinology.

Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing's syndrome.

PubMed

Di Dalmazi, Guido; Quinkler, Marcus; Deutschbein, Timo; Prehn, Cornelia; Rayes, Nada; Kroiss, Matthias; Berr, Christina M; Stalla, Günter; Fassnacht, Martin; Adamski, Jerzy; Reincke, Martin; Beuschlein, Felix

2017-08-01

Endogenous hypercortisolism is a chronic condition associated with severe metabolic disturbances and cardiovascular sequela. The aim of this study was to characterize metabolic alterations in patients with different degrees of hypercortisolism by mass-spectrometry-based targeted plasma metabolomic profiling and correlate the metabolomic profile with clinical and hormonal data. Cross-sectional study. Subjects ( n  = 149) were classified according to clinical and hormonal characteristics: Cushing's syndrome ( n  = 46), adrenocortical adenomas with autonomous cortisol secretion ( n  = 31) or without hypercortisolism ( n  = 27). Subjects with suspicion of hypercortisolism, but normal hormonal/imaging testing, served as controls ( n  = 42). Clinical and hormonal data were retrieved for all patients and targeted metabolomic profiling was performed. Patients with hypercortisolism showed lower levels of short-/medium-chain acylcarnitines and branched-chain and aromatic amino acids, but higher polyamines levels, in comparison to controls. These alterations were confirmed after excluding diabetic patients. Regression models showed significant correlation between cortisol after dexamethasone suppression test (DST) and 31 metabolites, independently of confounding/contributing factors. Among those, histidine and spermidine were also significantly associated with catabolic signs and symptoms of hypercortisolism. According to an discriminant analysis, the panel of metabolites was able to correctly classify subjects into the main diagnostic categories and to distinguish between subjects with/without altered post-DST cortisol and with/without diabetes in >80% of the cases. Metabolomic profiling revealed alterations of intermediate metabolism independently associated with the severity of hypercortisolism, consistent with disturbed protein synthesis/catabolism and incomplete β-oxidation, providing evidence for the occurrence of metabolic inflexibility in hypercortisolism. © 2017 European Society of Endocrinology.

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

PubMed

Robaczyk, Maciej G

2002-01-01

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

Relationship between effort-reward imbalance and hair cortisol concentration in female kindergarten teachers.

PubMed

Qi, Xingliang; Zhang, Jing; Liu, Yapeng; Ji, Shuang; Chen, Zheng; Sluiter, Judith K; Deng, Huihua

2014-04-01

The present study aims to investigate the relationship between effort-reward imbalance and hair cortisol concentration among teachers to examine whether hair cortisol can be a biomarker of chronic work stress. Hair samples were collected from 39 female teachers from three kindergartens. Cortisol was extracted from the hair samples with methanol, and cortisol concentrations were measured with high performance liquid chromatography-tandem mass spectrometry. Work stress was measured using the effort-reward imbalance scale. The ratio of effort to reward showed significantly positive association with hair cortisol concentration. The cortisol concentration in the system increases with the effort-reward imbalance. Measurement of hair cortisol can become a useful biomarker of chronic work stress. Copyright © 2014 Elsevier Inc. All rights reserved.

Low basal salivary cortisol is associated with teacher-reported symptoms of conduct disorder.

PubMed

Oosterlaan, Jaap; Geurts, Hilde M; Knol, Dirk L; Sergeant, Joseph A

2005-03-30

Cortisol has been implicated in psychobiological explanations of antisocial behavior. This study measured basal salivary cortisol in a sample of 25 children (age range 6 to 12 years) selected to vary in levels of antisocial behavior. Regression analyses were used to predict cortisol concentrations from parent- and teacher-reported symptoms. Parent-reported symptoms did not predict basal cortisol. Teacher-reported conduct disorder (CD) symptoms explained 38% of the variance in the cortisol concentrations, with high symptom severity associated with low cortisol. When a distinction was made between aggressive and non-aggressive CD symptoms, aggressive CD symptoms were more clearly related to low cortisol than non-aggressive CD symptoms. In contrast to previous research, no evidence was found for a mediating role of anxiety symptoms in the relationship between CD and cortisol. The results support biologically based models of antisocial behavior in children that involve reduced autonomic activity.

Longitudinal Changes in Spouses’ HPA Responses: Convergence in Cortisol Patterns During the Early Years of Marriage

PubMed Central

Laws, Holly; Sayer, Aline G.; Pietromonaco, Paula R.; Powers, Sally I.

2015-01-01

Objective Drawing on theories of bidirectional influence between relationship partners (Butler, 2011; Diamond & Aspinwall, 2003), the authors applied dyadic analytic methods to test convergence in cortisol patterns over time in newlywed couples. Methods Previous studies of bidirectional influence in couples’ cortisol levels (Liu, Rovine, Klein, & Almeida, 2013, Papp, Pendry, Simon, & Adam, 2013; Saxbe & Repetti, 2010) found significant covariation in couples’ daily cortisol levels over several days, but no studies have tested whether cortisol response similarity increases over time using a longitudinal design. In the present study, 183 opposite-sex couples (366 participants) engaged in a conflict discussion in a laboratory visit about 6 months after their marriage, and again about 2 years into the marriage. At each visit, spouses provided saliva samples that indexed cortisol levels before, during, and after the discussion. This multi-measure procedure enabled modeling of spouses’ cortisol trajectories around the conflict discussion. Results Findings showed significant convergence in couples’ cortisol trajectories across the early years of marriage; couples showed significantly greater similarity in cortisol trajectories around the conflict discussion as their relationship matured. Cohabitation length predicted stronger convergence in cortisol slopes prior to the conflict discussion. Couples’ relationship dissatisfaction was associated with a greater degree of convergence in spouses’ acute cortisol levels during the conflict discussion. Conclusions Findings suggest that spouses increasingly shape each other’s cortisol responses as their relationship matures. Findings also indicated that increased similarity in acute cortisol levels during conflict may be associated with poorer relationship functioning. PMID:26010721

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women.

PubMed

Lovallo, William R; Farag, Noha H; Vincent, Andrea S; Thomas, Terrie L; Wilson, Michael F

2006-03-01

Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg x 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Longitudinal changes in spouses' HPA responses: Convergence in cortisol patterns during the early years of marriage.

PubMed

Laws, Holly B; Sayer, Aline G; Pietromonaco, Paula R; Powers, Sally I

2015-11-01

Drawing on theories of bidirectional influence between relationship partners (Butler, 2011; Diamond & Aspinwall, 2003), the authors applied dyadic analytic methods to test convergence in cortisol patterns over time in newlywed couples. Previous studies of bidirectional influence in couples' cortisol levels (Liu, Rovine, Klein, & Almeida, 2013; Papp, Pendry, Simon, & Adam, 2013; Saxbe & Repetti, 2010) found significant covariation in couples' daily cortisol levels over several days, but no studies have tested whether cortisol response similarity increases over time using a longitudinal design. In the present study, 183 opposite sex couples (366 participants) engaged in a conflict discussion in a laboratory visit about 6 months after their marriage, and again about 2 years into the marriage. At each visit, spouses provided saliva samples that indexed cortisol levels before, during, and after the discussion. This multimeasure procedure enabled modeling of spouses' cortisol trajectories around the conflict discussion. Findings showed significant convergence in couples' cortisol trajectories across the early years of marriage; couples showed significantly greater similarity in cortisol trajectories around the conflict discussion as their relationship matured. Cohabitation length predicted stronger convergence in cortisol slopes prior to the conflict discussion. Couples' relationship dissatisfaction was associated with a greater degree of convergence in spouses' acute cortisol levels during the conflict discussion. Findings suggest that spouses increasingly shape each other's cortisol responses as their relationship matures. Findings also indicated that increased similarity in acute cortisol levels during conflict may be associated with poorer relationship functioning. (c) 2015 APA, all rights reserved).

The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.

PubMed

Jiménez-Castro, Mónica B; Negrete-Sánchez, Elsa; Casillas-Ramírez, Araní; Gulfo, Jose; Álvarez-Mercado, Ana I; Cornide-Petronio, María Eugenia; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

2017-04-25

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Developmental histories of perceived racial discrimination and diurnal cortisol profiles in adulthood: A 20-year prospective study

PubMed Central

Adam, Emma K.; Heissel, Jennifer A.; Zeiders, Katharine H.; Richeson, Jennifer A.; Ross, Emily C.; Ehrlich, Katherine B.; Levy, Dorainne J.; Kemeny, Margaret; Brodish, Amanda B.; Malanchuk, Oksana; Peck, Stephen C.; Fuller-Rowell, Thomas E.; Eccles, Jacquelynne S.

2015-01-01

Perceived racial discrimination (PRD) has been associated with altered diurnal cortisol rhythms in past cross-sectional research. We investigate whether developmental histories of PRD, assessed prospectively, are associated with adult diurnal cortisol profiles. One-hundred and twelve (N = 50 Black, N = 62 White) adults from the Maryland Adolescent Development in Context Study provided saliva samples in adulthood (at approximately age 32 years) at waking, 30 min after waking, and at bedtime for 7 days. Diurnal cortisol measures were calculated, including waking cortisol levels, diurnal cortisol slopes, the cortisol awakening response (CAR), and average daily cortisol (AUC). These cortisol outcomes were predicted from measures of PRD obtained over a 20-year period beginning when individuals were in 7th grade (approximately age 12). Greater average PRD measured across the 20-year period predicted flatter adult diurnal cortisol slopes for both Black and White adults, and a lower CAR. Greater average PRD also predicted lower waking cortisol for Black, but not White adults. PRD experiences in adolescence accounted for many of these effects. When adolescent and young adult PRD are entered together predicting cortisol outcomes, PRD experiences in adolescence (but not young adulthood) significantly predicted flatter diurnal cortisol slopes for both Black and White adults. Adolescent, but not young adult PRD, also significantly predicted lower waking and lower average cortisol for Black adults. Young adult PRD was, however, a stronger predictor of the CAR, predicting a marginally lower CAR for Whites, and a significantly larger CAR for Blacks. Effects were robust to controlling for covariates including health behaviors, depression, income and parent education levels. PRD experiences interacted with parent education and income to predict aspects of the diurnal cortisol rhythm. Although these results suggest PRD influences on cortisol for both Blacks and Whites, the key findings suggest that the effects are more pervasive for Blacks, affecting multiple aspects of the cortisol diurnal rhythm. In addition, adolescence is a more sensitive developmental period than adulthood for the impacts of PRD on adult stress biology. PMID:26352481

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

PubMed

Haas, C S; Rahvar, A-H; Danneberg, S; Lehnert, H; Moenig, H; Harbeck, B

2016-09-01

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

PubMed

Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

Hot flashes and midlife symptoms in relation to levels of salivary cortisol.

PubMed

Gerber, Linda M; Sievert, Lynnette L; Schwartz, Joseph E

2017-02-01

This study examined the relationship between salivary cortisol levels and hot flashes during midlife. Previous studies have shown that cortisol levels increase with hot flashes in the laboratory, and higher cortisol levels have been associated with more severe hot flashes. Salivary cortisol levels were also examined in relation to total number of midlife symptoms. Women aged 40-60 years (n=109) reported the presence or absence of 23 symptoms, including hot flashes, during the previous 2 weeks. Salivary samples were collected at waking, 30min after waking, 1h before bedtime, and at bedtime. The cortisol awakening response (CAR), cortisol daily decline (CDD), log transformed salivary cortisol levels at each time point, and mean cortisol levels were compared by hot flash report using t-tests. Logistic regression analyses were performed to assess the association between each cortisol measure and the presence or absence of hot flashes, after controlling for potential covariates. Salivary cortisol levels were not significantly associated with hot flashes or sum of symptoms. Hot flash report did not differentiate women who had a positive CAR from those who did not, or women who showed strong CDD from those who did not. Symptomatic women - defined by hot flash report or symptom total - were not found to have higher salivary cortisol levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress.

PubMed

Wosu, Adaeze C; Valdimarsdóttir, Unnur; Shields, Alexandra E; Williams, David R; Williams, Michelle A

2013-12-01

Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Differences in cortisol profiles and circadian adjustment time between nurses working night shifts and regular day shifts: A prospective longitudinal study.

PubMed

Niu, Shu-Fen; Chung, Min-Huey; Chu, Hsin; Tsai, Jui-Chen; Lin, Chun-Chieh; Liao, Yuan-Mei; Ou, Keng-Liang; O'Brien, Anthony Paul; Chou, Kuei-Ru

2015-07-01

This study explored the differences in the circadian salivary cortisol profiles between nurses working night shifts and regular day shifts following a slow rotating shift schedule to assess the number of days required for adjusting the circadian rhythm of salivary cortisol levels in nurses working consecutive night shifts and the number of days off required to restore the diurnal circadian rhythm of salivary cortisol levels. This was a prospective, longitudinal, parallel-group comparative study. The participants were randomly assigned to night and day-shift groups, and saliva samples were collected to measure their cortisol levels and circadian secretion patterns. Significant differences were observed in the overall salivary cortisol pattern parameters (cortisol awakening response, changes in cortisol profiles between 6 and 12h after awakening, and changes in cortisol profiles between 30 min and 12 h after awakening) from Days 2 to 4 of the workdays between both groups. However, on Day 2 of the days off, both groups exhibited similar cortisol profiles and the cortisol profiles in the night-shift group were restored. Nurses working night shifts require at least 4 days to adjust their circadian rhythms of cortisol secretions. Moreover, on changing from night shift to other shifts, nurses must be allowed more than 2 days off work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plasma cortisol in Alzheimer’s disease with or without depressive symptoms

PubMed Central

Zvěřová, Martina; Fišar, Zdeněk; Jirák, Roman; Kitzlerová, Eva; Hroudová, Jana; Raboch, Jiří

2013-01-01

Background Cortisol is presumed to be a risk factor for stress- and age-related disorders, such as depressive disorder and Alzheimer’s disease (AD). The aim of this study was to investigate the association of plasma cortisol concentration with AD in presence or absence of comorbid depressive symptoms. Material/Methods Plasma cortisol concentration was measured in 80 AD patients (35 of them with depressive symptoms), 27 elderly depressive patients without AD, and 37 elderly controls. Results Compared to controls, a significant increase of mean plasma cortisol was found in AD patients but not in depressive patients. Plasma cortisol was positively correlated with cognitive impairment in AD patients. We confirmed a U-shaped association between plasma cortisol and major depression and a linear association between plasma cortisol and AD without depressive symptoms. Significantly increased relative risk of disease in people with high plasma cortisol was found for AD with depressive symptoms and for AD with mild dementia. Conclusions Plasma cortisol reflects the degree of cognitive impairment in AD rather than the severity of comorbid depression. We confirmed that both hypercortisolemia and hypocortisolemia are associated with depressive disorder. Significant association between high plasma cortisol and AD was found, supporting the use of high plasma cortisol as a component of a panel of biochemical markers for AD with depressive symptoms as well as AD in the early stage of dementia development. PMID:23955525

Cortisol - urine

MedlinePlus

... page: //medlineplus.gov/ency/article/003703.htm Cortisol urine test To use the sharing features on this page, please enable JavaScript. The cortisol urine test measures the level of cortisol in the ...

Some blood chemistry values for the Rainbow Trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary; Chatterton, K.

1970-01-01

Normal distribution curves were graphically fitted to approximately 1400 clinical test values obtained from the plasma or kidney tissue of more than 200 yearling rainbow trout (Salmo gairdneri). Estimated normal ranges were ascorbate, 102–214 μg/g; blood urea nitrogen (BUN), 0.9–4.5 mg/100 ml; chloride, 84–132 mEq/liter; cholesterol, 161–365 mg/100 ml; cortisol, 1.5–18.5 μg/100 ml; glucose, 41–151 mg/100 ml; and total protein, 2–6 g/100 ml.

Spouses’ Cortisol Associations and Moderators: Testing Physiological Synchrony and Connectedness in Everyday Life

PubMed Central

Papp, Lauren M.; Pendry, Patricia; Simon, Clarissa D.; Adam, Emma K.

2012-01-01

In this study, associations were examined between cortisol levels of wives and husbands in 47 heterosexual married couples. Both partners’ salivary cortisol levels were measured at the same moments seven times a day on 2 typical weekdays. After accounting for the effects of the diurnal rhythm of cortisol and relevant control variables, dyadic hierarchical linear modeling indicated significant positive linkages between partners’ cortisol levels, consistent with the hypothesized within-couple physiological synchrony. Variables reflecting more (spousal presence) or less connectedness (loneliness, being alone) were also collected at the time of each cortisol sample. Results indicated that husbands’ cortisol levels were higher at moments they reported feeling lonelier and lower at moments they were in the presence of their spouse. Wives’ cortisol levels were higher at moments they were alone. In addition, wife-husband cortisol synchrony was stronger for husbands who spent relatively more time with their spouse across the study period—even after accounting for time spent with others in general. These findings suggest that marital partners evidence positive within-couple cortisol associations, and that connectedness (particularly physical closeness) may underpin spouses’ physiological synchrony. PMID:23763687

Children's diurnal cortisol responses to negative events at school and home.

PubMed

Bai, Sunhye; Robles, Theodore F; Reynolds, Bridget M; Repetti, Rena L

2017-09-01

This study examined the within-and between-person associations between daily negative events - peer problems, academic problems and interparental conflict - and diurnal cortisol in school-age children. Salivary cortisol levels were assessed four times per day (at wakeup, 30min later, just before dinner and at bedtime) on eight days in 47 youths ages 8-13 years old (60% female; M age=11.28, SD=1.50). The relative contributions of within- and between-person variances in each stressor were estimated in models predicting same-day diurnal cortisol slope, same-day bedtime cortisol, and next morning wakeup cortisol. Children who reported more peer problems on average showed flatter slopes of cortisol decline from wakeup to bedtime. However, children secreted more cortisol at wakeup following days when they had reported more peer or academic problems than usual. Interparental conflict was not significantly associated with diurnal cortisol. Findings from this study extend our understanding of short-term cortisol responses to naturally occurring problems in daily life, and help to differentiate these daily processes from the cumulative effects of chronic stress. Copyright © 2017. Published by Elsevier Ltd.

Positive upshots of cortisol in everyday life

PubMed Central

Hoyt, Lindsay T.; Zeiders, Katharine H.; Ehrlich, Katherine B.; Adam, Emma K.

2016-01-01

Cortisol, the major physiological end-product of the hypothalamic-pituitary-adrenal (HPA) axis, is usually associated with stress and negative affect. However, a new body of research highlights the complex, adaptive significance of elevated cortisol within individuals in everyday life. Whereas most studies do not have the power to test the dynamic transactions between cortisol and affect within a person throughout the entire waking day, we employed an intensive study protocol analyzing hourly diary reports of affect in relation to hourly salivary cortisol samples among 24 healthy adults from morning to bedtime, across two consecutive weekdays (n = 862 total samples). Utilizing multi-leveling modeling and focusing on within-person effects, we examined whether momentary increases in cortisol could be mood protective, or energy enhancing, in everyday life, supporting the cortisol boost hypothesis. Results revealed no significant associations between cortisol and current affective state; however, within-person increases in cortisol were significantly associated with subsequent rises in activeness, alertness, and relaxation, and trend-level reductions in stress and nervousness. This study adds to growing evidence that cortisol plays a positive role in regulating affect in everyday life. PMID:26950364

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome

PubMed Central

Torres-Harding, Susan; Sorenson, Matthew; Jason, Leonard; Maher, Kevin; Fletcher, Mary Ann; Reynolds, Nadia; Brown, Molly

2009-01-01

Hypocortisolism has been reported in chronic fatigue syndrome (CFS), with the significance of this finding to disease etiology unclear. This study examined cortisol levels and their relationships with symptoms in a group of 108 individuals with CFS. CFS symptoms examined included fatigue, pain, sleep difficulties, neurocognitive functioning, and psychiatric status. Alterations in cortisol levels were examined by calculation of mean daily cortisol, while temporal variation in cortisol function was examined by means of a regression slope. Additionally, deviation from expected cortisol diurnal pattern was determined via clinical judgment. Results indicated that fatigue and pain were associated with salivary cortisol levels. In particular, variance from the expected pattern of cortisol was associated with increased levels of fatigue. The implications of these findings are discussed. PMID:19701493

Development of salivary cortisol circadian rhythm in preterm infants.

PubMed

Ivars, Katrin; Nelson, Nina; Theodorsson, Annette; Theodorsson, Elvar; Ström, Jakob O; Mörelius, Evalotte

2017-01-01

To investigate at what age preterm infants develop a salivary cortisol circadian rhythm and identify whether it is dependent on gestational age and/or postnatal age. To evaluate whether salivary cortisol circadian rhythm development is related to behavioral regularity. To elucidate salivary cortisol levels in preterm infants during the first year of life. This prospective, longitudinal study included 51 preterm infants. 130 healthy full-term infants served as controls. Monthly salivary cortisol levels were obtained in the morning (07:30-09:30), at noon (10:00-12:00), and in the evening (19:30-21:30), beginning at gestational age week 28-32 and continuing until twelve months corrected age. Behavioral regularity was studied using the Baby Behavior Questionnaire. A salivary cortisol circadian rhythm was established by one month corrected age and persisted throughout the first year. The preterm infants showed a cortisol pattern increasingly more alike the full-term infants as the first year progressed. The preterm infants increase in behavioral regularity with age but no correlation was found between the development of salivary cortisol circadian rhythm and the development of behavior regularity. The time to establish salivary cortisol circadian rhythm differed between preterm and full-term infants according to postnatal age (p = 0.001) and was dependent on gestational age. Monthly salivary cortisol levels for preterm infants from birth until twelve months are presented. Additional findings were that topical corticosteroid medication was associated with higher concentrations of salivary cortisol (p = 0.02) and establishment of salivary cortisol circadian rhythm occurred later in infants treated with topical corticosteroid medication (p = 0.02). Salivary cortisol circadian rhythm is established by one month corrected age in preterm infants. Establishment of salivary cortisol circadian rhythm is related to gestational age rather than to postnatal age. Salivary cortisol circadian rhythm development is not related to behavioral regularity.

Associations between basal cortisol levels and memory retrieval in healthy young individuals.

PubMed

Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J F; Rasch, Björn

2013-11-01

Cortisol is known to affect memory processes. On the one hand, stress-induced or pharmacologically induced elevations of cortisol levels enhance memory consolidation. On the other hand, such experimentally induced elevations of cortisol levels have been shown to impair memory retrieval. However, the effects of individual differences in basal cortisol levels on memory processes remain largely unknown. Here we tested whether individual differences in cortisol levels predict picture learning and recall in a large sample. A total of 1225 healthy young women and men viewed two different sets of emotional and neutral pictures on two consecutive days. Both sets were recalled after a short delay (10 min). On Day 2, the pictures seen on Day 1 were additionally recalled, resulting in a long-delay (20 hr) recall condition. Cortisol levels were measured three times on Days 1 and 2 via saliva samples before encoding, between encoding and recall as well as after recall testing. We show that stronger decreases in cortisol levels during retrieval testing were associated with better recall performance of pictures, regardless of emotional valence of the pictures or length of the retention interval (i.e., 10 min vs. 20 hr). In contrast, average cortisol levels during retrieval were not related to picture recall. Remarkably during encoding, individual differences in average cortisol levels as well as changes in cortisol did not predict memory recall. Our results support previous findings indicating that higher cortisol levels during retrieval testing hinders recall of episodic memories and extend this view onto interindividual changes in basal cortisol levels.

The Cortisol Awakening Response and Cognition across the Adult Lifespan

PubMed Central

Ennis, Gilda E.; Moffat, Scott D.; Hertzog, Christopher

2016-01-01

Although the hippocampus is thought to play a central role in the regulation of the cortisol awakening response (CAR), results from past studies examining the relationship between the CAR and hippocampally-mediated memory and cognition have been mixed. Inconsistent findings may be due to the use of cortisol samples collected on only 1 to 2 days since reduced sampling can permit unstable situational factors to bias results. We used cortisol assessments from 10 consecutive days to test the relationship of the CAR to episodic memory, working memory, and processing speed in a sample of healthy young, middle-aged, and older adults (age range: 23 – 79 years; N = 56). We tested if the relationship between the CAR and cognition would depend upon age and also tested if other cortisol measures, specifically waking cortisol, diurnal cortisol output (i.e., area under the curve) and diurnal cortisol slope (linear and quadratic), would be related to cognition. We found that a more positive CAR slope was related to better episodic memory and that this relationship did not depend upon age. The CAR was not significantly related to working memory. The relationship of the CAR to processing speed was not significant when using a CAR measure that corrected for non-compliant cortisol sampling. We also found that higher waking cortisol was significantly related to better working memory, but not episodic memory or processing speed. Neither diurnal cortisol output nor diurnal linear cortisol slope was significantly related to cognitive functioning. Future work should investigate the mechanisms underpinning the relationship of the cortisol awakening process to cognitive functioning. PMID:27105036

Cortisol elevation post-hatch affects behavioural performance in zebrafish larvae.

PubMed

Best, Carol; Vijayan, Mathilakath M

2018-02-01

Maternal cortisol is essential for cortisol stress axis development and de novo production of this steroid commences only after hatch in zebrafish (Danio rerio). However, very little is known about the effect of elevated cortisol levels, during the critical period of stress axis activation, on larval performance. We tested the hypothesis that elevated cortisol levels post-hatch affect behavioural performance and this is mediated by glucocorticoid receptor (GR) activation in zebrafish larvae. The behavioural response included measuring larval activity in response to alternating light and dark cycles, as well as thigmotaxis. Zebrafish larvae at 3days post-fertilization were exposed to waterborne cortisol for 24h to mimic a steroid response to an early-life stressor exposure. Also, larvae were exposed to waterborne RU-486 (a GR antagonist) either in the presence or absence of cortisol to confirm GR activation. Co-treatment with RU-486 completely abolished the upregulation of cortisol-induced 11β-hydroxysteroid dehydrogenase type 2 transcript abundance, confirming GR signalling. Cortisol-exposed larvae displayed increased locomotor activity irrespective of light condition, but showed no changes in thigmotaxis. This cortisol-mediated behavioural response was not affected by co-treatment with RU-486. Cortisol exposure also did not modify the transcript abundances of GR and mineralocorticoid receptor (MR) in zebrafish larvae. Altogether, cortisol stress axis activation post-hatch increases locomotor activity in zebrafish larvae. Our results suggest that GR signalling may not be involved in this behavioural response, leading to the proposal that cortisol action via MR signalling may influence locomotor activity in zebrafish larvae. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol.

PubMed

Degand, Thibault; Monnet, Elisabeth; Durand, François; Grandclement, Emilie; Ichai, Philippe; Borot, Sophie; Qualls, Clifford R; Agin, Arnaud; Louvet, Alexandre; Dumortier, Jérôme; Francoz, Claire; Dumoulin, Gilles; Di Martino, Vincent; Dorin, Richard; Thevenot, Thierry

2015-09-01

Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol. Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis. 43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured. T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001). In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chronic stress, hair cortisol and depression: A prospective and longitudinal study of medical internship.

PubMed

Mayer, Stefanie E; Lopez-Duran, Nestor L; Sen, Srijan; Abelson, James L

2018-06-01

Stress plays a causal role in depression onset, perhaps via alteration of hypothalamic-pituitary-adrenal (HPA) axis functioning. HPA axis hyperactivity has been reported in depression, though inconsistently, and the nature of this relationship remains unclear, partly because cortisol measurement over time has been challenging. Development of hair cortisol assessment, a method that captures cortisol over prolonged periods of time, creates new possibilities. In this study, hair cortisol was incorporated into a prospective and longitudinal study of medical internship, stress and symptoms of depression. This provided a rare opportunity to 1) prospectively assess hair cortisol responses to stress, and 2) examine whether stress-induced changes in hair cortisol predict depressive symptom development. Hair cortisol, depressive symptoms, and stress-relevant variables (work hours, sleep, perceived stress, mastery/control) were assessed in interns (n = 74; age 25-33) before and repeatedly throughout medical internship. Hair cortisol sharply increased with stressor onset, decreased as internship continued, and rose again at year's end. Depressive symptoms rose significantly during internship, but were not predicted by cortisol levels. Hair cortisol also did not correlate with increased stressor demands (work hours, sleep) or stress perceptions (perceived stress, mastery/control); but these variables did predict depressive symptoms. Hair cortisol and depressive responses increased with stress, but they were decoupled, following distinct trajectories that likely reflected different aspects of stress reactivity. While depressive symptoms correlated with stressor demands and stress perceptions, the longitudinal pattern of hair cortisol suggested that it responded to contextual features related to anticipation, novelty/familiarity, and social evaluative threat. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of hair cortisol level in first-episodic and recurrent female patients with depression compared to healthy controls.

PubMed

Wei, Jinxue; Sun, Guizhi; Zhao, Liansheng; Yang, Xiao; Liu, Xiang; Lin, Dongtao; Li, Tao; Ma, Xiaohong

2015-04-01

Although accumulating evidence has shown increased cortisol levels in serum, saliva, or 24-h urine samples in depression, a number of studies did not find the association between cortisol levels and depression. Hair cortisol levels reflect long-term and historical information of cortisol and hair cortisol analysis has been applied in the research of psychiatric diseases. The aim of this study is to compare the hair cortisol levels between patients with depression and healthy controls. Hair cortisol levels of 22 first-episodic and 13 recurrent female patients with depression and 30 healthy controls were measured and compared using the electrochemiluminescence immunoassay. The relationship between hair cortisol levels and Hamilton depression scale (HAMD) or Hamilton anxiety scale (HAMA) scores were also examined. Before disease episode, no significant differences were observed among healthy controls, first-episodic patients and recurrent patients. In disease episode, the hair cortisol level in first-episodic patients was significantly higher than that in healthy controls or recurrent patients, while no significant difference was observed between recurrent patients and healthy controls. No significant correlation was found between HAMD or HAMA scores and hair cortisol levels in patients. First, long-term effects of antidepressants on the results cannot be excluded without detailed medication information of the recurrent patients. Second, sample sizes might be relatively small. Our results indicate that hair cortisol levels increased in disease episode in first-episodic, but not recurrent patients with depression, which may suggest that episodes of disease have influence on cortisol levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Cortisol awakening response and subsequent depression: prospective longitudinal study.

PubMed

Carnegie, Rebecca; Araya, Ricardo; Ben-Shlomo, Yoav; Glover, Vivette; O'Connor, Thomas G; O'Donnell, Kieran J; Pearson, Rebecca; Lewis, Glyn

2014-02-01

Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic-pituitary-adrenal function and potentially of stress reactivity. To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort. Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years. We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93-1.66, P = 0.14) before and 1.12 (95% CI 0.73-1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression. Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.

Cortisol in human milk predicts child BMI.

PubMed

Hahn-Holbrook, Jennifer; Le, Tran Bao; Chung, Anna; Davis, Elysia Poggi; Glynn, Laura M

2016-12-01

Breastfeeding has been linked to lower rates of childhood obesity. Human milk contains cortisol, known to regulate glucose storage and metabolism. The aim of this study was to to test the hypothesis that early exposure to cortisol in human breast milk helps to modulate infant body mass index (BMI) trajectories over the first 2 years of life. Growth curve modeling was used to examine whether infant exposure to cortisol in human milk at 3 months predicted changes in child body mass index percentile (BMIP) at 6, 12, and 24 months of age in 51 breastfeeding mother-child pairs. Infants exposed to higher milk cortisol levels at 3 months were less likely to exhibit BMIP gains over the first 2 years of life, compared with infants exposed to lower milk cortisol. By age 2, infants exposed to higher milk cortisol levels had lower BMIPs than infants exposed to lower milk cortisol. Milk cortisol was a stronger predictor of BMIP change in girls than boys. Cortisol exposure through human milk may help to program metabolic functioning and childhood obesity risk. Further, because infant formula contains only trace amounts of glucocorticoids, these findings suggest that cortisol in milk is a novel biological pathway through which breastfeeding may protect against later obesity. © 2016 The Obesity Society.

Impact of stressors in a natural context on release of cortisol in healthy adult humans: a meta-analysis.

PubMed

Michaud, Kathy; Matheson, Kimberly; Kelly, Owen; Anisman, Hymie

2008-05-01

Increased hypothalamic-pituitary-adrenal (HPA) activation, culminating in elevated circulating cortisol levels is a fundamental response to stressors. In animals, this neuroendocrine change is highly reliable and marked (approximately 5-10-fold elevations), whereas in humans, the increase of cortisol release is less pronounced, and even some potent life-threatening events (anticipation of surgery) only elicit modest cortisol increases. Meta-analysis of factors that influenced the increase of cortisol release in a laboratory context pointed to the importance of social evaluative threats and stressor controllability in accounting for the cortisol rise. The present meta-analysis, covering the period from 1978 through March 2007, was undertaken to identify the factors most closely aligned with cortisol increases in natural settings. It appeared that stressor chronicity was fundamental in predicting cortisol changes; however, this variable is often confounded by the stressor type, the stressor's controllability, as well as contextual factors, making it difficult to disentangle their relative contributions to the cortisol response. Moreover, several experiential factors (e.g. previous stressor experiences) may influence the cortisol response to ongoing stressors, but these are not readily deduced through a meta-analysis. Nevertheless, there are ample data suggesting that stressful events, through their actions on cortisol levels and reactivity, may influence psychological and physical pathology.

Antecedent longitudinal changes in body mass index are associated with diurnal cortisol curve features: The multi-ethnic study of atherosclerosis.

PubMed

Joseph, Joshua J; Wang, Xu; Diez Roux, Ana V; Sanchez, Brisa N; Seeman, Teresa E; Needham, Belinda L; Golden, Sherita Hill

2017-03-01

Prior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features. To examine the association of (1) prior annual BMI percent change over 7years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6years and (3) the association of change in cortisol features with change in BMI over 6years. Longitudinal study. Multi-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012). 1685 ethnically diverse men and women attended either MESA Stress exam (mean age 65±10years at MESA Stress I; mean age 69±9years at MESA Stress II). Log-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30min to 2h post-awakening), late decline slope (2h post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol. Over 7years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: -5.0%, -0.8%) and 3.0% (95% CI: -4.7%, -1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI≥30kg/m 2 , flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: -1%, 26.8%) in BMI, respectively). We found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Antecedent Longitudinal Changes in Body Mass Index are associated with Diurnal Cortisol Curve Features: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Joseph, Joshua J.; Wang, Xu; Roux, Ana V. Diez; Sanchez, Brisa N.; Seeman, Teresa E.; Needham, Belinda L.; Golden, Sherita Hill

2016-01-01

Context Prior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features. Objective To examine the association of (1) prior annual BMI percent change over 7 years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6 years and (3) the association of change in cortisol features with change in BMI over 6 years. Design Longitudinal study Setting Multi-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004-2006 & 2010-2012) Participants 1,685 ethnically diverse men and women attended either MESA Stress exam (mean age 65 ± 10 years at MESA Stress I; mean age 69 ± 9 years at MESA Stress II). Outcome Measures Log-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30 minutes to 2 hours post-awakening), late decline slope (2 hours post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol. Results Over 7 years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: −5.0%, −0.8%) and 3.0% (95% CI: −4.7%, −1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI ≥ 30 kg/m2, flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: −1%, 26.8%) in BMI, respectively). Conclusions We found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile. PMID:28183457

Reversible increase in maximal cortisol secretion rate in septic shock.

PubMed

Dorin, Richard I; Qualls, Clifford R; Torpy, David J; Schrader, Ronald M; Urban, Frank K

2015-03-01

Cortisol clearance is reduced in sepsis and may contribute to the development of impaired adrenocortical function that is thought to contribute to the pathophysiology of critical illness-related corticosteroid insufficiency. We sought to assess adrenocortical function using computer-assisted numerical modeling methodology to characterize and compare maximal cortisol secretion rate and free cortisol half-life in septic shock, sepsis, and healthy control subjects. Post hoc analysis of previously published total cortisol, free cortisol, corticosteroid-binding globulin, and albumin concentration data. Single academic medical center. Subjects included septic shock (n = 45), sepsis (n = 25), and healthy controls (n = 10). I.v. cosyntropin (250 μg). Solutions for maximal cortisol secretion rate and free cortisol half-life were obtained by least squares solution of simultaneous, nonlinear differential equations that account for free cortisol appearance and elimination as well as reversible binding to corticosteroid-binding globulin and albumin. Maximal cortisol secretion rate was significantly greater in septic shock (0.83 nM/s [0.44, 1.58 nM/s] reported as median [lower quartile, upper quartile]) compared with sepsis (0.51 nM/s [0.36, 0.62 nM/s]; p = 0.007) and controls (0.49 nM/s [0.42, 0.62 nM/s]; p = 0.04). The variance of maximal cortisol secretion rate in septic shock was also greater than that of sepsis or control groups (F test, p < 0.001). Free cortisol half-life was significantly increased in septic shock (4.6 min [2.2, 6.3 min]) and sepsis (3.0 min [2.3, 4.8 min] when compared with controls (2.0 min [1.2, 2.6 min]) (both p < 0.004). Results obtained by numerical modeling are consistent with comparable measures obtained by the gold standard stable isotope dilution method. Septic shock is associated with generally not only higher levels but also greater variance of maximal cortisol secretion rate when compared with control and sepsis groups. Additional studies would be needed to determine whether assessment of cortisol kinetic parameters such as maximal cortisol secretion rate and free cortisol half-life is useful in the diagnosis or management of critical illness-related corticosteroid insufficiency.

Association of the Period3 clock gene length polymorphism with salivary cortisol secretion among police officers

PubMed Central

Wirth, Michael; Burch, James; Violanti, John; Burchfiel, Cecil; Fekedulegn, Desta; Andrew, Michael; Zhang, Hongmei; Miller, Diane B.; Youngstedt, Shawn D.; Hébert, James R.; Vena, John E.

2013-01-01

OBJECTIVE This study evaluated whether measures of waking or diurnal cortisol secretion, or self-reported psychological disturbances differed among police officers with a Period3 (PER3) clock gene length polymorphism. METHODS The cortisol awakening response was characterized via the area under the salivary cortisol curve with respect to the increase (AUCI) or total waking cortisol (AUCG). Diurnal cortisol measures included the slope of diurnal cortisol and the diurnal AUCG. Psychological disturbances were characterized using the Center for Epidemiologic Studies Depression Scale, Impact of Events Scale, and Life Events Scale. RESULTS Officers with a 4/5 or 5/5 genotype had higher awakening AUCG and greater diurnal cortisol AUCG levels compared to officers with the 4/4 genotype. Among those working more afternoon or night shifts, waking AUCI and AUCG were greater among officers with a 4/5 or 5/5 genotype compared to the 4/4 referents. CONCLUSION Cortisol secretion was modified among police officers with different PER3 VNTR clock gene variants. PMID:23524621

Cortisol acutely reduces selective attention for erotic words in healthy young men.

PubMed

Putman, Peter; Berling, Sylvia

2011-10-01

Psychological stress prompts activity of the hypothalamic-pituitary-adrenal (HPA) axis resulting in increased release of cortisol. Long-term HPA aberrations have been observed for stress-related affective disorders but research into acute effects of cortisol on affect-regulation has only recently begun. Previous studies reported that exogenous cortisol acutely attenuated automatic attentional processing of task-irrelevant threatening information. This has been taken to suggest that cortisol may have acute anxiolytic properties, possibly through facilitating inhibition of threatening information. However, the role of cortisol in attentional inhibition of non-threatening arousing stimuli remained unclear. Therefore acute effects of 40 mg cortisol on performance of a masked and unmasked emotional Stroop task (EST) were assessed. Results for only the unmasked task demonstrated EST interference (interpreted as increased automatic attention) for erotic stimuli which was abolished by cortisol administration. This implies that effects of cortisol may not be restricted to attenuation of specifically anxiogenic information processing, as previously suggested. Copyright © 2011 Elsevier Ltd. All rights reserved.

Depression history as a moderator of relations between cortisol and shame responses to social-evaluative threat in young adults.

PubMed

Hellman, Natalie; Morris, Matthew C; Rao, Uma; Garber, Judy

2015-07-01

Changes in cortisol and shame are commonly elicited by psychosocial stressors involving social-evaluative threat. According to social self preservation theory, this coordinated psychobiological response is adaptive. Individuals with a history of depression, however, may exhibit diminished cortisol reactivity to acute stressors, which could interfere with coordinated cortisol and shame responses. The present study examined temporal relations between cortisol and shame responses to a psychosocial stress task in young adults who varied in their history of depression (56 remitted-depressed, 46 never-depressed). Lagged effects multilevel models revealed that depression history moderated relations between cortisol levels and shame ratings 25-55min later. The pattern of these interactions was similar: whereas higher cortisol levels predicted increases in shame in never-depressed individuals, cortisol levels were unrelated to shame responses in remitted-depressed individuals. Findings suggest a dissociation between cortisol and shame responses to stress in individuals with a history of depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of endurance exercise on levodopa-associated cortisol release and force increase in patients with Parkinson's disease.

PubMed

Müller, Thomas; Muhlack, Siegfried

2008-06-01

Levodopa (LD) application improves motor symptoms and reduces cortisol levels in patients with Parkinson's disease (PD). Endurance exercise enhances cortisol release in proportion to the intensity of the effort and thus may counteract the LD associated cortisol decrease. We measured levels of cortisol and LD over an 1-h long interval following administration of soluble 200 mg LD/50 mg benserazide with concomitant maximal grip strength assessment in 16 PD patients under cued conditions during rest and endurance exercise. The motor response, the plasma levels of cortisol and LD did not significantly differ between both conditions. Cortisol concentrations significantly decreased even during exercise. Grip strength only significantly went up during rest. Endurance exercise did not counteract the LD associated decreased cortisol release. Since cortisol improves muscle function, the lack of increase in maximal grip strength following LD administration during exercise may contribute to reduced exercise capacity, which is reported by PD patients.

Prolonged secretion of cortisol as a possible mechanism underlying stress and depressive behaviour

PubMed Central

Qin, Dong-dong; Rizak, Joshua; Feng, Xiao-li; Yang, Shang-chuan; Lü, Long-bao; Pan, Lei; Yin, Yong; Hu, Xin-tian

2016-01-01

Stress is associated with the onset of depressive episodes, and cortisol hypersecretion is considered a biological risk factor of depression. However, the possible mechanisms underlying stress, cortisol and depressive behaviours are inconsistent in the literature. This study examined the interrelationships among stress, cortisol and observed depressive behaviours in female rhesus macaques for the first time and explored the possible mechanism underlying stress and depressive behaviour. Female monkeys were video-recorded, and the frequencies of life events and the duration of huddling were analysed to measure stress and depressive behaviour. Hair samples were used to measure chronic cortisol levels, and the interactions between stress and cortisol in the development of depressive behaviour were further evaluated. Significant correlations were found between stress and depressive behaviour measures and between cortisol levels and depressive behaviour. Stress was positively correlated with cortisol levels, and these two factors interacted with each other to predict the monkeys’ depressive behaviours. This finding extends the current understanding of stress/cortisol interactions in depression, especially pertaining to females. PMID:27443987

Medium Access Control for Opportunistic Concurrent Transmissions under Shadowing Channels

PubMed Central

Son, In Keun; Mao, Shiwen; Hur, Seung Min

2009-01-01

We study the problem of how to alleviate the exposed terminal effect in multi-hop wireless networks in the presence of log-normal shadowing channels. Assuming node location information, we propose an extension of the IEEE 802.11 MAC protocol that sched-ules concurrent transmissions in the presence of log-normal shadowing, thus mitigating the exposed terminal problem and improving network throughput and delay performance. We observe considerable improvements in throughput and delay achieved over the IEEE 802.11 MAC under various network topologies and channel conditions in ns-2 simulations, which justify the importance of considering channel randomness in MAC protocol design for multi-hop wireless networks. PMID:22408556

Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

PubMed

Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

2013-04-29

Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes demonstrate that symptoms of MDD were reduced following effective treatment with an SSRI, and further, stress physiology was unlikely to be a key factor in this outcome. Further research is required to discriminate potential differences in underlying stress physiology for individuals with MDD who respond to antidepressant treatment, relative to those who experience treatment resistance.

Increasing correlations between personality traits and cortisol stress responses obtained by data aggregation.

PubMed

Pruessner, J C; Gaab, J; Hellhammer, D H; Lintz, D; Schommer, N; Kirschbaum, C

1997-11-01

Attempts to link personality traits and cortisol stress responses have often been inconclusive. The aim of this paper was to investigate this association by aggregating cortisol stress responses. Therefore, 20 healthy men were exposed to a task consisting of public speaking and mental arithmetics in front of an audience on five days. Six cortisol levels were measured in relation to the stressful task obtained at 10-min intervals on each day. Psychological assessment included the Questionnaire for Competence and Control (FKK) and the Giessen-Test (G-T). These questionnaires focus on assessing personality traits, i.e. locus of control and self-concept. Areas under the response curve (AUC) of the six cortisol samples were computed to obtain an index of the individual's cortisol stress response on each day. Since novelty is a random situational factor likely to mask individual differences in the stress response, the AUC cortisol stress responses of days two to five were consecutively aggregated, excluding the first day. Scales of the two questionnaires employed did not correlate with the AUC cortisol stress response of the first stress trial. The correlation pattern of the AUC cortisol measures of days two to five with the questionnaire scales was inconclusive. However, significant correlations emerged with an increasing number of cortisol stress responses aggregated. Correlations between the measure of social dominance and aggregated AUC cortisol stress responses rose from r = -.47 on day two of the experimental session to r = -.70 after aggregating days two to five. Similarly, measures of locus of control and cortisol stress responses became increasingly correlated with aggregation of several stress exposures. These data provide preliminary evidence for a relationship between questionnaire scales aiming at assessing personality traits and cortisol stress responses uncovered by repeated stress exposure and data aggregation. While novelty may mask the impact of personality on the cortisol stress response on the first exposure, differences in the ability to cope with the stressful situation may lead to different cortisol stress response patterns on subsequent stress exposures. With data aggregation, an association between the trait component of cortisol stress responses and questionnaire scales might be uncovered. For reliable investigation of correlations between personality variables and cortisol stress responses, repeated stress exposure and data aggregation is suggested.

Cortisol Test: MedlinePlus Lab Test Information

MedlinePlus

... page: https://medlineplus.gov/labtests/cortisoltest.html Cortisol Test To use the sharing features on this page, please enable JavaScript. What is a Cortisol Test? Cortisol is a hormone that affects almost every ...

CORTISOL CORRELATES WITH SEVERITY OF ILLNESS AND POORLY REFLECTS ADRENAL FUNCTION IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME

PubMed Central

Yehya, Nadir; Vogiatzi, Maria G.; Thomas, Neal J.; Srinivasan, Vijay

2016-01-01

Objective To test the association between random cortisol and severity of illness in a “real-world” application of current guidelines. Study design We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels prior to potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 μg/dL and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Results Of 357 children with ARDS, 155 (15 non-survivors, 10%) had vasopressors initiated with cortisol drawn prior to possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum p < 0.05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. Conclusions In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. PMID:27283464

Time-dependent effects of cortisol on the contextualization of emotional memories.

PubMed

van Ast, Vanessa A; Cornelisse, Sandra; Meeter, Martijn; Joëls, Marian; Kindt, Merel

2013-12-01

The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress hormone cortisol, acting via receptors located in the memory neurocircuitry. Cortisol via these receptors induces rapid nongenomic effects followed by slower genomic effects, which are thought to modulate cognitive function in opposite, complementary ways. Here, we targeted these time-dependent effects of cortisol during memory encoding and tested subsequent contextualization of emotional and neutral memories. In a double-blind, placebo-controlled design, 64 men were randomly assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes (rapid cortisol effects) before a memory encoding task; 2) received 10 mg hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3) received placebo at both times. During encoding, participants were presented with neutral and emotional words in unique background pictures. Approximately 24 hours later, context dependency of their memories was assessed. Recognition data revealed that cortisol's rapid effects impair emotional memory contextualization, while cortisol's slow effects enhance it. Neutral memory contextualization remained unaltered by cortisol, irrespective of the timing of the drug. This study shows distinct time-dependent effects of cortisol on the contextualization of specifically emotional memories. The results suggest that rapid effects of cortisol may lead to impaired emotional memory contextualization, while slow effects of cortisol may confer protection against emotional memory generalization. © 2013 Society of Biological Psychiatry.

Cortisol Correlates with Severity of Illness and Poorly Reflects Adrenal Function in Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Vogiatzi, Maria G; Thomas, Neal J; Srinivasan, Vijay

2016-10-01

To test the association between random cortisol and severity of illness in a "real-world" application of current guidelines. We performed a secondary analysis of a prospective observational cohort of acute respiratory distress syndrome (ARDS). Children with ARDS and vasopressor-dependent shock were identified and random cortisol levels before potential hydrocortisone initiation recorded. The cohort was dichotomized to cortisol < 18 and ≥ 18 μg/dL, and hydrocortisone use and outcomes compared. Of 357 children with ARDS, 155 (15 nonsurvivors; 10%) had vasopressors initiated with cortisol drawn before possible hydrocortisone use. Patients with cortisol < 18 μg/dL had lower severity of illness scores, fewer organ failures, and lower vasopressor scores (all rank-sum P < .05). No benefit was seen with hydrocortisone in either the entire cohort, or when dichotomized by a cortisol cutoff of 18 μg/dL. In patients with cortisol ≥ 18 μg/dL, hydrocortisone was associated with increased mortality after adjustment for either organ dysfunction or vasopressor score. In children with ARDS with vasopressor-dependent shock, low cortisol correlated with lower severity of illness. Random cortisol was a poor method of diagnosing adrenal insufficiency, and a strategy of hydrocortisone replacement for cortisol < 18 μg/dL did not target a population likely to benefit from hydrocortisone. Future guidelines should reconsider using random cortisol levels alone for assessing adrenal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Cortisol Induces Reactive Oxygen Species Through a Membrane Glucocorticoid Receptor in Rainbow Trout Myotubes.

PubMed

Espinoza, Marlen B; Aedo, Jorge E; Zuloaga, Rodrigo; Valenzuela, Cristian; Molina, Alfredo; Valdés, Juan A

2017-04-01

Cortisol is an essential regulator of neuroendocrine stress responses in teleosts. Cortisol predominantly affects target tissues through the genomic pathway, which involves interacting with cytoplasmic glucocorticoid receptors, and thereby, modulating stress-response gene expressions. Cortisol also produces rapid effects via non-genomic pathways, which do not involve gene transcription. Although cortisol-mediated genomic pathways are well documented in teleosts, non-genomic pathways are not fully understood. Moreover, no studies have focused on the contribution of non-genomic cortisol pathways in compensatory stress responses in fish. In this study, rainbow trout (Oncorhynchus mykiss) skeletal myotubes were stimulated with physiological concentrations of cortisol and cortisol-BSA, a membrane-impermeable agent, resulting in an early induction of reactive oxygen species (ROS). This production was not suppressed by transcription or translation inhibitors, suggesting non-genomic pathway involvement. Moreover, myotube preincubation with RU486 and NAC completely suppressed cortisol- and cortisol-BSA-induced ROS production. Subcellular fractionation analysis revealed the presence of cell membrane glucocorticoid receptors. Finally, cortisol-BSA induced a significant increase in ERK1/2 and CREB phosphorylation, as well as in CREB-dependent transcriptional activation of the pgc1a gene expression. The obtained results strongly suggest that cortisol acts through a non-genomic glucocorticoid receptor-mediated pathway to induce ROS production and contribute to ERK/CREB/PGC1-α signaling pathway activation as stress compensation mechanisms. J. Cell. Biochem. 118: 718-725, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Day-to-day dynamics of experience–cortisol associations in a population-based sample of older adults

PubMed Central

Adam, Emma K.; Hawkley, Louise C.; Kudielka, Brigitte M.; Cacioppo, John T.

2006-01-01

In 156 older adults, day-to-day variations in cortisol diurnal rhythms were predicted from both prior-day and same-day experiences, to examine the temporal ordering of experience–cortisol associations in naturalistic environments. Diary reports of daily psychosocial, emotional, and physical states were completed at bedtime on each of three consecutive days. Salivary cortisol levels were measured at wakeup, 30 min after awakening, and at bedtime each day. Multilevel growth curve modeling was used to estimate diurnal cortisol profiles for each person each day. The parameters defining those profiles (wakeup level, diurnal slope, and cortisol awakening response) were predicted simultaneously from day-before and same-day experiences. Prior-day feelings of loneliness, sadness, threat, and lack of control were associated with a higher cortisol awakening response the next day, but morning awakening responses did not predict experiences of these states later the same day. Same-day, but not prior-day, feelings of tension and anger were associated with flatter diurnal cortisol rhythms, primarily because of their association with higher same-day evening cortisol levels. Although wakeup cortisol levels were not predicted by prior-day levels of fatigue and physical symptoms, low wakeup cortisol predicted higher levels of fatigue and physical symptoms later that day. Results are consistent with a dynamic and transactional function of cortisol as both a transducer of psychosocial and emotional experience into physiological activation and an influence on feelings of energy and physical well-being. PMID:17075058

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome.

PubMed

Pazderska, A; Crowther, S; Govender, P; Conlon, K C; Sherlock, M; Gibney, J

2016-01-01

Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing's syndrome.

Hormonal treatment reduces psychobiological distress in gender identity disorder, independently of the attachment style.

PubMed

Colizzi, Marco; Costa, Rosalia; Pace, Valeria; Todarello, Orlando

2013-12-01

Gender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic-pituitary-adrenal system dysregulation and subjective stress. The objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. We used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self-reported perceived stress and the Adult Attachment Interview to determine attachment styles. At enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P < 0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P < 0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P < 0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be. © 2013 International Society for Sexual Medicine.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

PubMed

Leu-Semenescu, Smaranda; Arnulf, Isabelle; Decaix, Caroline; Moussa, Fathi; Clot, Fabienne; Boniol, Camille; Touitou, Yvan; Levy, Richard; Vidailhet, Marie; Roze, Emmanuel

2010-03-01

A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

Diurnal cortisol and mental well-being in middle and older age: evidence from four cohort studies

PubMed Central

Stafford, Mai; Ben-Shlomo, Yoav; Cooper, Cyrus; Gale, Catharine; Gardner, Michael P; Geoffroy, Marie-Claude; Power, Chris; Kuh, Diana; Cooper, Rachel

2017-01-01

Objectives We conducted an individual participant meta-analysis to test the hypothesis that cortisol patterns indicative of dysregulated hypothalamic–pituitary–adrenal axis functioning would be prospectively associated with poorer well-being at follow-up. Setting Four large UK-based cohort studies. Participants Those providing valid salivary or serum cortisol samples (n=7515 for morning cortisol; n=1612 for cortisol awakening response) at baseline (age 44–82) and well-being data on the Warwick Edinburgh Mental Wellbeing Scale at follow-up (0–8 years) were included. Results Well-being was not associated with morning cortisol, diurnal slope or awakening response though a borderline association with evening cortisol was found. Adjusting for sex and follow-up time, each 1 SD increase in evening cortisol was associated with a −0.47 (95% CI −1.00 to 0.05) point lower well-being. This was attenuated by adjustment for body mass index, smoking and socioeconomic position. Between-study heterogeneity was low. Conclusions This study does not support the hypothesis that diurnal cortisol is prospectively associated with well-being up to 8 years later. However, replication in prospective studies with cortisol samples over multiple days is required. PMID:29025828

Hair cortisol detection in dairy cattle by using EIA: protocol validation and correlation with faecal cortisol metabolites.

PubMed

Tallo-Parra, O; Manteca, X; Sabes-Alsina, M; Carbajal, A; Lopez-Bejar, M

2015-06-01

Hair may be a useful matrix to detect cumulative cortisol concentrations in studies of animal welfare and chronic stress. The aim of this study was to validate a protocol for cortisol detection in hair from dairy cattle by enzyme immunoassay (EIA). Seventeen adult Holstein-Friesian dairy cows were used during the milking period. Hair cortisol concentration was assessed in 25-day-old hair samples taken from the frontal region of the head, analysing black and white coloured hair separately. Concentrations of cortisol metabolites were determined in faeces collected twice a week during the same period of time. There was a high correlation between cortisol values in faeces and cortisol in white colour hair samples but such correlation was not significant with the black colour hair samples. The intra- and inter-assay coefficients of variation were 4.9% and 10.6%, respectively. The linearity showed R 2=0.98 and mean percentage error of -10.8 ± 1.55%. The extraction efficiency was 89.0 ± 23.52% and the parallelism test showed similar slopes. Cortisol detection in hair by using EIA seems to be a valid method to represent long-term circulating cortisol levels in dairy cattle.

Endogenous Cortisol Exposure and Declarative Verbal Memory: A Longitudinal Study of Healthy Older Adults.

PubMed

Segerstrom, Suzanne C; Geiger, Paul J; Boggero, Ian A; Schmitt, Fredrick A; Sephton, Sandra E

2016-01-01

Exposure to endogenous cortisol is associated with hippocampal degeneration and may contribute to problems with declarative memory, but effects of persistent versus phasic cortisol elevations have not been established. The present longitudinal investigation examined persistent individual differences and phasic changes in cortisol as they related to verbal memory, executive functions, and subjective cognitive function. Older adults (n = 132, aged 60-93 years) were followed up for up to 5 years. They were assessed annually for verbal memory and every 6 months for executive functions, subjective cognitive function, and cortisol area under the curve (averaged over 3 days). In multilevel models, persistently but not phasically higher cortisol was associated with worse verbal memory in both learning (t(181) = 2.99, p = .003) and recall (t(280) = 3.10, p = .002). This effect withstood adjustment for stress, depression, metabolic health, and age. There was evidence for attenuated primacy in learning with higher persistent cortisol. Phasic increases in cortisol were not associated with changes in memory, and cortisol was not related to executive functions or subjective cognitive function. Higher secretion of cortisol may, over time, contribute to memory dysfunction in older adults.

Shift work parameters and disruption of diurnal cortisol production in female hospital employees.

PubMed

Hung, Eleanor Wai Man; Aronson, Kristan J; Leung, Michael; Day, Andrew; Tranmer, Joan

2016-01-01

Shift work is associated with an increased risk of cardiovascular diseases (CVD). Disruption of cortisol production is a potential underlying mechanism. This study explored the associations of diurnal quantity and pattern of cortisol production in relation to (1) current shift work status (exclusive day versus rotating days and nights), (2) years of past shift work and (3) parameters of rotating shift work (timing, length and intensity). Female hospital employees (160 day workers and 168 rotating shift workers) from southeastern Ontario, Canada, participated in a cross-sectional study. Participants completed a baseline questionnaire and measures of body height, weight, and waist circumference were taken. Midstream urine samples were collected over two separate 24-hour periods to measure creatinine-adjusted cortisol. Total diurnal cortisol production and pattern were described with two measures of the area under the curve. The effect of shift work on cortisol was modeled using multivariable linear regression analyses. Cortisol production in day workers and shift workers on their day shift were similar; however, shift workers on the night shift had flatter diurnal cortisol curves and produced less cortisol. This suggests that night work is associated with an acute attenuation of cortisol production.

Overall cortisol, diurnal slope, and stress reactivity in psychosis: An experience sampling approach.

PubMed

Vaessen, Thomas; Kasanova, Zuzana; Hernaus, Dennis; Lataster, Johan; Collip, Dina; van Nierop, Martine; Myin-Germeys, Inez

2018-06-07

Results from experimental studies suggest that psychosis and psychosis liability are associated with increased cortisol levels and blunted cortisol reactivity, and that use of antipsychotics may reduce these aberrations. Here, we report on overall cortisol, diurnal slope, and cortisol stress reactivity in everyday life in psychosis and psychosis liability using the experience sampling method (ESM). Our sample consisted of individuals diagnosed with psychotic disorder currently on (MPD; n = 53) or off antipsychotic medication (NMPD; n = 20), first-degree relatives of psychotic patients (REL; n = 47), and healthy volunteers (HV; n = 67). Saliva samples were collected throughout the day on six consecutive days and analyzed for cortisol levels. Simultaneously, stressfulness of the current activity was assessed with ESM questionnaires. We found no group differences in overall cortisol level between groups, but REL had a steeper diurnal slope than HV; in MPD a trend was found in the same direction. Regarding reactivity to stressful activities, results indicated attenuation of the cortisol response in both patient groups compared to HV. These results do not confirm reports of increased cortisol levels in psychosis, but provide evidence of stress-related cortisol alterations in everyday life. Copyright © 2018 Elsevier Ltd. All rights reserved.

Temperature-responsive release of cortisol from its binding globulin: a protein thermocouple.

PubMed

Cameron, Angus; Henley, David; Carrell, Robin; Zhou, Aiwu; Clarke, Anthony; Lightman, Stafford

2010-10-01

Only 5% of circulating cortisol is active and unbound to carrier proteins. Because cortisol levels vary rapidly due to the pulsatile nature of cortisol secretion, the dynamics of cortisol binding are critical determinants of tissue levels of free cortisol and consequent hormonal signaling. The major glucocorticoid carrier protein is corticosteroid binding globulin (CBG), a member of the serpin family that undergoes conformational changes to bind and release hormones. This mechanism has been noted to be temperature responsive, and we have now investigated the effects of temperature on the binding of human CBG to both cortisol and progesterone. Recombinant human CBG was synthesized and used for binding studies with cortisol and progesterone between 34 and 43 C. Binding was monitored by recording the change in intrinsic protein fluorescence. Binding of the steroids to the other major carrier, serum albumin, was measured in a similar manner. There was no effect of temperature on the interaction between human serum albumin and either cortisol or progesterone. The association of both cortisol and progesterone with CBG is more than three orders of magnitude greater than that with HSA, and this interaction was extremely responsive to changes in temperature. The affinity of both cortisol and progesterone for CBG drops approximately 16-fold as temperature increases from 35 to 42 C. This study clearly shows that even within the clinically relevant range of temperatures found in humans, CBG acts as a protein thermocouple that is exquisitely sensitive to temperature change and will release cortisol in response to fever or external sources of heat. This has major implications for our understanding of cortisol regulation in febrile patients.

Marital status as a predictor of diurnal salivary cortisol levels and slopes in a community sample of healthy adults

PubMed Central

Chin, Brian; Murphy, Michael L. M.; Janicki-Deverts, Denise; Cohen, Sheldon

2017-01-01

Married people tend to be healthier than both the previously (bereaved, divorced, and separated) and never married, but the mechanisms through which this occurs remain unclear. To this end, research has increasingly focused on how psychological stress experienced by unmarried versus married individuals may differentially impact physiological systems related to health. One key system that is modulated by stress is the hypothalamic-pituitary-adrenal (HPA) axis, of which cortisol is a key hormonal product. Increased cortisol production and disruption of cortisol’s daily rhythm have been linked to poorer health outcomes. This study examined the association between current marital status and these two indices of cortisol in a community sample of 572 healthy men and women aged 21–55. It also tested whether marriage buffers against the effect of stress (perceived stress by marital status interaction) on cortisol production. Participants provided salivary cortisol samples during waking hours on three nonconsecutive separate days to calculate diurnal cortisol levels and slopes. Married individuals had lower cortisol levels than either their never married or previously married counterparts. Differences in cortisol levels were due at least in part to currently married individuals having a more rapid decline in cortisol through the afternoon hours compared to individuals who were never married (but not those who were previously married). Furthermore, there was an interaction between perceived stress and marital status in predicting cortisol levels. Specifically, higher stress was associated with higher cortisol levels for previously married individuals but not for the married or never married. The results of this study support cortisol as one candidate mechanism accounting for the association of marital status and health. PMID:28171850

Salivary cortisol day curves in Addison's disease in patients on hydrocortisone replacement.

PubMed

Ross, I L; Levitt, N S; Van der Walt, J S; Schatz, D A; Johannsson, G; Haarburger, D H; Pillay, T S

2013-01-01

Using salivary cortisol (SC) measurements, cortisol exposure in Addison's disease patients on hydrocortisone replacement was determined and compared with healthy controls. Cortisol pharmacokinetics was assessed in 31 patients with Addison's disease on replacement hydrocortisone doses (median daily dose 20 mg; range 5-50 mg) and 30 healthy control subjects. Saliva samples (n=16) were collected between 08:00 and 00:00 h in 1 day, using a passive drool technique. Cortisol exposure was evaluated by noncompartmental approach. In the patients, cortisol exposure was significantly higher than in controls: median inter-quartile range (IQR) peak cortisol (C(max)) 174.5 (59.3-837.0) vs. 6.50 (4.7-19.3) nmol/l, p=0.0001; area under the curve (AUC) 390.1 (177.1-928.9) vs. 21.4 (14.6-28.4) minutes*nmol/l, p=0.0001, trough cortisol level (C(min)) 0.49 (0.49-0.96) vs. 0.49 (0.49-0.49) nmol/l, p=0.02, occurring at 480.0 (0.1-660.0) vs. 405.0 (180.0-570.0) min, p=0.56. First peak cortisol was 174.5 (53.0-754.7) vs. 6.27 (3.90-8.47) nmol/l, p=0.0001 and second peak cortisol 18.90 (5.22-76.9) vs. 3.12 (1.76-4.79) nmol/l, p=0.0001. The time to first peak cortisol differed between the 2 groups, 30 (30-75) vs. 0.1 (0.1-30) minutes; p=0.0001. At doses studied, hydrocortisone replacement therapy results in cortisol pharmacokinetics being markedly different from endogenous cortisol profiles in healthy control subjects. Addison's disease patients had significantly higher SC levels compared to healthy control subjects. © Georg Thieme Verlag KG Stuttgart · New York.