Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Robotic Radiosurgery for Adrenal Gland Metastases

PubMed Central

Heidorn, Sarah-Charlotta; Kremer, Nikolaus; Muacevic, Alexander; Fürweger, Christoph

2017-01-01

Introduction The purpose of this study was to investigate the safety and efficacy of CyberKnife (CK) robotic radiosurgery for treatment of adrenal metastases. Methods We performed a retrospective analysis of 23 patients with adrenal metastases who had been treated with CK between October 2006 and December 2015. Fifteen patients received chemotherapy prior to radiosurgery, all patients underwent computer tomography (CT) fluoroscopically guided percutaneous placement of one to three gold fiducials into the adrenal gland. Nineteen patients were selected for single-fraction radiosurgery with a median dose of 22 Gy, four patients were treated in three fractions with a median dose of 13.5 Gy. Results Median follow-up time was 23.6 months. Four patients (17%) experienced local relapse during the evaluation period with a mean time of 19 months to tumor progression. The actuarial local tumor control rate was 95% after one year and 81% after two years. Three of the four patients with local recurrence were retreated with CK radiosurgery. Dynamic tumor tracking enabled accurate treatment with correlation errors less than 2 mm, despite extensive respiration-induced target motion up to 22 mm. Apart from nausea directly after treatment in five patients, we observed no early or late treatment-related side effects. Conclusions Single fraction robotic radiosurgery for adrenal gland metastases is a safe and effective treatment option for patients who are not eligible for surgical resection. PMID:28451479

Interrelationships between the thyroid gland and adrenal cortex during fear, cold and restraint in the sheep.

PubMed

Falconer, I R

1976-03-01

To examine the relationship between the functioning of the adrenal and thyroid glands in sheep, plasma cortisol concentration, concentration of protein-bound 125I from thyroid vein plasma, heart rate and blood pressure were measured in ewes bearing exteriorized thyroid glands. During these measurements stresses were imposed on the animals: fear induced by pistol shots or by a barking dog, cold by cooling and wetting, and physical restraint by a loose harness. Increases in plasma cortisol concentration of 2-6 mug/100 ml were observed with each type of stressor, the response rapidly decreasing with habituation of the animal. Increases in the concentration of protein-bound 125I from thyroid vein plasma were also observed repeatedly during cooling and wetting, occasionally after the introduction of a barking dog, and during continued restraint. Cooling and wetting was the only stress causing consistent parallel activation of the adrenal cortex and thyroid gland; the other stressors resulted in independent fluctuations of secretions, as indicated by plasma cortisol concentration and concentration of protein-bound 125I from thyroid vein plasma. No reciprocal relationship between thyroid gland and adrenal cortex activity was detected. It was concluded taht these ewes, which had been accustomed to normal experimental procedures for a period of 2 years, demonstrated functional independence of thyroid and adrenal cortical secretions when subjected to stress.

Autonomic control of adrenal function.

PubMed Central

Edwards, A V; Jones, C T

1993-01-01

Recent studies of adrenal function in conscious calves are reviewed. These have involved collecting the whole of the adrenal effluent blood from the right adrenal gland at intervals and, where necessary, prior functional hypophysectomy by destruction of the pituitary stalk under general halothane anaesthesia 3 d previously. The adrenal medulla was found to release numerous neuropeptides, in addition to catecholamines, in response to stimulation of the peripheral end of the right splanchnic nerve, which was carried out below behavioural threshold. Many of these responses were enhanced by stimulating intermittently at a relatively high frequency. Intra-aortic infusions of a relatively low dose of acetylcholine (4.5 nmol min-1 kg-1) elicited similar responses. In the adrenal cortex, agonists which either potentiated the steroidogenic response to ACTH or exerted a direct steroidogenic action included VIP, CGRP, CRF and ACh acting via muscarinic receptors. Stimulation of the peripheral end of the right splanchnic nerve strongly potentiated the steroidogenic response to ACTH and there is compelling evidence that the innervation normally plays an important part in cortisol secretion. PMID:8300417

Fetal Adrenal Gland in the Second Half of Gestation: Morphometrical Assessment with 3.0T Post-Mortem MRI

PubMed Central

Hou, Zhongyu; Ma, Jun; Feng, Lei; Lin, Xiangtao; Tang, Yuchun; Zhang, Xiaoli; Liu, Qingwei; Liu, Shuwei

2013-01-01

Background The morphometry of fetal adrenal gland is rarely described with MRI of high magnetic field. The purpose of this study is to assess the normal fetal adrenal gland length (AL), width (AW), height (AH), surface area (AS) and volume (AV) in the second half of gestation with 3.0T post-mortem MRI. Methods and Findings Fifty-two fetal specimens of 23–40 weeks gestational age (GA) were scanned by 3.0T MRI. Morphological changes and quantitative measurements of the fetal adrenal gland were analyzed. Asymmetry and sexual dimorphism were also obtained. The shape of the fetal adrenal gland did not change substantially from 23 to 40 weeks GA. The bilateral adrenal glands appeared as a ‘Y’, pyramidal or half-moon shape after reconstruction. There was a highly linear correlation between AL, AW, AH, AS, AV and GA. AW, AH, AS and AV were larger for the left adrenal gland than the right. No sexual dimorphism was found. Conclusions Our data delineated the normal fetal adrenal gland during the second half of gestation, and can serve as a useful precise reference for anatomy or in vivo fetus. PMID:24116052

Effect of acute heat stress on rat adrenal glands: a morphological and stereological study.

PubMed

Koko, Vesna; Djordjeviae, Jelena; Cvijiae, Gordana; Davidoviae, Vukosava

2004-11-01

The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.

EFFECTS OF PERTUSSIS SENSITIZATION AND ROENTGEN IRRADIATION ON THE ADRENAL GLANDS OF RATS AND MICE (in Japanese)

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

Nakamura, M.

1962-10-01

Histaminase activity was estimated by the coupled oxidation and deamination method in lung tissue from rats and mice followrng adrenal gland x irradiation, sensitization with B. pertussis, or pertussis sensitization followed by adrenal gland irradiation. Histamine activity was greatly reduced in lung tissue from animals sensitized with pertussis followed by adrenal irradiation, moderately reduced in lung tissue from pertussis sensitized animals, and slightly decreased in lung tissue from the adrenal irradiated group. The activity of succinoxidose and monoamine oxidose in lung tissue was not affected by either adrenal irradiation or pertussis sensitization. The possibility that steroid hormone balance may bemore » affected by disturbance of the adrenal glands in animals sensitized with pertussis is discussed. (C.H.)« less

Morphology and ultrastructure of the adrenal gland in Bactrian camels (Camelus bactrianus).

PubMed

Ye, Wen-Ling; Wang, Feng-Ling; Wang, Hong-Ju; Wang, Jian-Lin

2017-04-01

In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mouse genotypes drive the liver and adrenal gland clocks

NASA Astrophysics Data System (ADS)

Košir, Rok; Prosenc Zmrzljak, Uršula; Korenčič, Anja; Juvan, Peter; Ačimovič, Jure; Rozman, Damjana

2016-08-01

Circadian rhythms regulate a plethora of physiological processes. Perturbations of the rhythm can result in pathologies which are frequently studied in inbred mouse strains. We show that the genotype of mouse lines defines the circadian gene expression patterns. Expression of majority of core clock and output metabolic genes are phase delayed in the C56BL/6J line compared to 129S2 in the adrenal glands and the liver. Circadian amplitudes are generally higher in the 129S2 line. Experiments in dark - dark (DD) and light - dark conditions (LD), exome sequencing and data mining proposed that mouse lines differ in single nucleotide variants in the binding regions of clock related transcription factors in open chromatin regions. A possible mechanisms of differential circadian expression could be the entrainment and transmission of the light signal to peripheral organs. This is supported by the genotype effect in adrenal glands that is largest under LD, and by the high number of single nucleotide variants in the Receptor, Kinase and G-protein coupled receptor Panther molecular function categories. Different phenotypes of the two mouse lines and changed amino acid sequence of the Period 2 protein possibly contribute further to the observed differences in circadian gene expression.

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.

Ultrasonographic adrenal gland findings in healthy semi-captive cheetahs (Acinonyx jubatus).

PubMed

Kirberger, Robert M; Tordiffe, Adrian S W

2016-05-01

Cheetahs in captivity are believed to suffer from stress predisposing them to poor health. To date fecal glucocorticoids have been used as a non-invasive indicator of chronic stress. This study examines, the feasibility of transabdominal adrenal gland ultrasonography in cheetahs and determined normal adrenal measurements that can potentially be used as a more reliable indicator of chronic stress and/or adrenal function. Thirty-three adult cheetahs, aged between 2 and 13 years, accommodated in large off-display camps were examined over 9 days under general anesthesia. The adrenals were readily identified, with the right adrenal being more difficult to find and measure than the left, and were smaller than those expected in similar sized dogs. The left adrenal was shorter and slightly more oval shaped than the right with a length and cranial pole width at a 95% prediction interval of 16.3-22.4 and 4.1-8.7 mm. The same measurements for the right adrenal were 16.8-26.2 and 3.4-10.8 mm, respectively. Corticomedullary ratios were larger for the left adrenal. When corrected for body size, females had significantly longer and greater left adrenal corticomedullary ratios than males. Adrenal measurements did not correlate with left renal length, body size measurements, or enclosure size. Measurements that increased with age included the cortical and total adrenal widths. Adrenal ultrasonography offers potential benefits in assessment of individual cheetah adrenal pathology or the evaluation of stress induced adrenomegally especially in combination with other evaluations such as non-invasive fecal glucocorticoid analyses. Zoo Biol. 35:260-268, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Regulation of the Adrenal Cortex Function During Stress

NASA Technical Reports Server (NTRS)

Soliman, K. F. A.

1978-01-01

A proposal to study the function of the adrenal gland in the rat during stress is presented. In the proposed project, three different phases of experimentation will be undertaken. The first phase includes establishment of the circadian rhythm of both brain amines and glucocoticoids, under normal conditions and under chronic and acute stressful conditions. The second phase includes the study of the pharmacokinetics of glucocorticoid binding under normal and stress conditions. The third phase includes brain uptake and binding under different experimental conditions. In the outlined experiments brain biogenic amines will be evaluated, adrenal functions will be measured and stress effect on those parameters will be studied. It is hoped that this investigation can explain some of the complex relationships between the brain neurotransmitter and adrenal function.

Mixed cortical adenoma and composite pheochromocytoma-ganglioneuroma: an unusual corticomedullary tumor of the adrenal gland.

PubMed

Lau, Sean K; Chu, Peiguo G; Weiss, Lawrence M

2011-06-01

Adrenal neoplasms composed of more than one cell type and demonstrating a mixed histologic appearance are exceedingly rare. We report the clinical and pathologic features of a morphologically distinctive tumor of the adrenal gland composed of cortical, chromaffin, and neural cells. Histologically, the tumor consisted of intermixed areas of proliferating cortical cells resembling adrenal cortical adenoma, neoplastic chromaffin cells consistent with pheochromocytoma, and a ganglioneuromatous stroma. The presence of the cortical, medullary, and neural components within the tumor was confirmed by immunohistochemical studies. The present case serves to broaden the morphologic spectrum of mixed tumors that may be encountered in the adrenal gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Expression of 11β-hydroxysteroid dehydrogenase isoforms in canine adrenal glands treated with trilostane.

PubMed

Teshima, Takahiro; Matsumoto, Hirotaka; Kumagai, Takayuki; Kurano, Mai; Koyama, Hidekazu

2014-06-01

Trilostane, a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, is often used to treat canine hyperadrenocorticism. In some species, trilostane has been shown to have additional effects on steroid biosynthesis, and it has been postulated that trilostane might have effects on 11β-hydroxysteroid dehydrogenase (11β-HSD) in dogs. To investigate the effect of trilostane on 11β-HSD in canine adrenal glands, healthy Beagle dogs were treated with trilostane for 8 weeks. Trilostane treatment resulted in a significant decrease of the cortisol/cortisone ratio in the serum. The adrenal gland mRNA and protein expression levels of 11β-HSD type 1 and 11β-HSD type 2 were significantly higher and significantly lower respectively in dogs treated with trilostane compared to those in control healthy Beagle dogs. These findings suggest that trilostane may have an effect on 11β-HSD activity in canine adrenal glands. Copyright © 2014 Elsevier Ltd. All rights reserved.

Histological differences in the adrenal glands and cortisol levels of suckling dairy goat kids in enriched and non-enriched environments.

PubMed

Rosas-Trigueros, A P; Candanosa-Aranda, I E; Ducoing-Watty, A E; Gutiérrez-Molotla, J; Galindo, F; Sisto-Burt, A M

2017-12-01

Intensive production systems can negatively affect the welfare of goats. Environmental enrichment techniques can be used to reduce stress. The aim of this study was analyze the effect of environmental enrichment on the histological characteristics of adrenal glands, cortisol levels and weekly weight gain of suckling Alpine French male kids under confinement. A randomised design was used to test the effect of the treatment. The animals (n=20) were randomly assigned to two treatments (enriched and non-enriched) with two replicates each. Enrichment elements included elevated sacks of henequen, trunks, tires and coconuts. The cortisol levels were measured weekly. Male kids were euthanized when their weight reached 10kg, and immediately after euthanasia, samples of the adrenal glands were collected. The adrenal glands were weighed and measured, and histological sections were taken and fixed. Four hundred cells were measured from each animal, with two blind measurements taken from each sample. There were no significant differences between experimental groups (P>0.05) in the weigh, size, the area of cells from the glomerulosa and fasciculata areas of the adrenal glands, the cortisol levels and weekly weight gain. However, there were histological differences between the glomerular and fascicular zones of the left and right adrenal glands of the different groups (P<0.05). These findings suggest that adrenal glands of animals in non-enriched environment, contained histological changes, suggestive of increased activity. We suggest testing adrenal histology as an indicator of stress and recommend the use of environmental enrichment as a means to reduce stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland

PubMed Central

Torres-Farfan, Claudia; Valenzuela, Francisco J; Mondaca, Mauricio; Valenzuela, Guillermo J; Krause, Bernardo; Herrera, Emilio A; Riquelme, Raquel; Llanos, Anibal J; Seron-Ferre, Maria

2008-01-01

Although the fetal pineal gland does not secrete melatonin, the fetus is exposed to melatonin of maternal origin. In the non-human primate fetus, melatonin acts as a trophic hormone for the adrenal gland, stimulating growth while restraining cortisol production. This latter physiological activity led us to hypothesize that melatonin may influence some fetal functions critical for neonatal adaptation to extrauterine life. To test this hypothesis we explored (i) the presence of G-protein-coupled melatonin binding sites and (ii) the direct modulatory effects of melatonin on noradrenaline (norepinephrine)-induced middle cerebral artery (MCA) contraction, brown adipose tissue (BAT) lypolysis and ACTH-induced adrenal cortisol production in fetal sheep. We found that melatonin directly inhibits the response to noradrenaline in the MCA and BAT, and also inhibits the response to ACTH in the adrenal gland. Melatonin inhibition was reversed by the melatonin antagonist luzindole only in the fetal adrenal. MCA, BAT and adrenal tissue displayed specific high-affinity melatonin binding sites coupled to G-protein (Kd values: MCA 64 ± 1 pm, BAT 98.44 ± 2.12 pm and adrenal 4.123 ± 3.22 pm). Melatonin binding was displaced by luzindole only in the adrenal gland, supporting the idea that action in the MCA and BAT is mediated by different melatonin receptors. These direct inhibitory responses to melatonin support a role for melatonin in fetal physiology, which we propose prevents major contraction of cerebral vessels, restrains cortisol release and restricts BAT lypolysis during fetal life. PMID:18599539

Life-Threatening Complication During Percutaneous Ablation of Adrenal Gland Metastasis: Takotsubo Syndrome

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

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Buy, Xavier, E-mail: Xavier.buy@chru-strasbourg.f; Zickler, Pierre, E-mail: pierre.zickler@chru-strasbourg.f

2010-06-15

A rare life-threatening complication during percutaneous cryoablation of an adrenal gland metastasis from a lung carcinoma is reported. The patient presented hypertensive crisis at the beginning of the thawing cycle, followed by electrocardiographic change which necessitated interruption of the procedure and his transfer to the intensive care unit with suspicion of heart infarct. There was a slight increase in cardiac enzyme levels, and ventricular angiography demonstrated transient hypokinesis-dyskinesis of the mid left ventricular segments without apical involvement, while the coronary arteries showed no significant stenosis on coronarography. These findings led to the diagnosis of Takotsubo cardiomyopathy left ventricular dysfunction syndrome.more » This is the first case of Takotsubo cardiomyopathy occurring as a complication during percutaneous ablation of an adrenal gland tumor.« less

On the mode of action of ACTH on the isolated perfused adrenal gland

PubMed Central

Jaanus, Siret D.; Rosenstein, M. J.; Rubin, R. P.

1970-01-01

1. Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied. 2. Steroid outputs varied with the ACTH concentration, as well as with the duration of exposure to a given ACTH concentration. 3. Omission of calcium from the perfusion medium markedly depressed ACTH-evoked steroid release. The steroid output was directly related to the extracellular calcium concentration up to 0·5 mM. 4. During a constant exposure to ACTH, steroid output was maintained for at least 2-3 hr, provided that calcium was present in the perfusion medium. 5. Strontium, but not barium or magnesium, replaced calcium in maintaining the secretory response to ACTH. 6. Magnesium depressed ACTH-evoked secretion in the presence of calcium, and this depression of secretion was antagonized by increasing the calcium concentration. 7. Prolonged perfusion with sodium-free or potassium-free solutions did not markedly inhibit steroid output in response to ACTH. Excess potassium (56 mM) did not produce a consistent or marked increase in spontaneous steroid output and did not affect the response to ACTH. 8. The steroid content of adrenal glands perfused with Locke solution and exposed to ACTH was about 10% of the amount which was secreted. By contrast, adrenal glands perfused with calcium-free media and exposed to ACTH contained much higher amounts of steroid, despite the negligible amount secreted. 9. These data suggest that calcium plays a critical role in the mechanism of corticosteroid secretion from the adrenal cortex. PMID:4322584

Sex differences in oestrogen receptor levels in adrenal glands of sheep during the breeding season.

PubMed

van Lier, E; Meikle, A; Bielli, A; Akerberg, S; Forsberg, M; Sahlin, L

2003-11-01

The concentrations of the oestrogen receptor (ER), and the mRNA levels of ERalpha, progesterone receptor (PR) and insulin-like growth factor I (IGF-I) were characterised in adrenal glands and uterine tissue of adult Corriedale sheep during the breeding season. The sheep were of different sex and gonadal status. Ewes had higher levels of cytosolic ER in the adrenals than the rams (mean+/-S.E.M.: 7.3+/-2.0 fmol/mg protein and 2.5+/-1.0 fmol/mg protein, respectively; P=0.0091) and gonadectomy increased ER (mean+/-S.E.M.: 2.9+/-1.2 fmol/mg protein and 8.6+/-2.3 fmol/mg protein, intact and gonadectomised sheep, respectively; P=0.0071). No differences could be observed in mRNA levels for ERalpha and IGF-I in the adrenal glands of all of the sheep. PR mRNA levels were reduced in ovariectomised ewes and enhanced in castrated rams (sex x gonadal status: P=0.009). PR mRNA levels tended to be higher in ewes in the follicular phase than in ovariectomised ewes and intact rams (P<0.1). All of the animals had positive nuclear staining for ERalpha in the adrenal cortex, but no differences were observed between the groups. In this study, we demonstrated the existence of ER in the adrenal gland of sheep and found varying sensitivity to oestrogens as the ER levels differed among sex and gonadal status. These findings indicate that oestrogens most likely affect steroidogenesis directly at the adrenal cortex and suggest that oestrogens are partly responsible for the sex differences in cortisol secretion in sheep.

Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large White Pigs after Ventricular Fibrillation.

PubMed

Faa, Armando; Faa, Gavino; Papalois, Apostolos; Obinu, Eleonora; Locci, Giorgia; Pais, Maria Elena; Lelovas, Pavlos; Barouxis, Dimitrios; Pantazopoulos, Charalampos; Vasileiou, Panagiotis V; Iacovidou, Nicoletta; Xanthos, Theodoros

2016-01-01

Aim. To evaluate the effects of erythropoietin administration on the adrenal glands in a swine model of ventricular fibrillation and resuscitation. Methods. Ventricular fibrillation was induced via pacing wire forwarded into the right ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups: experimental group treated with bolus dose of erythropoietin (EPO) and control group which received normal saline. Cardiopulmonary resuscitation (CPR) was performed immediately after drug administration as per the 2010 European Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were monitored, mechanically ventilated, extubated, observed, and euthanized. At necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and routinely processed. Sections were stained with hematoxylin-eosin. Results. Oedema and apoptosis were the most frequent histological changes and were detected in all animals in the adrenal cortex and in the medulla. Mild and focal endothelial lesions were also detected. A marked interindividual variability in the degree of the intensity of apoptosis and oedema at cortical and medullary level was observed within groups. Comparing the two groups, higher levels of pathological changes were detected in the control group. No significant difference between the two groups was observed regarding the endothelial changes. Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has protective effects on the adrenal gland.

Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF) and apoptosis in fetal adrenal glands.

PubMed

Karaca, T; Hulya Uz, Y; Karabacak, R; Karaboga, I; Demirtas, S; Cagatay Cicek, A

2015-11-26

This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.

Effects of Hyperthyroidism on Expression of Vascular Endothelial Growth Factor (VEGF) and Apoptosis in Fetal Adrenal Glands

PubMed Central

Hulya Uz, Y.; Karabacak, R.; Karaboga, I.; Demirtas, S.; Cagatay Cicek, A.

2015-01-01

This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 µg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the ACTH and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis. PMID:26708182

Hedgehog signaling: endocrine gland development and function.

PubMed

Cohen, M Michael

2010-01-01

The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.

PubMed

Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

2015-02-01

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. © 2014 The Author(s).

Rare adrenal gland incidentaloma: an unusual Ewing's sarcoma family of tumor presentation and literature review.

PubMed

Guo, Hui; Chen, Shuaiqi; Liu, Shukun; Wang, Kaixuan; Liu, Erpeng; Li, Faping; Hou, Yuchuan

2017-04-04

Members of the Ewing's sarcoma family of tumor (ESFT) are malignant neoplasms and rarely observed in the adrenal gland. We report an extremely exceptional case of ESFT rising from the adrenal gland in a 57-year-old Chinese man. The patient was hospitalized with abdominal swelling for 2 months. Computed tomography (CT) scan revealed a nearly-circular mass measuring about 8.1 × 10.6 cm in the right adrenal region. The patient underwent right adrenal resection. Histopathologic examination found the tumor was composed of small round blue cells forming typical Homer-Wright rosettes in focal area. The immunohistochemical analysis confirmed the case to be ESFT, which was positive for membranous CD99 and nuclear FLI-1. The patient was scheduled for four courses of large doses of chemotherapy and died for cancer metastasis one year later after surgery. Histopathological evidence of Homer-Wright rosettes and immunohistochemical markers positivity, such as CD99 and FLI-1, are valuable factors for ESFT diagnosis, although cytogenetic analysis is considered as the gold standard. Complete surgery is the treatment of choice for ESFT and adjuvant radiotherapy and combination chemotherapy can significantly improve the survival rate of postoperative patients.

Consumption of sucrose from infancy increases the visceral fat accumulation, concentration of triglycerides, insulin and leptin, and generates abnormalities in the adrenal gland.

PubMed

Díaz-Aguila, Yadira; Castelán, Francisco; Cuevas, Estela; Zambrano, Elena; Martínez-Gómez, Margarita; Muñoz, Alvaro; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

2016-03-01

Consumption of sugar-sweetened beverages promotes the development of metabolic syndrome (MetS) and type 2 diabetes mellitus in humans. One factor related to the appearance of MetS components is the dysfunction of the adrenal gland. In fact, the experimental generation of hyperglycemia has been associated with morphological and microvascular changes in the adrenal glands of rats. We hypothesized that high sucrose consumption from infancy promotes histological disruption of the adrenal glands associated with the appearance of metabolic syndrome indicators. Male Wistar rats were separated at weaning (21 days old) into two groups: free access to tap water (control group, C) or 30 % sucrose diluted in water (sugar-fed group). After 12 weeks, high sucrose consumption promoted an increase in visceral fat accumulation, adipose cell number, and insulin resistance. Also, a rise in the concentration of triglycerides, very low-density lipoprotein, insulin and leptin was observed. In control rats, a histomorphometric asymmetry between the right and left adrenal glands was found. In the sugar-fed group, sucrose consumption produced a major change in adrenal gland asymmetry. No changes in corticosterone serum level were observed in either group. Our results suggest that a high sucrose liquid-diet from early life alters the morphology of adrenocortical zones, leading to MetS indicators.

Effects of long-term experimental diabetes on adrenal gland growth and phosphoribosyl pyrophosphate formation in growth hormone-deficient dwarf rats.

PubMed

Kunjara, Sirilaksana; Greenbaum, A Leslie; McLean, Patricia; Grønbaek, Henning; Flyvbjerg, Allan

2012-06-01

The availability of growth hormone (GH)-deficient dwarf rats with otherwise normal pituitary function provides a powerful tool to examine the relative role of hyperglycaemia and the reordering of hormonal factors in the hypertrophy-hyperfunction of the adrenal gland that is seen in experimental diabetes. Here, we examine the effects of long-term (6 months) experimental diabetes on the growth of the adrenal glands; their content of phosphoribosyl pyrophosphate (PRPP); and the activity of the PRPP synthetase, G6P dehydrogenase and 6PG dehydrogenase enzymes in GH-deficient dwarf rats compared to heterozygous controls. These parameters were selected in view of the known role of PRPP in both de novo and salvage pathways of purine and pyrimidine synthesis and in the formation of NAD, and in view of the role of the oxidative enzymes of the pentose phosphate pathway in both R5P formation and the generation of the NADPH that is required in reductive synthetic reactions. This study shows that GH deficiency prevents the increase in adrenal gland weight, PRPP synthetase, PRPP content and G6P dehydrogenase and 6PG dehydrogenase. This contrasts sharply with the heterozygous group that showed the expected increase in these parameters. The blood glucose levels of the groups of long-term diabetic rats, both GH-deficient and heterozygous, remained at an elevated level throughout the experiment. These results are fully in accord with earlier evidence from studies with somatostatin analogues which showed that the GH-insulin-like growth factor I (IGF-I)-axis plays a key role in the adrenal diabetic hypertrophy-hyperfunction syndrome. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Malignant Perivascular Epithelioid Cell Tumor (PEComa) of the Adrenal Gland: Report of a Rare Case Posing Diagnostic Challenge with the Role of Immunohistochemistry in the Diagnosis.

PubMed

Pant, Leela; Kalita, Dipti; Chopra, Ratna; Das, Abhijit; Jain, Gaurav

2015-05-01

Histological diagnosis of adrenal tumors is often challenging as diverse groups of tumors, both primaries and metastatic, may be seen in the adrenal gland with overlapping morphological features. Immunohistochemistry (IHC) plays the most important role in their diagnosis. Perivascular epithelioid cell tumor (PEComa), a rarely reported tumor in the adrenal gland, shares many features with another rare tumor sarcomatoid adrenocortical carcinoma (ACC). Extensive immunohistochemical study is required to distinguish this tumor from adrenocortical carcinoma and from other morphologically similar tumors. The unique combination of immunoreactivity for melanocytic markers, such as HMB-45 and Melan A, and myogenic markers, such as smooth muscle actin, is the hallmark of PEComas biological behavior, and prognosis of malignant PEComas is yet to be fully understood. Few cases of malignant PEComa have been reported in the adrenal gland. We report a case of malignant PEComa of the adrenal gland posing diagnostic challenge and compare its morphological and immunohistochemical features with those of sarcomatoid ACC.

A novel pipeline for adrenal tumour segmentation.

PubMed

Koyuncu, Hasan; Ceylan, Rahime; Erdogan, Hasan; Sivri, Mesut

2018-06-01

Adrenal tumours occur on adrenal glands surrounded by organs and osteoid. These tumours can be categorized as either functional, non-functional, malign, or benign. Depending on their appearance in the abdomen, adrenal tumours can arise from one adrenal gland (unilateral) or from both adrenal glands (bilateral) and can connect with other organs, including the liver, spleen, pancreas, etc. This connection phenomenon constitutes the most important handicap against adrenal tumour segmentation. Size change, variety of shape, diverse location, and low contrast (similar grey values between the various tissues) are other disadvantages compounding segmentation difficulty. Few studies have considered adrenal tumour segmentation, and no significant improvement has been achieved for unilateral, bilateral, adherent, or noncohesive tumour segmentation. There is also no recognised segmentation pipeline or method for adrenal tumours including different shape, size, or location information. This study proposes an adrenal tumour segmentation (ATUS) pipeline designed to eliminate the above disadvantages for adrenal tumour segmentation. ATUS incorporates a number of image methods, including contrast limited adaptive histogram equalization, split and merge based on quadtree decomposition, mean shift segmentation, large grey level eliminator, and region growing. Performance assessment of ATUS was realised on 32 arterial and portal phase computed tomography images using six metrics: dice, jaccard, sensitivity, specificity, accuracy, and structural similarity index. ATUS achieved remarkable segmentation performance, and was not affected by the discussed handicaps, on particularly adherence to other organs, with success rates of 83.06%, 71.44%, 86.44%, 99.66%, 99.43%, and 98.51% for the metrics, respectively, for images including sufficient contrast uptake. The proposed ATUS system realises detailed adrenal tumour segmentation, and avoids known disadvantages preventing accurate

Morphological and functional manifestations of rat adrenal-cortex response to sodium bromide administration under hypodynamic stress

NASA Technical Reports Server (NTRS)

Kirichek, L. T.; Zholudeva, V. I.

1979-01-01

Functional and morphological manifestations of adrenal cortex response to hypodynamia (2-hr immobilization on an operating table) under the influence of bromine preparations were studied. The sodium bromide was administered intraperitoneally in 100, 250, and 500 mg/kg doses once and repeatedly during ten days. The adrenal gland was evaluated functionally by ascorbic acid and cholesterol content and morphologically by coloring it with hematoxylin-eosin and Sudans for lipid revealing at freezing. Results are displayed in two tables and microphotographs. They are summarized as follows: the bromine weakens the functional state of the adrenal cortex in intact rats, causing changes similar to those under stress. During immobilization combined with preliminary bromine administration, a less pronounced stress reaction is noticeable.

Science review: Mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids

PubMed Central

Prigent, Hélène; Maxime, Virginie; Annane, Djillali

2004-01-01

This review describes current knowledge on the mechanisms that underlie glucocorticoid insufficiency in sepsis and the molecular action of glucocorticoids. In patients with severe sepsis, numerous factors predispose to glucocorticoid insufficiency, including drugs, coagulation disorders and inflammatory mediators. These factors may compromise the hypothalamic–pituitary axis (i.e. secondary adrenal insufficiency) or the adrenal glands (i.e. primary adrenal failure), or may impair glucocorticoid access to target cells (i.e. peripheral tissue resistance). Irreversible anatomical damages to the hypothalamus, pituitary, or adrenal glands rarely occur. Conversely, transient functional impairment in hormone synthesis may be a common complication of severe sepsis. Glucocorticoids interact with a specific cytosolic glucocorticoid receptor, which undergoes conformational changes, sheds heat shock proteins and translocates to the nucleus. Glucocorticoids may also interact with membrane binding sites at the surface of the cells. The molecular action of glucocorticoids results in genomic and nongenomic effects. Direct and indirect transcriptional and post-transcriptional effects related to the cytosolic glucocorticoid receptor account for the genomic effects. Nongenomic effects are probably subsequent to cytosolic interaction between the glucocorticoid receptor and proteins, or to interaction between glucocorticoids and specific membrane binding sites. PMID:15312206

Cerebellin in the rat adrenal gland: gene expression and effects of CER and [des-Ser1]CER on the secretion and growth of cultured adrenocortical cells.

PubMed

Rucinski, Marcin; Albertin, Giovanna; Spinazzi, Raffaella; Ziolkowska, Agnieszka; Nussdorfer, Gastone G; Malendowicz, Ludwick K

2005-03-01

Cerebellin (CER) is a regulatory peptide, originally isolated from rat cerebellum, which derives from the cleavage of precerebellin (Cbln), three types of which (Cbln1-3) have been identified in humans and rats. CER is also expressed in several extra-cerebellar tissues, including adrenal gland, and evidence has been provided that CER exerts a modulatory action on human and rat adrenal gland. Hence, we have investigated the expression of Cbln1-3 mRNAs and CER protein-immunoreactivity (IR) in the various zones of rat adrenal glands, and the effects of CER and its metabolite [des-Ser(1)]CER (des-CER) on the secretion and growth of cultured rat adrenocortical cells. Reverse transcription-polymerase chain reaction showed high and low expression of Cbln2 mRNA in zona glomerulosa (ZG) and zona fasciculata-reticularis, respectively. Cbln1 was not expressed, and Cbln3 mRNA was detected only in ZG. No Cbln expression was found in adrenal medulla. Immunocytochemistry demonstrated the presence of CER-IR exclusively in the adrenal cortex, the reaction being more intense in ZG. As expected, ACTH (10(-8) M) markedly enhanced corticosterone secretion and lowered proliferation rate of cultured adrenocortical cells. CER was ineffective, while des-CER exerted an ACTH-like effect, but only at the lowest concentration (10(-10) M). Taken together, these findings allow us to conclude that CER is expressed in rat adrenal cortex, and to suggest that CER conversion to des-CER by endopeptidases is needed for CER to exert its autocrine-paracrine regulatory functions.

Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

PubMed

Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

2014-01-01

Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

The content of catecholamines in the adrenal glands and sections of the brain under hypokinesia and injection of some neurotropic agents

NASA Technical Reports Server (NTRS)

Melnik, B. E.; Paladiy, E. S.

1980-01-01

The dynamics of catecholamine content were studied in the adrenal glands and in various region of the brain of white rats under hypokinesia and injections of neurotropic agents. Profound changes in body catecholamine balance occured as a result of prolonged acute restriction of motor activity. Adrenalin retention increased and noradrenanalin retention decreased in the adrenal glands, hypothalamus, cerebral hemispheres, cerebellum and medulla oblongata. Observed alterations in catecholamine retention varied depending upon the type of neurotropic substance utilized. Mellipramine increased catecholamine retention in the tissues under observation while spasmolytin brought about an increase in adrenalin concentration in the adrenals and a decrease in the brain.

[Adrenal tumours in childhood].

PubMed

Martos-Moreno, G A; Pozo-Román, J; Argente, J

2013-09-01

This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Impact of duration of critical illness on the adrenal glands of human intensive care patients.

PubMed

Boonen, Eva; Langouche, Lies; Janssens, Thomas; Meersseman, Philippe; Vervenne, Hilke; De Samblanx, Emilie; Pironet, Zoë; Van Dyck, Lisa; Vander Perre, Sarah; Derese, Inge; Van den Berghe, Greet

2014-11-01

Adrenal insufficiency is considered to be prevalent during critical illness, although the pathophysiology, diagnostic criteria, and optimal therapeutic strategy remain controversial. During critical illness, reduced cortisol breakdown contributes substantially to elevated plasma cortisol and low plasma ACTH concentrations. Because ACTH has a trophic impact on the adrenal cortex, we hypothesized that with a longer duration of critical illness, subnormal ACTH adrenocortical stimulation predisposes to adrenal insufficiency. Adrenal glands were harvested 24 hours or sooner after death from 13 long intensive care unit (ICU)-stay patients, 27 short ICU-stay patients, and 13 controls. Prior glucocorticoid treatment was excluded. MAIN OUTCOME AND MEASURE(S): Microscopic adrenocortical zonational structure was evaluated by hematoxylin and eosin staining. The amount of adrenal cholesterol esters was determined by Oil-Red-O staining, and mRNA expression of ACTH-regulated steroidogenic enzymes was quantified. The adrenocortical zonational structure was disturbed in patients as compared with controls (P < .0001), with indistinguishable adrenocortical zones present only in long ICU-stay patients (P = .003 vs. controls). Adrenal glands from long ICU-stay patients, but not those of short ICU-stay patients, contained 21% less protein (P = .03) and 9% more fluid (P = .01) than those from controls, whereas they tended to weigh less for comparable adrenal surface area. There was 78% less Oil-Red-O staining in long ICU-stay patients than in controls and in short-stay patients (P = .03), the latter similar to controls (P = .31). The mRNA expression of melanocortin 2 receptor, scavenger-receptor class B, member 1, 3-hydroxy-3-methylglutaryl-CoA reductase, steroidogenic acute regulatory protein, and cytochrome P450 cholesterol side-chain cleavage enzyme was at least 58% lower in long ICU-stay patients than in controls (all P ≤ .03) and of melanocortin 2 receptor, scavenger

The three subtypes of atrial natriuretic peptide (ANP) receptors are expressed in the rat adrenal gland.

PubMed

Grandclément, B; Ronsin, B; Morel, G

1997-03-01

Atrial natriuretic peptide (ANP) actions are mediated by highly selective and specific receptors. Three subtypes have been characterized and cloned: ANP receptor-A (or GC-A), -B (or GC-B) and -C (the so-called clearance receptor). In rat adrenal gland, the mRNA for each subtype was detected using 35S-dUTP or digoxigenin-11-dUTP specific labeled probes, and in situ hybridization at light and electron microscopic levels respectively. The three subtypes were expressed the most abundantly in the zona glomerulosa. The amount of GC-A mRNA expression, quantified using macro-autoradiography and densitometry, was higher than the amounts of GC-B mRNA and ANPR-C mRNA both in zona glomerulosa and medullary of adrenal gland. At electron microscopic level, the three subtypes of ANPR were revealed in glomerulosa cells. A noticeable signal was also present in the medullary area, especially for GC-A mRNA, in adrenaline-containing chromaffin cells. No signal was detected in noradrenaline-containing chromaffin cells. The subcellular localization of the three mRNAs is similar: in the cytoplasmic matrix and in the euchromatin of the nucleus in each cell of glomerulosa, and in the same compartments of the adrenaline-containing chromaffin cells. These data indicate that the adrenal gland is an important target tissue for ANP action both in glomerulosa cells and adrenaline-containing chromaffin cells. The mRNA expression levels were different for each ANPR subtype.

Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland--involvement of cAMP-responsive element modulator in epigenetic regulation of Cyp17a1.

PubMed

Košir, Rok; Zmrzljak, Ursula Prosenc; Bele, Tanja; Acimovic, Jure; Perse, Martina; Majdic, Gregor; Prehn, Cornelia; Adamski, Jerzy; Rozman, Damjana

2012-05-01

The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and Cyp21a1 are involved in the adrenal production of corticosteroids, whose circulating levels are circadian. cAMP signaling plays an important role in adrenal steroidogenesis. By using cAMP responsive element modulator (Crem) knockout mice, we show that CREM isoforms contribute to circadian expression of steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM-dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal glands. The data indicate that products of the Crem gene control the epigenetic repression of Cyp17 in mouse adrenal glands. © 2011 The Authors Journal compilation © 2011 FEBS.

Neurotrophins and their receptors in the rat pituitary gland: regulation of BDNF and trkB mRNA levels by adrenal hormones.

PubMed

Kononen, J; Soinila, S; Persson, H; Honkaniemi, J; Hökfelt, T; Pelto-Huikko, M

1994-12-01

We studied the expression of messenger ribonucleic acids (mRNAs) for neurotrophins and neurotrophin receptors in the rat pituitary gland and examined the influence of adrenal hormones on their mRNA levels, using in situ hybridization and Northern blot analysis. The only neurotrophin present at detectable levels in the pituitary was brain-derived neurotrophic factor (BDNF), which was observed in the anterior and intermediate lobes. Several transcripts of the putative receptor for BDNF, trkB, were present in the anterior and posterior lobes of the pituitary. A low amount of trkC mRNA was found in both the anterior and the intermediate lobe. Dexamethasone treatment decreased both BDNF and trkB mRNA levels in the anterior lobe of the pituitary. Adrenalectomy had no effect on trkB expression, but it decreased BDNF mRNA levels in comparison to the control animals. This effect could not be reversed by dexamethasone substitution, suggesting that BDNF, mRNA levels may be regulated not only by glucocorticoids but also by other adrenal hormones. These results demonstrate that BDNF, trkB and trkC are expressed in the pituitary gland and that glucocorticoids and possibly other adrenal hormones may modulate pituitary functions by regulating the expression of neurotrophic factors and their receptors. Whether BDNF acts as a secreted hormone, a trophic factor, or has autocrine/paracrine functions within the pituitary through its receptor, trkB, remains to be studied.

Adrenal collision tumor (parachordoma and ganglioneuroma): A case report.

PubMed

Lai, Yulin; Zhou, Liang; Hu, Jia; Li, Wenhua; Cui, Lin; Lai, Yongqing; Ni, Liangchao

2018-06-01

Adrenal collision tumors (ACTs) are distinct tumors that occur simultaneously in the same adrenal gland and are very rare. We herein report the case of a 56-year-old woman who was admitted to the hospital for medical imaging. The findings of the physical and laboratory examinations, including endocrine function, were unremarkable. Contrast-enhanced computed tomography of the abdomen revealed a 28×20×33-mm mass in the left adrenal medial limb, for which a laparoscopic surgery was performed. Postoperative pathological examination revealed two distinct tumors, namely a parachordoma and a ganglioneuroma. To the best of our knowledge, and following a thorough literature search, this is the first report of coexisting parachordoma and ganglioneuroma in the same adrenal gland.

Sex-specific prenatal stress effects on the rat reproductive axis and adrenal gland structure

PubMed Central

George, Susan O; Hogg, Charis O; Lai, Yu-Ting; Brunton, Paula J

2016-01-01

Abstract Social stress during pregnancy has profound effects on offspring physiology. This study examined whether an ethologically relevant social stress during late pregnancy in rats alters the reproductive axis and adrenal gland structure in post-pubertal male and female offspring. Prenatally stressed (PNS) pregnant rats (n=9) were exposed to an unfamiliar lactating rat for 10 min/day from day 16 to 20 of pregnancy inclusive, whereas control pregnant rats (n=9) remained in their home cages. Gonads, adrenal glands and blood samples were obtained from one female and one male from each litter at 11 to 12-weeks of age. Anogenital distance was measured. There was no treatment effect on body, adrenal or gonad weight at 11–12 weeks. PNS did not affect the number of primordial, secondary or tertiary ovarian follicles, numbers of corpora lutea or ovarian FSH receptor expression. There was an indication that PNS females had more primary follicles and greater ovarian aromatase expression compared with control females (both P=0.09). PNS males had longer anogenital distances (0.01±0.0 cm/g vs 0.008±0.00 cm/g; P=0.007) and higher plasma FSH concentrations (0.05 ng/mL vs 0.006 ng/mL; s.e.d.=0.023; P=0.043) compared with control males. There were no treatment effects on the number of Sertoli cells or seminiferous tubules, seminiferous tubule area, plasma testosterone concentration or testis expression of aromatase, FSH receptor or androgen receptor. PNS did not affect adrenal size. These data suggest that the developing male reproductive axis is more sensitive to maternal stress and that PNS may enhance aspects of male reproductive development. PMID:27026714

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies.

PubMed

Boyle, Molly H; Paranjpe, Madhav G; Creasy, Dianne M

2018-06-01

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.

[Thomas Addison and the adrenal gland].

PubMed

Smans, Lisanne C C J; Zelissen, Pierre M J

2012-01-01

The famous and beautifully illustrated monograph "On the Constitutional and Local Effects of Disease of the Suprarenal Capsules" was published by Thomas Addison in 1855. This was the first description of the disease that now bears his name. Thomas Addison provided the first real contribution to the knowledge of adrenal function after three centuries of non-productive speculation and is one of the founders of modern endocrinology.

Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses.

PubMed

Nussdorfer, G G; Mazzocchi, G

1998-01-01

Several cytokines, which are the major mediators of the inflammatory responses, are well-known to stimulate the hypothalamopituitary corticotropin-releasing hormone (CRH)/adrenocorticotropic hormone (ACTH) system, thereby evoking secretory responses by the adrenal cortex. Many of these cytokines, including interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (INF-gamma) are synthesized in the adrenal gland by both parenchymal cells and resident macrophages, and the release of some of them (e.g., IL-6 and TNF-alpha) is regulated by the main agonists of steroid hormone secretion (e.g., ACTH and angiotensin-II) and bacterial endotoxins. Adrenocortical and adrenomedullary cells are provided with specific receptors for IL-1, IL-2, and IL-6. IL-1 and TNF-alpha directly inhibit aldosterone secretion of zona glomerulosa cells, whereas IL-6 enhances it. IL-2, IL-3, IL-6, and INF-alpha are able to directly stimulate glucocorticoid production by zona fasciculata and zona reticularis cells, whereas IL-1 exerts an analogous effect through an indirect mechanism involving the stimulation of catecholamine release by chromaffin cells and/or the activation of the intramedullary CRH/ACTH system; again, TNF-alpha depresses glucocorticoid synthesis. IL-6 raises androgen secretion by inner adrenocortical layers. IL-1 enhances the proliferation of adrenocortical cells, and findings suggest that cytokines may control the apoptotic deletion of senescent zona reticularis cells. The relevance of the intraadrenal cytokine system in the fine-tuning of the secretion and growth of the adrenal cortex under normal conditions remains to be explored. However, indirect proof is available that local immune-endocrine interactions may play an important role in modulating adrenal responses to inflammatory and immune challenges and stresses.

Adrenal cortical oncocytoma mimicking pheochromocytoma.

PubMed

Kiriakopoulos, Andreas; Papaioannou, Dimitrios; Linos, Dimitrios

2011-01-01

Adrenal tumors present with clinical features and signs unique to their specific hormonal hypersecretion. However, there have been cases in which the clinical expression has been in conflict with the histologic features of the tumor. In this communication we report an unusual clinical presentation of an adrenal cortical tumor with histologic features of an oncocytoma that clinically mimicked a pheochromocytoma. A 49-year old man was referred to our Unit due to type B aortic dissection and a mass of the left adrenal gland. Computed tomography and magnetic resonance imaging confirmed the presence of aortic dissection extending from the left subclavian artery to both iliac arteries and also revealed a 6 cm tumor on the left adrenal gland. Preoperative endocrine evaluation showed a near tenfold increase of urinary vanillylmandelic acid (VMA) and metanephrine values. Transperitoneal laparoscopic adrenalectomy was successfully performed. The adrenal tumor proved to be an adrenal cortical neoplasm with histologic features of oncocytoma. Although the case of an adrenal cortical adenoma clinically mimicking a pheochromocytoma has been described in the literature, to the best of our knowledge, there has been no previous report of an adrenal cortical neoplasm with predominant features of oncocytoma.

[Progress in diagnosis and treatment of adrenal metastases tumor].

PubMed

Wu, Chu-jun; Qiu, Min; Ma, Lu-lin

2015-08-18

The adrenal gland is a common site of metastases, only second to pulmonary, liver and bone. The prevalence of adrenal metastases in patients with a history of cancer is between 10%-25%.The most common sites of origin are cancers of the lung, kidney, breast, gastrointestinal tract, and skin (melanoma).The mainstays of adrenal metastases diagnosis are computerized tomogramphy (CT), magnetic resonance imaging (MRI), and positron emission tomogramphy (PET). All patients should undergo complete hormonal evaluation to rule out functional adrenal tumors. Adrenal biopsy should be reserved for cases in which the results of non-invasive techniques are equivocal. In patients with isolated adrenal metastases, adrenalectomy is recommended, because of improved overall survival. For the patient with unresectable adrenal metastases tumor, radiotherapy and ablative therapy are feasible and useful methods for controlling adrenal metastases and offer patients opportunities for improved survival.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Protective effect of Brewer's yeast on methimazole-induced-adrenal atrophy (a stereological study).

PubMed

Dehghani, Farzaneh; Zabolizadeh, Jamal; Noorafshan, Ali; Panjehshahin, Mohammad Reza; Karbalay-Doust, Saied

2010-04-20

Induction of hypothyroidism by thioamide drugs will cause adrenal gland atrophy and decrease in its hormones. To prevent side effect on the adrenal gland, brewer's yeast, a natural product rich in vitamins and minerals was used. Serological techniques were applied to measure the volume of adrenal gland. For this purpose, 48 Sprague-Dawley rats were randomly divided into one control and three experimental groups. In group 1, methimazole was administered at the dose of 30 mg/kg/day days, in group 2, 120 mg/kg/day of, brewer's yeast, in group 3, 30 mg/kg/day of methimazole plus 120 mg/kg/day of brewer yeast, and for the control group, an equal volume of saline (0.5 ml/rat/day) was orally given. After 30 days, all the animals were anesthetized and their adrenal glands were removed, fixed, embedded and stained. The volume of different zones of the adrenal glands was estimated by Cavalieri principle and point counting methods. statistical analysis was performed using Mann-Withney test and p < 0.05 was considered as statistically significant. The results indicated that methimazole decreased the volume of fasciculata zone in the cortex of the adrenal gland and also decreased the blood cortisol level. Brewer's yeast reduced the methimazole side effects on this zone. In conclusion, it seems that the use of brewer's yeast could prevent methimazole-induced atrophy of the adrenal gland.

Sarcomatoid carcinoma of the adrenal gland: A case report and review of literature.

PubMed

Coli, Antonella; Di Giorgio, Andrea; Castri, Federica; Destito, Carmelo; Marin, Alfredo Wiel; Bigotti, Giulio

2010-01-15

Reports about adrenocortical carcinomas (AC) mixed with sarcomatous areas are very rare. The terminology and pathogenesis of such biphasic tumors remain controversial. Herein, we report a case of sarcomatoid carcinoma of the adrenal gland in a 75-year-old woman who presented with left abdominal pain of one month's standing. The results of abdominal ultrasonography and computed tomography (CT) showed the presence of a large heterogeneous adrenal mass. A left adrenalectomy and complete splenectomy were performed. Histologically, the neoplasm showed areas of adrenocortical carcinoma and areas of sarcomatoid spindle cell proliferation. When examined immunohistochemically, the carcinomatous cells stained positively for S-100 protein, Melan-A protein, and neuron-specific enolase (NSE), and focally for vimentin and the cytokeratin marker MNF 116. Also, the carcinomatous cells were immunoreactive to the monoclonal antibody HMB-45. The sarcomatous component expressed vimentin, as well as other smooth and skeletal muscle markers. Liver metastases appeared 3 months postoperatively. Twelve months after removal of the primary tumor, the patient died of her disease. To the best of our knowledge, only seven cases of adrenal sarcomatoid carcinoma have been reported in the medical literature. We review the reported cases according to the 2004 classification of the World Health Organization (WHO) of lung tumors, and highlight the histogenesis, diagnosis, and clinical course of this very aggressive tumor. Copyright 2009 Elsevier GmbH. All rights reserved.

Impact of chronic hypoxemia on blood flow to the brain, heart, and adrenal gland in the late-gestation IUGR sheep fetus.

PubMed

Poudel, Rajan; McMillen, I Caroline; Dunn, Stacey L; Zhang, Song; Morrison, Janna L

2015-02-01

In the fetus, there is a redistribution of cardiac output in response to acute hypoxemia, to maintain perfusion of key organs, including the brain, heart, and adrenal glands. There may be a similar redistribution of cardiac output in the chronically hypoxemic, intrauterine growth-restricted fetus. Surgical removal of uterine caruncles in nonpregnant ewe results in the restriction of placental growth (PR) and intrauterine growth. Vascular catheters were implanted in seven control and six PR fetal sheep, and blood flow to organs was determined using microspheres. Placental and fetal weight was significantly reduced in the PR group. Despite an increase in the relative brain weight in the PR group, there was no difference in blood flow to the brain between the groups, although PR fetuses had higher blood flow to the temporal lobe. Adrenal blood flow was significantly higher in PR fetuses, and there was a direct relationship between mean gestational PaO2 and blood flow to the adrenal gland. There was no change in blood flow, but a decrease in oxygen and glucose delivery to the heart in the PR fetuses. In another group, there was a decrease in femoral artery blood flow in the PR compared with the Control group, and this may support blood flow changes to the adrenal and temporal lobe. In contrast to the response to acute hypoxemia, these data show that there is a redistribution of blood flow to the adrenals and temporal lobe, but not the heart or whole brain, in chronically hypoxemic PR fetuses in late gestation. Copyright © 2015 the American Physiological Society.

Recovery of adrenal function in a patient with confirmed Addison's disease.

PubMed

Baxter, M; Gorick, S; Swords, F M

2013-01-01

Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery emerge, this may

Combination of three-dimensional ultrasound measurement of foetal adrenal gland enlargement and placental alpha microglobulin-1 for the prediction of the timing of delivery within seven days in women with threatened preterm labour and preterm labour.

PubMed

Santipap, Monchai; Phupong, Vorapong

2018-03-23

The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22-36 +6  weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour. Impact Statement What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth. What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour

Adrenal Incidentaloma

MedlinePlus

... or subclinical hypercortisolism: conditions caused by too much cortisol Hyperaldosteronism : too much aldosterone A pheochromocytoma: a rare ... in which the adrenal glands make too little cortisol and aldosterone, and too much androgen Cancer of ...

[Addison's disease : Primary adrenal insufficiency].

PubMed

Pulzer, A; Burger-Stritt, S; Hahner, S

2016-05-01

Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.

Intrinsic factors, adrenal gland morphology, and disease burden in captive cheetahs (Acinonyx jubatus) in South Africa.

PubMed

Gillis-Germitsch, Nina; Vybiral, Pamela-Rose; Codron, Daryl; Clauss, Marcus; Kotze, Antoinette; Mitchell, Emily P

2017-01-01

Adrenal gland weight (AW) and corticomedullary ratio (ACMR) are used as indicators of stress in animals. Captive cheetahs (Acinonyx jubatus) have higher ACMRs than free-ranging ones and stress has been linked to gastritis, amyloidosis, glomerulosclerosis, and myocardial fibrosis. We reviewed age, sex, body weight (BW), kidney weight (KW), and left AW and ACMR with necropsy findings in 51 South African captive cheetahs. Eleven common histopathologic lesions were counted for each animal as measure of its disease burden. Adrenal corticomedullary hyperplasia was significantly correlated with left AW and ACMR. Males had significantly higher AWs than females; other parameters showed no difference between the sexes. Disease burden, gastritis, and myocardial fibrosis were moderately correlated with adrenal morphology supporting prior evidence that gastritis and myocardial fibrosis are linked to stress. Glomerulosclerosis was not correlated with adrenal morphology and neither kidney nor liver amyloidosis contributed significantly to variation in AW or ACMR on multivariate analyses. Interstitial nephritis showed much stronger correlations with kidney and liver amyloidosis than gastritis. All three adrenal parameters were correlated with age; age was the only significant variable affecting ACMR on the multivariate analyses; and disease burden as well as systemic amyloidosis and kidney disease (except for fibrosis) showed moderate correlations with age. Age may, therefore, be important in the pathogenesis of disease in captive cheetahs, particularly of amyloidosis and kidney disease. None of the intrinsic measurements or adrenal parameters were sufficiently closely linked to disease to be used as ante-mortem proxies for disease burden or specific diseases. Zoo Biol. 36:40-49, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

PubMed Central

Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

2007-01-01

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8μg 100 g−1 day−1, s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases. PMID:17218354

Adrenal incidentaloma caused by extramedullary haematopoiesis: conservative management is optimal.

PubMed

Sekar, Suganya; Burad, Deepak; Abraham, Aby; Paul, Mazhuvanchary Jacob

2015-09-21

We present a thalassaemic patient with extramedullary haematopoiesis in the adrenal gland, which is one of the rare sites of involvement. A 29-year-old man presented with a history of anaemia since childhood which required blood transfusion recently. On examination, he had pallor, icterus and splenomegaly with no other palpable abdominal mass. He was diagnosed to have β-thalassaemia. Ultrasonography of the abdomen showed an incidental right adrenal mass with splenomegaly; CT revealed a large right adrenal mass with heterogeneous density. Adrenal adenoma, carcinoma and extramedullary haematopoiesis were considered in the differential diagnosis. After excluding a functioning tumour, the diagnosis was confirmed by ultrasound-guided biopsy. Since the patient was asymptomatic, the adrenal lesion was managed conservatively. 2015 BMJ Publishing Group Ltd.

Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

NASA Technical Reports Server (NTRS)

Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

1993-01-01

Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

Diagnosis and management of endocrine gland neoplasmas. Revision 1

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

Weller, R.E.

1994-03-01

Functional and nonfunctional neoplasms of the endocrine glands constitute some of the more challenging diagnostic and therapeutic problems in veterinary cancer medicine. This discussion will focus on the clinical signs and syndromes associated with neoplasms of the thyroid, adrenal, and parathyroid glands, and pancreas in companion animals and will concentrate on the mechanisms producing the clinical signs, diagnosis, staging, therapy and prognosis.

Adrenal trauma: Elvis Presley Memorial Trauma Center experience.

PubMed

Mehrazin, Reza; Derweesh, Ithaar H; Kincade, Matthew C; Thomas, Adam C; Gold, Robert; Wake, Robert W

2007-11-01

Adrenal gland injury is a potentially devastating event if unrecognized in the treatment course of a trauma patient. We reviewed our single-center experience and outcomes in patients with adrenal gland trauma. We performed a retrospective review of all patients presenting with trauma to the Regional Medical Center at Memphis who had adrenal gland injuries from January 1991 through March 2006. Each chart was reviewed with attention to the demographics, associated injuries, complications, and outcomes. Patients were stratified into two subgroups according to age (35 years or younger and older than 35 years) to allow for an age-based comparison between the two groups. Of 58,000 patients presenting with trauma, 130 (0.22%) were identified with adrenal injuries, of which 8 (6.2%) were isolated and 122 (93.8%) were not. Of these 130 patients, 125 (96.2%) had their injury diagnosed by computed tomography and 5 (3.8%) had their injury diagnosed during exploratory laparotomy. Right-sided injuries predominated (78.5%), with six (4.6%) bilateral. Four patients (3.1%) underwent adrenalectomy. Seven patients (5.4%) with adrenal injuries died. One patient (0.77%) required chronic steroid therapy. Patients older than 35 years were more likely to have complications such as deep venous thrombosis, pneumonia, and urinary tract infections. Patient age of 35 years or younger was associated with a significantly increased incidence of liver lacerations. Adrenal gland injury is uncommon, although mostly associated with greater injury severity. Although adding to morbidity, most are self-limited and do not require intervention.

Recovery of adrenal function in a patient with confirmed Addison's disease

PubMed Central

Baxter, M; Gorick, S; Swords, F M

2013-01-01

Summary Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Learning points Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery

[Adrenal tumors. Principles of diagnostics and operative treatment].

PubMed

Gonsior, A; Pfeiffer, H; Führer, D; Liatsikos, E; Schwalenberg, T; Stolzenburg, J-U

2010-05-01

Adrenal masses are very heterogeneous and comprise benign or malignant tumors, unilateral or bilateral masses and variable endocrine activity. Because of these attributes adrenal gland masses are a clinical challenge. This article gives a summary of diagnostic steps and indications for adrenal surgery including perioperative management.

Radioguided Adrenal Surgery

PubMed Central

Deus, Javier; Millera, Alfonso; Andrés, Alejandro; Prats, Enrique; Gil, Ismael; Suarez, Manuel; Salcini, José L.; Lahoz, Manuel

2015-01-01

Abstract The laparoscopic adrenalectomy is considered as the procedure of choice for the treatment of adrenal hyperplasia and tumor lesions. However, some special situations may limit the use of this method due to the difficulty to locate the gland and perform the lesion excision. We analyze 2 patients of a left adrenal tumor, explaining how they have overcome the difficulties in both situations. The first case was a patient with a history of intra-abdominal surgery and the other patient suffered from severe obesity. We performed with the use of the gamma probe, and the 2 cases, was of great help to access and glandular localization. The help of gamma probe test was achieved in the surgical bed, that removal was complete. The use of the portable gamma probe facilitated the access to the left adrenal gland as well as conducting the glandular excision without delay, despite the difficulties due to the intra abdominal surgery caused by the previous surgery, and in the case of severe obesity. PMID:26426608

Adrenal tuberculosis in Cushing's disease with bilateral macronodular adrenocortical hyperplasia.

PubMed

Kwon, Hyuk-Sang; Kim, Sang-Il; Yoo, Soon-Jib; Yoon, Kun-Ho; Lee, Kwang-Woo; Kang, Moon-Won; Son, Ho-Young; Kang, Sung-Koo; Cha, Bong-Yun

2006-04-01

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

PubMed

Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

2016-08-01

Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

Adrenal Gland and Lung Lesions in Gulf of Mexico Common Bottlenose Dolphins (Tursiops truncatus) Found Dead following the Deepwater Horizon Oil Spill.

PubMed

Venn-Watson, Stephanie; Colegrove, Kathleen M; Litz, Jenny; Kinsel, Michael; Terio, Karen; Saliki, Jeremiah; Fire, Spencer; Carmichael, Ruth; Chevis, Connie; Hatchett, Wendy; Pitchford, Jonathan; Tumlin, Mandy; Field, Cara; Smith, Suzanne; Ewing, Ruth; Fauquier, Deborah; Lovewell, Gretchen; Whitehead, Heidi; Rotstein, David; McFee, Wayne; Fougeres, Erin; Rowles, Teri

2015-01-01

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.

Adrenal Gland and Lung Lesions in Gulf of Mexico Common Bottlenose Dolphins (Tursiops truncatus) Found Dead following the Deepwater Horizon Oil Spill

PubMed Central

Venn-Watson, Stephanie; Colegrove, Kathleen M.; Litz, Jenny; Kinsel, Michael; Terio, Karen; Saliki, Jeremiah; Fire, Spencer; Carmichael, Ruth; Chevis, Connie; Hatchett, Wendy; Pitchford, Jonathan; Tumlin, Mandy; Field, Cara; Smith, Suzanne; Ewing, Ruth; Fauquier, Deborah; Lovewell, Gretchen; Whitehead, Heidi; Rotstein, David; McFee, Wayne; Fougeres, Erin; Rowles, Teri

2015-01-01

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths. PMID:25992681

Genetics Home Reference: primary macronodular adrenal hyperplasia

MedlinePlus

... too rapidly or in an uncontrolled way. ARMC5 gene mutations are believed to impair the protein's tumor-suppressor ... endocrine glands, including the adrenal glands. The GNAS gene mutations that cause PMAH are believed to result in ...

Partial recovery of adrenal function in a patient with autoimmune Addison's disease.

PubMed

Smans, L C C J; Zelissen, P M J

2008-07-01

To our knowledge, no case of remission in autoimmune Addison's disease has previously been reported. We describe a patient with primary adrenal insufficiency caused by autoimmune adrenalitis in whom partial remission was observed after 7 yr. A 39-yr-old male was referred because of extreme fatigue, weight loss, anorexia, nausea, and bouts of fever. During physical examination hyperpigmentation was seen. Laboratory tests showed a plasma cortisol of 0.02 micromol/l (08:30 h). Cortisol failed to increase during the ACTH stimulation test (0.02 to 0.03 micromol/l) and ACTH was markedly elevated (920 pmol/l). Adrenal auto-antibodies were weakly positive. A CT-scan showed no evidence of calcifications or other abnormalities of the adrenal glands. The diagnosis of autoimmune Addison's disease was made and replacement therapy with hydrocortisone and fludrocortisone was started. During the following years the dose of hydrocortisone was gradually decreased. Eventually, the patient decided to stop his medication completely. A repeated ACTH-stimulation test revealed a basal cortisol of 0.25 micromol/l and a peak cortisol of 0.30 micromol/l with a basal ACTH of 178 pmol/l. The patient did not have any complaints. Recovery of adrenal insufficiency, due to causes other than autoimmune adrenalitis, has been reported in the past. If our case of partial recovery of autoimmune adrenalitis is not unique this could have profound effects on treatment and follow-up of Addison's disease.

Renal and adrenal tumors: Pathology, radiology, ultrasonography, therapy, immunology

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

Lohr, E.; Leder, L.D.

1987-01-01

Aspects as diverse as radiology, pathology, urology, pediatrics and immunology have been brought together in one book. The most up-do-date methods of tumor diagnosis by CT, NMR, and ultrasound are covered, as are methods of catheter embolization and radiation techniques in case of primarily inoperable tumors. Contents: Pathology of Renal and Adrenal Neoplasms; Ultrasound Diagnosis of Renal and Pararenal Tumors; Computed-Body-Tomography of Renal Carcinoma and Perirenal Masses; Magnetic Resonance Imaging of Renal Mass Lesions; I-125 Embolotherapy of Renal Tumors; Adrenal Mass Lesions in Infants and Children; Computed Tomography of the Adrenal Glands; Scintigraphic Studies of Renal and Adrenal Function; Surgicalmore » Management of Renal Cell Carcinoma; Operative Therapy of Nephroblastoma; Nonoperative Treatment of Renal Cell Carcinoma; Prenatal Wilms' Tumor; Congenital Neuroblastoma; Nonsurgical Management of Wilms' Tumor; Immunologic Aspects of Malignant Renal Disease.« less

Thymic involution in the suspended rat - Adrenal hypertrophy and glucocorticoid receptor content

NASA Technical Reports Server (NTRS)

Steffen, J. M.; Musacchia, X. J.

1986-01-01

The relationship between thymic involution and adrenal hypertrophy is studied. The thymus, adrenal glands, and tissue water content are evaluated in male Sprague rats suspended in antiorthostatic (AO) or orthostatic (O) positions. A 50 percent decrease in the wet weight of the thymus and hypertrophy of the adrenal glands are observed during the seven days of AO suspension. After seven days of recovery the thymus weight is increased to control level; however, the hypertrophy of the adrenal glands remains unchanged. Thymic and renal responses in O postioned rats are similar to AO reactions. Thymic glucocorticoid (GC) receptor concentrations in the rats are analyzed; a 20 percent decrease in GC receptor site concentration, which is related to thymic involution, is detected in both AO and O rats. It is concluded that there is a temporal correlation between thymic involution and adrenal hypertrophy, which is not affected by AO positioning, and thymic involution is not associated with an increased sensitivity to GC.

Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

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

Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org; Vivian, Mark A.

Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

Diffuse large B-cell lymphoma solely involving bilateral adrenal glands and stomach: report of an extremely rare case with review of the literature.

PubMed

Wakabayashi, Mutsumi; Sekiguchi, Yasunobu; Shimada, Asami; Ichikawa, Kunimoto; Sugimoto, Keiji; Tomita, Shigeki; Izumi, Hiroshi; Nakamura, Noriko; Sawada, Tomohiro; Ohta, Yasunori; Komatsu, Norio; Noguchi, Masaaki

2014-01-01

A 60-year-old man complained of nausea, vomiting, decreased appetite, and a feeling of abdominal fullness in August 2013. Based on biopsy findings from an upper gastrointestinal endoscopy examination, a diagnosis of non-Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), non-GC type, was made. F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed abnormal accumulations solely in the gastric wall (SUVmax = 14.5), the left adrenal gland (SUVmax = 14.3), and the right adrenal gland (SUVmax = 8.5). The clinical stage (Ann Arbor) was IVA, the serum LDH level was within the reference range, and the International Prognostic Index (IPI) was low-intermediate. The serum soluble IL-2 receptor level was within the reference range, and there was no evidence of HIV, EB virus, or autoimmune disease. After the completion of 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and 2 parallel cycles of prophylactic intrathecal (I.T.), an upper gastrointestinal endoscopy and a FDG-PET/CT examination showed complete remission (CR). The patient received 8 cycles of ritsuximab therapy, 6 cycles of CHOP, and 3 cycles of I.T. The patient has maintained a CR for about 14 months. A literature search revealed that malignant lymphoma with involvement confined to the adrenal gland and gastrointestinal tract is exceedingly rare, and only 3 cases of malignant lymphoma have been reported, with involvement of the stomach in 2 cases and the duodenum in 1 case. All of the cases were diagnosed as DLBCL. The case described herein represents the third case with involvement of the stomach.

[Effect of combined oral contraceptives on the hypophyseo-thyroid and hypophyseo-adrenal systems in women with various anatomy of the thyroid gland].

PubMed

Zigizmund, V A; Sadykova, M Sh; Samoĭlova, O N; Moiseeva, O M

1988-11-01

Potential therapeutic effects of combined oral contraceptives (COC) rigevidon and ovidon (estrogen:gestagen ratio of 1:5) were studied in 97 women aged 19-35 years. With respect to the anatomical state of the thyroid, the patients were divided into two groups: group 1 included 42 women with normal thyroid function and group 2 included 55 women with euthyroid hyperplasia of the thyroid gland of stage I-II (the anatomical state of the thyroid gland was ranked according to the five-point Swiss scale adopted by WHO in 1975). All patients had a history of pregnancy, normal delivery, or abortion. The state of the pituitary-thyroid system was estimated by absorption of iodine isotopes in the thyroid tissue, and by the blood levels of thyrotropic hormone, thyroxine-binding globulin, thyroxine, and triiodothyronine. Activity of the pituitary- adrenal system was estimated by the blood levels of adrenocorticotropic hormone (ACTH) and cortisol. Blood samples were withdrawn 9 and 10 hours prior to the onset of COC administration, and after 24 and 48 weeks of COC use. The changes in the functional state of the pituitary- thyroid system in groups 1 and 2 were identical throughout the entire period of COC administration. Progressive increase in the levels of thyroxine and triiodothyronine was associated with inhibition of the thyrotropic function of the pituitary seen as decrease in thyrotropin levels. COC administration caused decrease in size of hyperplastic tyroid gland. Prior to COC administration, women in group 2 showed significant elevation of ACTH levels and marked decrease in ACTH levels and increase in cortisol levels in both groups. Normalization of the size of thyroid gland indicated that COC be used therapeutically in patients with thyroid hyperplasia.

Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

PubMed Central

Gehrand, Ashley; Bruder, Eric D.; Hoffman, Matthew J.; Engeland, William C.; Moreno, Carol

2014-01-01

The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. PMID:25394830

Photosensitizer-induced fluorescence of the rat adrenal gland and rat pheochromocytoma cells (PC 12) by meso-tetra(hydroxyphenyl)chlorin (mTHPC)

NASA Astrophysics Data System (ADS)

Colombo-Benkmann, Mario; Muhm, Markus; Gahlen, Johannes; Heym, Christine; Senninger, Norbert

1997-12-01

Rat adrenal glands exhibit an intense mTHPC-induced fluorescence. The objective of our study was the identification of adrenal cells exhibiting mTHPC-induced fluorescence under normal conditions and under stimulation of adrenal proliferation by reserpine. Furthermore mTHPC-uptake of rat pheochromocytoma (PC 12) cells was investigated. Four male Wistar rats received 0.5 mg mTHPC/kg iv 48 hours before perfusion. Furthermore four rats received reserpine (2 mg/kg im od), bromo-deoxy-uridine (BrdU; 50 mg/kg ip od) each for one week and mTHPC (0.5 mg/kg) 48 hours before perfusion. BrdU was detected immunohistochemically. PC 12-cells were incubated with 0.5 mg mTHPC/l culture medium for 24 or 48 hours. Cells and tissues were examined by fluorescence microscopy. The adrenal cortex exhibited an intense mTHPC-induced fluorescence. The adrenal medulla fluoresced faintly. Reserpine increased fluorescence of intramedullary cells, not coinciding with adrenal proliferation. Cortical fluorescence remained unchanged. PC 12-cells lying singly or in small groups and differentiating cells showed a more intense mTHPC- induced fluorescence than confluent cells. Differences of cortical and medullary uptake of mTHPC are independent of proliferation and may be explained by lipophilia of mTHPC, since adrenocytes have an uptake mechanism for cholesterol. The difference of mTHPC-uptake between PC 12-cells and chromaffin cells implicate the possibility of photodynamic applications for medullary neoplasia.

Ca(2+) signaling mechanisms in bovine adrenal chromaffin cells.

PubMed

Weiss, Jamie L

2012-01-01

Calcium (Ca(2+)) is a crucial intracellular messenger in physiological aspects of cell signaling. Adrenal chromaffin cells are the secretory cells from the adrenal gland medulla that secrete catecholamines, which include epinephrine and norepinephrine important in the 'fight or flight' response. Bovine adrenal chromaffin cells have long been used as an important model for secretion -(exocytosis) not only due to their importance in the short-term stress response, but also as a neuroendocrine model of neurotransmtter release, as they have all the same exocytotic proteins as neurons but are easier to prepare, culture and use in functional assays. The components of the Ca(2+) signal transduction cascade and it role in secretion has been extensively characterized in bovine adrenal chromaffin cells. The Ca(2+) sources, signaling molecules and how this relates to the short-term stress response are reviewed in this book chapter in an endeavor to generally -overview these mechanisms in a concise and uncomplicated manner.

Aldo-Keto Reductases 1B in Adrenal Cortex Physiology

PubMed Central

Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A. Marie

2016-01-01

Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

Equine fetal adrenal, gonadal and placental steroidogenesis.

PubMed

Legacki, Erin L; Ball, Barry A; Corbin, C Jo; Loux, Shavahn C; Scoggin, Kirsten E; Stanley, Scott D; Conley, Alan J

2017-10-01

Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA. Tissue steroid concentrations generally paralleled those in serum with time. Adrenal and gonadal tissue pregnenolone concentrations were similar and 100-fold higher than those in allantochorion. DHEA was far higher in gonads than adrenals and progesterone was higher in adrenals than gonads. Androstenedione decreased with GA in adrenals but not in gonads. Transcript analysis generally supported these data. CYP17A1 was higher in fetal gonads than adrenals or allantochorion, and HSD3B1 was higher in fetal adrenals and allantochorion than gonads. CYP11A1 transcript was also significantly higher in adrenals and gonads than allantochorion and CYP19 and SRD5A1 transcripts were higher in allantochorion than either fetal adrenals or gonads. Given these data, and their much greater size, the fetal gonads are the source of DHEA and likely contribute more than fetal adrenal glands to circulating fetal pregnenolone concentrations. Low CYP11A1 but high HSD3B1 and SRD5A1 transcript abundance in allantochorion, and low tissue pregnenolone, suggests that endogenous placental pregnenolone synthesis is low and likely contributes little to equine placental 5α-reduced pregnane secretion. © 2017 Society for Reproduction and Fertility.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

PubMed

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-05-01

Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks

PubMed Central

Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

2018-01-01

Abstract Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic–pituitary–adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases. PMID:29713692

Classic congenital adrenal hyperplasia and puberty.

PubMed

Charmandari, Evangelia; Brook, Charles G D; Hindmarsh, Peter C

2004-11-01

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.

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

Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

PubMed Central

Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

2016-01-01

In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

Factors other than light affecting the pineal gland: hypophysectomy, testosterone, dihydrotestosterone, estradiol, cryptorchidism, and stress

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

Urry, R.L.; Dougherty, K.A.; Frehn, J.L.

The article reviews those factors other than light that affect the activity of the pineal gland. Both testosterone and dihydroterosterone were shown to have tissue-specific inhibitory effects on pineal MAO activity concomitant with an increased activity of the gland. The effect also was tissue-specific. Bilateral and unilateral experimental cryptorchidism also decreased pineal MAO activity 3 to 4 weeks after surgery. Acute stresses appear to increase adrenal catecholamine output (epinephrine and norepinephrine) as well as to stimulate local adrenergic pathways, while chronic stress, such as starvation, appears to act through the adrenal corticosteroids by decreasing pineal MAO activity thereby indirectly increasingmore » melatonin synthesis. Thus, both components of the adrenal gland appear to act in concert to increase effectively melatonin synthesis by the pineal function----the latter specifically inhibits HIOMT activity. These observations indicate that many factors other than light affect pineal morphology and melatonin synthesis. The pineal appears to be a true neuroendocrine organ that is affected by hypophysectomy and is responsive to feedback and control from other organs within the mammalian organism. (auth)« less

Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.

PubMed

Milosević, Verica Lj; Stevanović, Darko M; Nesić, Dejan M; Sosić-Jurjević, Branka T; Ajdzanović, Vladimir Z; Starcević, Vesna P; Severs, Walter B

2010-06-01

Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism.

PubMed

Babaya, Naru; Makutani, Yukako; Noso, Shinsuke; Hiromine, Yoshihisa; Ito, Hiroyuki; Taketomo, Yasunori; Ueda, Kazuki; Ushijima, Hokuto; Komoike, Yoshifumi; Yamazaki, Yuto; Sasano, Hironobu; Kawabata, Yumiko; Ikegami, Hiroshi

2017-12-06

We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

The pineal gland from development to function.

PubMed

Sapède, Dora; Cau, Elise

2013-01-01

The pineal gland is a small neuroendocrine organ whose main and most conserved function is the nighttime secretion of melatonin. In lower vertebrates, the pineal gland is directly photosensitive. In contrast, in higher vertebrates, the direct photosensitivity of the pineal gland had been lost. Rather, the action of this gland as a relay between environmental light conditions and body functions involves reception of light information by the retina. In parallel to this sensory regression, the pineal gland (and its accessory organs) appears to have lost several functions in relation to light and temperature, which are important in lower vertebrate species. In humans, the functions of the pineal gland overlap with the functions of melatonin. They are extremely widespread and include general effects both on cell protection and on more precise functions, such as sleep and immunity. Recently, the role of melatonin has received a considerable amount of attention due to increased cancer risk in shift workers and the discovery that patients suffering from neurodegenerative diseases, autism, or depression exhibit abnormal melatonin rhythms. © 2013 Elsevier Inc. All rights reserved.

Adrenal Ewing's Sarcoma in an Elderly Man.

PubMed

Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

2018-02-15

Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

The effect of bedrest on adrenal function

NASA Technical Reports Server (NTRS)

Leach, C. S.; Hulley, S. B.; Rambaut, P. C.; Dietlein, L. F.

1973-01-01

Eight male subjects were subjected to continuous bedrest for 24-80 weeks for the purpose of studying metabolic responses. Three of the subjects did supine exercises daily during part of the study. Adrenal function was examined in relation to adrenal cortical and medullary excretions. The results reveal an increase in hydrocortisone throughout the test period, a decrease in norepinephrine and no change in epinephrine. These data suggest that exercise could decrease the severity of deconditioning caused by bedrest.

Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex.

PubMed

Prüss, Harald; Tedeschi, Andrea; Thiriot, Aude; Lynch, Lydia; Loughhead, Scott M; Stutte, Susanne; Mazo, Irina B; Kopp, Marcel A; Brommer, Benedikt; Blex, Christian; Geurtz, Laura-Christin; Liebscher, Thomas; Niedeggen, Andreas; Dirnagl, Ulrich; Bradke, Frank; Volz, Magdalena S; DeVivo, Michael J; Chen, Yuying; von Andrian, Ulrich H; Schwab, Jan M

2017-11-01

Acute spinal cord injury (SCI) causes systemic immunosuppression and life-threatening infections, thought to result from noradrenergic overactivation and excess glucocorticoid release via hypothalamus-pituitary-adrenal axis stimulation. Instead of consecutive hypothalamus-pituitary-adrenal axis activation, we report that acute SCI in mice induced suppression of serum norepinephrine and concomitant increase in cortisol, despite suppressed adrenocorticotropic hormone, indicating primary (adrenal) hypercortisolism. This neurogenic effect was more pronounced after high-thoracic level (Th1) SCI disconnecting adrenal gland innervation, compared with low-thoracic level (Th9) SCI. Prophylactic adrenalectomy completely prevented SCI-induced glucocorticoid excess and lymphocyte depletion but did not prevent pneumonia. When adrenalectomized mice were transplanted with denervated adrenal glands to restore physiologic glucocorticoid levels, the animals were completely protected from pneumonia. These findings identify a maladaptive sympathetic-neuroendocrine adrenal reflex mediating immunosuppression after SCI, implying that therapeutic normalization of the glucocorticoid and catecholamine imbalance in SCI patients could be a strategy to prevent detrimental infections.

[Participation of pineal gland in antistressor activity of adaptogenic drugs].

PubMed

Arushanian, É B; Beĭer, É V

2015-01-01

Chronic stress produces some morphological changes in rats, including thymus weight reduction, adrenal hypertrophy, and peptic ulcers in stomach. Repeated administration of phytoadaptogenic drugs (ginseng and bilobil) decreased these stress-induced disorders. The antistressor activity of drugs was attenuated upon by removal of the pineal gland. Histochemical and morphometric investigation of pineal tissues in stressed animals showed that that the pharmacological effect was accompanied by increasing functional activity of the pineal gland. It is suggested that pineal mobilization may participate in antistressor activity of phytoadaptogenic drugs.

Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

PubMed

Müller, Mareike Hildegard; Rödel, Franz; Rüb, Udo; Korf, Horst-Werner

2015-02-01

The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos, J.

1980-01-01

The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

Posterior retroperitoneoscopic adrenal surgery for clinical and subclinical Cushing's syndrome in patients with bilateral adrenal disease.

PubMed

Lowery, Aoife J; Seeliger, Barbara; Alesina, Pier F; Walz, Martin K

2017-08-01

The treatment of hypercortisolism for patients with bilateral adrenal disease (BAD) is controversial. Bilateral total adrenalectomy results in permanent hypocortisolaemia requiring lifelong steroid replacement. A more conservative surgical approach, with less than bilateral total adrenalectomy (leaving functional adrenal tissue either unilaterally or bilaterally), represents an alternative option; however, long-term outcome or recurrence data are limited. We report our experience with the surgical management of hypercortisolism caused by BAD. Between 2004 and 2016, 42 patients (12 male, 30 female; mean age 58 ± 10 years) with clinical or subclinical Cushing's syndrome (CS/sCS) caused by BAD underwent adrenal surgery via the posterior retroperitoneoscopic approach. Adrenal surgery was defined as "adrenalectomy" when total gland excision was performed or "resection" when a partial or subtotal adrenal resection was performed. Clinical, radiological and biochemical parameters were evaluated preoperatively and postoperatively. Seventy adrenal operations performed in total included unilateral resection (n = 3), unilateral adrenalectomy (n = 15), bilateral resection (n = 9), adrenalectomy and contralateral resection (n = 14) and bilateral total adrenalectomy (n = 3). Median operating time was 47.5 min (30-150) with no difference between unilateral and bilateral (synchronous included) procedures (p = 0.15). Mortality was zero. Clavien-Dindo grade of postoperative complications was I (n = 5) and IV (n = 3). All but one patient with CS and 17/31 patients with sCS received postoperative steroid supplementation for a median duration of 20 (1.5-129) months. After median follow-up of 40 months (3-129), the remission rate was 92%; 11 patients required ongoing steroid supplementation. There were three biochemical recurrences (two underwent contralateral resection); two patients with new/progressive radiological nodularity are biochemically eucortisolaemic. A

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids.

PubMed

Yarnell, Kelly; Purcell, Rebecca S; Walker, Susan L

2016-04-25

Adrenal activity can be assessed in the equine species by analysis of feces for corticosterone metabolites. During a potentially aversive situation, corticotrophin releasing hormone (CRH) is released from the hypothalamus in the brain. This stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, which in turn stimulates release of glucocorticoids from the adrenal gland. In horses the glucocorticoid corticosterone is responsible for several adaptations needed to support equine flight behaviour and subsequent removal from the aversive situation. Corticosterone metabolites can be detected in the feces of horses and assessment offers a non-invasive option to evaluate long term patterns of adrenal activity. Fecal assessment offers advantages over other techniques that monitor adrenal activity including blood plasma and saliva analysis. The non-invasive nature of the method avoids sampling stress which can confound results. It also allows the opportunity for repeated sampling over time and is ideal for studies in free ranging horses. This protocol describes the enzyme linked immunoassay (EIA) used to assess feces for corticosterone, in addition to the associated biochemical validation.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition.

PubMed

Strickland, Corinne D; Eberhardt, Steven C; Bartlett, Mary R; Nelson, Jeffrey; Kim, Helen; Morrison, Leslie A; Hart, Blaine L

2017-08-01

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

Adrenal tuberculosis after a pheochromocytoma: a misleading tumoral presentation.

PubMed

Hiéronimus, S; Bernard, J-L; Chevallier, P; Chevallier, A; Chyderiotis, G; Fenichel, P; Landraud, L

2007-06-01

Adrenal gland involvement could account for 6% of active tuberculosis. The diagnosis of this extrapulmonary form of tuberculosis is difficult, especially when presenting as unilateral adrenal tumor. This report describes an unusual case of adrenal tuberculosis presenting as a tumor occurring shortly after surgical removal of an adrenal pheochromocytoma located in the opposite gland, in a 63-year-old woman with a previous history of breast cancer. At initial presentation, the patient suffered from symptomatic paroxysmal hypertension. A pheochromocytoma in the left adrenal was diagnosed and resected. One year later, while physical examination and biological parameters were unremarkable, an enhanced adrenal computed tomography (CT) scan showed a right adrenal mass mimicking the CT features of the resected pheochromocytoma. A peripheral tissular rim delineating a central hypodensity characterized this tumor. Magnetic resonance imaging (MRI) showed the same findings on gadolinium-enhanced T1-weighted slices, while the mass was not seen on T2-weighted images. No tumoral signal loss was observed on out of phase images when using the in phase-out of phase T1-weighted sequence. Because of the tumoral evolution and the uncertainty of the nature of that lesion, the patient underwent a second adrenalectomy. Definitive diagnosis was provided by culture of tissue sample, which resulted in the identification of Mycobacterium tuberculosis. In an era of tuberculosis resurgence, this unusual case underscores the necessity of keeping in mind adrenal tuberculosis as a possible differential diagnosis in adrenal tumors of uncertainty nature. It stresses the importance of culture of biopsy tumor, whenever feasible, to avoid unnecessary operations. In the near future, interferon-gamma assay could be a valuable means to recognize extrapulmonary forms of tuberculosis.

Unusual Differentiation to Pheochromocytoma-Like Cells in an Adrenal Neuroblastoma After Chemotherapy: A Case Report and Literature Review.

PubMed

Tatekawa, Yukihiro

2015-01-01

The authors present a case of 3-year-old female with Stage 4 neuroblastoma originating from the left adrenal gland. Biopsy of the left adrenal tumor showed neuroblastoma. After three courses of chemotherapy, the left adrenal gland including the left adrenal tumor was surgically removed. Pathological findings of the resected tumor revealed that most of the neuroblastoma tissues changed to pheochromocytoma-like cells. The tumor cells were arranged in well-defined nests surrounded by a delicate fibrovascular stroma and had granular eosinophilic cytoplasm, and round to oval nuclei. Immunohistological analysis of the biopsy samples showed strongly positive Ganglioside GD2-staining cells, whereas almost all of the tumor cells in the resected specimen were Ganglioside GD2-negative; cells were very weakly stained. The authors suggest that a part of the neuroblastoma in the left adrenal gland exhibited unusual differentiation toward pheochromocytic lineage Ganglioside GD2-negative neuroblastoma in a patient who had been treated with intensive chemotherapy.

High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease.

PubMed

Venizelos, I; Venizelos, J; Tamiolakis, D; Lambropoulou, M; Alexiadis, G; Petrakis, G; Papadopoulos, N

2007-08-01

We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3

PubMed Central

Vidal, Valerie; Sacco, Sonia; Rocha, Ana Sofia; da Silva, Fabio; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

2016-01-01

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. PMID:27313319

Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

ERIC Educational Resources Information Center

Resnick, Susan M.; And Others

1986-01-01

Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

Variant adrenal venous anatomy in 546 laparoscopic adrenalectomies.

PubMed

Scholten, Anouk; Cisco, Robin M; Vriens, Menno R; Shen, Wen T; Duh, Quan-Yang

2013-04-01

Knowing the types and frequency of adrenal vein variants would help surgeons identify and control the adrenal vein during laparoscopic adrenalectomy. To establish the surgical anatomy of the main vein and its variants for laparoscopic adrenalectomy and to analyze the relationship between variant adrenal venous anatomy and tumor size, pathologic diagnosis, and operative outcomes. In a retrospective review of patients at a tertiary referral hospital, 506 patients underwent 546 consecutive laparoscopic adrenalectomies between April 22, 1993, and October 21, 2011. Patients with variant adrenal venous anatomy were compared with patients with normal adrenal venous anatomy regarding preoperative variables (patient and tumor characteristics [size and location] and clinical diagnosis), intraoperative variables (details on the main adrenal venous drainage, any variant venous anatomy, duration of operation, rate of conversion to hand-assisted or open procedure, and estimated blood loss), and postoperative variables (transfusion requirement, reoperation for bleeding, duration of hospital stay, and histologic diagnosis). Laparoscopic adrenalectomy. Prevalence of variant adrenal venous anatomy and its relationship to tumor characteristics, pathologic diagnosis, and operative outcomes. Variant venous anatomy was encountered in 70 of 546 adrenalectomies (13%). Variants included no main adrenal vein identifiable (n = 18), 1 main adrenal vein with additional small veins (n = 11), 2 adrenal veins (n = 20), more than 2 adrenal veins (n = 14), and variants of the adrenal vein drainage to the inferior vena cava and hepatic vein or of the inferior phrenic vein (n = 7). Variants occurred more often on the right side than on the left side (42 of 250 glands [17%] vs. 28 of 296 glands [9%], respectively; P = .02). Patients with variant anatomy compared with those with normal anatomy had larger tumors (mean, 5.1 vs 3.3 cm, respectively; P < .001), more pheochromocytomas (24 of 70 [35%] vs

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

PubMed

Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo

2002-04-01

To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

PubMed

Gallo-Payet, Nicole

2016-05-01

The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH. © 2016 Society for Endocrinology.

State of hypophsis-adrenal gland in conditions of vibration pathology and its correction in experiment.

PubMed

Kapanadze, N

2006-08-01

Vibration is one of the pathological factors, which causes various alterations in the cells and organs. The goal of the research was the investigation of the hypophysis-adrenal gland system during the vibration and possible methods of its correction. The experiment was held on 70 grown-up male rats from 180 to 200 gr in weight. An hour vibroseance was carried out daily during two months period. According to the means of treatment animals were divided into three groups. The control group was consisted of 10 animals. In the first group (experimental vibratory pathology without any therapy) concentration of AKTH began to increase and reached 154% by the 20th day; by the 40th day it was 130%; AKTH concentration decreased up to 87% by the 60th day. The corticosterone in the blood plasma increased gradually and by the 20th day reached approximately 188%, which by the 40th day gradually decreased to 156%, and by the 60th day it was 129%. The second group was composed of animals, which underwent liquid oxygen therapy after the vibroseance. The AKTH content in the blood plasma of the second group animals was less increased: by the 20th day it reached 134%, by the 40th day it was 117%, and by the 60th day it decreased to 84%. The corticosterone concentration in the second group was lower by the 20th day it was 168%; by the 40th day it reached approximately 143%, and by the 60th day decreased to 127%. The third group was composed of retabolil treated animals. The AKTH concentration in animals by the 20th day reached 206%, and then decreased gradually, and by the 40th day it was 189%, and by the 60th day decreased to 145%. The corticosterone content in the blood plasma was high. By the 20th day the concentration was 263%, then it gradually decreased and by the 40th day reached 242%, and by the 60th day it was 199%. According to the experimental data vibration leads to the activation of hypophysis-adrenal gland system. Increased AKTH initiated increase of corticosterone.

Asymptomatic myelolipoma of the adrenal.

PubMed

Hadjigeorgi, C; Lafoyianni, S; Pontikis, Y; Van Vliet-Constantinidou, C

1992-01-01

Myelolipoma of the adrenal gland is a rare benign tumour which seldom produces symptoms unless it attains considerable size or hemorrhages into itself. Histologically the tumor is composed of varying proportions of fat and bone marrow elements. We present a case of a male child, with homozygous beta thalassemia and asymptomatic myelolipoma.

From Appearance of Adrenal Autoantibodies to Clinical Symptoms of Addison's Disease: Natural History.

PubMed

Betterle, Corrado; Garelli, Silvia; Presotto, Fabio; Furmaniak, Jadwiga

2016-01-01

Recent progress in the immunopathology field has greatly improved our understanding of the natural history of autoimmune diseases, particularly of Addison's disease. Addison's disease is known to be a chronic illness characterized by adrenocortical gland insufficiency that develops following a long and mainly asymptomatic period, characterized by the presence of circulating autoantibodies directed to adrenal cortex antigens. In this chapter we describe the groups of subjects at risk of developing Addison's disease, together with the diagnostic tests considered the most appropriate for evaluating adrenal function: determination of basal plasma adrenocorticotropic hormone (ACTH) levels, plasma renin activity, plasma aldosterone and cortisol levels, and cortisol levels after intravenous stimulation with ACTH (ACTH test). The employment of specific clinical, immunological and functional criteria in the subjects with autoantibodies to the adrenal cortex allows identifying those at risk of developing overt disease. The independent risk factors for the progression to adrenal failure have also been identified and they contribute to different risks of developing clinical Addison's disease. Based on the risk level, the subjects should be monitored over time to observe early signs of adrenal dysfunction, and start substitutive treatment as soon as possible. For patients presenting with high risk, prevention strategies and trials might be available. © 2016 S. Karger AG, Basel.

The Aging Lacrimal Gland: Changes in Structure and Function

PubMed Central

Rocha, Eduardo M.; Alves, Monica; Rios, J. David; Dartt, Darlene A.

2014-01-01

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed. PMID:18827949

The aging lacrimal gland: changes in structure and function.

PubMed

Rocha, Eduardo M; Alves, Monica; Rios, J David; Dartt, Darlene A

2008-10-01

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

The adrenal capsule is a signaling center controlling cell renewal and zonation through Rspo3.

PubMed

Vidal, Valerie; Sacco, Sonia; Rocha, Ana Sofia; da Silva, Fabio; Panzolini, Clara; Dumontet, Typhanie; Doan, Thi Mai Phuong; Shan, Jingdong; Rak-Raszewska, Aleksandra; Bird, Tom; Vainio, Seppo; Martinez, Antoine; Schedl, Andreas

2016-06-15

Adrenal glands are zonated endocrine organs that are essential in controlling body homeostasis. How zonation is induced and maintained and how renewal of the adrenal cortex is ensured remain a mystery. Here we show that capsular RSPO3 signals to the underlying steroidogenic compartment to induce β-catenin signaling and imprint glomerulosa cell fate. Deletion of RSPO3 leads to loss of SHH signaling and impaired organ growth. Importantly, Rspo3 function remains essential in adult life to ensure replenishment of lost cells and maintain the properties of the zona glomerulosa. Thus, the adrenal capsule acts as a central signaling center that ensures replacement of damaged cells and is required to maintain zonation throughout life. © 2016 Vidal et al.; Published by Cold Spring Harbor Laboratory Press.

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

PubMed

Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

1988-11-01

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

PubMed Central

Schalling, M; Dagerlind, A; Brené, S; Hallman, H; Djurfeldt, M; Persson, H; Terenius, L; Goldstein, M; Schlesinger, D; Hökfelt, T

1988-01-01

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla. Images PMID:2903502

Mammary gland tumors in irradiated and untreated guinea pigs

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

Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.

1986-01-01

This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in themore » morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.« less

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands

PubMed Central

Nishimoto, Koshiro; Tomlins, Scott A.; Kuick, Rork; Cani, Andi K.; Giordano, Thomas J.; Hovelson, Daniel H.; Liu, Chia-Jen; Sanjanwala, Aalok R.; Edwards, Michael A.; Gomez-Sanchez, Celso E.; Nanba, Kazutaka; Rainey, William E.

2015-01-01

Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression. Herein, we hypothesized that APCCs have APA-related aldosterone-stimulating somatic gene mutations. APCCs were studied in 42 normal adrenals from kidney donors. To clarify APCC molecular characteristics, we used microarrays to compare the APCC transcriptome with conventional adrenocortical zones [zona glomerulosa (ZG), zona fasciculata, and zona reticularis]. The APCC transcriptome was most similar to ZG but with an enhanced capacity to produce aldosterone. To determine if APCCs harbored APA-related mutations, we performed targeted next generation sequencing of DNA from 23 APCCs and adjacent normal adrenal tissue isolated from both formalin-fixed, paraffin-embedded, and frozen tissues. Known aldosterone driver mutations were identified in 8 of 23 (35%) APCCs, including mutations in calcium channel, voltage-dependent, L-type, α1D-subunit (CACNA1D; 6 of 23 APCCs) and ATPase, Na+/K+ transporting, α1-polypeptide (ATP1A1; 2 of 23 APCCs), which were not observed in the adjacent normal adrenal tissue. Overall, we show three major findings: (i) APCCs are common in normal adrenals, (ii) APCCs harbor somatic mutations known to cause excess aldosterone production, and (iii) the mutation spectrum of aldosterone-driving mutations is different in APCCs from that seen in APA. These results provide molecular support for APCC as a precursor of PA. PMID:26240369

Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues.

PubMed

Morimoto, Ryo; Satoh, Fumitoshi; Murakami, Osamu; Hirose, Takuo; Totsune, Kazuhito; Imai, Yutaka; Arai, Yoichi; Suzuki, Takashi; Sasano, Hironobu; Ito, Sadayoshi; Takahashi, Kazuhiro

2008-07-01

Adrenomedullin 2/intermedin (AM2/IMD) is a new member of calcitonin/calcitonin gene-related peptide family. AM is expressed in various tumors including adrenocortical tumors and modulates tumor growth. The AM2/IMD expression has not been studied, however, in adrenal tumors. The expression of AM2/IMD and AM was therefore studied in human adrenal tumors and attached non-neoplastic adrenal tissues by immunocytochemistry (ICC). Immunoreactive (IR)-AM2/IMD was measured by RIA. Furthermore, the expression of AM2/IMD and its receptor components, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) 1, 2, and 3 mRNA in these tissues was studied by reverse transcription PCR (RT-PCR). ICC showed that AM2/IMD and AM immunoreactivities were localized in adrenocortical tumors and pheochromocytomas. AM2/IMD and AM immunoreactivities were detected in medulla of attached non-neoplastic tissues, while the degree of immunoreactivity for AM2/IMD and AM in cortices of attached adrenals was relatively weak or undetectable. RIA detected IR-AM2/IMD in adrenal tumors (0.414+/-0.12 to 0.786+/-0.27 pmol/g wet weight, mean+/-S.E.M.) and attached adrenal tissues (0.397+/-0.052 pmol/g wet weight). Reverse-phase high-performance liquid chromatography showed one broad peak eluted in the similar position to synthetic AM2/IMD with several minor peaks. RT-PCR showed expression of AM2/IMD, CRLR, and RAMP1, RAMP2, and RAMP3 mRNA in tissues of adrenal tumors and attached adrenal glands. In conclusion, AM2/IMD is expressed in human adrenal tumors and attached non-neoplastic adrenal tissues and may play (patho-)physiological roles in normal and neoplastic adrenals as an autocrine/paracrine regulator.

Bilateral adrenal histoplasmosis: endoscopic ultrasound-guided fine needle aspiration as a method of diagnosis and assessment.

PubMed

Azhar, J Khairul; Jacqueline, H S G; Tony, L K H; Tan, B H; Steven, J M

2011-12-01

We report a case of a healthy 78-year-old indonesian man who presented with chronic weight loss, poor appetite and lethargy. CT abdomen showed bilateral adrenal masses. EUS-guided FNA was performed on the left adrenal gland. Histopathology report was Histoplasma Capsulatum. He recovered well with antifungal treatment without any complication. In this case, we found that the role of EUS -guided FNA was not only limited to diagnosis but also helped in the prognosis of the disease since the method was able to assess the general anatomy of the adrenal gland better than other imaging modalities due to its close proximity and direct visualization.

Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

PubMed

Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

2013-11-28

Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of

Adrenal Oncocytic Neoplasm with Paradoxical Loss of Important Mitochondrial Steroidogenic Protein: The 18 kDA Translocator Protein

PubMed Central

Ciancio, Gaetano; Nielsen, Gunnlaugur Petur; Jorda, Merce

2017-01-01

The adrenal glands produce a variety of hormones that play a key role in the regulation of blood pressure, electrolyte homeostasis, metabolism, immune system suppression, and the body's physiologic response to stress. Adrenal neoplasms can be asymptomatic or can overproduce certain hormones that lead to different clinical manifestations. Oncocytic adrenal neoplasms are infrequent tumors that arise from cells in the adrenal cortex and display a characteristic increase in the number of cytoplasmic mitochondria. Since the rate-limiting step in steroidogenesis includes the transport of cholesterol across the mitochondrial membranes, in part carried out by the 18-kDa translocator protein (TSPO), we assessed the expression of TSPO in a case of adrenal oncocytic neoplasm using residual adrenal gland of the patient as internal control. We observed a significant loss of TSPO immunofluorescence expression in the adrenal oncocytic tumor cells when compared to adjacent normal adrenal tissue. We further confirmed this finding by employing Western blot analysis to semiquantify TSPO expression in tumor and normal adrenal cells. Our findings could suggest a potential role of TSPO in the tumorigenesis of this case of adrenocortical oncocytic neoplasm. PMID:29318061

Direct effects of recurrent hypoglycaemia on adrenal catecholamine release.

PubMed

Orban, Branly O; Routh, Vanessa H; Levin, Barry E; Berlin, Joshua R

2015-01-01

In Type 1 and advanced Type 2 diabetes mellitus, elevation of plasma epinephrine plays a key role in normalizing plasma glucose during hypoglycaemia. However, recurrent hypoglycaemia blunts this elevation of plasma epinephrine. To determine whether recurrent hypoglycaemia affects peripheral components of the sympatho-adrenal system responsible for epinephrine release, male rats were administered subcutaneous insulin daily for 3 days. These recurrent hypoglycaemic animals showed a smaller elevation of plasma epinephrine than saline-injected controls when subjected to insulin-induced hypoglycaemia. Electrical stimulation of an adrenal branch of the splanchnic nerve in recurrent hypoglycaemic animals elicited less release of epinephrine and norepinephrine than in controls, without a change in adrenal catecholamine content. Responsiveness of isolated, perfused adrenal glands to acetylcholine and other acetylcholine receptor agonists was also unchanged. These results indicate that recurrent hypoglycaemia compromised the efficacy with which peripheral neuronal activity stimulates adrenal catecholamine release and demonstrate that peripheral components of the sympatho-adrenal system were directly affected by recurrent hypoglycaemia. © The Author(s) 2014.

Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas.

PubMed

Kann, Peter Herbert

2016-01-01

Endoscopic ultrasound (EUS) imaging of adrenal glands and its application to diagnostic procedures of adrenal diseases has been reported since 1998. It can be considered a relevant advantage in the field of adrenal diseases. Indeed, EUS allows the detection of adrenal lesions (even very small ones) and their characterization, the assessment of malignancy criteria, the early detection of neoplastic recurrences, the preoperative identification of morphologically healthy parts of the glands, the differentiation of extra-adrenal from adrenal tumors, and of the pathological entities associated with adrenal insufficiency, and the fine-needle aspiration biopsy (EUS-FNA) of suspicious lesions. At the same time, its clinical relevance depends on the experience of the endosonographer. Moreover, EUS is also by far the best and most sensitive imaging technique to detect and assess the follow-up of pancreatic manifestation of MEN1 disease. It furthermore enables the preoperatively localization of insulinomas and critical structures in their neighborhood, and may be relevant in planning surgical strategy. A positive EUS in a case of insulinoma furthermore confirms the endocrine diagnosis, especially considering the differential diagnosis of hypoglycemia factitia by oral antidiabetics. It can be supplemented by EUS-FNA. Again, it has to be considered that EUS may reveal false positive and false negative results, and the quality of the findings largely depends on the endosonographer's skills and experience. The most important technical details together with the advantages and limitations of EUS, and the pathognomonic characteristic of benign and malignant disorders of the adrenals and pancreas are presented here. © 2016 S. Karger AG, Basel.

Ewing's sarcoma arising from the adrenal gland in a young male: a case report.

PubMed

Zahir, Muhammad Nauman; Ansari, Tayyaba Zehra; Moatter, Tariq; Memon, Wasim; Pervez, Shahid

2013-12-13

Ewing's sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing's Sarcoma, although very rare, is extremely aggressive and commonly fatal. A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease.Computed tomography scans revealed a large peripherally enhancing mass in the hepatorenal area, biopsy of which showed a neoplastic lesion composed of small round blue cells which exhibited abundance of glycogen and stained diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization demonstrated gene rearrangement at chromosome 22q12 which confirmed the diagnosis of Ewing's sarcoma. Staging scans revealed pulmonary metastasis and hence he was commenced on systemic chemotherapy. This case report highlights the importance of keeping Ewing's sarcoma in mind when a young patient presents with a large non-functional adrenal mass.

Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

PubMed Central

de Souza, Patrícia Reis; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda

2016-01-01

The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

PubMed

Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

2015-01-01

Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

CCAAT/enhancer-binding protein β is involved in the breed-dependent transcriptional regulation of 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase in adrenal gland of preweaning piglets.

PubMed

Li, Xian; Li, Runsheng; Jia, Yimin; Sun, Zhiyuan; Yang, Xiaojing; Sun, Qinwei; Zhao, Ruqian

2013-11-01

The enzyme 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase (3β-HSD) catalyzes the biosynthesis of all steroid hormones. The molecular mechanisms regulating porcine adrenal 3β-HSD expression in different breeds are still poorly understood. In this study, we aimed to compare the expression of 3β-HSD between preweaning purebred Large White (LW) and Erhualian (EHL) piglets and to explore the potential factors regulating 3β-HSD transcription. EHL had significantly higher serum levels of cortisol (P<0.01) and testosterone (P<0.01), which were associated with significantly higher expression of 3β-HSD mRNA (P<0.01) and protein (P<0.05) in the adrenal gland, compared with LW piglets. The 5' flanking region of the porcine 3β-HSD gene showed significant sequence variations between breeds, and the sequence of EHL demonstrated an elevated promoter activity (P<0.05) in luciferase reporter gene assay. Higher adrenal expression of 3β-HSD in EHL was accompanied with higher CCAAT/enhancer binding protein β (C/EBPβ) expression (P<0.05), enriched histone H3 acetylation (P<0.05) and C/EBPβ binding to 3β-HSD promoter (P<0.05). In addition, higher androgen receptor (AR) (P=0.06) and lower glucocorticoid receptor (GR) (P<0.05) were detected in EHL. Co-immunoprecipitation analysis revealed interactions of C/EBPβ with both AR and GR. These results indicate that the C/EBPβ binding to 3β-HSD promoter is responsible, at least in part, for the breed-dependent 3β-HSD expression in adrenal gland of piglets. The sequence variations of 3β-HSD promoter and the interactions of AR and/or GR with C/EBPβ may also participate in the regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

News about the genetics of congenital primary adrenal insufficiency.

PubMed

Roucher-Boulez, Florence; Mallet-Motak, Delphine; Tardy-Guidollet, Véronique; Menassa, Rita; Goursaud, Claire; Plotton, Ingrid; Morel, Yves

2018-04-13

Primary adrenal insufficiency (PAI) is characterized by impaired production of steroid hormones due to an adrenal cortex defect. This condition incurs a risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relating to oxidative stress have opened the way to research on genes unrelated to the adrenal gland. Identification of causal mutations in a gene responsible for PAI allows genetic counseling, guidance of follow-up and prevention of complications. This is particularly true for stress oxidative anomalies, as extra-adrenal manifestations may occur due to the sensitivity to oxidative stress of other organs such as the heart, thyroid, liver, kidney and pancreas. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Serotonin involvement in pituitary-adrenal function

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Kellar, K. J.; Kent, D.; Gonzales, C.; Berger, P. A.; Barchas, J. D.

1977-01-01

Experiments clarifying the effects of serotonin (5-HT) in the regulation of the hypothalamic-pituitary-adrenocortical system are surveyed. Lesion experiments which seek to determine functional maps of serotonergic input to areas involved in regulation are reported. Investigations of the effects of 5-HT levels on the plasma ACTH response to stress and the diurnal variation in basal plasma corticosterone are summarized, and the question of whether serotonergic transmission is involved in the regulation of all aspects of pituitary-adrenal function is considered with attention to the stimulatory and inhibitory action of 5-HT.

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.

THE ROLE OF THE PINEAL GLAND AND OF ENVIRONMENTAL LIGHTING IN THE REGULATION OF THE ENDOCRINE AND REPRODUCTIVE SYSTEMS OF RODENTS.

DTIC Science & Technology

PHOTOPERIODISM, REPRODUCTION(PHYSIOLOGY)), (*ENDOCRINE GLANDS , REPRODUCTION(PHYSIOLOGY)), RODENTS, REPRODUCTIVE SYSTEM, EYE, EXCISION, TESTES, OVARIES, ADRENAL GLANDS , THYROID GLAND , IODINE, THIOUREA, RATS, HAMSTERS

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient.

PubMed

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase.

An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient

PubMed Central

Marmouch, Hela; Arfa, Sondes; Mohamed, Saoussen Cheikh; Slim, Tensim; Khochtali, Ines

2016-01-01

Metastases of solid tumors to the pituitary gland are often asymptomatic or appereas as with diabetes insipid us. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The presentation with an acute adrenal insufficiency is a rare event. A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary opacity. Computed tomography scan of the chest showed a multiples tumors with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases. This case emphasizes the need for an etiological investigation of acute adrenal insufficiency after treatment of acute phase. PMID:27200139

Laparoscopic Management of an Adrenal Leiomyoma in an AIDS Patient. A Case Report and Review of the Literature

PubMed Central

White, Alan; Kaleya, Ronald

2005-01-01

Objectives: Laparoscopic management of adrenal masses has been well described. Immunologically compromised patients can obtain significant benefit from these minimally invasive procedures. We describe a case of an enlarging smooth muscle tumor of the adrenal gland in an acquired immunodeficiency syndrome (AIDS) patient and review the sparse literature available on this subject. Case Report: A 49-year-old female with AIDS complaining of vague abdominal discomfort was found to have a left adrenal mass. Significant enlargement of the mass was noted during routine follow-up. The patient underwent an elective laparoscopic left adrenalectomy without complications. Pathological review found the mass to be a rare adrenal leiomyoma. Discussion: Benign, smooth muscle tumors arising from the adrenal glands are rare. A review of the literature does reveal a propensity for these tumors to occur in the immunocompromised population. Conclusion: The ability to manage these tumors laparoscopically is of significant benefit to patients. PMID:16121885

Neonatal overfeeding increases capacity for catecholamine biosynthesis from the adrenal gland acutely and long-term in the male rat.

PubMed

Sominsky, Luba; Ong, Lin Kooi; Ziko, Ilvana; Dickson, Phillip W; Spencer, Sarah J

2018-07-15

A poor nutritional environment during early development has long been known to increase disease susceptibility later in life. We have previously shown that rats that are overfed as neonates (i.e. suckled in small litters (4 pups) relative to control conditions (12 pups)) show dysregulated hypothalamic-pituitary-adrenal axis responses to immune stress in adulthood, particularly due to an altered capacity of the adrenal to respond to an immune challenge. Here we hypothesised that neonatal overfeeding similarly affects the sympathomedullary system, testing this by investigating the biochemical function of tyrosine hydroxylase (TH), the first rate-limiting enzyme in the catecholamine synthesis. We also examined changes in adrenal expression of the leptin receptor and in mitogen-activated protein kinase (MAPK) signalling. During the neonatal period, we saw age-dependent changes in TH activity and phosphorylation, with neonatal overfeeding stimulating increased adrenal TH specific activity at postnatal days 7 and 14, along with a compensatory reduction in total TH protein levels. This increased TH activity was maintained into adulthood where neonatally overfed rats exhibited increased adrenal responsiveness 30 min after an immune challenge with lipopolysaccharide, evident in a concomitant increase in TH protein levels and specific activity. Neonatal overfeeding significantly reduced the expression of the leptin receptor in neonatal adrenals at postnatal day 7 and in adult adrenals, but did not affect MAPK signalling. These data suggest neonatal overfeeding alters the capacity of the adrenal to synthesise catecholamines, both acutely and long term, and these effects may be independent of leptin signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma.

PubMed

Nadolski, Amy C; Markovich, Jessica E; Jennings, Samuel H; Mahony, Orla M

2016-10-01

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior.

Mammary development, hyperestrogenemia, and hypocortisolemia in a male cat with an adrenal cortical carcinoma

PubMed Central

Nadolski, Amy C.; Markovich, Jessica E.; Jennings, Samuel H.; Mahony, Orla M.

2016-01-01

A 14-year-old neutered male domestic shorthaired cat was diagnosed with an adrenal cortical carcinoma causing hyperestrogenemia that resulted in mammary hyperplasia and sexual behavior. A right adrenalectomy and mammary gland biopsy were performed. Adrenal cortical neoplasia should be ruled out in any neutered male cat with mammary development and/or exhibiting sexual behavior. PMID:27708447

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Hernandez, Karen Gomez; Mete, Ozgur

2015-06-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinicopathological correlates of adrenal Cushing's syndrome.

PubMed

Duan, Kai; Gomez Hernandez, Karen; Mete, Ozgur

2015-03-01

Endogenous Cushing's syndrome is a rare endocrine disorder that incurs significant cardiovascular morbidity and mortality, due to glucocorticoid excess. It comprises adrenal (20%) and non-adrenal (80%) aetiologies. While the majority of cases are attributed to pituitary or ectopic corticotropin (ACTH) overproduction, primary cortisol-producing adrenal cortical lesions are increasingly recognised in the pathophysiology of Cushing's syndrome. Our understanding of this disease has progressed substantially over the past decade. Recently, important mechanisms underlying the pathogenesis of adrenal hypercortisolism have been elucidated with the discovery of mutations in cyclic AMP signalling (PRKACA, PRKAR1A, GNAS, PDE11A, PDE8B), armadillo repeat containing 5 gene (ARMC5) a putative tumour suppressor gene, aberrant G-protein-coupled receptors, and intra-adrenal secretion of ACTH. Accurate subtyping of Cushing's syndrome is crucial for treatment decision-making and requires a complete integration of clinical, biochemical, imaging and pathology findings. Pathological correlates in the adrenal glands include hyperplasia, adenoma and carcinoma. While the most common presentation is diffuse adrenocortical hyperplasia secondary to excess ACTH production, this entity is usually treated with pituitary or ectopic tumour resection. Therefore, when confronted with adrenalectomy specimens in the setting of Cushing's syndrome, surgical pathologists are most commonly exposed to adrenocortical adenomas, carcinomas and primary macronodular or micronodular hyperplasia. This review provides an update on the rapidly evolving knowledge of adrenal Cushing's syndrome and discusses the clinicopathological correlations of this important disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

State of some peripheral organs during laser puncture correction of ovarian functional deficiency

NASA Astrophysics Data System (ADS)

Vylegzhanina, T. A.; Kuznetsova, Tatiana I.; Maneeva, O.; Ryzhkovskaya, E. L.; Yemelianova, A.

2001-01-01

The findings from studies on structural and functional parameters of the adrenal, thyroid, and pineal glands in conditions of ovarian hypofunction and after its correction by laser puncture are presented. An experimentally induced hypofunction of the ovaries was shown to be accompanied by a decreased hormonal synthesis in the cortical fascicular zone. The epiphysis showed ultra structural signs of increased functional activity. Application of a helium-neon laser to biologically active points of the ovarian reflexogenic zone induced normalization of the ovarian cycle, potentiating of the adrenal functional state, and a decreased thyroid hormone production and abolished the activatory effect of the dark regime on the functional state of the pineal gland.

EFFECT OF INFLAMMATION ON LACRIMAL GLAND FUNCTION

PubMed Central

Zoukhri, Driss

2005-01-01

The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sjögren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states. PMID:16309672

Rifampicin-induced adrenal crisis in a patient with tuberculosis: a therapeutic challenge.

PubMed

Denny, Nicholas; Raghunath, Sarika; Bhatia, Praveen; Abdelaziz, Muntasir

2016-11-29

A 55-year-old Indian man presented with productive cough and a large left pleural effusion. Pleural fluid culture grew Mycobacterium tuberculosis, and he was started on antituberculosis therapy. One week later, the patient presented to hospital with drowsiness, dehydration and hypotension. He was transferred to critical care and only improved after starting hydrocortisone and stopping rifampicin. His short synACTHen test subsequently confirmed primary adrenal insufficiency, and a CT of the abdomen showed bilateral adrenal enlargement. Rifampicin is known to accelerate cortisol metabolism. We report the rare case of a rifampicin-induced adrenal crisis as a first presentation of Addison's disease in a patient with tuberculous infiltration of the adrenal glands. 2016 BMJ Publishing Group Ltd.

Adrenal cortex expression quantitative trait loci in a German Holstein × Charolais cross.

PubMed

Brand, Bodo; Scheinhardt, Markus O; Friedrich, Juliane; Zimmer, Daisy; Reinsch, Norbert; Ponsuksili, Siriluck; Schwerin, Manfred; Ziegler, Andreas

2016-10-06

The importance of the adrenal gland in regard to lactation and reproduction in cattle has been recognized early. Caused by interest in animal welfare and the impact of stress on economically important traits in farm animals the adrenal gland and its function within the stress response is of increasing interest. However, the molecular mechanisms and pathways involved in stress-related effects on economically important traits in farm animals are not fully understood. Gene expression is an important mechanism underlying complex traits, and genetic variants affecting the transcript abundance are thought to influence the manifestation of an expressed phenotype. We therefore investigated the genetic background of adrenocortical gene expression by applying an adaptive linear rank test to identify genome-wide expression quantitative trait loci (eQTL) for adrenal cortex transcripts in cattle. A total of 10,986 adrenal cortex transcripts and 37,204 single nucleotide polymorphisms (SNPs) were analysed in 145 F2 cows of a Charolais × German Holstein cross. We identified 505 SNPs that were associated with the abundance of 129 transcripts, comprising 482 cis effects and 17 trans effects. These SNPs were located on all chromosomes but X, 16, 24 and 28. Associated genes are mainly involved in molecular and cellular functions comprising free radical scavenging, cellular compromise, cell morphology and lipid metabolism, including genes such as CYP27A1 and LHCGR that have been shown to affect economically important traits in cattle. In this study we showed that adrenocortical eQTL affect the expression of genes known to contribute to the phenotypic manifestation in cattle. Furthermore, some of the identified genes and related molecular pathways were previously shown to contribute to the phenotypic variation of behaviour, temperament and growth at the onset of puberty in the same population investigated here. We conclude that eQTL analysis appears to be a useful approach providing

Evidence for chronic stress in captive but not free-ranging cheetahs (Acinonyx jubatus) based on adrenal morphology and function.

PubMed

Terio, Karen A; Marker, Laurie; Munson, Linda

2004-04-01

The cheetah (Acinonyx jubatus) is highly endangered because of loss of habitat in the wild and failure to thrive in captivity. Cheetahs in zoos reproduce poorly and have high prevalences of unusual diseases that cause morbidity and mortality. These diseases are rarely observed in free-ranging cheetahs but have been documented in cheetahs that have been captured and held in captive settings either temporarily or permanently. Because captivity may be stressful for this species and stress is suspected as contributing to poor health and reproduction, this study aimed to measure chronic stress by comparing baseline concentrations of fecal corticoid metabolites and adrenal gland morphology between captive and free-ranging cheetahs. Additionally, concentrations of estradiol and testosterone metabolites were quantified to determine whether concentrations of gonadal steroids correlated with corticoid concentration and to assure that corticosteroids in the free-ranging samples were not altered by environmental conditions. Concetntrations of fecal corticoids, estradiol, and testosterone were quantified by radioimmunoassay in 20 free-ranging and 20 captive cheetahs from samples collected between 1994 and 1999. Concentrations of baseline fecal corticoids were significantly higher (p = 0.005) in captive cheetahs (196.08 +/- 36.20 ng/g dry feces) than free-ranging cheetahs (71.40 +/- 14.35 ng/g dry feces). Testosterone concentrations were lower in captive male cheetahs (9.09 +/- 2.84 ng/g dry feces) than in free-ranging cheetahs (34.52 +/- 12.11 ng/g dry feces), which suggests suppression by elevated corticoids in the captive males. Evidence for similar sulppression of estradiol concentrations in females was not present. Adrenal corticomedullary ratios were determined on midsagittal sections of adrenal glands from 13 free-ranging and 13 captive cheetahs obtained between 1991 and 2002. The degree of vacuolation of cortical cells in the zona fasciculata was graded for each animal

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Case report of a bilateral adrenal myelolipoma associated with Cushing disease.

PubMed

Park, Se Yoon; Kwak, Mi Kyung; Kim, Hye Jeong; Park, Hyeong Kyu; Suh, Kyo-Il; Yoo, Myung Hi; Jin, So Young; Yun, Sumi; Byun, Dong Won

2017-12-01

Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Monitoring the Secretory Behavior of the Rat Adrenal Medulla by High-Performance Liquid Chromatography-Based Catecholamine Assay from Slice Supernatants

PubMed Central

De Nardi, Frédéric; Lefort, Claudie; Bréard, Dimitri; Richomme, Pascal; Legros, Christian; Guérineau, Nathalie C.

2017-01-01

Catecholamine (CA) secretion from the adrenal medullary tissue is a key step of the adaptive response triggered by an organism to cope with stress. Whereas molecular and cellular secretory processes have been extensively studied at the single chromaffin cell level, data available for the whole gland level are much scarcer. We tackled this issue in rat by developing an easy to implement experimental strategy combining the adrenal acute slice supernatant collection with a high-performance liquid chromatography-based epinephrine and norepinephrine (NE) assay. This technique affords a convenient method for measuring basal and stimulated CA release from single acute slices, allowing thus to individually address the secretory function of the left and right glands. Our data point that the two glands are equally competent to secrete epinephrine and NE, exhibiting an equivalent epinephrine:NE ratio, both at rest and in response to a cholinergic stimulation. Nicotine is, however, more efficient than acetylcholine to evoke NE release. A pharmacological challenge with hexamethonium, an α3-containing nicotinic acetylcholine receptor antagonist, disclosed that epinephrine- and NE-secreting chromaffin cells distinctly expressed α3 nicotinic receptors, with a dominant contribution in NE cells. As such, beyond the novelty of CA assays from acute slice supernatants, our study contributes at refining the secretory behavior of the rat adrenal medullary tissue, and opens new perspectives for monitoring the release of other hormones and transmitters, especially those involved in the stress response. PMID:28993760

GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

PubMed Central

Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

2016-01-01

Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal

Extra-adrenal glucocorticoid synthesis in the intestinal epithelium: more than a drop in the ocean?

PubMed

Noti, Mario; Sidler, Daniel; Brunner, Thomas

2009-07-01

Glucocorticoids (GC) are lipophilic hormones commonly used as therapeutics in acute and chronic inflammatory disorders such as inflammatory bowel disease due to their attributed anti-inflammatory and immunosuppressive actions. Although the adrenal glands are the major source of endogenous GC, there is increasing evidence for the production of extra-adrenal GC in the brain, thymus, skin, vasculature, and the intestine. However, the physiological relevance of extra-adrenal-produced GC remains still ambiguous. Therefore, this review attracts attention to discuss possible biological benefits of extra-adrenal-synthesized GC, especially focusing on the impact of locally synthesized GC in the regulation of intestinal immune responses.

Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats.

PubMed

Campbell, Jonathan E; Király, Michael A; Atkinson, Daniel J; D'souza, Anna M; Vranic, Mladen; Riddell, Michael C

2010-07-01

exercise, likely because of adaptations that occur primarily in the adrenal glands.

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

2013-01-01

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland. PMID:24084941

Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma

PubMed Central

Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

2011-01-01

Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5–6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement. PMID:22679235

Laparoscopic resection of a large (11 cm) adrenal phaeochromocytoma.

PubMed

Chaudhary, Ranjit; Deshmukh, Abhijeet; Singh, Kulwant; Biswas, Rakesh

2011-09-13

Pheochromocytoma is a rare cause of hypertension. Usually the tumour arises in the adrenal and the only cure is surgical extirpation. Laparoscopic adrenalectomy is the gold standard. Traditionally, laparoscopic removal of adrenal tumour of more than 5-6 cm in size is contraindicated. The authors removed a 11×8 cm phaeochromocytoma by laparoscopic approach without any complications. A 52-year-old male presented with complaints of throbbing headache with palpitations. On evaluation, he was found to be severely hypertensive and his blood sugar levels were moderately elevated. Radiological investigations revealed a 11×8 cm left supra renal mass. A provisional diagnosis of left pheochromocytoma was made which was strengthened by the fact that 24 hourly urine sample revealed elevated vanillylmandelic acid levels. The authors decided to surgically extirpate the adrenal mass. This was successfully accomplished by a laparoscopic transperitoneal approach. No complications were encountered. Histopathology showed pheochromocytoma of left adrenal gland without capsular involvement.

Adrenal Venous Sampling: Where Is the Aldosterone Disappearing to?

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

Solar, Miroslav; Ceral, Jiri, E-mail: ceral.jiri@fnhk.c; Krajina, Antonin

Adrenal venous sampling (AVS) is generally considered to be the gold standard in distinguishing unilateral and bilateral aldosterone hypersecretion in primary hyperaldosteronism. However, during AVS, we noticed a considerable variability in aldosterone concentrations among samples thought to have come from the right adrenal glands. Some aldosterone concentrations in these samples were even lower than in samples from the inferior vena cava. We hypothesized that the samples with low aldosterone levels were unintentionally taken not from the right adrenal gland, but from hepatic veins. Therefore, we sought to analyze the impact of unintentional cannulation of hepatic veins on AVS. Thirty consecutivemore » patients referred for AVS were enrolled. Hepatic vein sampling was implemented in our standardized AVS protocol. The data were collected and analyzed prospectively. AVS was successful in 27 patients (90%), and hepatic vein cannulation was successful in all procedures performed. Cortisol concentrations were not significantly different between the hepatic vein and inferior vena cava samples, but aldosterone concentrations from hepatic venous blood (median, 17 pmol/l; range, 40-860 pmol/l) were markedly lower than in samples from the inferior vena cava (median, 860 pmol/l; range, 460-4510 pmol/l). The observed difference was statistically significant (P < 0.001). Aldosterone concentrations in the hepatic veins are significantly lower than in venous blood taken from the inferior vena cava. This finding is important for AVS because hepatic veins can easily be mistaken for adrenal veins as a result of their close anatomic proximity.« less

A review of the anatomy and clinical significance of adrenal veins.

PubMed

Cesmebasi, Alper; Du Plessis, Maira; Iannatuono, Mark; Shah, Sameer; Tubbs, R Shane; Loukas, Marios

2014-11-01

The adrenal veins may present with a multitude of anatomical variants, which surgeons must be aware of when performing adrenalectomies. The adrenal veins originate during the formation of the prerenal inferior vena cava (IVC) and are remnants of the caudal portion of the subcardinal veins, cranial to the subcardinal sinus in the embryo. The many communications between the posterior cardinal, supracardinal, and subcardinal veins of the primordial venous system provide an explanation for the variable anatomy. Most commonly, one central vein drains each adrenal gland. The long left adrenal vein joins the inferior phrenic vein and drains into the left renal vein, while the short right adrenal vein drains immediately into the IVC. Multiple variations exist bilaterally and may pose the risk of surgical complications. Due to the potential for collaterals and accessory adrenal vessels, great caution must be taken during an adrenalectomy. Adrenal venous sampling, the gold standard in diagnosing primary hyperaldosteronism, also requires the clinician to have a thorough knowledge of the adrenal vein anatomy to avoid iatrogenic injury. The adrenal vein acts as an important conduit in portosystemic shunts, thus the nature of the anatomy and hypercoagulable states pose the risk of thrombosis. © 2014 Wiley Periodicals, Inc.

Radiotherapy Dose-Volume Effects on Salivary Gland Function

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

Deasy, Joseph O., E-mail: jdeasy@radonc.wustl.ed; Moiseenko, Vitali; Marks, Lawrence

2010-03-01

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. Amore » lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.« less

Metastasis of Non-Muscle-Invasive Bladder Cancer Into the Thyroid Gland: A Literature Review Accompanied by a Rare Case

PubMed Central

Tuncer, Murat; Faydaci, Gokhan; Altin, Gokhan; Kibar, Sermin; Sanli, Arif; Bilgici, Dilek

2014-01-01

Bladder cancer is the most prevalent malignancy of the urinary tract. About 90% of bladder cancers are urothelial carcinomas. Seventy percent of cases newly diagnosed are superficial diseases; roughly 30% of newly diagnosed cases are muscle-invasive metastatic diseases. Bladder urothelial carcinoma primarily metastasizes into regional lymph nodes and then into liver, lung, mediastinum, bone, and adrenal gland. In our case, non-muscle-invasive bladder cancer metastasized into the bone, mediastinum, iliac lymph node, and adrenal and thyroid glands. This is the first reported case in the current literature in which urothelial carcinoma metastasized into the thyroid gland. PMID:24648880

Adrenal 11-beta hydroxysteroid dehydrogenase activity in response to stress.

PubMed

Zallocchi, Marisa; Matković, Laura; Damasco, María C

2004-06-01

This work studied the effect of stresses produced by simulated gavage or gavage with 200 mmol/L HCl two hours before adrenal extraction, on the activities of the 11beta-hydroxysteroid dehydrogenase 1 and 11beta-hydroxysteroid dehydrogenase 2 isoforms present in the rat adrenal gland. These activities were determined on immediately prepared adrenal microsomes following incubations with 3H-corticosterone and NAD+ or NADP+. 11-dehydrocorticosterone was measured as an end-product by TLC, and controls were adrenal microsomes from rats kept under basal (unstressed) conditions. 11beta-hydroxysteroid dehydrogenase 1 activity, but not 11beta-hydroxysteroid dehydrogenase 2 activity, was increased under both stress-conditions. Homeostatically, the stimulation of 11beta-hydroxysteroid dehydrogenase 1 activity would increase the supply of glucocorticoids. These, in turn, would activate the enzyme phenylethanolamine N-methyl transferase, thereby improving the synthesis of epinephrine as part of the stress-response.

Light Stimulates the Mouse Adrenal through a Retinohypothalamic Pathway Independent of an Effect on the Clock in the Suprachiasmatic Nucleus

PubMed Central

Kiessling, Silke; Sollars, Patricia J.; Pickard, Gary E.

2014-01-01

The brain's master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed to peripheral organs: 1) via retinal input to SCN clock neurons; 2) via retinal input to non-clock neurons in the SCN; or 3) via retinal input to hypothalamic regions neighboring the SCN. It is very well documented that light-induced responses of the SCN clock (i.e., clock gene expression, neural activity, and behavioral phase shifts) occur primarily during the subjective night. Thus to determine the role of the SCN clock in transmitting photic signals to descending autonomic circuits, we compared the phase dependency of light-evoked responses in the SCN and a peripheral oscillator, the adrenal gland. We observed light-evoked clock gene expression in the mouse adrenal throughout the subjective day and subjective night. Light also induced adrenal corticosterone secretion during both the subjective day and subjective night. The irradiance threshold for light-evoked adrenal responses was greater during the subjective day compared to the subjective night. These results suggest that retinohypothalamic signals may be relayed to the adrenal clock during the subjective day by a retinal pathway or cellular mechanism that is independent of an effect of light on the SCN neural clock network and thus may be important for the temporal integration of physiology and metabolism. PMID:24658072

Diagnostic performance of multidetector computed tomography in distinguishing unilateral from bilateral abnormalities in primary hyperaldosteronism: comparison of multidetector computed tomography with adrenal vein sampling.

PubMed

Raman, Siva P; Lessne, Mark; Kawamoto, Satomi; Chen, Yifei; Salvatori, Roberto; Prescott, Jason D; Fishman, Elliot K

2015-01-01

The management of patients with primary hyperaldosteronism (PH) varies depending on whether the unregulated aldosterone secretion localizes to a single unilateral adrenal gland, traditionally determined using adrenal vein sampling (AVS). This study seeks to determine if the performance of multidetector computed tomography (MDCT) examinations performed using the latest scanner technology can reasonably match the results of AVS, and potentially avoid AVS in some patients. Computed tomographic scans in 56 patients with PH were independently reviewed by 2 radiologists for the presence of adrenal nodules and qualitative adrenal thickening. Results were correlated with AVS results. Of 35 patients with MDCT evidence of unilateral nodules, the imaging findings correctly predicted AVS localization in only 23 (65.7%) cases. When stratified by size, MDCT was accurate in only 71.4% of cases for nodules measuring 10 mm or less, and only 55.0% of cases for nodules measuring 11 to 20 mm. Of the 12 cases where MDCT did not correctly localize, AVS localized to the contralateral adrenal gland in 4 cases, whereas AVS suggested no lateralization in 8 cases. In patients with normal bilateral adrenal glands on MDCT, 2/7 (28.6%) of cases demonstrated unilateral localization on AVS, and in patients with bilateral adrenal nodules, only 3/14 (21.4%) did not demonstrate lateralization on AVS. Multidetector computed tomography, even when performed with the latest generation of MDCT scanners, does not offer sufficient diagnostic accuracy to replace AVS in patients with PH.

Role of adrenals in the mobilization of carbohydrate and fat resources after overstimulation of rats

NASA Technical Reports Server (NTRS)

Khechninashvili, G. G.

1980-01-01

The role of the cortical and cerebral layers of the adrenal glands in mobilizing carbohydrate and fatty resources in response to the effect of an extreme stimulant was investigated. It is shown that following adrenodemedullation and adrenalectomy, the leading role is played by the secretion of the adrenal medullary layer, whereas the role of suprarenals in the mobilization of fats is only slightly pronounced.

Pituitary gland volumes in bipolar disorder.

PubMed

Clark, Ian A; Mackay, Clare E; Goodwin, Guy M

2014-12-01

Bipolar disorder has been associated with increased Hypothalamic-Pituitary-Adrenal axis function. The mechanism is not well understood, but there may be associated increases in pituitary gland volume (PGV) and these small increases may be functionally significant. However, research investigating PGV in bipolar disorder reports mixed results. The aim of the current study was twofold. First, to assess PGV in two novel samples of patients with bipolar disorder and matched healthy controls. Second, to perform a meta-analysis comparing PGV across a larger sample of patients and matched controls. Sample 1 consisted of 23 established patients and 32 matched controls. Sample 2 consisted of 39 medication-naïve patients and 42 matched controls. PGV was measured on structural MRI scans. Seven further studies were identified comparing PGV between patients and matched controls (total n; 244 patients, 308 controls). Both novel samples showed a small (approximately 20mm(3) or 4%), but non-significant, increase in PGV in patients. Combining the two novel samples showed a significant association of age and PGV. Meta-analysis showed a trend towards a larger pituitary gland in patients (effect size: .23, CI: -.14, .59). While results suggest a possible small difference in pituitary gland volume between patients and matched controls, larger mega-analyses with sample sizes greater even than those used in the current meta-analysis are still required. There is a small but potentially functionally significant increase in PGV in patients with bipolar disorder compared to controls. Results demonstrate the difficulty of finding potentially important but small effects in functional brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of DDT on bobwhite quail adrenal gland

USGS Publications Warehouse

Lehman, J.W.; Peterle, T.J.; Mulls, C.M.

1974-01-01

A wide range of responses to sublethal levels of DDT exist, many of which are species specific and vary within each species depending upon age, sex, and physiological state. Sublethal levels of DDT do cause an increase in the adrenal cortical tissue of bobwhite quail, which may cause increased secretion of corticosteroids, and in turn affect reproduction. A delicate homeostatic balance exists within the avian endocrine system which may be disturbed by feeding sublethal levels of chlorinated hydrocarbon pesticides. This adverse effect on the endocrine system may cause subtle reproductive failures which go unnoticed until the population is greatly reduced.

A case of adrenal Cushing's syndrome with bilateral adrenal masses.

PubMed

Guo, Ya-Wun; Hwu, Chii-Min; Won, Justin Ging-Shing; Chu, Chia-Huei; Lin, Liang-Yu

2016-01-01

A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6β-iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2μg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and (131)I-NP-59 scintigraphy are good diagnostic methods for Cushing's syndrome presenting with bilateral adrenal masses. The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein-wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses.

Double NF1 Inactivation Affects Adrenocortical Function in NF1Prx1 Mice and a Human Patient

PubMed Central

Kobus, Karolina; Hartl, Daniela; Ott, Claus Eric; Osswald, Monika; Huebner, Angela; von der Hagen, Maja; Emmerich, Denise; Kühnisch, Jirko; Morreau, Hans; Hes, Frederik J.; Mautner, Victor F.; Harder, Anja; Tinschert, Sigrid; Mundlos, Stefan; Kolanczyk, Mateusz

2015-01-01

Background Neurofibromatosis type I (NF1, MIM#162200) is a relatively frequent genetic condition, which predisposes to tumor formation. Apart from tumors, individuals with NF1 often exhibit endocrine abnormalities such as precocious puberty (2,5–5% of NF1 patients) and some cases of hypertension (16% of NF1 patients). Several cases of adrenal cortex adenomas have been described in NF1 individuals supporting the notion that neurofibromin might play a role in adrenal cortex homeostasis. However, no experimental data were available to prove this hypothesis. Materials and Methods We analysed Nf1Prx1 mice and one case of adrenal cortical hyperplasia in a NF1patient. Results In Nf1Prx1 mice Nf1 is inactivated in the developing limbs, head mesenchyme as well as in the adrenal gland cortex, but not the adrenal medulla or brain. We show that adrenal gland size is increased in NF1Prx1 mice. Nf1Prx1 female mice showed corticosterone and aldosterone overproduction. Molecular analysis of Nf1 deficient adrenals revealed deregulation of multiple proteins, including steroidogenic acute regulatory protein (StAR), a vital mitochondrial factor promoting transfer of cholesterol into steroid making mitochondria. This was associated with a marked upregulation of MAPK pathway and a female specific increase of cAMP concentration in murine adrenal lysates. Complementarily, we characterized a patient with neurofibromatosis type I with macronodular adrenal hyperplasia with ACTH-independent cortisol overproduction. Comparison of normal control tissue- and adrenal hyperplasia- derived genomic DNA revealed loss of heterozygosity (LOH) of the wild type NF1 allele, showing that biallelic NF1 gene inactivation occurred in the hyperplastic adrenal gland. Conclusions Our data suggest that biallelic loss of Nf1 induces autonomous adrenal hyper-activity. We conclude that Nf1 is involved in the regulation of adrenal cortex function in mice and humans. PMID:25775093

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

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

PubMed Central

Cook, Jason B; Nelli, Stephanie M; Neighbors, Mackenzie R; Morrow, Danielle H; O'Buckley, Todd K; Maldonado-Devincci, Antoniette M; Morrow, A Leslie

2014-01-01

The neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a positive modulator of GABAA receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic–pituitary–adrenal axis and elevates 3α,5α-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3α,5α-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3α,5α-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3α,5α-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3α,5α-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3α,5α-THP following ADX. In subcortical regions, 3α,5α-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3α,5α-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3α,5α-THP levels in several subcortical regions; however, the adrenal glands contribute to 3α,5α-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3α,5α-THP induction by ethanol is not due to a lack of colocalization of 3α,5α-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO). PMID:24566803

Is salivary gland function altered in noninsulin-dependent diabetes mellitus and obesity-insulin resistance?

PubMed

Ittichaicharoen, Jitjiroj; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2016-04-01

Salivary gland dysfunction in several systemic diseases has been shown to decrease the quality of life in patients. In non-insulin dependent diabetes mellitus (NIDDM), inadequate salivary gland function has been evidenced to closely associate with this abnormal glycemic control condition. Although several studies demonstrated that NIDDM has a positive correlation with impaired salivary gland function, including decreased salivary flow rate, some studies demonstrated contradictory findings. Moreover, the changes of the salivary gland function in pre-diabetic stage known as insulin resistance are still unclear. The aim of this review is to comprehensively summarize the current evidence from in vitro, in vivo and clinical studies regarding the relationship between NIDDM and salivary gland function, as well as the correlation between obesity and salivary gland function. Consistent findings as well as controversial reports and the mechanistic insights regarding the effect of NIDDM and obesity-insulin resistance on salivary gland function are also presented and discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

The spectrum of STAT functions in mammary gland development

PubMed Central

Hughes, Katherine; Watson, Christine J.

2012-01-01

The signal transducer and activator of transcription (STAT) family of transcription factors have a spectrum of functions in mammary gland development. In some cases these roles parallel those of STATs in other organ systems, while in other instances the function of individual STATs in the mammary gland is specific to this tissue. In the immune system, STAT6 is associated with differentiation of T helper cells, while in the mammary gland, it has a fundamental role in the commitment of luminal epithelial cells to the alveolar lineage. STAT5A is required for the production of luminal progenitor cells from mammary stem cells and is essential for the differentiation of milk producing alveolar cells during pregnancy. By contrast, the initiation of regression following weaning heralds a dramatic and specific activation of STAT3, reflecting its pivotal role in the regulation of cell death and tissue remodeling during mammary involution. Although it has been demonstrated that STAT1 is regulated during a mammary developmental cycle, it is not yet determined whether it has a specific, non-redundant function. Thus, the mammary gland constitutes an unusual example of an adult organ in which different STATs are sequentially activated to orchestrate the processes of functional differentiation, cell death and tissue remodeling. PMID:24058764

Computational Model of Adrenal Steroidogenesis to Predict Biochemical Response to Endocrine Disruptors

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme mediated reactions. The activity of steroidogenic enzymes can be altered by various endocrine disrupters (ED), ...

Functioning adrenal tumours in children and adolescents: an institutional experience.

PubMed

Mishra, A; Agarwal, G; Misra, A K; Agarwal, A; Mishra, S K

2001-02-01

The purpose of the present paper was to carry out an audit of clinicopathological profile and treatment outcome in 13 children with functioning adrenal tumours. The medical records of 13 children with functioning adrenal tumours who were managed between June 1990 and January 1999 were reviewed. Demographic data, clinical features, biochemical and localization studies, operative details and follow-up records were studied. Children with neuroblastoma were excluded. The mean age was 7.4 +/- 5.3 years. Seven patients had Cushing's syndrome (CS), two patients had virilizing tumours, three patients had phaeochromocytoma (PCC) and one patient had Conn's syndrome. All patients (except one child with CS) were treated surgically. Two children with adrenocortical carcinoma (ACCa) died during the perioperative period. Histopathological diagnosis was adrenal cortical adenoma (ACAd) in four patients, ACCa in five patients and PCC in three patients. Two ACCa patients died of metastases at 12 and 14 months, respectively, while the third is alive and well at 30 months. Children with ACAd are alive and well at 91, 56, 32 and 27 months postoperatively. Children with PCC are free of disease (normal urinary metanephrines) at 63, 18 and 8 months after surgery but require antihypertensive drugs in low doses. The outcome of surgery is good in cases of ACAd and PCC. Although outcome is poor in ACCa, surgery remains the mainstay of treatment and offers good palliation.

Right adrenal vein: comparison between adaptive statistical iterative reconstruction and model-based iterative reconstruction.

PubMed

Noda, Y; Goshima, S; Nagata, S; Miyoshi, T; Kawada, H; Kawai, N; Tanahashi, Y; Matsuo, M

2018-06-01

To compare right adrenal vein (RAV) visualisation and contrast enhancement degree on adrenal venous phase images reconstructed using adaptive statistical iterative reconstruction (ASiR) and model-based iterative reconstruction (MBIR) techniques. This prospective study was approved by the institutional review board, and written informed consent was waived. Fifty-seven consecutive patients who underwent adrenal venous phase imaging were enrolled. The same raw data were reconstructed using ASiR 40% and MBIR. The expert and beginner independently reviewed computed tomography (CT) images. RAV visualisation rates, background noise, and CT attenuation of the RAV, right adrenal gland, inferior vena cava (IVC), hepatic vein, and bilateral renal veins were compared between the two reconstruction techniques. RAV visualisation rates were higher with MBIR than with ASiR (95% versus 88%, p=0.13 in expert and 93% versus 75%, p=0.002 in beginner, respectively). RAV visualisation confidence ratings with MBIR were significantly greater than with ASiR (p<0.0001, both in the beginner and the expert). The mean background noise was significantly lower with MBIR than with ASiR (p<0.0001). Mean CT attenuation values of the RAV, right adrenal gland, IVC, and hepatic vein were comparable between the two techniques (p=0.12-0.91). Mean CT attenuation values of the bilateral renal veins were significantly higher with MBIR than with ASiR (p=0.0013 and 0.02). Reconstruction of adrenal venous phase images using MBIR significantly reduces background noise, leading to an improvement in the RAV visualisation compared with ASiR. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Adrenal insufficiency is prevalent in HbE/β-thalassaemia paediatric patients irrespective of their clinical severity and transfusion requirement.

PubMed

Nakavachara, Pairunyar; Viprakasit, Vip

2013-12-01

Transfusion dependency is known to cause endocrinopathies in patients with thalassaemia such as adrenal insufficiency, because transfusion-related iron overload is injurious to endocrine organs. Children with HbE/ß-thalassaemia vary greatly in red cell transfusion requirement and some are transfusion dependent (TD), whereas others are nontransfusion dependent (NTD). Because iron overload is thought to be the primary cause of adrenal insufficiency, TD children with HbE/ß-thalassaemia are considered likely candidates for the development of adrenal insufficiency, while the adrenal function of NTD children is generally considered to be normal. As yet, the prevalence of adrenal insufficiency among children with NTD HbE/β-thalassaemia is not known. The present study was performed to (i) assess the prevalence of adrenal insufficiency in children with both TD and NTD HbE/β-thalassaemia and to evaluate whether there is any difference in the prevalence of adrenal insufficiency between both groups and (ii) determine the type of adrenal insufficiency (primary or secondary). We investigated the prevalence of adrenal insufficiency among TD (n = 42) and NTD (n = 43) children with HbE/β-thalassaemia by assessing morning serum cortisol levels, and we distinguished between primary and secondary adrenal insufficiency by assessing the cortisol responses following the 1- and 250-μg ACTH stimulation tests. The prevalence of adrenal insufficiency among TD and NTD children with HbE/β-thalassaemia was 50% and 53·5%, respectively. By using the 250-μg ACTH stimulation test, at least 39% and 23·5% were diagnosed with adrenal gland hypofunction in TD and NTD children, respectively. This is the first study to show that adrenal insufficiency is common among all children with HbE/β-thalassaemia, irrespective of their transfusion history or requirement. Our findings have important implications for the clinical management of these children. © 2013 John Wiley & Sons Ltd.

Effect of Space Flight on Adrenal Medullary Function

NASA Technical Reports Server (NTRS)

Lelkes, Peter I.

1999-01-01

We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

Adrenocorticotropin receptors: Functional expression from rat adrenal mRNA in Xenopus laevis oocytes

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

Mertz, L.M.; Catt, K.J.

1991-10-01

The adrenocorticotropin (ACTH) receptor, which binds corticotropin and stimulates adenylate cyclase and steroidogenesis in adrenocortical cells, was expressed in Xenopus laevis oocytes microinjected with rat adrenal poly(A){sup +} RNA. Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand-stimulated cAMP production. Injection of 5-40 ng of adrenal mRNA caused dose-dependent increases in ACTH-responsive cAMP production. Size fractionation of rat adrenal poly(A){sup +}RNA by sucrose density-gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1.1-to 2.0-kilobase fraction. These data indicate that ACTH receptors can be expressed from adrenal mRNAmore » in Xenopus oocytes and are fully functional in terms of ligand specificity and signal generation. The extracellular cAMP response to ACTH is a sensitive and convenient index of receptor expression. This system should permit more complete characterization and expression cloning of the ACTH receptor.« less

[Composite pheochromocytoma: A rare adrenal tumor].

PubMed

Robinet, Gwladys; Rioux-Leclercq, Nathalie; Manunta, Andréa; Mathieu, Romain; Tissier, Frédérique; Peyronnet, Benoit; Kammerer-Jacquet, Solène-Florence

2017-04-01

Composite pheochromocytoma is a rare tumor of the adrenal medulla composed of pheochromocytoma and neuroblastic tumor. We report the case of a composite pheochromocytoma detected in a patient with neurofibromatosis type 1. A 61-year-old male patient presented occasional sweats with palpitation and moderate high blood pressure. Urinary catecholamine level was increased. CT scan showed a heterogeneous tumor limited to the adrenal gland. Histologically, the tumor showed two components: pheochromocytoma and ganglioneuroma and was diagnosed as a composite pheochromocytoma. This tumor is particularly associated with neurofibromatosis type 1, the NF1 germline gene mutation may be involved in its physiopathology. Composite pheochromocytoma is a rare tumor whose pheochromocytoma component is suspected clinically but the final diagnosis is assessed by pathological examination. Prognosis is still difficult to establish due to the rarity of these tumors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

PubMed

Nam, Kihoon; Maruyama, Christina L; Wang, Ching-Shuen; Trump, Bryan G; Lei, Pedro; Andreadis, Stelios T; Baker, Olga J

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function

PubMed Central

Nam, Kihoon; Maruyama, Christina L.; Wang, Ching-Shuen; Trump, Bryan G.; Lei, Pedro; Andreadis, Stelios T.

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration. PMID:29095857

Adrenal maturation, nutritional status, and mucosal immunity in Bolivian youth.

PubMed

Hodges-Simeon, Carolyn R; Prall, Sean P; Blackwell, Aaron D; Gurven, Michael; Gaulin, Steven J C

2017-09-10

Humans-and several other apes-exhibit a unique pattern of post-natal adrenal maturation; however, the causes and consequences of variation in adrenal development are not well understood. In this study, we examine developmental and age-related maturation of the adrenal gland (measured via dehydroepiandrosterone-sulfate [DHEA-S]) for potential life-history associations with growth and mucosal immunity in a rural population of immune-challenged Bolivian juveniles and adolescents. Salivary DHEA-S, anthropometrics, and salivary mucosal immunity (secretory IgA [sIgA]) were measured in 171 males and females, aged 8-23. Males with greater energy (i.e. fat) stores showed higher DHEA-S levels. Controlling for age and energetic condition (to control for phenotypic correlation), higher DHEA-S was associated with higher mucosal immunity (sIgA) among both males and females. Higher DHEA-S levels were positively associated with growth (i.e. height and strength) in males. In accordance with predictions derived from life-history theory, males with higher energy stores secrete more adrenal androgens. This suggests that adrenal maturation is costly and subject to constraints; that is, only males with sufficient reserves will invest in accelerated adrenal maturation. Further, DHEA-S appears to have a measureable influence on immunocompetence in adolescent males and females; therefore, deficits in DHEA-S may have important consequences for health and maturation during this period. Adrenal maturation is an important, but understudied component of human growth and development. © 2017 Wiley Periodicals, Inc.

Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.

PubMed

Cheng, Behling; Al-Shammari, Fatema H; Ghader, Isra'a A; Sequeira, Fatima; Thakkar, Jitendra; Mathew, Thazhumpal C

2017-07-01

Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRβ were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insulin-Like Growth Factor-1 Preserves Salivary Gland Function After Fractionated Radiation

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

Limesand, Kirsten H., E-mail: limesank@u.arizona.ed; Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Avila, Jennifer L.

Purpose: Radiotherapy for head-and-neck cancer consists of fractionated radiation treatments that cause significant damage to salivary glands leading to chronic salivary gland dysfunction with only limited prevention and treatment options currently available. This study examines the feasibility of IGF-1 in preserving salivary gland function following a fractionated radiation treatment regimen in a pre-clinical model. Methods and Materials: Mice were exposed to fractionated radiation, and salivary gland function and histological analyses of structure, apoptosis, and proliferation were evaluated. Results: In this study, we report that treatment with fractionated doses of radiation results in a significant level of apoptotic cells in FVBmore » mice after each fraction, which is significantly decreased in transgenic mice expressing a constitutively active mutant of Akt1 (myr-Akt1). Salivary gland function is significantly reduced in FVB mice exposed to fractionated radiation; however, myr-Akt1 transgenic mice maintain salivary function under the same treatment conditions. Injection into FVB mice of recombinant insulin-like growth factor-1 (IGF-1), which activates endogenous Akt, suppressed acute apoptosis and preserved salivary gland function after fractionated doses of radiation 30 to 90 days after treatment. FVB mice exposed to fractionated radiation had significantly lower levels of proliferating cell nuclear antigen-positive salivary acinar cells 90 days after treatment, which correlated with a chronic loss of function. In contrast, FVB mice injected with IGF-1 before each radiation treatment exhibited acinar cell proliferation rates similar to those of untreated controls. Conclusion: These studies suggest that activation of IGF-1-mediated pathways before head-and-neck radiation could modulate radiation-induced salivary gland dysfunction and maintain glandular homeostasis.« less

Salivary Gland NK Cells Are Phenotypically and Functionally Unique

PubMed Central

Brossay, Laurent

2011-01-01

Natural killer (NK) cells and CD8+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or Treg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells. PMID:21249177

Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy.

PubMed

Miró-Mur, Francesc; Laredo, Carlos; Renú, Arturo; Rudilosso, Salvatore; Zhao, Yashu; Amaro, Sergio; Llull, Laura; Urra, Xabier; Planas, Anna M; Chamorro, Ángel

2018-03-13

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30-21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation. Copyright © 2018. Published by Elsevier Inc.

Brain serotonin and pituitary-adrenal functions

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

1973-01-01

It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

Anatomical Variations of the Right Adrenal Vein: Concordance Between Multidetector Computed Tomography and Catheter Venography.

PubMed

Omura, Kensuke; Ota, Hideki; Takahashi, Yuuki; Matsuura, Tomonori; Seiji, Kazumasa; Arai, Yoichi; Morimoto, Ryo; Satoh, Fumitoshi; Takase, Kei

2017-03-01

Adrenal venous sampling is the most reliable diagnostic procedure to determine surgical indications in primary aldosteronism. Because guidelines recommend multidetector computed tomography (CT) to evaluate the adrenal gland, some past reports used multidetector CT as a guide for adrenal venous sampling. However, the detailed anatomy of the right adrenal vein and its relationship with an accessory hepatic vein remains uncertain. The purpose of this study was to describe detailed anatomical variations of the right adrenal vein and to determine the concordance between CT and catheter venography in patients with primary aldosteronism. In total, 440 consecutive patients who underwent adrenal venous sampling were included. Four-phase dynamic CT was performed. Anatomical locations and variations of the right adrenal vein and its relationship with the accessory hepatic vein were compared with catheter venographic findings. Successful catheterization was achieved in 437 patients (99%). The right adrenal vein was visualized in the late arterial phase with CT in 420 patients (95%). The right adrenal vein formed a common trunk with the accessory hepatic vein in 87 patients (20%). CT identified the correct craniocaudal level of the orifice in 354 patients (84%). Anatomical variations, location, and angle of inflow of the right adrenal vein based on CT demonstrated high concordance with catheter venography. CT may provide useful information for preparation before adrenal venous sampling. © 2017 American Heart Association, Inc.

[The effect of hydra peptide morphogen on the levels of beta-endorphin and some blood and adrenal hormones in albino rats].

PubMed

Murzina, N B; Khomichuk, A Iu; Timoshin, S S; Obukhova, G G; Anosova, O A; Berezina, G P

1991-10-01

The influence of PMH on the level of beta-endorphin and some hormones of blood and adrenal glands was studied. The dose A (10 mkg/kg) and dose W (100 mkg/kg) of PMH were used in our experiments. Earlier it has been discovered, that PMH in such doses stimulated the processes of cell division in 24 hours since the moment of injection. The stimulation was dose-dependent. Within 24 hours PMH in A dose decreased the concentration of beta-endorphin in the blood 2.7-fold, ad in dose W increased it 2 times. The level of corticosterone in blood and adrenal glands after the injection of PMH in dose A exceeded the control data trustworthy in 4 and 24 hours since the moment of injection. In dose B in 4 hours 1.5-fold reduction of corticosterone concentration took place in the blood. Increase in epinephrine level in adrenal glands was observed after PMH administration in two doses. Content of T3 increased in 4 hours after PMH injection in dose B. The role of hormonal changes in stimulating cell division accompanied by PMH injection is discussed. The data received show that PMH influences directly proliferative processes.

Establishment of Functional Acinar-like Cultures from Human Salivary Glands

PubMed Central

Jang, S.I.; Ong, H.L.; Gallo, A.; Liu, X.; Illei, G.

2015-01-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers—namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. PMID:25416669

Establishment of functional acinar-like cultures from human salivary glands.

PubMed

Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

2015-02-01

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients. © International & American Associations for Dental Research 2014.

Cell-To-Cell Communication in Bilateral Macronodular Adrenal Hyperplasia Causing Hypercortisolism

PubMed Central

Lefebvre, Hervé; Duparc, Céline; Prévost, Gaëtan; Bertherat, Jérôme; Louiset, Estelle

2015-01-01

It has been well established that, in the human adrenal gland, cortisol secretion is not only controlled by circulating corticotropin but is also influenced by a wide variety of bioactive signals, including conventional neurotransmitters and neuropeptides, released within the cortex by various cell types such as chromaffin cells, neurons, cells of the immune system, adipocytes, and endothelial cells. These different types of cells are present in bilateral macronodular adrenal hyperplasia (BMAH), a rare etiology of primary adrenal Cushing’s syndrome, where they appear intermingled with adrenocortical cells in the hyperplastic cortex. In addition, the genetic events, which cause the disease, favor abnormal adrenal differentiation that results in illicit expression of paracrine regulatory factors and their receptors in adrenocortical cells. All these defects constitute the molecular basis for aberrant autocrine/paracrine regulatory mechanisms, which are likely to play a role in the pathophysiology of BMAH-associated hypercortisolism. The present review summarizes the current knowledge on this topic as well as the therapeutic perspectives offered by this new pathophysiological concept. PMID:25941513

THE INFLUENCE OF CERTAIN FACTORS, ESPECIALLY EMOTIONAL DISTURBANCES, ON THE EPINEPHRIN CONTENT OF THE ADRENALS

PubMed Central

Stewart, G. N.; Rogoff, J. M.

1916-01-01

1. No evidence has been obtained that in cats and dogs with the nerves of one adrenal cut, emotional disturbances cause depletion of the epinephrin store of the normally innervated adrenal as compared with its fellow. 2. The depletion of the epinephrin store in cats under morphine is not dependent upon so called morphine fright, since a similar depletion is found in dogs in which, as is known, morphine produces symptoms the reverse of those of fright. 3. The signs of morphine fright can all be elicited by administering morphine to a cat in which one adrenal has been removed and the nerve supply of the other cut, and in which accordingly no detectable liberation of epinephrin takes place. 4. The reactions of the denervated iris elicited by emotional disturbance, asphyxia, or etherization in a cat, one of whose adrenals has been removed and the nerves of the other cut, do not differ from these reactions in cats whose adrenals have not been interfered with. 5. The influence of postoperative edema of the adrenal in diminishing the epinephrin load, and the recuperation of the load after a time, have been studied in rabbits. 6. The diminution in the epinephrin store of the adrenals which follows operations on animals (postoperative depletion) has been studied. It is only in part associated with the anesthesia, since it may be as marked 6 or 8 hours after an operation lasting less than 1 hour as after 6 or 8 hours' anesthesia without operation. 7. One adrenal was removed in rabbits and the epinephrin content of the remaining gland assayed at varying periods of time after removal of the first, the periods being longer than the time necessary for recovery from the postoperative depletion. In general, the second adrenal contained more epinephrin than the first, sometimes double the amount. 8. Marked depletion of the epinephrin store of innervated adrenals as compared with the corresponding denervated glands was seen in animals dead of infections of various kinds. 9. As shown

Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential Factors and Reference Intervals

PubMed Central

Hart, Leslie B.; Wells, Randall S.; Kellar, Nick; Balmer, Brian C.; Hohn, Aleta A.; Lamb, Stephen V.; Rowles, Teri; Zolman, Eric S.; Schwacke, Lori H.

2015-01-01

Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs) for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone) that account for the influence of intrinsic (e.g., age, sex) and extrinsic (e.g., time) factors. Ultimately, these reference intervals will be used to gauge an individual’s response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs) were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000–2012). Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05), and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91–4.21 µg/dL) and following biological sampling aboard a research vessel (95% RI: 2.32–6.68 µg/dL). To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34) had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time) were not observed in the current project (p<0.05). Also, approximately 16% of

Adrenal Hormones in Common Bottlenose Dolphins (Tursiops truncatus): Influential Factors and Reference Intervals.

PubMed

Hart, Leslie B; Wells, Randall S; Kellar, Nick; Balmer, Brian C; Hohn, Aleta A; Lamb, Stephen V; Rowles, Teri; Zolman, Eric S; Schwacke, Lori H

2015-01-01

Inshore common bottlenose dolphins (Tursiops truncatus) are exposed to a broad spectrum of natural and anthropogenic stressors. In response to these stressors, the mammalian adrenal gland releases hormones such as cortisol and aldosterone to maintain physiological and biochemical homeostasis. Consequently, adrenal gland dysfunction results in disruption of hormone secretion and an inappropriate stress response. Our objective herein was to develop diagnostic reference intervals (RIs) for adrenal hormones commonly associated with the stress response (i.e., cortisol, aldosterone) that account for the influence of intrinsic (e.g., age, sex) and extrinsic (e.g., time) factors. Ultimately, these reference intervals will be used to gauge an individual's response to chase-capture stress and could indicate adrenal abnormalities. Linear mixed models (LMMs) were used to evaluate demographic and sampling factors contributing to differences in serum cortisol and aldosterone concentrations among bottlenose dolphins sampled in Sarasota Bay, Florida, USA (2000-2012). Serum cortisol concentrations were significantly associated with elapsed time from initial stimulation to sample collection (p<0.05), and RIs were constructed using nonparametric methods based on elapsed sampling time for dolphins sampled in less than 30 minutes following net deployment (95% RI: 0.91-4.21 µg/dL) and following biological sampling aboard a research vessel (95% RI: 2.32-6.68 µg/dL). To examine the applicability of the pre-sampling cortisol RI across multiple estuarine stocks, data from three additional southeast U.S. sites were compared, revealing that all of the dolphins sampled from the other sites (N = 34) had cortisol concentrations within the 95th percentile RI. Significant associations between serum concentrations of aldosterone and variables reported in previous studies (i.e., age, elapsed sampling time) were not observed in the current project (p<0.05). Also, approximately 16% of Sarasota Bay

[Functional morphology of the submandibular salivary glands of white rats during aging involution].

PubMed

Rybakova, M G

1979-12-01

Functional morphology of different zones of submandibular glands of albino rats was studied quantitatively with due regard for the stages of neuroendocrine system involution. It is shown that function of salivary glands during ageing is not altered; cyclic fluctuations with estral cycle phases are maintained similarly to those in young animals. But the basal level of proteins and mucopolysaccharides is reduced, their mean levels being equal to the minimal level in young animals. On the other hand, activation of enzymes responsible for energy and transport processes takes place and their relationships change. The data obtained prove the relationship between salivary and endocrine glands and confirm the viewpoint that in early age involution disintegration occurs between different parameters of the functional activity of salivary glands rather than there take place changes in their function.

Diagnosis of adrenal insufficiency.

PubMed

Dorin, Richard I; Qualls, Clifford R; Crapo, Lawrence M

2003-08-05

The cosyntropin stimulation test is the initial endocrine evaluation of suspected primary or secondary adrenal insufficiency. To critically review the utility of the cosyntropin stimulation test for evaluating adrenal insufficiency. The MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency. Studies with fewer than 5 persons with primary or secondary adrenal insufficiency or with fewer than 10 persons as normal controls were excluded. For secondary adrenal insufficiency, only studies that stratified participants by integrated tests of adrenal function were included. Summary receiver-operating characteristic (ROC) curves were generated from all studies that provided sensitivity and specificity data for 250-microg and 1-microg cosyntropin tests; these curves were then compared by using area under the curve (AUC) methods. All estimated values are given with 95% CIs. At a specificity of 95%, sensitivities were 97%, 57%, and 61% for summary ROC curves in tests for primary adrenal insufficiency (250-microg cosyntropin test), secondary adrenal insufficiency (250-microg cosyntropin test), and secondary adrenal insufficiency (1-microg cosyntropin test), respectively. The area under the curve for primary adrenal insufficiency was significantly greater than the AUC for secondary adrenal insufficiency for the high-dose cosyntropin test (P < 0.001), but AUCs for the 250-microg and 1-microg cosyntropin tests did not differ significantly (P > 0.5) for secondary adrenal insufficiency. At a specificity of 95%, summary ROC analysis for the 250-microg cosyntropin test yielded a positive likelihood ratio of 11.5 (95% CI, 8.7 to 14.2) and a negative likelihood ratio of 0.45 (CI, 0.30 to 0.60) for the diagnosis of secondary adrenal insufficiency. Cortisol response to cosyntropin varies considerably among healthy persons. The cosyntropin test performs well in patients with primary adrenal insufficiency, but the

Uterine glands: development, function and experimental model systems

PubMed Central

Cooke, Paul S.; Spencer, Thomas E.; Bartol, Frank F.; Hayashi, Kanako

2013-01-01

Development of uterine glands (adenogenesis) in mammals typically begins during the early post-natal period and involves budding of nascent glands from the luminal epithelium and extensive cell proliferation in these structures as they grow into the surrounding stroma, elongate and mature. Uterine glands are essential for pregnancy, as demonstrated by the infertility that results from inhibiting the development of these glands through gene mutation or epigenetic strategies. Several genes, including forkhead box A2, beta-catenin and members of the Wnt and Hox gene families, are implicated in uterine gland development. Progestins inhibit uterine epithelial proliferation, and this has been employed as a strategy to develop a model in which progestin treatment of ewes for 8 weeks from birth produces infertile adults lacking uterine glands. More recently, mouse models have been developed in which neonatal progestin treatment was used to permanently inhibit adenogenesis and adult fertility. These studies revealed a narrow and well-defined window in which progestin treatments induced permanent infertility by impairing neonatal gland development and establishing endometrial changes that result in implantation defects. These model systems are being utilized to better understand the molecular mechanisms underlying uterine adenogenesis and endometrial function. The ability of neonatal progestin treatment in sheep and mice to produce infertility suggests that an approach of this kind may provide a contraceptive strategy with application in other species. Recent studies have defined the temporal patterns of adenogenesis in uteri of neonatal and juvenile dogs and work is underway to determine whether neonatal progestin or other steroid hormone treatments might be a viable contraceptive approach in this species. PMID:23619340

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

PubMed

Castinetti, Frederic; Qi, Xiao-Ping; Walz, Martin K; Maia, Ana Luiza; Sansó, Gabriela; Peczkowska, Mariola; Hasse-Lazar, Kornelia; Links, Thera P; Dvorakova, Sarka; Toledo, Rodrigo A; Mian, Caterina; Bugalho, Maria Joao; Wohllk, Nelson; Kollyukh, Oleg; Canu, Letizia; Loli, Paola; Bergmann, Simona R; Biarnes Costa, Josefina; Makay, Ozer; Patocs, Attila; Pfeifer, Marija; Shah, Nalini S; Cuny, Thomas; Brauckhoff, Michael; Bausch, Birke; von Dobschuetz, Ernst; Letizia, Claudio; Barczynski, Marcin; Alevizaki, Maria K; Czetwertynska, Malgorzata; Ugurlu, M Umit; Valk, Gerlof; Plukker, John T M; Sartorato, Paola; Siqueira, Debora R; Barontini, Marta; Szperl, Malgorzata; Jarzab, Barbara; Verbeek, Hans H G; Zelinka, Tomas; Vlcek, Petr; Toledo, Sergio P A; Coutinho, Flavia L; Mannelli, Massimo; Recasens, Monica; Demarquet, Lea; Petramala, Luigi; Yaremchuk, Svetlana; Zabolotnyi, Dmitry; Schiavi, Francesca; Opocher, Giuseppe; Racz, Karoly; Januszewicz, Andrzej; Weryha, Georges; Henry, Jean-Francois; Brue, Thierry; Conte-Devolx, Bernard; Eng, Charis; Neumann, Hartmut P H

2014-05-01

The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339

Adrenal gland involvement in the regulation of renal 11beta-hydroxysteroid dehydrogenase 2.

PubMed

Zallocchi, Marisa Laura; Matkovic, Laura; Calvo, Juan Carlos; Damasco, María Cristina

2004-06-01

Renal 11beta-hydroxysteroid dehydrogenase 2 (HSD2) catalyzes the conversion of active glucocorticoids to inert 11beta-keto compounds, thereby preventing the illicit binding of these hormones to mineralocorticoid receptors (MRs) and, thus, conferring aldosterone specificity. Absence or inhibition of HSD2 activity, originates a hypertensive syndrome with sodium retention and increased potassium elimination. Recent studies from our laboratory reported an increment of HSD2 activity in intact-stressed rats. To evaluate the adrenal involvement in this increase, we analyzed HSD2 activity and protein abundance in Intact, Sham-operated, and adrenalectomized rats under stress situations (gavage with an overload of 200 mM HCl (10 ml) and simulated gavage) or with corticosterone replacement. HSD2 activity was assessed in renal microsomal preparations obtained from different groups of animals. HSD2 protein abundance was measured by Western-blot. Circulating corticosterone was determined by radioimmunoassay. Sham-operated animals showed an increase in HSD2 activity and abundance compared to Intact and adrenalectomized rats suggesting the involvement of stress-related adrenal factors in HSD2 regulation. In the case of acidotic adrenalectomized animals, there was an increase in renal HSD2 activity when, along with the HCl overload, the rats were injected with corticosterone. This increment occurred without an increase in enzyme abundance. These results suggest the importance of circulating levels of glucocorticoids to respond to a metabolic acidosis, through regulation of HSD2 stimulation. The group subjected to a simulated gavage showed an increase in enzyme activity and protein abundance, thus demonstrating the need for both adrenal and extra-factors in the modulation of renal HSD2. The adrenalectomized animals injected with different doses of corticosterone, produced a progressive increase in enzyme activity and abundance, being significant for the dose of 68 microg

[Structuro-functional units of the salivary and lacrimal glands].

PubMed

Kostilenko, Iu P; Mysliuk, I V; Deviatkin, E A

1986-09-01

By means of the multilayer graphic and plastic reconstruction methods using series of semithin sections, spatial tridimensional organization of the epithelial complexes and blood microcirculatory bed in the rat palatal salivary glands and the lacrimal gland of the human newborn have been studied. Since their ducts serve not only for discharging their secrete into the external medium, but also for accumulation (as collectors), the sublobular unit--adenomere should be referred to as a part of elementary level of organization of the epithelial complexes. The adenomere has in its composition a collecting centrally situating duct. However, while studying structure of the blood microcirculatory bed, it is found out that there is not any strict territorial correspondence between its functional units and structural units of the glandular epithelium. Nevertheless, giving a great importance to a tight syntopic connection of the collecting ducts of the adenomeres with the postcapillary venules (that belong to filtrating microvessels), these are sublobular units--adenomeres that are distinguished as structural-functional units in the glands.

Functional salivary gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Ogawa, Miho; Oshima, Masamitsu; Imamura, Aya; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Nakajima, Kei; Hirayama, Masatoshi; Tachikawa, Tetsuhiko; Tsuji, Takashi

2013-01-01

Salivary gland hypofunction, also known as xerostomia, occurs as a result of radiation therapy for head cancer, Sjögren’s syndrome or aging, and can cause a variety of critical oral health issues, including dental decay, bacterial infection, mastication dysfunction, swallowing dysfunction and reduced quality of life. Here we demonstrate the full functional regeneration of a salivary gland that reproduces the morphogenesis induced by reciprocal epithelial and mesenchymal interactions through the orthotopic transplantation of a bioengineered salivary gland germ as a regenerative organ replacement therapy. The bioengineered germ develops into a mature gland through acinar formations with a myoepithelium and innervation. The bioengineered submandibular gland produces saliva in response to the administration of pilocarpine and gustatory stimulation by citrate, protects against oral bacterial infection and restores normal swallowing in a salivary gland-defective mouse model. This study thus provides a proof-of-concept for bioengineered salivary gland regeneration as a potential treatment of xerostomia. PMID:24084982

Modulation of the phenotype and function of Mycobacterium tuberculosis-stimulated dendritic cells by adrenal steroids.

PubMed

Angerami, Matias; Suarez, Guadalupe; Pascutti, Maria Fernanda; Salomon, Horacio; Bottasso, Oscar; Quiroga, Maria Florencia

2013-07-01

Cell-mediated immunity, cytokines induced during the specific immune response and T-cell populations are crucial factors for containing Mycobacterium tuberculosis infection. Recent reports suggest a cross-regulation between adrenal steroids (glucocorticoids and dehydroepiandrosterone, DHEA) and the function of antigen-presenting cells (APCs). Therefore, we investigated the role of adrenal hormones on the functional capacity of M. tuberculosis-induced dendritic cells (DCs). Cortisol significantly inhibited the functions of M. tuberculosis-induced DCs. Interestingly, the presence of DHEA enhanced the M. tuberculosis-induced expression of MHC I, MHC II and CD86 and also increased ERK1/2 phosphorylation. Moreover, DHEA improved the production of IL-12 in response to M. tuberculosis stimulation, diminished IL-10 secretion and could not modify TNF-α synthesis. Importantly, we observed that DHEA enhanced the antigen-specific T-cell proliferation and IFN-γ production induced by M. tuberculosis-stimulated DC. These data show for the first time the relevance of the adrenal axis (especially of DHEA) in the modulation of DC function in the context of tuberculosis, a disease where the induction of a Th1 environment by APCs is crucial for the development of an effective immune response to the mycobacteria.

Fryns anophthalmia-plus syndrome with hypoplastic adrenal glands.

PubMed

Ozalp, O; Ozcimen, E E; Yilmaz, Z; Yanik, F; Sahin, F I

2008-01-01

We report a family with two consequent sibs with anophthalmia and cleft lip and palate. A 27 year old woman married to her first cousin was counseled for anophthalmia and cleft lip and palate detected during routine fetal ultrasonographic examination on the 23rd week of the pregnancy. Her obstetric history revealed a healthy girl aged 7 years and a boy with anophthalmia and cleft lip and palate who lived for 20 days in the neonatal intensive care unit. The current pregnancy was terminated after the diagnosis, and post mortem examination of the fetus revealed pre-maxilla agenesis, anophthalmia, cerebral ventricular dilatation, adrenal hypoplasia and single umbilical artery. Chromosome analysis resulted in normal karyotypes of the fetus and both parents. The inheritance pattern was regarded as autosomal recessive and the family was informed about the condition and risks during genetic counseling.

Virilization caused by an ectopic adrenal tumor located behind the iliopsoas muscle.

PubMed

Mavroudis, Konstantinos; Aloumanis, Kyriakos; Papapetrou, Peter D; Voros, Dionisios; Spanos, Iraklis

2007-06-01

Virilization due to androgen-secreting neoplasms in women is a result of androgen overproduction from benign or malignant tumors that are found in the ovaries or rarely in the adrenal glands. Virilizing tumors that arise from ectopic adrenal tissue are extremely rare. We describe a very rare case of an ectopic androgen-producing adrenal tumor. Case report study. Endocrinology outpatient department of university-affiliated teaching hospital. A 45-year-old woman with symptoms of virilization of abrupt onset and rapid progression, with high serum androgen hormone levels and normal glucocorticoid secretion. Basal hormonal levels, stimulation and suppression tests, imaging techniques, and selective venous sampling. Localization and surgical removal of the source of androgen production. An ectopic mass was detected behind the left iliopsoas muscle. The patient was operated on and an oblong-shaped lesion, weighing 6 g, was removed. Histologically, the tissue was identified to be of adrenal origin. Postoperatively the androgen levels decreased to normal levels. This case illustrates difficulties in detecting and localizing the rare contingence of an ectopic adrenocortical androgen-secreting tumor.

Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease.

PubMed

Hackman, Kathryn L; Davis, Anna L; Curnow, Paul A; Serpell, Jonathan W; McLean, Catriona A; Topliss, Duncan J

2010-01-01

To report a case of Cushing syndrome due to apparently sporadic primary pigmented nodular adrenal disease in a young woman. We describe the clinical, biochemical, radiologic, and histologic findings of Cushing syndrome due to the rare condition of primary pigmented nodular adrenal disease. A 30-year-old woman presented with a 2-year history of worsening itch without rash over her shoulders and arms and weight gain, particularly around the abdomen and face. Careful questioning did not elicit any history of exogenous glucocorticoid use (systemic or topical), including hydrocortisone. On examination, the patient had a slightly rounded and plethoric face, a small buffalo hump, central adiposity, and thin skin with a few small striae on her inner thighs. No features of the Carney complex were observed. Investigations showed hypercortisolism with suppressed corticotropin and normal adrenal imaging despite documentation of enlarged adrenal glands at removal. High-dose dexamethasone administration was followed by a decrease in urinary free cortisol excretion rather than a paradoxical rise as previously reported in primary pigmented nodular adrenal disease. No mutations were detected in the PRKAR1A gene. Primary pigmented nodular adrenal disease should be suspected in patients with corticotropin-independent Cushing syndrome who have normal adrenal imaging. The role of genetic testing in apparently sporadic cases is not established, but cumulative experience may be helpful in defining the frequency of PRKAR1A mutations.

Testosterone-secreting adrenal adenoma in a peripubertal girl

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

Kamilaris, T.C.; DeBold, C.R.; Manolas, K.J.

1987-11-13

A 15-year-old girl who presented with primary amenorrhea and virilization had an adrenocortical adenoma that secreted predominantly testosterone. To the authors' knowledge, she is the first peripubertal and second youngest patient with a testosterone-secreting adrenal tumor described. Serum dehydroepiandrosterone sulfate and urinary 17-ketosteroid an 17-hydroxycorticosteroid levels were normal. A tumor was located by a computed tomographic (CT) scan and by uptake of 6-..beta..-(/sup 75/Se) selenomethylnorcholesterol. Microscopic examination of the tumor showed typical features of an adrenocortical adenoma with no histologic features characteristic of Leydig cells. Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started fourmore » months later. Finding the source of testosterone in a virilized patient can be difficult. Eleven of the 14 previously described patients with testosterone-secreting adrenal tumors initially underwent misdirected surgery on the ovaries. Review of these cases revealed that results of hormone stimulation and suppression tests are unreliable and that these tumors are usually large. Therefore, CT scanning of the adrenal glands is recommended in all patients suspected of having a testosterone-secreting tumor.« less

[Morphological studies of rat adrenal glands after space flight on "Kosmos-1667"].

PubMed

Prodan, N G; Bara'nska, V

1989-01-01

Histological and histomorphometric examinations of rat adrenals after a 7-day flight revealed the following changes: blood congestion in the cortex and medulla, progressive delipoidization of the cortex, slight enlargement of the nuclear volume of glomerular and fascicular zones, vacuolization of the cytoplasm of medulla cells, reduction of the area of noradrenocyte islets and cell nuclei of the medulla; the adrenal weight remained however unchanged. It is concluded that an early period of adaptation to microgravity was accompanied by a weak stress-reaction. Upon return to Earth the rats developed an acute gravitational stress. From the morphological point of view the stress manifested as: increased volume of nuclei in fascicular cells, decreased content of lipids in them, and greater vacuolization of the cytoplasm of medulla cells. The lack of medulla hypertrophy, reduction of the area of noradrenocyte islets and nuclei of medulla cells suggest that 7-day exposure to microgravity did not exert of stimulating effect on the sympathetic system of rats.

Comparative endocrinology of testicular, adrenal and thyroid function in captive Asian and African elephant bulls.

PubMed

Brown, Janine L; Somerville, Malia; Riddle, Heidi S; Keele, Mike; Duer, Connie K; Freeman, Elizabeth W

2007-04-01

Concentrations of serum testosterone, cortisol, thyroxine (free and total T4), triiodothyronine (free and total T3) and thyroid stimulating hormone (TSH) were measured to assess adrenal and thyroid function as they relate to testicular activity and musth in captive elephants. Blood samples were collected approximately weekly from Asian (n=8) and African (n=12) bulls at seven facilities for periods of 4 months to 9.5 years. Age ranges at study onset were 8-50 years for Asian and 10-21 years for African elephants. Based on keeper logs, seven Asian and three African bulls exhibited behavioral and/or physical (temporal gland secretion, TGS, or urine dribbling, UD) signs of musth, which lasted 2.8+/-2.5 months in duration. Serum testosterone was elevated during musth, with concentrations often exceeding 100 ng/ml. Patterns of testosterone secretion and musth varied among bulls with no evidence of seasonality (P>0.05). Only three bulls at one facility exhibited classic, well-defined yearly musth cycles. Others exhibited more irregular cycles, with musth symptoms often occurring more than once a year. A number of bulls (1 Asian, 9 African) had consistently low testosterone (<10 ng/ml) and never exhibited significant TGS or UD. At facilities with multiple bulls (n=3), testosterone concentrations were highest in the oldest, most dominant male. There were positive correlations between testosterone and cortisol for six of seven Asian and all three African males that exhibited musth (range, r=0.23-0.52; P<0.05), but no significant correlations for bulls that did not (P>0.05). For the three bulls that exhibited yearly musth cycles, TSH was positively correlated (range, r=0.22-0.28; P<0.05) and thyroid hormones (T3, T4) were negatively correlated (range, r=-0.25 to -0.47; P<0.05) to testosterone secretion. In the remaining bulls, there were no clear relationships between thyroid activity and musth status. Overall mean testosterone and cortisol concentrations increased with age

[Evaluation of salivary gland function in women with autoimmune thyroid diseases].

PubMed

Koczor-Rozmus, Aleksandra; Zwirska-Korczala, Krystyna; Sadlak-Nowicka, Jadwiga; Ilewicz, Leşzek; Mayer-Parka, Danuta; Wierucka-Młynarczyk, Beata

2003-01-01

The function of the salivary glands is regulated by nervous system which influences salivary circulation. Moreover the volume of secreted saliva depends on the humoral agents, including thyroid hormones. The aim of the study was to determine the quantity of the secreted mixed resting and stimulated saliva in women with autoimmune thyroid diseases (AITD) depending on the function of the thyroid gland (hyperthyroidism, hypothyroidism and euthyroidism). The association between thyroid antibody concentrations (TPO-Ab, Tg-Ab, TR-Ab) and volume of secreted saliva was also examined. Studies were performed in 106 women suffering from AITD and 15 healthy volunteers. In hyperthyroid women there was a decrease in volumes of resting (57.14%) and stimulated (89.29%) saliva. Similarly, a decrease in secretion of resting (75%) and stimulated (66.67%) saliva was shown in hypothyroid women. In euthyroid patients with AITD there was a partial normalisation of salivary glands function. The negative correlation between concentrations of TPO-Ab, Tg-Ab and the volume of resting and stimulated saliva was found. In conclusion, AITD may be associated with disturbances in salivary secretion which depends on thyroid hormones production. It can be suggested that autoimmunological processes within salivary glands may influence their function.

Spontaneous Massive Adrenal Hemorrhage: A Management Dilemma

PubMed Central

Agarwal, Anshuman

2015-01-01

Abstract Adrenal hemorrhage (AH) is a rare but life-threatening condition. Small focal hemorrhage may present subclinically, but massive hemorrhage may lead to rapid cardiovascular collapse and ultimately death if not diagnosed appropriately and treated quickly. Most cases reported in the literature have been treated conservatively. In an event of increasing hemorrhage during conservative management, it may be tricky to intervene surgically because of the hematoma around the gland. Here we describe a case where we managed a large spontaneous AH by a combination of angioembolization and laparoscopic adrenalectomy. PMID:27579389

Functional adrenal cortex preservation: A good reason for posterior retroperitoneal endoscopic approach.

PubMed

Vidal, Óscar; Delgado-Oliver, Eduardo; Díaz Del Gobbo, Rafael; Hanzu, Felicia; Squarcia, Mattia; Martínez, Daniel; Fuster, David; Fondevila, Constantino

2018-05-24

Cortical-sparing adrenalectomy is a suitable treatment for hereditary and sporadic bilateral pheochromocytoma, in cases of low risk of malignancy, to reduce the possibility of adrenal insufficiency assuming the chance of local recurrence. The aim of the study is to analyze the functional results of partial adrenalectomy by retroperitoneal endoscopic approach in single-adrenal patients or patients requiring bilateral adrenalectomy. Prospective study between January 2015 and February 2016 including pheochromocytoma patients diagnosed with low risk of malignant mutations. All patients agreed to be included in the study. Experienced endocrine surgeons who have been trained in minimally invasive endocrine surgery performed the procedure using the same surgical technique. Demographic variables and clinical characteristics were collected, subsequently carrying out the descriptive analysis of the data. A total of 6 patients were registered, four associated with MEN type 2 syndrome and two in the context of VHL syndrome. Retroperitoneoscopic resection was performed without laparoscopic or open conversion and no postoperative complications; the average hospital stay was 2.5 days. Preservation of the functional cortex without corticosteroids was achieved in 5 (83%) of out 6 cases with a follow-up of 26.2 ± 6 months. Today, these 5 patients have a preserved adrenal function without hormone replacement. Cortical-sparing adrenalectomy by the retroperitoneal endoscopic approach, in expert hands, is safe and feasible for the treatment of hereditary and sporadic pheochromocytoma in a context of low malignancy, making it possible to avoid the need for corticoid replacement in most cases. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Bioprinting of a functional vascularized mouse thyroid gland construct.

PubMed

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Image-Guided Ablation of Adrenal Lesions

PubMed Central

Yamakado, Koichiro

2014-01-01

Although laparoscopic adrenalectomy has remained the standard of care for the treatment for adrenal tumors, percutaneous image-guided ablation therapy, such as chemical ablation, radiofrequency ablation, cryoablation, and microwave ablation, has been shown to be clinically useful in many nonsurgical candidates. Ablation therapy has been used to treat both functioning adenomas and malignant tumors, including primary adrenal carcinoma and metastasis. For patients with functioning adenomas, biochemical and symptomatic improvement is achieved in 96 to 100% after ablation; for patients with malignant adrenal neoplasms, however, the survival benefit from ablation therapy remains unclear, though good initial results have been reported. This article outlines the current role of ablation therapy for adrenal lesions, as well as identifying some of the technical considerations for this procedure. PMID:25049444

How to learn from patients: Fuller Albright's exploration of adrenal function.

PubMed

Schwartz, T B

1995-08-01

Fuller Albright (1900-1969) was acknowledged as the preeminent clinical and investigative endocrinologist of his day by many of his contemporaries, but his many achievements are all but unknown to the present generation of physicians. This article describes how he used his clinical knowledge and a few tools--the measurement of urinary 17-ketosteroid excretion and the administration of methyltestosterone--to elucidate the major hormonal functions of the adrenal cortex and to clarify the pathophysiology of the Cushing syndrome. In addition, in a tour de force of clinical reasoning, he predicted, 5 years before the event, the discovery of a hormone that would reverse the endocrinologic abnormalities of congenital adrenal hyperplasia. Fittingly, he and pioneer pediatric endocrinologist Lawson Wilkins were the first to treat this disease successfully with cortisone.

Diffusion-Weighted Magnetic Resonance Imaging to Evaluate Major Salivary Gland Function Before and After Radiotherapy

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

Dirix, Piet; Keyzer, Frederik de; Vandecaveye, Vincent

2008-08-01

Purpose: To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC). Methods and Materials: DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy. Results: Before RT, the mean ADC value at rest was significantly lower in the parotidmore » than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy. Conclusions: Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.« less

Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells.

PubMed

Inoue, Masumi; Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

2012-09-15

Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at -78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K(+) (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of -5 mV and a negative slope below -40 mV. External application of La(3+) had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve.

Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells

PubMed Central

Harada, Keita; Matsuoka, Hidetada; Nakamura, Jun; Warashina, Akira

2012-01-01

Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at −60 mV. This inward current was partially suppressed by quinine with an IC50 of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at −78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K+ (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of −5 mV and a negative slope below −40 mV. External application of La3+ had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve. PMID:22744007

Cosmos 1887 mission overview - Effects of microgravity on rat body and adrenal weights and plasma constituents

NASA Technical Reports Server (NTRS)

Grindeland, R. E.; Vasques, M.; Arnaud, S. B.; Popova, I. A.

1990-01-01

Tissues of male, specific pathogen-free Wistar rats flown on the Cosmos 1887 biosatellite are studied. First the mission is described, and then analytical methods are outlined. It is noted that flight rats grew more slowly and had larger adrenal glands than earth gravity controls. Analysis of plasma reveals increased concentrations of hepatic alkaline phosphatase, glucose, urea nitrogen, and creatinine in flight rats. In contrast, electrolytes, total protein, albumin, corticosteron, prolactin, and immunoreactive growth hormone levels are unchanged. However, testosterone concentration is marginally decreased after flight and thyroid hormone levels are suggestive of reduced thyroid function.

Pharmacological Activation of the EDA/EDAR Signaling Pathway Restores Salivary Gland Function following Radiation-Induced Damage

PubMed Central

Hill, Grace; Headon, Denis; Harris, Zoey I.; Huttner, Kenneth; Limesand, Kirsten H.

2014-01-01

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170

Identification of factors that function in Drosophila salivary gland cell death during development using proteomics

PubMed Central

McPhee, C K; Balgley, B M; Nelson, C; Hill, J H; Batlevi, Y; Fang, X; Lee, C S; Baehrecke, E H

2013-01-01

Proteasome inhibitors induce cell death and are used in cancer therapy, but little is known about the relationship between proteasome impairment and cell death under normal physiological conditions. Here, we investigate the relationship between proteasome function and larval salivary gland cell death during development in Drosophila. Drosophila larval salivary gland cells undergo synchronized programmed cell death requiring both caspases and autophagy (Atg) genes during development. Here, we show that ubiquitin proteasome system (UPS) function is reduced during normal salivary gland cell death, and that ectopic proteasome impairment in salivary gland cells leads to early DNA fragmentation and salivary gland condensation in vivo. Shotgun proteomic analyses of purified dying salivary glands identified the UPS as the top category of proteins enriched, suggesting a possible compensatory induction of these factors to maintain proteolysis during cell death. We compared the proteome following ectopic proteasome impairment to the proteome during developmental cell death in salivary gland cells. Proteins that were enriched in both populations of cells were screened for their function in salivary gland degradation using RNAi knockdown. We identified several factors, including trol, a novel gene CG11880, and the cop9 signalsome component cop9 signalsome 6, as required for Drosophila larval salivary gland degradation. PMID:22935612

Adrenal oncocytic phaeochromocytoma with putative adverse histologic features: a unique case report and review of the literature.

PubMed

Kasem, Kais; Lam, Alfred K-Y

2014-12-01

Oncocytic phaeochromocytomas are exceedingly rare tumours. To date, there are three reported cases in the literature. This report describes a case of adrenal oncocytic phaeochromocytoma with unique features and malignant potential in a 68-year-old man. The patient presented with an incidental non-functional mass discovered on routine radiological investigation, which was subsequently excised. Histologically, the tumour cells showed oncocytic features with high-grade nuclear abnormalities and foci of extension to the peri-adrenal fat. Immunohistochemistry performed was positive for chromogranin, CD56, S-100 and p53 and negative for inhibin, HMB-45, EMA, AE1/AE3, Cam 5.2 and calretinin. Electron microscopy showed electron dense granules of neurosecretory type, which confirmed the diagnosis. The malignant potential of the tumour was assessed on available histologic scoring systems, which demonstrated a high malignant potential. However, no recurrence was detected after 5 years of follow-up. Compared to all the previously reported cases of oncocytic phaeochromocytoma, this patient was the oldest on presentation, was the only case with identified high malignant potential and has the longest follow-up. A review of the literature showed that all the oncocytic phaeochromocytomas reported were non-functional, non-metastasizing and were described in women. To conclude, oncocytic phaeochromocytoma should be in the differential diagnoses of oncocytic tumours of the adrenal gland. Additional studies are needed to predict the behaviour of this entity.

Functional Zonation of the Adult Mammalian Adrenal Cortex

PubMed Central

Vinson, Gavin P.

2016-01-01

The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Moreover, each zone has its specific mechanism of regulation, though ACTH has actions throughout. Finally, the cells of the cortex originate from a stem cell population in the outer cortex or capsule, and migrate centripetally, changing their phenotype as they progress through the zones. Recent progress in understanding the development of the gland and the distribution of steroidogenic enzymes, trophic hormone receptors, and other factors suggests that this model needs refinement. Firstly, proliferation can take place throughout the gland, and although the stem cells are certainly located in the periphery, zonal replenishment can take place within zones. Perhaps more importantly, neither the distribution of enzymes nor receptors suggest that the individual zones are necessarily autonomous in their production of steroid. This is particularly true of the glomerulosa, which does not seem to have the full suite of enzymes required for aldosterone biosynthesis. Nor, in the rat anyway, does it express MC2R to account for the response of aldosterone to ACTH. It is known that in development, recruitment of stem cells is stimulated by signals from within the glomerulosa. Furthermore, throughout the cortex local regulatory factors, including cytokines, catecholamines and the tissue renin-angiotensin system, modify and refine the effects of the systemic trophic factors. In these and other ways it more and more appears that the functions of the gland should be viewed as an integrated whole, greater than the sum of its component parts. PMID:27378832

Adrenal haemorrhage due to heparin-induced thrombocytopenia.

PubMed

Ketha, Siva; Smithedajkul, Patrick; Vella, Adrian; Pruthi, Rajiv; Wysokinski, Waldemar; McBane, Robert

2013-04-01

Adrenal haemorrhage (AH) is a rare but potentially devastating complication of heparin-induced thrombocytopenia (HIT). Neither the prevalence nor the natural history of AH due to HIT are known. The objectives of this study were to identify the spectrum of AH causes, to characterise the frequency of AH due to HIT and determine the natural history of HIT-associated AH. All patients with incident adrenal haemorrhage from January 2002 through June 2012 seen at the Mayo Clinic were identified. Over this time frame, there were a total of 115 patients with AH of which 11 cases (10%; mean age 67 ± 8 years; 73% female) were associated with HIT. Of these, all but one occurred in the postoperative setting and involved both adrenal glands (89%) with acute adrenal insufficiency at the time of diagnosis. Cases were found incidentally during an evaluation for fever, shock, abdominal pain or mental status changes. All HIT patients experienced venous thrombosis at other locations including deep venous thromboses (n=14), pulmonary emboli (n= 4) and arterial thrombosis (n=2). Four patients undergoing total knee arthroplasty had "spontaneous HIT" with AH in the absence of identifiable heparin exposure. Other causes of AH included trauma (29%), sepsis (15%), antiphospholipid antibody syndrome (10%), and metastatic disease (12%). In conclusion, AH is an important but seldom recognised presumed thrombotic complication of HIT, which usually occurs in the postoperative period, especially after orthopaedic procedures. This syndrome can occur in the apparent absence of heparin exposure, especially following major joint replacement surgery.

Adrenocortical Gap Junctions and Their Functions

PubMed Central

Bell, Cheryl L.; Murray, Sandra A.

2016-01-01

Adrenal cortical steroidogenesis and proliferation are thought to be modulated by gap junction-mediated direct cell–cell communication of regulatory molecules between cells. Such communication is regulated by the number of gap junction channels between contacting cells, the rate at which information flows between these channels, and the rate of channel turnover. Knowledge of the factors regulating gap junction-mediated communication and the turnover process are critical to an understanding of adrenal cortical cell functions, including development, hormonal response to adrenocorticotropin, and neoplastic dedifferentiation. Here, we review what is known about gap junctions in the adrenal gland, with particular attention to their role in adrenocortical cell steroidogenesis and proliferation. Information and insight gained from electrophysiological, molecular biological, and imaging (immunocytochemical, freeze fracture, transmission electron microscopic, and live cell) techniques will be provided. PMID:27445985

Transthoracic Adrenal Biopsy Procedure Using Artificial Carbon Dioxide Pneumothorax as Outpatient Procedure

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

Favelier, Sylvain; Guiu, Severine; Cherblanc, Violaine

2013-08-01

Many routes have been described for percutaneous adrenal gland biopsy. They require either a complex non-axial path or a long hydrodissection or even pass through an organ thereby increasing complications. We describe here an approach using an artificially-induced carbon dioxide (CO{sub 2}) pneumothorax, performed as an outpatient procedure in a 57-year-old woman. Under local anaesthesia, 200 ml of CO{sub 2} was injected in the pleural space through a Veress needle under computed tomography fluoroscopy, to clear the lung parenchyma from the biopsy route. Using this technique, transthoracic adrenal biopsy can be performed under simple local anaesthesia as an safely outpatientmore » procedure.« less

Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

PubMed

Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

2015-01-01

Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

Expression of estrogen, estrogen related and androgen receptors in adrenal cortex of intact adult male and female rats.

PubMed

Trejter, Marcin; Jopek, Karol; Celichowski, Piotr; Tyczewska, Marianna; Malendowicz, Ludwik K; Rucinski, Marcin

2015-01-01

Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available. Therefore the present study aimed to characterize, at the level of mRNA, expression of these receptors in specific components of adrenal cortex of intact adult male and female rats. Studies were performed on adult male and female (estrus) Wistar rats. Total RNA was isolated from adrenal zona glomerulosa (ZG) and fasciculate/reticularis (ZF/R). Expression of genes were evaluated by means of Affymetrix® Rat Gene 1.1 ST Array Strip and QPCR. By means of Affymetrix® Rat Gene 1.1 ST Array we examined adrenocortical sex differences in the expression of nearly 30,000 genes. All data were analyzed in relation to the adrenals of the male rats. 32 genes were differentially expressed in ZG, and 233 genes in ZF/R. In the ZG expression levels of 24 genes were lower and 8 higher in female rats. The more distinct sex differences were observed in the ZF/R, in which expression levels of 146 genes were lower and 87 genes higher in female rats. Performed analyses did not reveal sex differences in the expression levels of both androgen (AR) and estrogen (ER) receptor genes in the adrenal cortex of male and female rats. Therefore matrix data were validated by QPCR. QPCR revealed higher expression levels of AR gene both in ZG and ZF/R of male than female rats. On the other hand, QPCR did not reveal sex-related differences in the expression levels of ERα, ERβ and non-genomic GPR30 (GPER-1) receptor. Of those genes expression levels of ERα genes were the highest. In studied adrenal samples the relative expression of ERα mRNA was higher than ERβ m

“Unclassical” Combination of Smell Dysfunction, Altered Abdominal Nociception and Human Hypertension Associated “Classical” Adrenal-Augmentation

PubMed Central

Leon-Ariza, Daniel S.; Leon-Ariza, Juan S.; Leon-Sarmiento, Fidias E.

2015-01-01

We report a 33-year-old female patient, who arrived to the emergency ward with an abdominal pain that suddenly started 10 days before admission. Simultaneously, the patient developed sudden arterial hypertension and smell disturbances. Conventional medical treatment for pain and arterial hypertension was effortless. Laboratory tests ruled out pancreatitis. Metanephrines in her urine were also normal. A dual-phase intravenous contrast computed tomography of the abdomen showed a large mass within left adrenal gland. Adrenocortical adenoma was diagnosed. The mass was not hypervascularized but positive for synaptophysin and chromogranin A. Importantly, these proteins are heavily involved with acetylcholine metabolism. The triad of olfactory disorders, pain and arterial hypertension normalized after surgically extracting the adrenal mass. To our knowledge, this medical case is the first reported patient exhibiting immediate recovery of such unclassical triad of local and remote findings. The function and dysfunction of key nanocholinergic pathways involved with smell, blood pressure and nociception would explain the pathophysiology of this unique medical case. PMID:26688704

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

PubMed

Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

2015-04-16

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

PubMed

Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

2006-01-01

We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone-secreting adrenal phaeochromocytoma: review of the literature and report of a case

PubMed Central

Ruggeri, R.M.; Ferraù, F.; Campennì, A.; Simone, A.; Barresi, V.; Giuffrè, G.; Tuccari, G.; Baldari, S.; Trimarchi, F.

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochromocytoma, causing ectopic Cushing’s syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous, 9-cm mass in the right adrenal gland, and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region, corresponding to the adrenal mass. The patient underwent laparoscopic surgery and formalin-fixed and paraffin-embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed. Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma, which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing’s disease was dependent on CRH overproduction by the pheochromocytoma, in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas, and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas, suggesting that these tumours may represent potential target for octreotide treatment.

Immunohistochemical localization and functional characterization of somatostatin receptor subtypes in a corticotropin releasing hormone- secreting adrenal phaeochromocytoma: review of the literature and report of a case.

PubMed

Ruggeri, Rosaria M; Ferraù, F; Campennì, A; Simone, A; Barresi, V; Giuffrè, G; Tuccari, G; Baldari, S; Trimarchi, F

2009-01-01

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochro-mocytoma,causing ectopic Cushing's syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous,9-cm mass in the right adrenal gland,and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region,corresponding to the adrenal mass.The patient underwent laparoscopic surgery and formalin-fixed and paraffin embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed.Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma,which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing's disease was dependent on CRH overproduction by the pheochromocytoma,in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas,and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas,suggesting that these tumours may represent potential target for octreotide treatment.

Chromatographic evidence for high-molecular-mass galanin immunoreactivity in pig and cat adrenal glands.

PubMed

Bauer, F E; Adrian, T E; Yanaihara, N; Polak, J M; Bloom, S R

1986-06-09

Galanin was measured by radioimmunoassay in extracts of pig, cat and rat adrenals using non-C- and mid to C-terminally directed antibodies. The extracts were fractioned by gel chromatography and HPLC. The non-C-terminal galanin immunoreactivity in pig was 92.8 +/- 11.7 pmol/g, in cat 9.1 +/- 0.9 pmol/g and in rat less than 1 pmol/g. Two higher molecular forms of galanin have been identified in both pig and cat adrenal. One major large form behaves as if it was N-terminally extended (Kav pig 0.58, cat 0.48) and the other, a very high-molecular-mass form (Kav pig 0.10, 0.24, cat 0.10), as if it had both N- and C-terminal extensions.

[Comparative ultrastructural study of parotid gland, lacrimal gland and pituitary gland between miniature pig and mouse].

PubMed

Yan, Xing; Hai, Bo; Sun, Yi-lin; Zhang, Chun-mei; Wang, Song-ling

2009-02-01

To study the ultrastructure of parotid glands, lacrimal glands and pituitary glands between miniature pig and mouse. Five adult miniature pigs and 5 mice were studied. Ultrastructure of their parotid glands, lacrimal glands, and pituitary glands was observed. The secretary granules in acinar cell of miniature pig parotid glands showed higher density and more aequalis than those of mice. The cell apparatus in acinar cell of mouse parotid glands were more plentiful than those of miniature pigs. The secretary granules on blood vessel wall were richer in parotid gland of miniature pigs compared with mouse parotid gland. Lacrimal gland had the similar ultrastructure to parotid gland in these two animals. Many blood vessel antrum were found in pituitary glands of these two animals. Compared with mouse parotid glands, there are more secretary granules in acinar cells and vascular endothelial cells in miniature pig parotid glands, which might enter blood stream and have function of endocrine secretion.

A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials

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

Roesink, Judith M.; Schipper, Maria; Busschers, Wim

2005-11-15

Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion ofmore » radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.« less

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress.

PubMed

Santana, Magda M; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C; Kaster, Manuella P; Aveleira, Célia A; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia

2015-10-01

Stress has been considered determinant in the etiology of depression. The adrenal medulla plays a key role in response to stress by releasing catecholamines, which are important to maintain homeostasis. We aimed to study the adrenal medulla in a mouse model of depression induced by 21 days of unpredictable chronic stress (UCS). We observed that UCS induced a differential and time-dependent change in adrenal medulla. After 7 days of UCS, mice did not show depressive-like behavior, but the adrenal medullae show increased protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH and PNMT), Neuropeptide Y, the SNARE protein SNAP-25, the catecholamine transporter VMAT2 and the chromaffin progenitor cell markers, Mash1 and Phox2b. Moreover, 7 days of UCS induced a decrease in the chromaffin progenitor cell markers, Sox9 and Notch1. This suggests an increased capacity of chromaffin cells to synthesize, store and release catecholamines. In agreement, after 7 days, UCS mice had higher NE and EP levels in adrenal medulla. Opposite, when mice were submitted to 21 days of UCS, and showed a depressive like behavior, adrenal medullae had lower protein and/or mRNA levels of catecholamine biosynthetic enzymes (TH, DβH, PNMT), catecholamine transporters (NET, VMAT1), SNARE proteins (synthaxin1A, SNAP25, VAMP2), catecholamine content (EP, NE), and lower EP serum levels, indicating a reduction in catecholamine synthesis, re-uptake, storage and release. In conclusion, this study suggests that mice exposed to UCS for a period of 21 days develop a depressive-like behavior accompanied by an impairment of adrenal medullary function. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Adrenal responses of large whales: Integrating fecal aldosterone as a complementary biomarker to glucocorticoids.

PubMed

Burgess, Elizabeth A; Hunt, Kathleen E; Kraus, Scott D; Rolland, Rosalind M

2017-10-01

Until now, physiological stress assessment of large whales has predominantly focused on adrenal glucocorticoid (GC) measures. Elevated GC concentrations in feces (fGC) are known to reflect stressful disturbances, such as fishing gear entanglement and human-generated underwater noise, in North Atlantic right whales (Eubalaena glacialis). However, there can be considerable variation in GC production as a function of sex and life history stage, which may confound the interpretation of fGC levels. Additionally, GC antibodies used in immunoassays can cross-react with other fecal metabolites (i.e., non-target steroids), potentially influencing fGC data. Here, aldosterone concentrations (fALD; aldosterone and related metabolites) were measured in fecal samples from right whales (total n=315 samples), including samples from identified individuals of known life history (n=82 individual whales), to evaluate its utility as a complementary biomarker to fGC for identifying adrenal activation. Concentrations of fALD were positively correlated with fGCs in right whales (r=0.59, P<0.001), suggesting concurrent secretion of these hormones by the adrenal gland. However, fALD levels were less influenced by concentrations of reproductive steroids in feces, minimizing the potential confounder of assay cross-reactivity in samples with highly skewed hormone ratios. Across different life history states for right whales, fALD concentrations showed similar patterns to those reported for fGC, with higher levels in pregnant females (35.9±7.6ng/g) followed by reproductively mature males (9.5±0.9ng/g) (P<0.05), providing further evidence of elevated adrenal activation in these groups of whales. The addition of fALD measurement as a biomarker of adrenal activation may help distinguish between intrinsic and external causes of stress hormone elevations in large whales, as well as other free-living wildlife species, providing a more comprehensive approach for associating adrenal activation with

Laparoscopic and robotic adrenal surgery: transperitoneal approach.

PubMed

Okoh, Alexis K; Berber, Eren

2015-10-01

Recent advances in technology and the need to decrease surgical morbidity have led a rapid progress in laparoscopic adrenalectomy (LA) over the past decade. Robotics is attractive to the surgeon owing to the 3-dimensional image quality, articulating instruments, and stable surgical platform. The safety and efficacy of robotic adrenalectomy (RA) have been demonstrated by several reports. In addition, RA has been shown to provide similar outcomes compared to LA. Development of adrenal surgery has involved the description of several surgical approaches including the anterior transperitoneal, lateral transperitoneal (LT) and posterior retroperitoneal (PR). Among these, the most frequently preferred technique is LT adrenalectomy, primarily due to the surgeon's familiarity of the operative field, wider working space and visibility. The LT technique is suitable for the resection of larger, unilateral tumors and in scenarios where conversion to an open transperitoneal approach is warranted, it offers a lesser burden. Also, the larger view of the entire abdominal cavity and excellent exposure of both adrenal glands and surrounding structures provided by the LT technique render it safe and feasible in pediatric and pregnant individuals.

A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex

PubMed Central

Horvath, Anelia; Giatzakis, Christoforos; Tsang, Kitman; Greene, Elizabeth; Osorio, Paulo; Boikos, Sosipatros; Libè, Rossella; Patronas, Yianna; Robinson-White, Audrey; Remmers, Elaine; Bertherat, Jerôme; Nesterova, Maria; Stratakis, Constantine A.

2009-01-01

Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms of BAH have been associated with complex syndromes such as Carney Complex and McCune Albright syndrome or may present as isolated micronodular adrenocortical disease (iMAD) usually in children and young adults with CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A) sequencing defects as low-penetrance predisposing factors for iMAD and related abnormalities; we also described a mutation (c.914A>C/H305P) in cAMP-specific PDE8B, in a patient with iMAD. In this study we further characterize this mutation; we also found a novel PDE8B isoform, highly expressed in the adrenal gland. This mutation is shown to significantly affect the ability of the protein to degrade cAMP in vitro. Tumor tissues from patients with iMAD and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) showed down-regulated PDE8B expression (compared to normal adrenal cortex). Pde8b is detectable in the adrenal gland of newborn mice and is widely expressed in other mouse tissues. We conclude that PDE8B is another PDE gene linked to iMAD; it is a candidate causative gene for other adrenocortical lesions linked to the cAMP-signaling pathway, and possibly for tumors in other tissues. PMID:18431404

Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex

PubMed Central

Kovacs, K.; Horvath, E.; Singer, W.

1973-01-01

Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex. Images PMID:4131694

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.

Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

PubMed

Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

2010-01-01

Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

The short Synacthen (corticotropin) test can be used to predict recovery of hypothalamo-pituitary-adrenal axis function.

PubMed

Pofi, Riccardo; Feliciano, Chona; Sbardella, Emilia; Argese, Nicola; Woods, Conor P; Grossman, Ashley B; Jafar-Mohammadi, Bahram; Gleeson, Helena; Lenzi, Andrea; Isidori, Andrea M; Tomlinson, Jeremy W

2018-05-25

The 250μg Short Synacthen (corticotropin) Test (SST) is the most commonly used tool to assess hypothalamo-pituitary-adrenal (HPA) axis function. There are many potentially reversible causes of adrenal insufficiency (AI), but currently no data to guide clinicians as to the frequency of repeat testing or likelihood of HPA axis recovery. To use the SST results to predict recovery of adrenal function. A retrospective analysis of data from 1912 SSTs. 776 patients with reversible causes of AI were identified who had at least two SSTs performed. A subgroup analysis was performed on individuals previously treated with suppressive doses of glucocorticoids (n=110). Recovery of HPA axis function. SST 30-minute cortisol levels above or below 350nmol/L (12.7μg/dL) best predicted HPA axis recovery (AUC ROC=0.85; median recovery time 334 vs. 1368 days, p=8.5x10-13): 99% of patients with a 30-minute cortisol >350nmol/L recovered adrenal function within 4-years, compared with 49% in those with cortisol levels <350nmol/L. In patients exposed to suppressive doses of glucocorticoids, delta cortisol (30-minute - basal) was the best predictor of recovery (AUC ROC = 0.77; median recovery time 262 vs. 974 days, p=7.0x10-6). No patient with a delta cortisol <100nmol (3.6μg/dL) and a subsequent random cortisol <200nmol/L (7.3μg/dL) measured approximately 1-year later recovered HPA axis function. Cortisol levels across an SST can be used to predict recovery of AI and may guide the frequency of repeat testing and inform both clinicians and patients as to the likelihood of restoration of HPA axis function.

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

PubMed

Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus

PubMed Central

Riquelme, Raquel A; Sánchez, Gina; Liberona, Leonel; Sanhueza, Emilia M; Giussani, Dino A; Blanco, Carlos E; Hanson, Mark A; Llanos, Aníbal J

2002-01-01

The hypothesis that nitric oxide plays a key role in the regulation of adrenal blood flow and plasma concentrations of cortisol and catecholamines under basal and hypoxaemic conditions in the llama fetus was tested. At 0.6-0.8 of gestation, 11 llama fetuses were surgically prepared for long-term recording under anaesthesia with vascular and amniotic catheters. Following recovery all fetuses underwent an experimental protocol based on 1 h of normoxaemia, 1 h of hypoxaemia and 1 h of recovery. In nine fetuses, the protocol occurred during fetal i.v. infusion with saline and in five fetuses during fetal i.v. treatment with the nitric oxide synthase inhibitor l-NAME. Adrenal blood flow was determined by the radiolabelled microsphere method during each of the experimental periods during saline infusion and treatment with l-NAME. Treatment with l-NAME during normoxaemia led to a marked fall in adrenal blood flow and a pronounced increase in plasma catecholamine concentrations, but it did not affect plasma ACTH or cortisol levels. In saline-infused fetuses, acute hypoxaemia elicited an increase in adrenal blood flow and in plasma ACTH, cortisol, adrenaline and noradrenaline concentrations. Treatment with l-NAME did not affect the increase in fetal plasma ACTH, but prevented the increments in adrenal blood flow and in plasma cortisol and adrenaline concentrations during hypoxaemia in the llama fetus. In contrast, l-NAME further enhanced the increase in fetal plasma noradrenaline. These data support the hypothesis that nitric oxide has important roles in the regulation of adrenal blood flow and adrenal corticomedullary functions during normoxaemia and hypoxaemia functions in the late gestation llama fetus. PMID:12356897

Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

PubMed

Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

2016-06-01

Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

Management of adolescents with congenital adrenal hyperplasia

PubMed Central

Merke, Deborah P; Poppas, Dix P

2014-01-01

The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

Diagnosis and classification of Addison's disease (autoimmune adrenalitis).

PubMed

Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire

2014-01-01

Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.

Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

PubMed Central

Mendichovszky, Iosif A.; Powlson, Andrew S.; Manavaki, Roido; Aigbirhio, Franklin I.; Cheow, Heok; Buscombe, John R.; Gurnell, Mark; Gilbert, Fiona J.

2016-01-01

Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism. PMID:27869719

Serotonin and pituitary-adrenal function. [in rat under stress

NASA Technical Reports Server (NTRS)

Berger, P. A.; Barchas, J. D.; Vernikos-Danellis, J.

1974-01-01

An investigation is conducted to evaluate the response of the pituitary-adrenal system to a stress stimulus in the rat. In the investigation brain serotonin synthesis was inhibited with p-chlorophenylalanine. In other tests the concentration of serotonin was enhanced with precursors such as tryptophan or 5-hydroxytryptophan. On the basis of the results obtained in the study it is speculated that in some disease states there is a defect in serotonergic neuronal processes which impairs pituitary-adrenal feedback mechanisms.

Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis

PubMed Central

Charchaflie, R. J.; Fernandez, L. Bustos; Perec, C. J.; Gonzalez, E.; Marzi, A.

1974-01-01

Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested. PMID:4852110

Immunolocalization and distribution of functional temperature-sensitive TRP channels in salivary glands.

PubMed

Sobhan, Ubaidus; Sato, Masaki; Shinomiya, Takashi; Okubo, Migiwa; Tsumura, Maki; Muramatsu, Takashi; Kawaguchi, Mitsuru; Tazaki, Masakazu; Shibukawa, Yoshiyuki

2013-11-01

Transient receptor potential (TRP) cation channels are unique cellular sensors involved in multiple cellular functions. Their role in salivary secretion remains to be elucidated. The expression and localization of temperature-sensitive TRP channels in salivary (submandibular, sublingual and parotid) glands were analyzed by immunohistochemistry and quantitative real-time reverse transcription plus the polymerase chain reaction (RT-PCR). The effects of various TRP channel agonists on carbachol (CCh)-induced salivary secretion in the submandibular gland and on the intracellular Ca(2+) concentration ([Ca(2+)]i) in a submandibular epithelial cell line were also investigated. Immunohistochemistry revealed the expression of TRP-melastatin subfamily member 8 (TRPM8) and TRP-ankyrin subfamily member 1 (TRPA1) in myoepithelial, acinar and ductal cells in the sublingual, submandibular and parotid glands. In addition, TRP-vanilloid subfamily member 1 (TRPV1), TRPV3 and TRPV4 were also expressed in myoepithelial, acinar and ductal cells in all three types of gland. Quantitative real-time RT-PCR results demonstrated the mRNA expression of TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1 in acinar and ductal cells in these salivary glands. Perfusion of the entire submandibular gland with the TRPV1 agonist capsaicin (1 μM) via the submandibular artery significantly increased CCh-induced salivation, whereas perfusion with TRPM8 and TRPA1 agonists (0.5 μM WS12 and 100 μM allyl isothiocyanate) decreased it. Application of agonists for each of the thermosensitive TRP channels increased [Ca(2+)]i in a submandibular epithelial cell line. These results indicate that temperature-sensitive TRP channels are localized and distributed in acinar, ductal and myoepithelial cells in salivary glands and that they play a functional role in the regulation and/or modulation of salivary secretion.

ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

PubMed

Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

1999-01-01

The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

Adrenal Fatigue

MedlinePlus

... unlikely to cover the costs. What is the theory behind adrenal fatigue? Supporters of adrenal fatigue believe ... by producing hormones like cortisol. According to the theory of adrenal fatigue, when people are faced with ...

Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

PubMed Central

Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian

2017-01-01

Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B), β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands. PMID:29464184

Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function.

PubMed

Xing, Juan; Petranka, John G; Davis, Felicity M; Desai, Pooja N; Putney, James W; Bird, Gary S

2014-03-01

Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.

Human Parotid Gland Alpha-Amylase Secretion as a Function of Chronic Hyperbaric Exposure

DTIC Science & Technology

1979-01-01

parotid ...Pullman, WA 99163 Gilman, S. C, G. J. Fischer, R. J. Biersner, R. D. Thornton, and D. A. Miller. 1979. Human parotid gland alpha-amylase secretion...as a function of chronic hyperbaric exposure. Undersea Biomed. Res. 6(3):303-307.—Secretion of a-amylase by the human parotid gland increased

Laparoscopic and robotic adrenal surgery: transperitoneal approach

PubMed Central

Okoh, Alexis K.

2015-01-01

Recent advances in technology and the need to decrease surgical morbidity have led a rapid progress in laparoscopic adrenalectomy (LA) over the past decade. Robotics is attractive to the surgeon owing to the 3-dimensional image quality, articulating instruments, and stable surgical platform. The safety and efficacy of robotic adrenalectomy (RA) have been demonstrated by several reports. In addition, RA has been shown to provide similar outcomes compared to LA. Development of adrenal surgery has involved the description of several surgical approaches including the anterior transperitoneal, lateral transperitoneal (LT) and posterior retroperitoneal (PR). Among these, the most frequently preferred technique is LT adrenalectomy, primarily due to the surgeon’s familiarity of the operative field, wider working space and visibility. The LT technique is suitable for the resection of larger, unilateral tumors and in scenarios where conversion to an open transperitoneal approach is warranted, it offers a lesser burden. Also, the larger view of the entire abdominal cavity and excellent exposure of both adrenal glands and surrounding structures provided by the LT technique render it safe and feasible in pediatric and pregnant individuals. PMID:26425457

Immunohistochemical sweat gland profiles.

PubMed

Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

2013-09-01

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

Impact of selective pituitary gland incision or resection on hormonal function after adenoma or cyst resection.

PubMed

Barkhoudarian, Garni; Cutler, Aaron R; Yost, Sam; Lobo, Bjorn; Eisenberg, Amalia; Kelly, Daniel F

2015-12-01

With the resection of pituitary lesions, the anterior pituitary gland often obstructs transsphenoidal access to the lesion. In such cases, a gland incision and/or partial gland resection may be required to obtain adequate exposure. We investigate this technique and determine the associated risk of post-operative hypopituitarism. All patients who underwent surgical resection of a pituitary adenoma or Rathke cleft cyst (RCC) between July 2007 and January 2013 were analyzed for pre- and post-operative hormone function. The cohort of patients with gland incision/resection were compared to a case-matched control cohort of pituitary surgery patients. Total hypophysectomy patients were excluded from outcome analysis. Of 372 operations over this period, an anterior pituitary gland incision or partial gland resection was performed in 79 cases (21.2 %). These include 53 gland incisions, 12 partial hemi-hypophysectomies and 14 resections of thinned/attenuated anterior gland. Diagnoses included 64 adenomas and 15 RCCs. New permanent hypopituitarism occurred in three patients (3.8 %), including permanent DI (3) and growth hormone deficiency (1). There was no significant difference in the rate of worsening gland dysfunction nor gain of function. Compared to a control cohort, there was a significantly lower incidence of transient DI (1.25 vs. 11.1 %, p = 0.009) but no significant difference in permanent DI (3.8 vs. 4.0 %) in the gland incision group. Selective gland incisions and gland resections were performed in over 20 % of our cases. This technique appears to minimize traction on compressed normal pituitary gland during removal of large lesions and facilitates better visualization and removal of cysts, microadenomas and macroadenomas.

Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis

PubMed Central

Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han

2016-01-01

Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate–limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/−) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency–induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/−) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency–induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. PMID:26471128

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

PubMed

Bauer, F E; Hacker, G W; Terenghi, G; Adrian, T E; Polak, J M; Bloom, S R

1986-12-01

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.

Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency.

PubMed

Turcu, Adina F; Nanba, Aya T; Chomic, Robert; Upadhyay, Sunil K; Giordano, Thomas J; Shields, James J; Merke, Deborah P; Rainey, William E; Auchus, Richard J

2016-05-01

To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11β-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin-embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11β-hydroxyandrostenedione, 11-ketoandrostenedione 11β-hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11β-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess. © 2016 European Society of Endocrinology.

Bilateral symmetrical adrenal hypermetabolism on FDG PET/CT due to Cushing syndrome in well differentiated neuroendocrine carcinoma.

PubMed

Aktas, G E; Soyluoglu Demir, S; Sarikaya, A

2016-01-01

The (18)F-FDG PET/CT scan has been suggested for whole-body imaging to identify ectopic adrenocorticotrophic hormone secreting tumours, but there are some challenges involved. The case of a patient is presented, who was admitted with the pre-diagnosis of ectopic ACTH syndrome. On the CT, a nodular lesion was detected in the medial segment of the right lung. The FDG uptake of the lesion seemed to be increased visually, but was not pathological quantitatively (SUVmax: 1.8) on the PET/CT. There was also diffuse increased uptake (SUVmax: 14.2) in the enlarged adrenal glands. The lesion was reported as a possible malignant lesion with low FDG affinity, such as a low grade neuroendocrine tumour, while the diffuse enlarged adrenal glands with high uptake were interpreted as diffusely hyperplasic, due to Cushing's syndrome. The patient was treated with a surgical wedge resection. The histopathological diagnosis confirmed that the tumour was a grade 1 well-differentiated neuroendocrine carcinoma. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions.

PubMed

Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A; Oei, Nicole Y; Cobbaert, Christa M; Ballieux, Bart E; van der Grond, Jeroen; Westendorp, Rudi G; Pijl, Hanno; van Heemst, Diana

2015-01-01

The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls). During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity. Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant.

Plasma free metanephrines in healthy cats, cats with non-adrenal disease and a cat with suspected phaeochromocytoma.

PubMed

Wimpole, Justin A; Adagra, Carl F M; Billson, Mark F; Pillai, Dilo N; Foster, Darren J

2010-06-01

Phaeochromocytomas are catecholamine-secreting tumours of the adrenal glands and are rare in cats. Plasma metanephrine levels are widely considered the diagnostic test of choice for phaeochromocytoma in people but have not been investigated in cats. In this study plasma free normetanephrine and metanephrine levels were measured using high-pressure liquid chromatography in healthy cats, sick cats with non-adrenal disease and in a cat with a suspected phaeochromocytoma. Plasma normetanephrine was significantly higher in sick cats with non-adrenal disease compared to healthy cats (P<0.05) and markedly higher in the cat with a suspected phaeochromocytoma when compared to either group. Plasma metanephrine was not significantly different in any of the groups. This study establishes a first-line guide reference range for plasma metanephrine and normetanephrine levels in healthy cats and cats with non-adrenal disease. These results provide rationale for further studies to establish the use of plasma normetanephrine levels as a potential diagnostic test for phaeochromocytoma in the cat. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

The Role of Cholesterol Utilization in a Computational Adrenal Steroidogenesis Model to Improve Predictability of Biochemical Responses to Endocrine Active Chemicals

EPA Science Inventory

Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

The Rapalogue, CCI-779, improves salivary gland function following radiation.

PubMed

Morgan-Bathke, Maria; Harris, Zoey I; Arnett, Deborah G; Klein, Rob R; Burd, Randy; Ann, David K; Limesand, Kirsten H

2014-01-01

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side

Perifornical hypothalamic pathway to the adrenal gland: Role for glutamatergic transmission in the glucose counter-regulatory response.

PubMed

Sabetghadam, A; Korim, W S; Verberne, A J M

2017-03-01

Adrenaline is an important counter-regulatory hormone that helps restore glucose homeostasis during hypoglycaemia. However, the neurocircuitry that connects the brain glucose sensors and the adrenal sympathetic outflow to the chromaffin cells is poorly understood. We used electrical microstimulation of the perifornical hypothalamus (PeH) and the rostral ventrolateral medulla (RVLM) combined with adrenal sympathetic nerve activity (ASNA) recording to examine the relationship between the RVLM, the PeH and ASNA. In urethane-anaesthetised male Sprague-Dawley rats, intermittent single pulse electrical stimulation of the rostroventrolateral medulla (RVLM) elicited an evoked ASNA response that consisted of early (60±3ms) and late peaks (135±4ms) of preganglionic and postganglionic activity. In contrast, RVLM stimulation evoked responses in lumbar sympathetic nerve activity that were almost entirely postganglionic. PeH stimulation also produced an evoked excitatory response consisting of both preganglionic and postganglionic excitatory peaks in ASNA. Both peaks in ASNA following RVLM stimulation were reduced by intrathecal kynurenic acid (KYN) injection. In addition, the ASNA response to systemic neuroglucoprivation induced by 2-deoxy-d-glucose was abolished by bilateral microinjection of KYN into the RVLM. This suggests that a glutamatergic pathway from the perifornical hypothalamus (PeH) relays in the RVLM to activate the adrenal SPN and so modulate ASNA. The main findings of this study are that (i) adrenal premotor neurons in the RVLM may be, at least in part, glutamatergic and (ii) that the input to these neurons that is activated during neuroglucoprivation is also glutamatergic. Copyright © 2017 Elsevier B.V. All rights reserved.

Pleiotrophin (PTN) Expression and Function and in the Mouse Mammary Gland and Mammary Epithelial Cells

PubMed Central

Rosenfield, Sonia M.; Bowden, Emma T.; Cohen-Missner, Shani; Gibby, Krissa A.; Ory, Virginie; Henke, Ralf T.; Riegel, Anna T.; Wellstein, Anton

2012-01-01

Expression of the heparin-binding growth factor, pleiotrophin (PTN) in the mammary gland has been reported but its function during mammary gland development is not known. We examined the expression of PTN and its receptor ALK (Anaplastic Lymphoma Kinase) at various stages of mouse mammary gland development and found that their expression in epithelial cells is regulated in parallel during pregnancy. A 30-fold downregulation of PTN mRNA expression was observed during mid-pregnancy when the mammary gland undergoes lobular-alveolar differentiation. After weaning of pups, PTN expression was restored although baseline expression of PTN was reduced significantly in mammary glands of mice that had undergone multiple pregnancies. We found PTN expressed in epithelial cells of the mammary gland and thus used a monoclonal anti-PTN blocking antibody to elucidate its function in cultured mammary epithelial cells (MECs) as well as during gland development. Real-time impedance monitoring of MECs growth, migration and invasion during anti-PTN blocking antibody treatment showed that MECs motility and invasion but not proliferation depend on the activity of endogenous PTN. Increased number of mammospheres with laminin deposition after anti-PTN blocking antibody treatment of MECs in 3D culture and expression of progenitor markers suggest that the endogenously expressed PTN inhibits the expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion. In vivo, PTN activity was found to inhibit ductal outgrowth and branching via the inhibition of phospho ERK1/2 signaling in the mammary epithelial cells. We conclude that PTN delays the maturation of the mammary gland by maintaining mammary epithelial cells in a progenitor phenotype and by inhibiting their differentiation during mammary gland development. PMID:23077670

The epigenetic landscape of mammary gland development and functional differentiation

USDA-ARS?s Scientific Manuscript database

Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600

A Case of Hypertensive Crisis without a Surge in Adrenal Hormones after Radiofrequency Ablation as a Treatment for Primary Hepatocellular Carcinoma.

PubMed

Lee, Kyung Jin; Ryu, Soo Hyung

2017-10-25

Radiofrequency ablation (RFA) is a minimally invasive procedure that has been considered as a relatively safe treatment for patients with small hepatocellular carcinoma (HCC). However, RFA has been shown to be associated with complications including mechanical and thermal damage. A 74-year-old man with hepatitis C virus-associated HCC was admitted to our hospital. Abdominal computed tomography revealed two lobulated-HCC in segments 4 and 5. He had no medical history of hypertension and cardiac disease. During RFA, blood pressure was elevated to 200/140 mmHg. There was no evidence of pulmonary embolism, aortic dissection, or ischemic heart disease. Laboratory findings for catecholamine surge were all within normal limits. After continuous intravenous nitroglycerin and oral beta-blocker treatment, patient's blood pressure gradually decreased and back within the normal range. Hypertensive crisis after RFA treatment for HCC is rare. Most reported cases of hypertensive crisis during RFA were related to adrenal gland injury with a release of catecholamine. In our case, the site of HCC was not close to the adrenal gland, and there was no evidence of catecholamine surge. Herein, we report a very rare case of hypertensive crisis without a surge in adrenal hormones after RFA treatment for HCC.

Adrenal venous sampling in a patient with adrenal Cushing syndrome

PubMed Central

Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

2015-01-01

The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

Parotid Gland Function After Radiotherapy: The Combined Michigan and Utrecht Experience

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

Dijkema, Tim, E-mail: T.Dijkema@umcutrecht.n; Raaijmakers, Cornelis P.J.; Ten Haken, Randall K.

2010-10-01

Purpose: To analyze the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head-and-neck (HN) cancer. Patients and Methods: A total of 222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and 1 year after RT using Lashley cups at both centers. A flow ratio <25% of pretreatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman model. Results: Amore » total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined NTCP analysis based on mean dose resulted in a TD{sub 50} (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP. Conclusions: A definite NTCP curve for parotid gland function 1 year after RT is presented, based on mean dose. No threshold dose was observed, and TD{sub 50} was equal to 40 Gy.« less

Modes of adaptation of peripheral neuroendocrine mechanisms of the sympatho-adrenal system to short-term stress as studied in two inbred rat strains.

PubMed

Gilad, G M; Jimerson, D C

1981-02-09

Alterations in mechanisms involved in catecholamine (CA) and corticosterone (B) regulation following short periods of stress have been investigated in two inbred rat strains: a strain more reactive to stress, Wistar-Kyoto (WK), and a less reactive strain, Brown-Norway (BN). Measurements after decapitation stress alone and after decapitation following different periods of immobilization stress, indicate that: (a) plasma CA levels immediately after severe stress (i.e. decapitation) are directly related to the behavioral reactivity of the two rat strains to stress but inversely related to adrenal gland size, their content of CA and biosynthetic enzymes, and to plasma levels of MHPG; (b) levels of B in adrenal glands and in plasma after stress are similar in both strains, in spite of different gland sizes; (c) CAT activity in presynaptic sympathetic terminals is directly related to plasma CA after short-term stress; and (d) liver COMT activity is directly related to plasma CA levels after stress, but inversely plasma levels of MHPG. The implications of the findings are discussed further in the text and lead to the conclusion that the BN strain represents a mode of a slower response to stressful stimuli than WK.

Robotic assisted versus pure laparoscopic surgery of the adrenal glands: a case-control study comparing surgical techniques.

PubMed

Morelli, Luca; Tartaglia, Dario; Bronzoni, Jessica; Palmeri, Matteo; Guadagni, Simone; Di Franco, Gregorio; Gennai, Andrea; Bianchini, Matteo; Bastiani, Luca; Moglia, Andrea; Ferrari, Vincenzo; Fommei, Enza; Pietrabissa, Andrea; Di Candio, Giulio; Mosca, Franco

2016-11-01

The role of the da Vinci Robotic System ® in adrenal gland surgery is not yet well defined. The goal of this study was to compare robotic-assisted surgery with pure laparoscopic surgery in a single center. One hundred and 16 patients underwent minimally invasive adrenalectomies in our department between June 1994 and December 2014, 41 of whom were treated with a robotic-assisted approach (robotic adrenalectomy, RA). Patients who underwent RA were matched according to BMI, age, gender, and nodule dimensions, and compared with 41 patients who had undergone laparoscopic adrenalectomies (LA). Statistical analysis was performed using the Student's t test for independent samples, and the relationship between the operative time and other covariates were evaluated with a multivariable linear regression model. P < 0.05 was considered significant. Mean operative time was significantly shorter in the RA group compared to the LA group. The subgroup analysis showed a shorter mean operative time in the RA group in patients with nodules ≥6 cm, BMI ≥ 30 kg/m 2 and in those who had previous abdominal surgery (p < 0.05). Results from the multiple regression model confirmed a shorter mean operative time with RA with nodules ≥6 cm (p = 0.010). Conversion rate and postoperative complications were 2.4 and 4.8 % in the LA group and 0 and 4.8 % in the RA group. In our experience, RA shows potential benefits compared to classic LA, in particular on patients with nodules ≥6 cm, BMI ≥ 30 kg/m2, and with previous abdominal surgery.

Antiaging Gene Klotho Regulates Adrenal CYP11B2 Expression and Aldosterone Synthesis.

PubMed

Zhou, Xiaoli; Chen, Kai; Wang, Yongjun; Schuman, Mariano; Lei, Han; Sun, Zhongjie

2016-06-01

Deficiency of the antiaging gene Klotho (KL) induces renal damage and hypertension through unknown mechanisms. In this study, we assessed whether KL regulates expression of CYP11B2, a key rate-limiting enzyme in aldosterone synthesis, in adrenal glands. We found that haplodeficiency of KL(+/-) in mice increased the plasma level of aldosterone by 16 weeks of age, which coincided with spontaneous and persistent elevation of BP. Blockade of aldosterone actions by eplerenone reversed KL deficiency-induced hypertension and attenuated the kidney damage. Protein expression of CYP11B2 was upregulated in adrenal cortex of KL(+/-) mice. KL and CYP11B2 proteins colocalized in adrenal zona glomerulosa cells. Silencing of KL upregulated and overexpression of KL downregulated CYP11B2 expression in human adrenocortical cells. Notably, silencing of KL decreased expression of SF-1, a negative transcription factor of CYP11B2, but increased phosphorylation of ATF2, a positive transcription factor of CYP11B2, which may contribute to upregulation of CYP11B2 expression. Therefore, these results show that KL regulates adrenal CYP11B2 expression. KL deficiency-induced spontaneous hypertension and kidney damage may be partially attributed to the upregulation of CYP11B2 expression and aldosterone synthesis. Copyright © 2016 by the American Society of Nephrology.

Physiological basis for the etiology, diagnosis, and treatment of adrenal disorders: Cushing's syndrome, adrenal insufficiency, and congenital adrenal hyperplasia.

PubMed

Raff, Hershel; Sharma, Susmeeta T; Nieman, Lynnette K

2014-04-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing's syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing's syndrome). Endogenous Cushing's syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing's syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. © 2014 American Physiological Society.

Function of the parotid gland in juvenile recurrent parotitis: a case series.

PubMed

Xie, Li-song; Pu, Yi-ping; Zheng, Ling-yan; Yu, Chuang-qi; Wang, Zhi-jun; Shi, Huan

2016-04-01

Our aim was to find out how the parotid gland functions in 44 patients with juvenile recurrent parotitis, and to assess the value of measuring the serum amylase activity. Clinical and personal details were recorded, and all patients had their serum amylase activity measured together with sialography during the chronic phase. The function of the gland was classified by sialographic images. The chi square test and Spearman's rank correlation coefficient were used in the statistical analyses. There was a significant association between the degree of glandular function and serum amylase activity (p=0.014). The patients with unilateral and bilateral disease differed significantly in their degree of glandular function (p=0.020), those with bilateral disease having poorer function. There were no significant correlations between other clinical variables and glandular function. Serum amylase activity is an important diagnostic variable in juvenile recurrent parotitis, and poor parotid function reflects the severity of the disease. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Diagnosis and management of pediatric adrenal insufficiency.

PubMed

Uçar, Ahmet; Baş, Firdevs; Saka, Nurçin

2016-08-01

Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

Body Mass Changes Associated With Hyper-Gravity are Independent of Adrenal Derived Hormones

NASA Technical Reports Server (NTRS)

Wade, Charles E.; Moran, Megan M.; Wang, Tommy J.; Baer, Lisa A.; Yuan, Fang; Fung, Cyra K.; Stein, T. Peter; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Exposure to hyper-gravity results in a number of metabolic changes associated with increases in catecholamines and corticosterone. These changes result in a loss of body and fat mass. To assess the role of hormones derived from the adrenal gland in the changes we studied sham operated (SO) and adrenalectomized (ADX) male rats exposed to hyper-gravity of 2 G for 14 days. Control groups at 1 G were also studied. Urinary epinephrine (EPI) and corticosterone (CORT) were reduced in ADX animals. In response to 2 G there was an increase in urinary EPI and CORT in SO rats, while levels were unchanged in ADX animals. Both groups of animals had similar increases in urinary norepinephrine levels. The reductions of body mass gain in response to 2 G were the same in both groups. The decrease in relative fat mass was greater in ADX. Energy intake and expenditure were not different between groups. In response of returning to 1 G for 24 hours and reexposure to hyper-gravity there were no differences between SO and ADX in the changes of food and water intake, body mass or activity. The changes in metabolism with exposure to hyper-gravity do not appear to require hormones derived from the adrenal gland. The increase in lypolysis and alterations body and fat mass appear to be modulated by sympathetically derived norepinehrine.

HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

EPA Science Inventory

Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

Abstract
The studies review...

Magnolol stimulates steroidogenesis in rat adrenal cells

PubMed Central

Wang, Seu-Mei; Lee, Li-Jen; Huang, Yu-Tsung; Chen, Jian-Jiun; Chen, Yuh-Lien

2000-01-01

This study investigated the effect of magnolol, a compound purified from Magnolia officinalis, on glucocorticoid production by primary adrenal cell culture.Magnolol increased corticosterone secretion in a dose-dependent manner, this effect being maximal at 40 μM. A similar effect was seen in a minced adrenal gland system.In magnolol-treated cells, the number and total area of cytoplasmic lipid droplets were reduced, suggesting a high utilization rate of cholesterol esters stored in lipid droplets. In control cells, the capsule of the lipid droplet was clearly delineated by immunostaining with antibody A2, whereas capsular staining was discontinuous or undetectable following magnolol treatment. The percentage of decapsulated cells increased significantly from 20% in the control group to 80% in the magnolol-treated group.Magnolol-induced steroidogenesis was not mediated either via the traditional ACTH-cyclic AMP-protein kinase A pathway or by protein kinase C, since the intracellular cyclic AMP level did not change and inhibition of protein kinase A or C did not block the action of magnolol. Furthermore, calcium/calmodulin-dependent protein kinase II was not involved in magnolol-induced steroidogenesis.The stimulatory effect of magnolol on steroidogenesis apparently requires new protein synthesis, since cycloheximide inhibited magnolol-induced corticosterone production by 50%.Although other studies have shown that high concentrations of magnolol inhibit acyl-CoA: cholesterol acyltransferase and 11β-hydroxysteroid dehydrogenase in a cell-free system, our data show that, in adrenal cell cultures, low concentrations of magnolol have a stimulatory effect on steroidogenesis, and the glucocorticoid produced may explain the effective control of asthma by Magnolia officinalis. PMID:11082125

Functional differences in the acinar cells of the murine major salivary glands.

PubMed

Kondo, Y; Nakamoto, T; Jaramillo, Y; Choi, S; Catalan, M A; Melvin, J E

2015-05-01

In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl(-)-dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca(2+)] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl(-) efflux and the protein levels of the Ca(2+)-activated Cl(-) channel TMEM16A, the major apical Cl(-) efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na(+)-K(+)-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl(-) uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl(-) movement, including the transporter activities of the Cl(-) uptake and efflux pathways, and intracellular Ca(2+) mobilization. © International & American Associations for Dental Research 2015.

[Adrenal incidentaloma: a clinical problem related to imaging].

PubMed

de Bruijne, E L E; Burgmans, J P J; Krestin, G P; Pols, H A P; van den Meiracker, A H; de Herder, W W

2005-08-13

Two female patients, 68 and 67 years of age, were referred for right abdominal pain and pyelonephritis, respectively. During the diagnostic work-up, an unsuspected adrenal mass was found in both patients. Hormonal evaluation and imaging showed a benign non-hyperactive functioning adenoma in one patient and a pheochromocytoma in the other. Both patients were successfully treated with endoscopic adrenalectomy. Wider application and improvement of abdominal imaging procedures have caused an increase of incidentally detected adrenal masses, posing a common clinical problem. Typically, a diagnosis can be made on the basis of the characteristic radiological image. The exact nature of the defect is often unclear and further evaluation is required to determine functionality and possible malignancy. An algorithm is presented for the management of adrenal incidentalomas.

Bilateral adrenal masses: a single-centre experience

PubMed Central

Bandgar, Tushar; Khare, Shruti; Jadhav, Swati; Lila, Anurag; Goroshi, Manjunath; Kasaliwal, Rajeev; Khadilkar, Kranti; Shah, Nalini S

2016-01-01

Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies. PMID:27037294

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

PubMed Central

Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

2014-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control. PMID:24715566

The clypeal gland: a new exocrine gland in termite imagoes (Isoptera: Serritermitidae, Rhinotermitidae, Termitidae).

PubMed

Křížková, Barbora; Bourguignon, Thomas; Vytisková, Blahoslava; Sobotník, Jan

2014-11-01

Social insects possess a rich set of exocrine organs producing diverse pheromones and defensive compounds. This is especially true for termite imagoes, which are equipped with several glands producing, among others, sex pheromones and defensive compounds protecting imagoes during the dispersal flight and colony foundation. Here, we describe the clypeal gland, a new termite exocrine organ occurring in the labro-clypeal region of imagoes of most Rhinotermitidae, Serritermitidae and Termitidae species. The clypeal gland of Coptotermes testaceus consists of class 1 (modified epidermal cell) and class 3 (bicellular gland unit) secretory cells. Ultrastructural features suggest that the gland secretes volatile compounds and proteins, probably after starting the reproduction. One peculiar feature of the gland is the presence of multiple secretory canals in a single canal cell, a feature never observed before in other insect glands. Although the function of the gland remains unknown, we hypothesize that it could produce secretion signalling the presence of functional reproductives or their need to be fed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Extrapulmonary disseminated tuberculosis with tuberculous adrenalitis: a stitch in time saves nine.

PubMed

Rajasekharan, Chandrasekharan; Ajithkumar, Sivasankarannair; Anto, Varghese; Parvathy, Rajasekharan

2013-05-17

A 40-year-old manual labourer presented with easy fatiguability, recurrent vomiting and loss of weight of 3 months, duration. Upon examination, there was significant axillary and cervical lymphadenopathy. No pallor, icterus or clubbing was evident. There was generalised hyperpigmentation and multiple oral ulcers. The blood pressure 90/60 mm Hg in the right upper limb in the supine position. Investigations showed a low serum cortisol. Mantoux test was strongly positive (20 mm).A fine needle aspiration biopsy of the cervical lymph node revealed reactive changes. Bone marrow aspiration and biopsy were normal. Cervical lymph node biopsy showed caseating granulomas suggestive of tuberculous lymphadenitis. A CT scan of the abdomen showed bilaterally enlarged adrenal glands with hypodense areas suggestive of necrosis. He was diagnosed with extrapulmonary disseminated tuberculosis with tuberculous adrenalitis. He was started on directly observed therapy (DOTS) for disseminated tuberculosis and 40 mg of prednisolone. He is improving with treatment.

Actions of hypoxia on catecholamine synthetic enzyme mRNA expression before and after development of adrenal innervation in the sheep fetus

PubMed Central

Adams, M B; McMillen, I C

2000-01-01

We have investigated adrenal mRNA expression of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) following acute hypoxia in fetal sheep before (< 105 days gestation, n = 20) and after (> 125 days gestation, n = 20) the development of adrenal innervation and following pretreatment with the nicotinic receptor anatgonist hexamethonium (n = 12). Total RNA was extracted from fetal adrenal glands collected at specific time points at 3-20 h after the onset of either hypoxia (∼50% reduction in fetal arterial oxygen saturation (SO2) for 30 min), or normoxia. Before 105 days, there was a decrease in adrenal TH mRNA expression at 20 h after hypoxia and adrenal TH mRNA expression was directly related to the changes in arterial PO2 measured during normoxia and hypoxia. After 125 days, adrenal TH mRNA levels were suppressed for up to 12 h following hypoxia. In both age groups, adrenal PNMT mRNA expression increased at 3-5 h after hypoxia and was inversely related to the changes in fetal arterial PO2 during normoxia or hypoxia. After 125 days, the administration of hexamethonium (25 mg kg−1, I. V.) reduced TH mRNA but not PNMT mRNA expression after normoxia. After hexamethonium pretreatment, there was no significant change in either adrenal TH or PNMT mRNA expression following hypoxia. We conclude that acute hypoxia differentially regulates adrenal TH and PNMT mRNA expression in the fetal sheep both before and after the development of adrenal innervation. After the development of adrenal innervation, however, the effect of acute hypoxia upon adrenal TH and PNMT mRNA expression is dependent upon neurogenic input acting via nicotinic receptors. PMID:11118487

Imaging of adrenal masses with emphasis on adrenocortical tumors.

PubMed

Sundin, Anders

2012-01-01

Because of the more widespread and frequent use of cross-sectional techniques, mainly computed tomography (CT), an increasing number of adrenal tumors are detected as incidental findings ("incidentalomas"). These incidentaloma patients are much more frequent than those undergoing imaging because of symptoms related to adrenal disease. CT and magnetic resonance imaging (MRI) are in most patients sufficient for characterization and follow-up of the incidentaloma. In a minor portion of patients, biochemical screening reveals a functional tumor and further diagnostic work-up and therapy need to be performed according to the type of hormonal overproduction. In oncological patients, especially when the morphological imaging criteria indicate an adrenal metastasis, biopsy of the lesion should be considered after pheochromocytoma is ruled out biochemically. In the minority of patients in whom CT and MRI fail to characterize the tumor and when time is of essence, functional imaging mainly by positron emission tomography (PET) is available using various tracers. The most used PET tracer, [(18)F]fluoro-deoxy-glucose ((18)FDG), is able to differentiate benign from malignant adrenal tumors in many patients. (11)C-metomidate ((11)C-MTO) is a more specialized PET tracer that binds to the 11-beta-hydroxylase enzyme in the adrenal cortex and thus makes it possible to differ adrenal tumors (benign adrenocortical adenoma and adrenocortical cancer) from those of non-adrenocortical origin.

Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

PubMed

Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

2017-07-15

OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION IN THE DIAGNOSIS OF ADRENAL METASTASIS IN A HIGH-RISK POPULATION.

PubMed

Zhang, Catherine D; Erickson, Dana; Levy, Michael J; Gleeson, Ferga C; Salomao, Diva R; Delivanis, Danae A; Bancos, Irina

2017-12-01

While the left adrenal gland is readily accessible via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), data regarding the utility of EUS-FNA in the diagnosis of adrenal lesions remain limited. We aimed to ( 1) describe the clinical context, adverse event rate, and diagnostic performance of EUS-FNA, and ( 2) compare the safety profile and diagnostic accuracy of EUS-FNA with percutaneous adrenal biopsy. Single-center, retrospective cohort study. Medical records of patients who underwent adrenal EUS-FNA from 2005-2016 were reviewed. Biopsy outcomes were evaluated using a predefined reference standard. Results were compared to patients who underwent percutaneous biopsy (n = 419; 1994-2014) at the same institution. A total of 121 patients underwent EUS-FNA of 122 adrenal lesions (left [n = 121]; right [n = 1]; mean lesion size, 1.8 cm). Cytology was positive for malignancy in 35 (29%), suspicious for malignancy in 1 (1%), atypical in 1 (1%), negative for malignancy in 81 (66%), and nondiagnostic in 4 (3%). No adverse events were reported. EUS-FNA diagnosed metastasis with a sensitivity of 100%, specificity of 97.4%, positive predictive value of 91.7%, and negative predictive value of 100%. When compared to percutaneous biopsy, lesion size (1.8 cm vs. 3.7 cm; P<.001) and biopsy site (99% vs. 62% left adrenal; P<.001) were significantly different. EUS-FNA adverse event rate was lower than percutaneous biopsy (0% vs. 4%; P = .024), but nondiagnostic rates were similar (3.3% vs. 4.8%; P = .48). EUS-FNA is a sensitive technique to sample adrenal lesions in patients at high risk for adrenal metastasis with fewer adverse events compared to percutaneous biopsy. CI = confidence interval CT = computed tomography EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration NPV = negative predictive value PPV = positive predictive value TUS = transabdominal ultra-sound.

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function.

PubMed

Concepcion, Axel R; Vaeth, Martin; Wagner, Larry E; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S; Cuk, Mario; Yule, David I; Feske, Stefan

2016-11-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release-activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel-deficient patients and mice with ectodermal tissue-specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice.

p.R182C mutation in Korean twin with congenital lipoid adrenal hyperplasia

PubMed Central

Park, Hye Won; Kwak, Byung Ok; Kim, Gu-Hwan; Yoo, Han-Wook

2013-01-01

Congenital lipoid adrenal hyperplasia (CLAH) is the most severe form of congenital adrenal hyperplasia which is caused by mutations in the steroidogenic acute regulatory protein (StAR). The mutations in StAR gene resulted in failure of the transport cholesterol into mitochondria for steroidogenesis in the adrenal gland. Twin sisters (A, B) with normal 46, XX were born at 36+2 gestational week, premature to nonrelated parents. They had symptoms as hyperpigmentation, slightly elevated potassium level and low level of sodium. Laboratory finding revealed normal 17-hydroxyprogesterone level, elevated adrenocorticotropin hormone (A, 4,379.2 pg/mL; B, 11,616.1 pg/mL), and high plasma renin activity (A, 49.02 ng/mL/hr; B, 52.7 ng mL/hr). However, the level of plasma cortisol before treatment was low (1.5 µg/dL) in patient B but normal (8.71 µg/dL) in patient A. Among them, only patient A was presented with adrenal insufficiency symptoms which was suggestive of CLAH and prompted us to order a gene analysis in both twin. The results of gene analysis of StAR in twin revealed same heterozygous conditions for c.544C>T (Arg182Cys) in exon 5 and c.722C>T (Gln258*) in exon 7. We report the first case on the mutation of p.R182C in exon 5 of the StAR gene in Korea. PMID:24904850

Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

PubMed

Surapaneni, Dinesh Kumar; Adapa, Sree Rama Shiva Shanker; Preeti, Kumari; Teja, Gangineni Ravi; Veeraragavan, Muruganandam; Krishnamurthy, Sairam

2012-08-30

Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities. The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit. CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively. Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities. The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and

Functional ectopic adrenal carcinoma in a dog

PubMed Central

Taylor, Jim A.; Lee, Maris S.; Nicholson, Matthew E.; Justin, Robert B.

2014-01-01

An 11-year-old spayed female pit bull terrier was presented with a 2-month history of polyuria, polydipsia, polyphagia, and panting. Serum chemistry, blood and urine analysis, and tests for hyperadrenocorticism suggested an adrenal tumor. Abdominal ultrasound identified a mass caudal to the right kidney. The mass was completely excised and histopathology was consistent with endocrine carcinoma. Three years later there was no evidence of recurrence or metastasis. PMID:25183891

Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases.

PubMed

Melo, Homero José de Farias E; Goldman, Suzan M; Szejnfeld, Jacob; Faria, Juliano F; Huayllas, Martha K P; Andreoni, Cássio; Kater, Cláudio E

2014-01-01

To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the detection of adrenal nodules and differentiation between benign and malignant masses (adenomas, pheochromocytomas, carcinomas and metastases). A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years) presenting with 138 adrenal nodules/masses were prospectively assessed. A multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical shift imaging sequence. The following ratios were calculated: choline (Cho)/creatine (Cr), 4.0-4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2, 100% sensitivity, 98.2% specificity (differences between adenomas/pheochromocytomas and carcinomas/ metastases); 4.0-4.3 ppm/Cr ≥ 1.5, 92.3% sensitivity, 96.9% specificity (differences between carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ -7.449, 90.9% sensitivity and 77.8% specificity (differences between pheochromocytomas and carcinomas/adenomas). Information provided by 2D-1H-MRS were effective and allowed for the differentiation between adrenal masses and nodules in most cases of lesions with > 1.0 cm in diameter.

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

On approaches to the functional restoration of salivary glands damaged by radiation therapy for head and neck cancer, with a review of related aspects of salivary gland morphology and development.

PubMed

Redman, R S

2008-06-01

Radiation therapy for cancer of the head and neck can devastate the salivary glands and partially devitalize the mandible and maxilla. As a result, saliva production is drastically reduced and its quality adversely altered. Without diligent home and professional care, the teeth are subject to rapid destruction by caries, necessitating extractions with attendant high risk of necrosis of the supporting bone. Innovative techniques in delivery of radiation therapy and administration of drugs that selectively protect normal tissues can reduce significantly the radiation effects on salivary glands. Nonetheless, many patients still suffer severe oral dryness. I review here the functional morphology and development of salivary glands as these relate to approaches to preventing and restoring radiation-induced loss of salivary function. The acinar cells are responsible for most of the fluid and organic material in saliva, while the larger ducts influence the inorganic content. A central theme of this review is the extent to which the several types of epithelial cells in salivary glands may be pluripotential and the circumstances that may influence their ability to replace cells that have been lost or functionally inactivated due to the effects of radiation. The evidence suggests that the highly differentiated cells of the acini and large ducts of mature glands can replace themselves except when the respective pools of available cells are greatly diminished via apoptosis or necrosis owing to severely stressful events. Under the latter circumstances, relatively undifferentiated cells in the intercalated ducts proliferate and redifferentiate as may be required to replenish the depleted pools. It is likely that some, if not many, acinar cells may de-differentiate into intercalated duct-like cells and thus add to the pool of progenitor cells in such situations. If the stress is heavy doses of radiation, however, the result is not only the death of acinar cells, but also a marked

Adrenal Insufficiency

MedlinePlus

... three types of steroid hormones. In adrenal insufficiency (AI), the cortex does not make enough steroid hormones. ... unlike “adrenal fatigue.” There are two kinds of AI: • Primary AI, also called Addison’s disease. In this ...

Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System

PubMed Central

Burford, Natalie G.; Webster, Natalia A.; Cruz-Topete, Diana

2017-01-01

The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA) axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart. PMID:29035323

Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.

PubMed

Burford, Natalie G; Webster, Natalia A; Cruz-Topete, Diana

2017-10-16

The collective of endocrine organs acting in homeostatic regulation-known as the hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

Leg tendon glands in male bumblebees ( Bombus terrestris): structure, secretion chemistry, and possible functions

NASA Astrophysics Data System (ADS)

Jarau, Stefan; Žáček, Petr; Šobotník, Jan; Vrkoslav, Vladimír; Hadravová, Romana; Coppée, Audrey; Vašíčková, Soňa; Jiroš, Pavel; Valterová, Irena

2012-12-01

Among the large number of exocrine glands described in bees, the tarsal glands were thought to be the source of footprint scent marks. However, recent studies showed that the compounds used for marking by stingless bees are secreted by leg tendon instead of tarsal glands. Here, we report on the structure of leg tendon glands in males of Bombus terrestris, together with a description of the chemical composition of their secretions and respective changes of both during the males' lives. The ultrastructure of leg tendon glands shows that the secretory cells are located in three independent regions, separated from each other by unmodified epidermal cells: in the femur, tibia, and basitarsus. Due to the common site of secretion release, the organ is considered a single secretory gland. The secretion of the leg tendon glands of B. terrestris males differs in its composition from those of workers and queens, in particular by (1) having larger proportions of compounds with longer chain lengths, which we identified as wax esters; and (2) by the lack of certain hydrocarbons (especially long chain dienes). Other differences consist in the distribution of double bond positions in the unsaturated hydrocarbons that are predominantly located at position 9 in males but distributed at seven to nine different positions in the female castes. Double bond positions may change chemical and physical properties of a molecule, which can be recognized by the insects and, thus, may serve to convey specific information. The function of male-specific compounds identified from their tendon glands remains elusive, but several possibilities are discussed.

Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function

PubMed Central

Concepcion, Axel R.; Vaeth, Martin; Wagner, Larry E.; Eckstein, Miriam; Hecht, Lee; Yang, Jun; Crottes, David; Seidl, Maximilian; Shin, Hyosup P.; Weidinger, Carl; Cameron, Scott; Turvey, Stuart E.; Issekutz, Thomas; Meyts, Isabelle; Lacruz, Rodrigo S.; Cuk, Mario; Yule, David I.

2016-01-01

Eccrine sweat glands are essential for sweating and thermoregulation in humans. Loss-of-function mutations in the Ca2+ release–activated Ca2+ (CRAC) channel genes ORAI1 and STIM1 abolish store-operated Ca2+ entry (SOCE), and patients with these CRAC channel mutations suffer from anhidrosis and hyperthermia at high ambient temperatures. Here we have shown that CRAC channel–deficient patients and mice with ectodermal tissue–specific deletion of Orai1 (Orai1K14Cre) or Stim1 and Stim2 (Stim1/2K14Cre) failed to sweat despite normal sweat gland development. SOCE was absent in agonist-stimulated sweat glands from Orai1K14Cre and Stim1/2K14Cre mice and human sweat gland cells lacking ORAI1 or STIM1 expression. In Orai1K14Cre mice, abolishment of SOCE was associated with impaired chloride secretion by primary murine sweat glands. In human sweat gland cells, SOCE mediated by ORAI1 was necessary for agonist-induced chloride secretion and activation of the Ca2+-activated chloride channel (CaCC) anoctamin 1 (ANO1, also known as TMEM16A). By contrast, expression of TMEM16A, the water channel aquaporin 5 (AQP5), and other regulators of sweat gland function was normal in the absence of SOCE. Our findings demonstrate that Ca2+ influx via store-operated CRAC channels is essential for CaCC activation, chloride secretion, and sweat production in humans and mice. PMID:27721237

Radioprotective Effect of Lidocaine on Function and Ultrastructure of Salivary Glands Receiving Fractionated Radiation

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

Hakim, Samer George, E-mail: samer.hakim@mkg-chir.mu-luebeck.de; Benedek, Geza Attila; Su Yuxiong

2012-03-15

Purpose: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. Methods and Materials: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary glandmore » function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. Results: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. Conclusions: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands.« less

Pineal gland function is required for colon antipreneoplastic effects of physical exercise in rats.

PubMed

Frajacomo, F T T; de Paula Garcia, W; Fernandes, C R; Garcia, S B; Kannen, V

2015-10-01

Light-at-night exposure enhances the risk of cancer. Colon cancer is among the most dangerous tumors affecting humankind. Physical exercise has shown positive effects against colon cancer. Here, we investigated whether pineal gland modulates antipreneoplastic effects of physical exercise in the colon. Surgical and non-surgical pineal impairments were performed to clarify the relationship between the pineal gland activity and manifestation of colonic preneoplastic lesions. Next, a progressive swimming training was applied in rats exposed or not to either non-surgical pineal impairment or carcinogen treatment for 10 weeks. Both surgical and non-surgical pineal impairments increased the development of colon preneoplasia. It was further found that impairing the pineal gland function, higher rates of DNA damage were induced in colonic epithelial and enteric glial cells. Physical exercise acted positively against preneoplasia, whereas impairing the pineal function with constant light exposure disrupts its positive effects on the development of preneoplastic lesions in the colon. This was yet related to increased DNA damage in glial cells and enteric neuronal activation aside from serum melatonin levels. Our findings suggest that protective effects of physical exercise against colon cancer are dependent on the pineal gland activity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Domestication Effects on Stress Induced Steroid Secretion and Adrenal Gene Expression in Chickens.

PubMed

Fallahsharoudi, Amir; de Kock, Neil; Johnsson, Martin; Ubhayasekera, S J Kumari A; Bergquist, Jonas; Wright, Dominic; Jensen, Per

2015-10-16

Understanding the genetic basis of phenotypic diversity is a challenge in contemporary biology. Domestication provides a model for unravelling aspects of the genetic basis of stress sensitivity. The ancestral Red Junglefowl (RJF) exhibits greater fear-related behaviour and a more pronounced HPA-axis reactivity than its domesticated counterpart, the White Leghorn (WL). By comparing hormones (plasmatic) and adrenal global gene transcription profiles between WL and RJF in response to an acute stress event, we investigated the molecular basis for the altered physiological stress responsiveness in domesticated chickens. Basal levels of pregnenolone and dehydroepiandrosterone as well as corticosterone response were lower in WL. Microarray analysis of gene expression in adrenal glands showed a significant breed effect in a large number of transcripts with over-representation of genes in the channel activity pathway. The expression of the best-known steroidogenesis genes were similar across the breeds used. Transcription levels of acute stress response genes such as StAR, CH25 and POMC were upregulated in response to acute stress. Dampened HPA reactivity in domesticated chickens was associated with changes in the expression of several genes that presents potentially minor regulatory effects rather than by means of change in expression of critical steroidogenic genes in the adrenal.

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics

PubMed Central

Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

2017-01-01

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3′-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3′-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH. PMID:28401898

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.

PubMed

Doleschall, Márton; Luczay, Andrea; Koncz, Klára; Hadzsiev, Kinga; Erhardt, Éva; Szilágyi, Ágnes; Doleschall, Zoltán; Németh, Krisztina; Török, Dóra; Prohászka, Zoltán; Gereben, Balázs; Fekete, György; Gláz, Edit; Igaz, Péter; Korbonits, Márta; Tóth, Miklós; Rácz, Károly; Patócs, Attila

2017-06-01

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Therefore, a systematic assessment of the genetic and evolutionary relationships between c.955C>T, CYP21A2 haplotypes and the RCCX copy number variation (CNV) structures, which harbor CYP21A2, was performed. In total, 389 unrelated Hungarian individuals with European ancestry (164 healthy subjects, 125 patients with non-functioning adrenal incidentaloma and 100 patients with classical CAH) as well as 34 adrenocortical tumor specimens were studied using a set of experimental and bioinformatic methods. A unique, moderately frequent (2%) haplotypic RCCX CNV structure with three repeated segments, abbreviated to LBSASB, harboring a CYP21A2 with a c.955C>T variant in the 3'-segment, and a second CYP21A2 with a specific c.*12C>T (rs150697472) variant in the middle segment occurred in all c.955C>T carriers with normal steroid levels. The second CYP21A2 was free of CAH-causing mutations and produced mRNA in the adrenal gland, confirming its functionality and ability to rescue the carriers from CAH. Neither LBSASB nor c.*12C>T occurred in classical CAH patients. However, CAH-causing CYP21A2 haplotypes with c.955C>T could be derived from the 3'-segment of LBSASB after the loss of functional CYP21A2 from the middle segment. The c.*12C>T indicated a functional CYP21A2 and could distinguish between non-pathogenic and pathogenic genomic contexts of the c.955C>T variant in the studied European population. Therefore, c.*12C>T may be suitable as a marker to avoid this genetic confound and improve the diagnosis of CAH.

Regulation of Calcium Channels and Exocytosis in Mouse Adrenal Chromaffin Cells by Prostaglandin EP3 Receptors

PubMed Central

Jewell, Mark L.; Breyer, Richard M.

2011-01-01

Prostaglandin (PG) E2 controls numerous physiological functions through a family of cognate G protein-coupled receptors (EP1–EP4). Targeting specific EP receptors might be therapeutically useful and reduce side effects associated with nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors that block prostanoid synthesis. Systemic immune challenge and inflammatory cytokines have been shown to increase expression of the synthetic enzymes for PGE2 in the adrenal gland. Catecholamines and other hormones, released from adrenal chromaffin cells in response to Ca2+ influx through voltage-gated Ca2+ channels, play central roles in homeostatic function and the coordinated stress response. However, long-term elevation of circulating catecholamines contributes to the pathogenesis of hypertension and heart failure. Here, we investigated the EP receptor(s) and cellular mechanisms by which PGE2 might modulate chromaffin cell function. PGE2 did not alter resting intracellular [Ca2+] or the peak amplitude of nicotinic acetylcholine receptor currents, but it did inhibit CaV2 voltage-gated Ca2+ channel currents (ICa). This inhibition was voltage-dependent and mediated by pertussis toxin-sensitive G proteins, consistent with a direct Gβγ subunit-mediated mechanism common to other Gi/o-coupled receptors. mRNA for all four EP receptors was detected, but using selective pharmacological tools and EP receptor knockout mice, we demonstrated that EP3 receptors mediate the inhibition of ICa. Finally, changes in membrane capacitance showed that Ca2+-dependent exocytosis was reduced in parallel with ICa. To our knowledge, this is the first study of EP receptor signaling in mouse chromaffin cells and identifies a molecular mechanism for paracrine regulation of neuroendocrine function by PGE2. PMID:21383044

Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling.

PubMed

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

2018-01-01

Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH.

Relative adrenal insufficiency in severe congestive heart failure with preserved systolic function: a case report.

PubMed

Lovelock, Joshua D; Coslet, Sandra; Johnson, Marie; Rich, Stuart; Gomberg-Maitland, Mardi

2007-09-01

Relative adrenal insufficiency in critically ill patients is an important syndrome in septic shock. The insufficient stress response of the hypothalamic-pituitary-adrenal axis in acute illness contributes to hemodynamic instability. Treatment of this state in septic shock improves patient outcomes. In this report, we describe the case of a patient with severe diastolic dysfunction who presented in cardiogenic shock associated with relative adrenal insufficiency and had a complete recovery with corticosteroid replacement. Alteration of the hypothalamic-pituitary-adrenal axis may be more prevalent than suspected in end-stage heart failure, and the diagnosis and treatment of this syndrome may ultimately improve outcomes in a subgroup of heart failure patients.

Traumatic and non-traumatic adrenal emergencies.

PubMed

Chernyak, Victoria; Patlas, Michael N; Menias, Christine O; Soto, Jorge A; Kielar, Ania Z; Rozenblit, Alla M; Romano, Luigia; Katz, Douglas S

2015-12-01

Multiple traumatic and non-traumatic adrenal emergencies are occasionally encountered during the cross-sectional imaging of emergency department patients. Traumatic adrenal hematomas are markers of severe polytrauma, and can be easily overlooked due to multiple concomitant injuries. Patients with non-traumatic adrenal emergencies usually present to an emergency department with a non-specific clinical picture. The detection and management of adrenal emergencies is based on cross-sectional imaging. Adrenal hemorrhage, adrenal infection, or rupture of adrenal neoplasm require immediate detection to avoid dire consequences. More often however, adrenal emergencies are detected incidentally in patients being investigated for non-specific acute abdominal pain. A high index of suspicion is required for the establishment of timely diagnosis and to avert potentially life-threatening complications. We describe cross-sectional imaging findings in patients with traumatic and non-traumatic adrenal hemorrhage, adrenal infarctions, adrenal infections, and complications of adrenal masses.

The role of neurotrophins related to stress in saliva and salivary glands.

PubMed

Saruta, Juri; Sato, Sadao; Tsukinoki, Keiichi

2010-10-01

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are well-studied neurotrophins involved in neurogenesis, differentiation, growth, and maintenance of selected peripheral and central populations of neuronal cells during development and adulthood. Neurotrophins, in concert with the hypothalamic-pituitary-adrenal (HPA) axis, play key roles in modulating brain plasticity and behavioral coping, especially during ontogenetic critical periods, when the developing brain is particularly sensitive to external stimuli. Early life events, such as psychophysical stress, affect NGF and BDNF levels and induce dysregulation of the HPA axis, thereby affecting brain development and contributing to inter-individual differences in vulnerability to stress or psychiatric disorders. Immobilization stress modifies BDNF mRNA expression in some organs. We studied the effect of immobilization stress on BDNF and its receptor tyrosine receptor kinase B (TrkB) in rat submandibular glands, and found increased BDNF expression in duct cells under immobilization stress. Upon further investigation on the influence of salivary glands on plasma BDNF using an acute immobilization stress model, we found that acute immobilization stress lasting 60 min significantly increases the plasma BDNF level. However, plasma BDNF elevation is markedly suppressed in bilaterally sialoadenectomized rats. This suggests that salivary glands may be the primary source of plasma BDNF under acute immobilization stress. This report reviews the structure of salivary glands, the role of neurotrophins in salivary glands, and the significance of BDNF in saliva and salivary glands, followed by a summary of the evidence that indicates the relationship between immobilization stress and BDNF expression within salivary glands.

Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

NASA Astrophysics Data System (ADS)

Pradhan, Swati

Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

Zonal differences in the distribution and morphology of lipid droplets using 4-amino-pyrazolo-(3,4 d) pyrimidine to lower cholesterol level in the rat adrenal.

PubMed

Szabó, D; Somogyi, J; Acs, Z; Mihály, K

1980-01-01

The effect of reduced blood and adrenal cholesterol levels on adrenocortical lipid droplets have been examined by treating adult rats with 4-amino-pyrazolo-(3,4 d) pyrimidine (4-APP), a drug that inhibits hepatic secretion of lipoproteins. Lowering the blood cholesterol level and the cholesterol content of the adrenals was associated with a marked reduction in the lipid droplets and with a simultaneous increase in their electron density in the inner cortical zones. In the zona glomerulosa cells, no perceptible differences were found in the quantity and morphology of lipid droplets. These data suggest that reduced blood and adrenal cholesterol levels do not affect lipids located in the zona glomerulosa and in the inner cortical zones in the same way, probably due to differences in their intracellular lipid dynamism. Noteworthy, that in spite of the marked lipid depletion, the adrenal glands retained their responsiveness to ACTH stimulation.

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

Armc5 deletion causes developmental defects and compromises T-cell immune responses

PubMed Central

Hu, Yan; Lao, Linjiang; Mao, Jianning; Jin, Wei; Luo, Hongyu; Charpentier, Tania; Qi, Shijie; Peng, Junzheng; Hu, Bing; Marcinkiewicz, Mieczyslaw Martin; Lamarre, Alain; Wu, Jiangping

2017-01-01

Armadillo repeat containing 5 (ARMC5) is a cytosolic protein with no enzymatic activities. Little is known about its function and mechanisms of action, except that gene mutations are associated with risks of primary macronodular adrenal gland hyperplasia. Here we map Armc5 expression by in situ hybridization, and generate Armc5 knockout mice, which are small in body size. Armc5 knockout mice have compromised T-cell proliferation and differentiation into Th1 and Th17 cells, increased T-cell apoptosis, reduced severity of experimental autoimmune encephalitis, and defective immune responses to lymphocytic choriomeningitis virus infection. These mice also develop adrenal gland hyperplasia in old age. Yeast 2-hybrid assays identify 16 ARMC5-binding partners. Together these data indicate that ARMC5 is crucial in fetal development, T-cell function and adrenal gland growth homeostasis, and that the functions of ARMC5 probably depend on interaction with multiple signalling pathways. PMID:28169274

Cryptochrome 2 expression level is critical for adrenocorticotropin stimulation of cortisol production in the capuchin monkey adrenal.

PubMed

Torres-Farfan, C; Abarzua-Catalan, L; Valenzuela, F J; Mendez, N; Richter, H G; Valenzuela, G J; Serón-Ferré, M

2009-06-01

Timely production of glucocorticoid hormones in response to ACTH is essential for survival by coordinating energy intake and expenditure and acting as homeostatic regulators against stress. Adrenal cortisol response to ACTH is clock time dependent, suggesting that an intrinsic circadian oscillator in the adrenal cortex contributes to modulate the response to ACTH. Circadian clock gene expression has been reported in the adrenal cortex of several species. However, there are no reports accounting for potential involvement of adrenal clock proteins on cortisol response to ACTH. Here we explored whether the clock protein cryptochrome 2 (CRY2) knockdown modifies the adrenal response to ACTH in a primate. Adrenal gland explants from adult capuchin monkey (n = 5) were preincubated for 6 h with transfection vehicle (control) or with two different Cry2 antisense and sense probes followed by 48 h incubation in medium alone (no ACTH) or with 100 nm ACTH. Under control and sense conditions, ACTH increased cortisol production, whereas CRY2 suppression inhibited ACTH-stimulated cortisol production. Expression of the steroidogenic enzymes steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase at 48 h of incubation was increased by ACTH in control explants and suppressed by Cry2 knockdown. Additionally, we found that Cry2 knockdown decreased the expression of the clock gene brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (Bmal1) at the mRNA and protein levels. Altogether these results strongly support that the clock protein CRY2 is involved in the mechanism by which ACTH increases the expression of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase. Thus, adequate expression levels of components of the adrenal circadian clock are required for an appropriate cortisol response to ACTH.

Persistent Primary Aldosteronism Despite Iatrogenic Adrenal Hemorrhage After Adrenal Vein Sampling

PubMed Central

Okamura, Keisuke; Okuda, Tetsu; Shirai, Kazuyuki; Abe, Ichiro; Kobayashi, Kunihisa; Ishii, Tatsu; Haraoka, Seiji; Urata, Hidenori

2018-01-01

Before surgery for primary aldosteronism (PA), localization is evaluated with adrenal vein sampling (AVS). A 56-year-old Japanese woman had a right adrenal mass, hypokalemia, and a high aldosterone/renin ratio. Stress tests confirmed the diagnosis of PA. Subsequently, preoperative AVS was performed and right adrenal hemorrhage (AH) occurred unexpectedly. Because hypertension persisted, laparoscopic right adrenalectomy was performed. Postoperatively, the blood pressure was normalized. Pathological examination revealed an adrenal cortical adenoma largely unaffected by necrosis and hemorrhage. Previous reports have also indicated that AH may not ameliorate PA. We discussed the clinical progress of AH and the measures to prevent causing AH. PMID:29238437

Effect of calcium(ion) uptake by rat adrenal mitochondria on pregnenolone formation and spectral properties of cytochrome P-450.

PubMed

Simpson, E R; Williams-Smith, D L

1975-10-09

The effect of calcium on pregnenolone formation from endogenous precursors has been studied in mitochondria from rat decapsulated and capsular adrenal glands. In the presence of succinate, addition of calcium chloride in the concentration range 20-150 muM caused an inhibition of pregnenolone formation in both decapsulated and capsular adrenal mitochondria. 11beta-hydroxylation of added deoxycosticosterone in decapsulated adrenal mitochondria was also inhibited. Under these conditions, calcium inhibited the reduction of adrenodoxin, a component of the cytochrome P-450 reductase system, presumably because uptake of calcium by the mitochondria competes with energy-linked transhydrogenase for high-energy intermediates. For this reason, incubations were carried out in the presence of succinate plus isocitrate plus NADP+. Under these conditions, calcium chloride in the concentration range 120-875 muM caused a 2-4-fold stimulation of pregnenolone formation, but had no effect on corticosterone formation from added deoxycorticosterone. The effect of calcium on the optical spectra of cytochrome P-450 has also been examined in mitochondria from decapsulated and capsular rat adrenals. In the presence of succinate, calcium induced a spectral change resembling a type I difference spectrum of cytochrome P-450. Thus it appears that uptake of calcium by adrenal mitochondria can stimulate pregnenolone formation by increasing the interaction of mitochondrial cytochrome P-450 with endogenous substrate.

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review

PubMed Central

Mula-Abed, Waad-Allah S.; Ahmed, Riyaz; Ramadhan, Fatima A.; Al-Kindi, Manal K.; Al-Busaidi, Noor B.; Al-Muslahi, Hilal N.; Al-Lamki, Mohammad A.

2015-01-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario. PMID:26421121

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: 
A Case Report and Literature Review.

PubMed

Mula-Abed, Waad-Allah S; Ahmed, Riyaz; Ramadhan, Fatima A; Al-Kindi, Manal K; Al-Busaidi, Noor B; Al-Muslahi, Hilal N; Al-Lamki, Mohammad A

2015-09-01

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient's history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario.

Effects of acute administration of ethanol on the rat adrenal cortex.

PubMed

Milovanović, Tatjana; Budec, Mirela; Balint-Perić, Ljiljana; Koko, Vesna; Todorović, Vera

2003-09-01

The purpose of this study was to investigate the effect of a single dose of ethanol on rat adrenal cortex and to determine whether the estrous cycle can influence this effect of ethanol. Adult female Wistar rats showing proestrus or diestrus Day 1 (n = 12) were treated intraperitoneally with ethanol (4 g/kg body weight). Untreated (n = 15) and saline-injected (n = 14) rats were used as controls. The animals were sacrificed by decapitation 0.5 hour after ethanol administration. Stereological analysis was performed on paraffin sections of adrenal glands stained with AZAN, and the following parameters were determined: absolute volume of the zona glomerulosa, the zona fasciculata and the zona reticularis, numerical density, volume and the mean diameter of adrenocortical cells and of their nuclei, and diameter and length of capillaries. The diameter and volume of adrenocortical cells in the zona fasciculata and the zona reticularis were significantly increased by acute ethanol treatment at proestrus. In the same group of animals, a single dose of ethanol induced significant decrease in numerical density of adrenocortical cells and of their nuclei in all three zones. Increased length of capillaries of the zona fasciculata as well as enhanced level of serum corticosterone was found in ethanol-treated rats at both phases of the estrous cycle, proestrus and diestrus Day 1. The obtained results indicate that a single dose of ethanol activates adrenal cortex in female rats and that the effect is more pronounced on morphometric parameters at proestrus.

Functional morphology of femoral glands in the Tegu lizard, Tupinambis merianae.

PubMed

Chamut, Silvia; Valdez, Valeria García; Manes, Mario E

2009-04-01

Several lizards have femoral glands, which have an influence in various reproductive behaviors. In this paper we describe the morphological organization of the femoral glands in the Tegu, Tupinambis merianae, by means of light and electron microscopy. Even though these glands are present in both genders, secretions during the reproductive period can only be found in males. The glandular parenchyma, which is organized in numerous secretory units, consists of keratinocyte-like cells and granular cells. The holocrine secretion is constituted from both cells, which lose their integrity and become a semi-amorphous material, reinforced by keratin sheets. The discharges of each unit merge together into a solid cylinder of secretion, surrounded by epithelial cells, that is extruded to the exterior. The keratin sheets and epithelial layers that surround both the complete and partial secretions form a sort of structural support suitable for the type of territorial demarcation characteristic of the species. The granular cells, supposedly the producers of pheromones, are characterized by the presence of electron-dense granules and multilaminar membranous bodies that show ultrastructural changes of unknown function. The free granules in the secretion cylinder may act as pheromone deposits.

Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization.

PubMed

Satani, Nozomi; Ota, Hideki; Seiji, Kazumasa; Morimoto, Ryo; Kudo, Masataka; Iwakura, Yoshitsugu; Ono, Yoshikiyo; Nezu, Masahiro; Omata, Kei; Ito, Sadayoshi; Satoh, Fumitoshi; Takase, Kei

2016-01-01

To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion. The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.9 years ± 11 [standard deviation]). A microcatheter was inserted in first-degree tributary veins. Unilateral aldosterone hypersecretion at the adrenal central vein was determined according to the lateralization index after cosyntropin stimulation. Excess aldosterone secretion at the adrenal tributary vein was considered to be present when the aldosterone/cortisol ratio from this vein exceeded that from the external iliac vein; suppressed secretion was indicated by the opposite pattern. Categoric variables were expressed as numbers and percentages; continuous variables were expressed as means ± standard errors of the mean. The AVS success rate, indicated by a selectivity index of 5 or greater, was 98% (64 of 65). The mean numbers of sampled tributaries on the left and right sides were 2.11 and 1.02, respectively. The following diagnoses were made on the basis of S-AVS results: unilateral aldosterone hypersecretion in 30 patients, bilateral hypersecretion without suppressed segments in 22 patients, and bilateral hypersecretion with at least one suppressed segment in 12 patients. None of the patients experienced severe complications. S-AVS could be used to identify heterogeneous intra-adrenal aldosterone secretion. Patients who have bilateral aldosterone-producing adenomas can be treated with adrenal-sparing surgery or other minimally invasive local therapies if any suppressed segment is identified at S-AVS. © RSNA, 2015.

Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

PubMed Central

Mello, Marcelo F.; Faria, Alvaro A.; Mello, Andrea F.; Carpenter, Linda L.; Tyrka, Audrey R.; Price, Lawrence H.

2015-01-01

Objective The aim of this paper was to examine the relationship between childhood maltreatment and adult psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. Method A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. Results There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. Discussion The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. Conclusion Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses. PMID:19967199

Is the eccrine gland an integral, functionally important component of the human scalp pilosebaceous unit?

PubMed

Poblet, Enrique; Jiménez-Acosta, Francisco; Hardman, Jonathan A; Escario, Eduardo; Paus, Ralf

2016-02-01

The pilosebaceous unit (PSU) and the eccrine sweat gland (ESG) are classically described as completely independent skin appendages. However, careful inspection of scalp follicular units reveals that the secretory segment of the ESG spatially approximates the hair follicle in a position below the sebaceous gland and the insertion of the arrector pili muscle. Therefore, we propose here that, contrary to conventional wisdom, the PSU and the ESG should not be viewed in isolation, and may form instead, along with the arrector pili muscle and the apocrine gland (where present),one functional unit. For this, we suggest the more inclusive term of 'Hair Cluster' (HC). If confirmed, e.g. by 3D imaging techniques, the novel concept of a functional HC, whose individual components may communicate via secreted molecules and may share selected progenitor cell populations for HC repair/regeneration, has major physiological and pathological implications, which are briefly discussed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

NASA Astrophysics Data System (ADS)

Rigatos, Gerasimos

2016-12-01

It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse.

PubMed

Suto, Jun-Ichi

2012-11-06

Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes responsible for the QTLs will be

Quantitative trait locus mapping of genes associated with vacuolation in the adrenal X-zone of the DDD/Sgn inbred mouse

PubMed Central

2012-01-01

Background Adrenal gland of mice contains a transient zone between the adrenal cortex and the adrenal medulla: the X-zone. There are clear strain differences in terms of X-zone morphology. Nulliparous females of the inbred mouse DDD strain develop adrenal X-zones containing exclusively vacuolated cells, whereas females of the inbred mouse B6 strain develop X-zones containing only non-vacuolated cells. The X-zone vacuolation is a physiologic process associated with the X-zone degeneration and is tightly regulated by genetic factors. Identification of the genetic factors controlling such strain differences should help analyze the X-zone function. In this study, a quantitative trait locus (QTL) analysis for the extent of X-zone vacuolation was performed for two types of F2 female mice: F2Ay mice (F2 mice with the Ay allele) and F2 non-Ay mice (F2 mice without the Ay allele). These were produced by crossing B6 females and DDD.Cg-Ay males. DDD.Cg-Ay is a congenic mouse strain for the Ay allele at the agouti locus and is used for this study because a close association between the X-zone morphology and the agouti locus genotype has been suggested. The Ay allele is dominant and homozygous lethal; therefore, living Ay mice are invariably heterozygotes. Results Single QTL scans identified significant QTLs on chromosomes 1, 2, 6, and X for F2 non-Ay mice, and on chromosomes 2, 6, and 12 for F2Ay mice. The QTL on chromosome 2 was considered to be because of the agouti locus, which has been suggested to be associated with X-zone vacuolation. A significant QTL that interacted with the agouti locus was identified on chromosome 8. Conclusions The extent of X-zone vacuolation in DDD females was controlled by multiple genes with complex interactions. The murine X-zone is considered analogous structure to the human fetal zone. Therefore, the results of this study will aid in understanding function of not only of the X-zone but also of the human fetal zone. Identifying the genes

Functional Involvement of Carbonic Anhydrase in the Lysosomal Response to Cadmium Exposure in Mytilus galloprovincialis Digestive Gland

PubMed Central

Caricato, Roberto; Giordano, M. Elena; Schettino, Trifone; Lionetto, M. Giulia

2018-01-01

Carbonic anhydrase (CA) is a ubiquitous metalloenzyme, whose functions in animals span from respiration to pH homeostasis, electrolyte transport, calcification, and biosynthetic reactions. CA is sensitive to trace metals in a number of species. In mussels, a previous study demonstrated CA activity and protein expression to be enhanced in digestive gland by cadmium exposure. The aim of the present work was to investigate the functional meaning, if any, of this response. To this end the study addressed the possible involvement of CA in the lysosomal system response of digestive gland cells to metal exposure. The in vivo exposure to acetazolamide, specific CA inhibitor, significantly inhibited the acidification of the lysosomal compartment in the digestive gland cells charged with the acidotropic probe LysoSensor Green D-189, demonstrating in vivo the physiological contribution of CA to the acidification of the lysosomes. Under CdCl2 exposure, CA activity significantly increased in parallel to the increase of the fluorescence of LysoSensor Green charged cells, which is in turn indicative of proliferation and/or increase in size of lysosomes. Acetazolamide exposure was able to completely inhibit the cadmium induced Lysosensor fluorescence increase in digestive gland cells. In conclusion, our results demonstrated the functional role of CA in the lysosomal acidification of Mytilus galloprovincialis digestive gland and its involvement in the lysosomal activation following cadmium exposure. CA induction could physiologically respond to a prolonged increased requirement of H+ for supporting lysosomal acidification during lysosomal activation. PMID:29670538

[Morphofunctional and molecular bases of pineal gland aging].

PubMed

Khavinson, V Kh; Lin'kova, N S

2012-01-01

The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery

PubMed Central

Vidal Fortuny, J.; Belfontali, V.; Sadowski, S. M.; Karenovics, W.; Guigard, S.

2016-01-01

Background Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. Methods Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. Results Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3·3(1·4) pmol/l and 2·27(0·10) mmol/l respectively on POD 1, and 4·0(1.6) pmol/l and 2·32(0·08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. Conclusion PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID:26864909

Neglected issues concerning teaching human adrenal steroidogenesis in popular biochemistry textbooks.

PubMed

Han, Zhiyong; Elliott, Mark S

2017-11-01

In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand health consequences caused by deficiencies of enzymes in the adrenal steroidogenic pathways. However, popular biochemistry textbooks contain insufficient information and may sometimes give students a misimpression about certain aspects of human adrenal steroidogenesis. This article highlights two neglected issues in teaching human adrenal steroidogenesis in popular biochemistry textbooks. The purpose of this article is to draw attention to these issues. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):469-474, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality.

PubMed

Bancos, Irina; Hazeldine, Jon; Chortis, Vasileios; Hampson, Peter; Taylor, Angela E; Lord, Janet M; Arlt, Wiebke

2017-04-01

Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection. We undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis ( n =  37) or bilateral adrenalectomy ( n =  5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects. Neutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P  < 0.0001). Phenotypically, the percentage of NK cells expressing the activating receptors NKG2D and NKp46 was significantly lower in PAI, as was the surface density of NKG2D (all P  < 0.0001). Intracellular granzyme B expression was significantly increased in NK cells from PAI patients ( P  < 0.01). Adrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI. © 2017 The authors.

Adrenohepatic fusion: Adhesion or invasion in primary virilizant giant adrenal carcinoma? Implications for surgical resection. Two case report and review of the literature.

PubMed

Alastrué Vidal, Antonio; Navinés López, Jordi; Julián Ibáñez, Juan Francisco; De la Ossa Merlano, Napoleón; Botey Fernandez, Mireia; Sampere Moragues, Jaume; Sánchez Torres, Maria Del Carmen; Barluenga Torres, Eva; Fernández-Llamazares Rodríguez, Jaime

2016-01-01

Adrenohepatic fusion means union between the adrenal gland and the liver, intermingling its parenchymas. It is not possible to identify this condition by image tests. Its presence implies radical and multidisciplinar approach. We report two female cases of 45 and 50 years old with clinical virilization and palpable mass on the abdominal right upper quadrant corresponding to adrenocortical carcinoma with hepatic fusion. The contrast-enhanced tomography showed an indistinguishable mass involving the liver and the right adrenal gland. In the first case, the patient had a two-time operation, the former removing only the adrenal carcinoma, and the second performing a radical surgery after an early relapse. In the second case, a radical right en bloc adrenohepatectomy was performed. Both cases were pathologically reported as liver-infiltrating adrenal carcinoma. Only in the second case the surgery was radical effective as first intention to treat, with 3 years of disease-free survival. ACC is a rare entity with poor prognosis. The major indicators of malignancy are tumour diameter over 6cm, local invasion or metastasis, secretion of corticosteroids, virilization and hypertension and hypokalaemia. The parenchymal fusion of the adrenal cortical layer can be misdiagnosed as hepatocellular carcinoma with adhesion with the Glisson capsule. AHF in such cases may be misinterpreted during surgery, what may impair its resectability, and therefore the survival. The surgical treatment must be performed en bloc, often using liver vascular control. Postoperative treatment must be offered immediately after surgery. We report two consecutive rare cases of adrenohepatic fusion in giant right adrenocortical carcinoma, not detectable by imaging, what has important implications for the surgical decision-making. As radical surgery is the best choice to offer a curative treatment, it has to be performed by a multidisciplinary well-assembled team, counting with endocrine and liver surgeons

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation.

PubMed

Marmary, Yitzhak; Adar, Revital; Gaska, Svetlana; Wygoda, Annette; Maly, Alexander; Cohen, Jonathan; Eliashar, Ron; Mizrachi, Lina; Orfaig-Geva, Carmit; Baum, Bruce J; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H

2016-03-01

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. ©2016 American Association for Cancer Research.

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

PubMed

Kley, H K; Abendroth, H; Hehrmann, R; Müller, A; Keck, E; Schneitler, H; Elsässer, H; Krüskemper, H L

1984-01-16

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

PubMed

Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

2006-02-01

The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

Cognitive function in patients with primary adrenal insufficiency (Addison's disease).

PubMed

Schultebraucks, Katharina; Wingenfeld, Katja; Heimes, Jana; Quinkler, Marcus; Otte, Christian

2015-05-01

Patients with primary adrenal insufficiency (AI) need to replace glucocorticoids and mineralocorticoids that act on glucocorticoid (GR) and mineralocorticoid receptors (MR). Both receptors are highly expressed in the hippocampus and are closely associated with cognitive function, which might be impaired by insufficient or increased GR and MR stimulation. However, little is known about cognitive function in patients with AI. It was examined whether patients with AI exhibit worse cognitive function compared to sex-, age-, and education-matched controls. Cognitive function (executive function, concentration, verbal memory, visual memory, working memory, and autobiographical memory) was assessed in 30 patients with AI (mean age 52.4 yrs. ±14.4, n=21 women, mean duration of illness 18.2 yrs. ±11.1) and 30 matched controls. We also measured depressive symptoms, body mass index (BMI), and blood pressure. Patients with AI showed more depressive symptoms, had a greater BMI and lower systolic blood pressure compared to controls. Adjusted analyses controlling for these variables revealed that patients with AI performed significantly worse in verbal learning (F=7.8, p=.007). Executive function, concentration, working memory, verbal memory, visuospatial memory, and autobiographical memory did not differ between groups. No clinically relevant cognitive impairment was found in patients with AI compared to matched controls. Even long-term glucocorticoid and mineralocorticoid substitution over almost two decades appears to have only subtle effects on cognition in patients with AI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neglected Issues Concerning Teaching Human Adrenal Steroidogenesis in Popular Biochemistry Textbooks

ERIC Educational Resources Information Center

Han, Zhiyong; Elliott, Mark S.

2017-01-01

In the human body, the adrenal steroids collectively regulate a plethora of fundamental functions, including electrolyte and water balance, blood pressure, stress response, intermediary metabolism, inflammation, and immunity. Therefore, adrenal steroidogenesis is an important biochemistry topic for students to learn in order for them to understand…

Polycystic ovarian disease: the adrenal connection.

PubMed

Marouliss, George B; Triantafillidis, Ioannis K

2006-01-01

Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

Modulating the pituitary-adrenal response to stress

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.

1975-01-01

Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

Adrenal suppression in bronchiectasis and the impact of inhaled corticosteroids.

PubMed

Holme, J; Tomlinson, J W; Stockley, R A; Stewart, P M; Barlow, N; Sullivan, A L

2008-10-01

The present study identified three patients with bronchiectasis receiving inhaled corticosteroids (ICSs) who had symptomatic adrenal suppression secondary to ICS. The prevalence of adrenal suppression is unknown in bronchiectasis. The frequency of adrenal suppression and the impact of ICS use in bronchiectasis patients were examined. In total, 50 outpatients (33 receiving ICSs) underwent a short Synacthen test and completed a St George's Respiratory Questionnaire (SGRQ). Symptoms of adrenal suppression, steroid use and lung function were compared between subjects who were suppressed and those who were not. Adrenal suppression was evident in 23.5% of subjects who did not receive ICSs and 48.5% of those who did. Basal cortisol and the increments by which cortisol increased 30 min after Synacthen were lower in suppressed than in nonsuppressed subjects. The incremental cortisol rise was negatively correlated with SGRQ impacts and total score, suggesting a worse quality of life in those who had an impaired adrenal response. The greatest frequency of generalised symptoms was seen in the suppressed group. A significant proportion of subjects with bronchiectasis have evidence of adrenal suppression, and this is increased when inhaled corticosteroids are also used. Impairment of the cortisol response to stimulation is associated with poorer health status.

Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding

NASA Technical Reports Server (NTRS)

Heybach, J. P.; Vernikos-Danellis, J.

1979-01-01

Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0-5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.

A novel organotypic 3D sweat gland model with physiological functionality

PubMed Central

Grüdl, Sabine; Banowski, Bernhard; Giesen, Melanie; Sättler, Andrea; Proksch, Peter; Welss, Thomas; Förster, Thomas

2017-01-01

Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers. To resemble the in vivo situation as close as possible, we applied the hanging drop cultivation technology regaining most of the markers when cultured in its natural spherical environment. To compare the organotypic 3D sweat gland model versus human sweat glands in vivo, we compared markers relevant for the eccrine sweat gland using transcriptomic and proteomic analysis. Comparing the marker profile, a high in vitro-in vivo correlation was shown. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), muscarinic acetylcholine receptor M3 (CHRM3), Na+-K+-Cl- cotransporter 1 (NKCC1), calcium-activated chloride channel anoctamin-1 (ANO1/TMEM16A), and aquaporin-5 (AQP5) are found at significant expression levels in the 3D model. Moreover, cholinergic stimulation with acetylcholine or pilocarpine leads to calcium influx monitored in a calcium flux assay. Cholinergic stimulation cannot be achieved with the sweat gland cell line NCL-SG3 used as a sweat gland model system. Our results show clear benefits of the organotypic 3D sweat gland model versus 2D cultures in terms of the expression of essential eccrine sweat gland key regulators and in the physiological response to stimulation. Taken together, this novel organotypic 3D sweat gland model shows a good in vitro-in vivo correlation and is an appropriate alternative for screening of potential bioactives

Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.

PubMed

Belgorosky, Alicia; Baquedano, María Sonia; Guercio, Gabriela; Rivarola, Marco A

2009-03-01

Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.

A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development.

PubMed

Musumeci, Giuseppe; Castorina, Sergio; Castrogiovanni, Paola; Loreto, Carla; Leonardi, Rosi; Aiello, Flavia Concetta; Magro, Gaetano; Imbesi, Rosa

2015-01-01

The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved.

Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency.

PubMed

Hershkovitz, Eli; Arafat, Maram; Loewenthal, Neta; Haim, Alon; Parvari, Ruti

2015-09-01

The nicotinamide nucleotide transhydrogenase (NNT) enzyme is the main generator of nicotinamide adenine dinucleotide phosphate-oxidase in the mitochondrion. Mutations of the NNT gene have been recently implicated in familial glucocorticoid deficiency. We describe the long-term clinical course of a NNT-deficient 20-year-old patient with combined adrenal failure who had developed a testicular adrenal rest tumor and precocious puberty. The patient's medical records were reviewed. Whole-exome sequencing was performed on DNA obtained from the patient and family members. The patient experienced Addisonian crisis at 10 months of age. Enlarged testicular volume and precocious puberty, accompanied by increased testosterone levels, were noted at 6 years. Testicular biopsy revealed a adrenal rest tumor, which regressed after intensification of glucocorticoid treatment. Genetic studies disclosed a c.1163A>C, p.Tyr388Ser substitution on the NNT gene. This mutation is predicted to be damaging to NNT function. We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.

Notch-Dependent Pituitary SOX2+ Stem Cells Exhibit a Timed Functional Extinction in Regulation of the Postnatal Gland

PubMed Central

Zhu, Xiaoyan; Tollkuhn, Jessica; Taylor, Havilah; Rosenfeld, Michael G.

2015-01-01

Summary Although SOX2+ stem cells are present in the postnatal pituitary gland, how they are regulated molecularly and whether they are required for pituitary functions remain unresolved questions. Using a conditional knockout animal model, here we demonstrate that ablation of the canonical Notch signaling in the embryonic pituitary gland leads to progressive depletion of the SOX2+ stem cells and hypoplastic gland. Furthermore, we show that the SOX2+ stem cells initially play a significant role in contributing to postnatal pituitary gland expansion by self-renewal and differentiating into distinct lineages in the immediate postnatal period. However, we found that within several weeks postpartum, the SOX2+ stem cells switch to an essentially dormant state and are no longer required for homeostasis/tissue adaptation. Our results present a dynamic tissue homeostatic model in which stem cells provide an initial contribution to the growth of the neonatal pituitary gland, whereas the mature gland can be maintained in a stem cell-independent fashion. PMID:26651607

Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

PubMed Central

Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

2009-01-01

Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

GLI1+ progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue.

PubMed

Dörner, Julia; Martinez Rodriguez, Verena; Ziegler, Ricarda; Röhrig, Theresa; Cochran, Rebecca S; Götz, Ronni M; Levin, Mark D; Pihlajoki, Marjut; Heikinheimo, Markku; Wilson, David B

2017-02-05

As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1 + progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Gli1-creER T2 ) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1 + cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1 + progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1 + progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Amhr2, Foxl2) in response to GDX. These findings support the premise that GLI1 + progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tips to facilitate a preoperative diagnosis of adrenal ganglioneuroma. Report of a challenging experience and review of the literature.

PubMed

Proposito, Delia; De Lucia, Francesca; Giannella, Alessandra; Frangella, Francesca; Pappalardo, Giuseppe; Santangelo, Maria; Magagnano, Domenico

2016-02-10

Ganglioneuroma (GN) is the most uncommon and the most benign tumor among neuroblastic neoplasms, and in 29.7% of cases it finds in an adrenal gland. Usually asymptomatic, this tumor is detected incidentally in the majority of cases. It is generally challenging to obtain a precise diagnosis of adrenal ganglioneuroma (AGN) before surgery. Misdiagnosis rate of AGN on CT and MRI is 64.7% and clinicians and surgeons are often lacking in knowledge of this rare disease. For this reason, we pointed out the clinical, biochemical, radiologic and pathologic features of AGN in an our experience, with the aim to find out if there are some features able to facilitate a preoperative diagnosis. The present article also includes a review of the relevant literature in order to compare laparoscopic versus open adrenalectomy. Right AGN in a 42-year-old woman, in whom preoperative diagnosis was very difficult and only histopathological studies of the surgical specimen established the exact diagnosis. The patient underwent bilateral subcostal laparotomy for a large mass (sized measuring 14.5 x 11.6 x 6.5 cm.) and a right adrenalectomy was performed. Postoperative recovery was uneventful and the patient, at 12-months follow-up, is disease-free and in good health. Authors stress the importance of interdisciplinary collaboration between surgeons, radiologists and endocrinologists to optimize clinical management and surgical indications. Careful evaluation by endocrine examinations and multiple imaging procedures are necessary to provide a differential diagnosis. Surgeons should consider a diagnosis of AGN in case of: 1) an adrenal incidentaloma; 2) a nonfunctioning tumor with no elevated hormonal secretions, in which compressive symptoms may occur; 3) a homogeneous, encapsulated mass, with well-defined edges, without invasion of nearby structures (no vascular involvement), with presence of calcifications and nonenhanced attenuation of <40 HU on CT; 4) a homogeneous hypointense adrenal mass

A Comparison of Raman Spectral Features of Frozen and Deparaffinized Tissues in Neuroblastoma and Ganglioneuroma

NASA Astrophysics Data System (ADS)

Devpura, Suneetha; Thakur, Jagdish S.; Poulik, Janet M.; Rabah, Raja; Naik, Vaman M.; Naik, Ratna

2012-02-01

We have investigated the cellular regions in neuroblastoma and ganglioneuroma using Raman spectroscopy and compared their spectral characteristics with those of normal adrenal gland. Thin sections from both frozen and deparaffinized tissues, obtained from the same tissue specimen, were studied in conjunction with the pathological examination of the tissues. We found a significant difference in the spectral features of frozen sections of normal adrenal gland, neuroblastoma, and ganglioneuroma when compared to deparaffinized tissues. The quantitative analysis of the Raman data using chemometric methods of principal component analysis and discriminant function analysis obtained from the frozen tissues show a sensitivity and specificity of 100% each. The biochemical identification based on the spectral differences shows that the normal adrenal gland tissues have higher levels of carotenoids, lipids, and cholesterol compared to the neuroblastoma and ganglioneuroma frozen tissues. However, deparaffinized tissues show complete removal of these biochemicals in adrenal tissues. This study demonstrates that Raman spectroscopy combined with chemometric methods can successfully distinguish neuroblastoma and ganglioneuroma at cellular level.

Change in energy expenditure and brain and adrenal content of catecholamines in rats during muscular loading and hypokinesia

NASA Technical Reports Server (NTRS)

Rozanova, V. D.; Savkiv, T. G.; Khodorova, N. A.

1980-01-01

In male 1-7 month old rats, the growth and the protein content of skeletal muscles were higher than in female rats while the O2 consumption and the heart rate were lower. This is combined with reduction of the thyroid gland weight and of catecholamine content in adrenals at the age of 7 months. The development of male and female rats (1-7 month) under conditions of systematic muscular loads increases the growth tempo and protein of skeletal muscles and intensifies the degree of reduction of energy expenditure and the heart rate. This is accomplished by the greater reduction of relative weight of the thyroid gland and, at the age of 7 months, by reduction of the noradrenaline content in the brainstem. Hypodynamic conditions have the exact opposite effect.

Bioengineered Lacrimal Gland Organ Regeneration in Vivo

PubMed Central

Hirayama, Masatoshi; Tsubota, Kazuo; Tsuji, Takashi

2015-01-01

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID:26264034

Mammary Gland Development

PubMed Central

Macias, Hector

2012-01-01

The mammary gland develops through several distinct stages. The first transpires in the embryo as the ectoderm forms a mammary line that resolves into placodes. Regulated by epithelial/mesenchymal interactions, the placodes descend into the underlying mesenchyme and produce the rudimentary ductal structure of the gland present at birth. Subsequent stages of development – pubertal growth, pregnancy, lactation and involution – occur postnatally under the regulation of hormones. Puberty initiates branching morphogenesis, which requires growth hormone and estrogen, as well as IGF1, to create a ductal tree that fills the fat pad. Upon pregnancy the combined actions of progesterone and prolactin generate alveoli, which secrete milk during lactation. Lack of demand for milk at weaning initiates the process of involution whereby the gland is remodeled back to its pre-pregnancy state. These processes require numerous signaling pathways that have distinct regulatory functions at different stages of gland development. Signaling pathways also regulate a specialized subpopulation of mammary stem cells that fuel the dramatic changes in the gland occurring with each pregnancy. Our knowledge of mammary gland development and mammary stem cell biology has significantly contributed to our understanding of breast cancer and has advanced the discovery of therapies to treat this disease. PMID:22844349

Gene Expression in Human Accessory Lacrimal Glands of Wolfring

PubMed Central

Ubels, John L.; Gipson, Ilene K.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Van Dyken, Rachel E.; Hatton, Mark P.

2012-01-01

Purpose. The accessory lacrimal glands are assumed to contribute to the production of tear fluid, but little is known about their function. The goal of this study was to conduct an analysis of gene expression by glands of Wolfring that would provide a more complete picture of the function of these glands. Methods. Glands of Wolfring were isolated from frozen sections of human eyelids by laser microdissection. RNA was extracted from the cells and hybridized to gene expression arrays. The expression of several of the major genes was confirmed by immunohistochemistry. Results. Of the 24 most highly expressed genes, 9 were of direct relevance to lacrimal function. These included lysozyme, lactoferrin, tear lipocalin, and lacritin. The glands of Wolfring are enriched in genes related to protein synthesis, targeting, and secretion, and a large number of genes for proteins with antimicrobial activity were detected. Ion channels and transporters, carbonic anhydrase, and aquaporins were abundantly expressed. Genes for control of lacrimal function, including cholinergic, adrenergic, vasoactive intestinal polypeptide, purinergic, androgen, and prolactin receptors were also expressed in gland of Wolfring. Conclusions. The data suggest that the function of glands of Wolfring is similar to that of main lacrimal glands and are consistent with secretion electrolytes, fluid, and protein under nervous and hormonal control. Since these glands secrete directly onto the ocular surface, their location may allow rapid response to exogenous stimuli and makes them readily accessible to topical drugs. PMID:22956620

Morphological Features of the Porcine Lacrimal Gland and Its Compatibility for Human Lacrimal Gland Xenografting

PubMed Central

Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations. PMID:24069265

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

PubMed

Henker, Robert; Scholz, Michael; Gaffling, Simone; Asano, Nagayoshi; Hampel, Ulrike; Garreis, Fabian; Hornegger, Joachim; Paulsen, Friedrich

2013-01-01

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations.

Angiotensin II receptors in cortical and medullary adrenal tumors.

PubMed

Opocher, G; Rocco, S; Cimolato, M; Vianello, B; Arnaldi, G; Mantero, F

1997-03-01

Several pieces of evidences suggest that angiotensin II (Ang II) has mitogenic effects, and a link between Ang II receptors and adrenal tumors can be suggested. In various adrenal tumors, aldosterone-producing adenoma (APA), Cushing's adrenal adenomas (Cush), pheochromocytomas (Pheo), and adrenal carcinomas, we studied the density, affinity, and subtype of Ang II receptors. Ang II binding was tested in cell membrane homogenates. [125I]Ang II was used as ligand, and Losartan and CGP 42112 were used as selective Ang II type 1 and type 2 antagonists, respectively. In APA, Ang II receptor density was 178.5 +/- 82.7 fmol/mg: however, due to the high degree of variability, the receptor density was not significantly higher than that in nontumorous adrenal cortex (59.3 +/- 8.4 fmol/mg). In Cush, the receptor density (27.6 +/- 8.2 fmol/mg; P < 0.05) was significantly lower than that in controls, whereas in Pheo and cortical carcinoma, Ang II binding was very low and in several cases almost undetectable. There was no remarkable difference in the Ang II receptor affinity among all tissues tested. The ratio between type 1 and type 2 Ang II receptors showed a large prevalence of type 1 in controls, APA, and three cases of Cush; in two cases of Cush, this ratio was reversed. In conclusion, our data indicate that Ang II receptors are normally expressed in APA and can also be detected in Cush, whereas they have a very low density in Pheo and adrenal carcinoma. Therefore, Ang II receptors are not involved in the lack of response to Ang II that is characteristic of APA; additionally, a reduction of Ang II receptors can be associated with dedifferentiation or malignancy of adrenal tumors. Further investigation of the expression and functional characterization of Ang II receptors is required to better clarify their possible role in adrenal tumorigenesis.

Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

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

Luijk, Peter van; Faber, Hette; Schippers, Jacobus M.

2009-07-15

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) ofmore » both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation. Results: Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of 1 to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss. Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT.« less

In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

PubMed Central

Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

2014-01-01

We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

Characterization of human pineal gland proteome.

PubMed

Yelamanchi, Soujanya D; Kumar, Manish; Madugundu, Anil K; Gopalakrishnan, Lathika; Dey, Gourav; Chavan, Sandip; Sathe, Gajanan; Mathur, Premendu P; Gowda, Harsha; Mahadevan, Anita; Shankar, Susarla K; Prasad, T S Keshava

2016-11-15

The pineal gland is a neuroendocrine gland located at the center of the brain. It is known to regulate various physiological functions in the body through secretion of the neurohormone melatonin. Comprehensive characterization of the human pineal gland proteome has not been undertaken to date. We employed a high-resolution mass spectrometry-based approach to characterize the proteome of the human pineal gland. A total of 5874 proteins were identified from the human pineal gland in this study. Of these, 5820 proteins were identified from the human pineal gland for the first time. Interestingly, 1136 proteins from the human pineal gland were found to contain a signal peptide domain, which indicates the secretory nature of these proteins. An unbiased global proteomic profile of this biomedically important organ should benefit molecular research to unravel the role of the pineal gland in neuropsychiatric and neurodegenerative diseases.

Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

PubMed

Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

2017-03-01

Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

Salivation induced better lacrimal gland function in dry eyes.

PubMed

Pramanik, T; Ghising, R

2009-12-01

The dry eye syndrome is a common eye symptom causing blurry vision. To meet the demand of the modem world students and professionals are compelled to expose themselves to the computer screen for long stretch of time, which is one of the causes of dry eye. It is not always feasible to instil eyes with artificial tears time to time to protect them from dryness. Rather to adopt any simple physiological process associated with optimum lacrimation is a better option to keep eyes moist during computer works. Volunteers (n = 22) having mild dry eyes participated in this study. Tear production was assessed by Schirmer test by keeping Schirmer strip on ocular surface for 5 minutes and recording the length of the moistened area. Then the subject was allowed to keep a piece of lopsy candy (a sour fruit pulp mixed with sugar that is sweet and sour in taste) in mouth for 5 minutes that caused salivation. During salivation, again tear production was assessed. [It was standardized in such a way that, the length of the moistened strip will be 25 - 30 mm for normal eyes, 15 - 10 mm for dry eye, 06 - 10 mm for mild dry eye, 02 - 05 mm for moderate dryness and 00 - 01 mm for severe dry eye.] Tear production was found to be increased significantly (supported by increased length of moistened area of Schirmer strip) during salivation especially in dry eye in all volunteers. The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins; secretion of which are under tight neural control. Anticholinergic agents play an important role in ocular dryness because of hypo-secretion. The sensory root of facial nucleus contains efferent preganglionic parasympathetic fibers for submandibular and sublingual salivary gland and lacrimal gland. The sensory root conveys gustatory fibers from the presulcul area (anterior two-third) of the tongue via the chorda tympani and via the palatine and greater petrosal nerve, taste fibers from

Endocrine system: part 2.

PubMed

Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

2014-06-03

This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

PubMed

Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

2005-07-01

Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated

Actions of placental and fetal adrenal steroid hormones in primate pregnancy.

PubMed

Pepe, G J; Albrecht, E D

1995-10-01

It is clear that steroid hormones of placental and fetal adrenal origin have critically important roles in regulating key physiological events essential to the maintenance of pregnancy and development of the fetus for extrauterine life. Thus, progesterone has suppressive actions on lymphocyte proliferation and activity and on the immune system to prevent rejection of the developing fetus and placenta (see Fig. 9). Progesterone also suppresses the calcium-calmodulin-MLCK system and thus activity of uterine smooth muscle, thereby promoting myometrial quiescence to ensure the maintenance of pregnancy. Estrogen enhances uteroplacental blood flow and possibly placental neovascularization to provide optimal gas exchange and the nutrients required for the rapidly developing fetus and placenta. In turn, estrogen has specific stimulatory effects on the receptor-mediated uptake of LDL by, and P-450scc activity within, syncytiotrophoblasts, thus promoting the biosynthesis of progesterone. Moreover, there is an estrogen-dependent developmental regulation of expression of the LDL receptor and NAD-dependent 11 beta-HSD in the placenta, processes reflecting functional/biochemical differentiation of the trophoblast cells with advancing gestation. The increase in 11 beta-HSD causes a change in transplacental corticosteroid metabolism, which results in activation of the HPAA in the fetus. As a result of this cascade of events, there is an increase in expression of pituitary POMC/ACTH and key enzymes, e.g. 3 beta-HSD and P-450 17 alpha-hydroxylase, important for de novo cortisol formation by, and consequently maturation of, the fetal adrenal gland. In turn, cortisol has well defined actions on surfactant biosynthesis and consequently fetal lung maturation, as well as effects on placental CRH/POMC release, which may be important to the initiation of labor. At midgestation, estrogen also selectively feeds back on the fetal adrenal to suppress DHA and maintain physiologically normal

Molecular characterization and functional significance of the Vti family of SNARE proteins in tick salivary glands

PubMed Central

Villarreal, Ashley M.; Adamson, Steven W.; Browning, Rebecca E.; Khem Raj, B.C.; Sajid, Muhammad Sohail; Karim, Shahid

2013-01-01

Exocytosis involves membrane fusion between secretory vesicles and the plasma membrane. The Soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs) and their receptor proteins (SNAREs) interact to fuse vesicles with the membrane and trigger the release of their sialosecretome out of the tick salivary gland cells. In this study, we examined the functional significance of the Vti family of SNARE proteins of blood-feeding Amblyomma maculatum and A. americanum. Vti1A and Vti1B have been implicated in multiple functional roles in vesicle transport. QRT-PCR studies demonstrated that the highest transcriptional expression of vti1a and vti1b genes occurs in unfed salivary glands, suggesting that elevated secretory vesicle formation occurs prior to feeding but continues at low rates after blood feeding commences. Vti1A and Vti1B localize to the secretory vesicles in unfed tick salivary glands in immunofluorescence microscopy studies. Knockdown of vti1a and vti1b by RNA interference resulted in a significant decrease in the engorged tick weight compared to the control during prolonged blood-feeding on the host. RNA interference of vti1a or vti1b impaired oviposition and none of the ticks produced eggs masses. Surprisingly, the double knockdown did not produce a strong phenotype and ticks fed normally on the host and produced egg masses, suggesting a compensatory mechanism exists within the secretory system which may have been activated in the double knockdown. These results suggest an important functional role of the Vti family of SNARE proteins in tick blood feeding and ultimately oviposition. Understanding the basic functions of the Vti family of SNARE proteins in salivary glands may lead to better ways to prevent tick attachment and transmission of tick-borne diseases. PMID:23499931

Metoclopramide unmasks potentially misleading contralateral suppression in patients undergoing adrenal vein sampling for primary aldosteronism.

PubMed

Rossitto, Giacomo; Miotto, Diego; Battistel, Michele; Barbiero, Giulio; Maiolino, Giuseppe; Bisogni, Valeria; Sanga, Viola; Rossi, Gian Paolo

2016-11-01

As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS). Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping. We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis. We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype. Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion.

PubMed

Crivellato, Enrico; Belloni, Anna; Nico, Beatrice; Nussdorfer, Gastone G; Ribatti, Domenico

2004-03-01

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)- and noradrenaline (NA)-storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline-containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA-releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail-like projections of their limiting membranes. Thirty 150-nm-diameter membrane-bound vesicles with a moderately electron-dense or -lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells. Copyright 2004 Wiley-Liss, Inc.

Comparative Analysis of 2-D Versus 3-D Ultrasound Estimation of the Fetal Adrenal Gland Volume and Prediction of Preterm Birth

PubMed Central

Turan, Ozhan M.; Turan, Sifa; Buhimschi, Irina A.; Funai, Edmund F.; Campbell, Katherine H.; Bahtiyar, Ozan M.; Harman, Chris R.; Copel, Joshua A.; Baschat, Ahmet A; Buhimschi, Catalin S.

2013-01-01

Objective We aim to test the hypothesis that 2D fetal AGV measurements offer similar volume estimates as volume calculations based on 3D technique Methods Fetal AGV was estimated by 3D ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2D measurements of the same blocks (0.523× length × width × depth). Comparisons were performed by intra-class correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The cAGV (AGV/fetal weight) was calculated for both methods and compared for prediction of PTB within 7 days. Results Among 168 volumes, there was a significant correlation between 3D and 2D methods (ICC=0.979[95%CI: 0.971-0.984]). The coefficient of repeatability for the 3D was superior to the 2D method (Intra-observer 3D: 30.8, 2D:57.6; inter-observer 3D: 12.2, 2D: 15.6). Based on 2D calculations, a cAGV≥433mm3/kg, was best for prediction of PTB (sensitivity: 75%(95%CI=59-87); specificity: 89%(95%CI=82-94). Sensitivity and specificity for the 3D cAGV (cut-off ≥420mm3/kg) was 85%(95%CI=70-94) and 95%(95%CI=90-98), respectively. In receiver-operating-curve curve analysis, 3D cAGV was superior to 2D cAGV for prediction of PTB (z=1.99, p=0.047). Conclusion 2D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3D AGV calculations for prediction of PTB. PMID:22644825

Pheromones and exocrine glands in Isoptera.

PubMed

Costa-Leonardo, Ana Maria; Haifig, Ives

2010-01-01

Termites are eusocial insects that have a peculiar and intriguing system of communication using pheromones. The termite pheromones are composed of a blend of chemical substances and they coordinate different social interactions or activities, including foraging, building, mating, defense, and nestmate recognition. Some of these sociochemicals are volatile, spreading in the air, and others are contact pheromones, which are transmitted by trophallaxis and grooming. Among the termite semiochemicals, the most known are alarm, trail, sex pheromones, and hydrocarbons responsible for the recognition of nestmates. The sources of the pheromones are exocrine glands located all over the termite body. The principal exocrine structures considered pheromone-producing glands in Isoptera are the frontal, mandibular, salivary or labial, sternal, and tergal glands. The frontal gland is the source of alarm pheromone and defensive chemicals, but the mandibular secretions have been little studied and their function is not well established in Isoptera. The secretion of salivary glands involves numerous chemical compounds, some of them without pheromonal function. The worker saliva contains a phagostimulating pheromone and probably a building pheromone, while the salivary reservoir of some soldiers contains defensive chemicals. The sternal gland is the only source of trail-following pheromone, whereas sex pheromones are secreted by two glandular sources, the sternal and tergal glands. To date, the termite semiochemicals have indicated that few molecules are involved in their chemical communication, that is, the same compound may be secreted by different glands, different castes and species, and for different functions, depending on the concentration. In addition to the pheromonal parsimony, recent studies also indicate the occurrence of a synergic effect among the compounds involved in the chemical communication of Isoptera. Copyright © 2010 Elsevier Inc. All rights reserved.

Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice

PubMed Central

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

2014-01-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. PMID:23499051

Regulation of IL-17 family members by adrenal hormones during experimental sepsis in mice.

PubMed

Bosmann, Markus; Meta, Fabien; Ruemmler, Robert; Haggadone, Mikel D; Sarma, J Vidya; Zetoune, Firas S; Ward, Peter A

2013-04-01

Severe sepsis is a life-threatening disease that causes major morbidity and mortality. Catecholamines and glucocorticoids often have been used for the treatment of sepsis. Several recent studies have suggested a potential role of IL-17 during the development and progression of sepsis in small animal models. In this study, the cross-talk of catecholamines and glucocorticoids with members of the IL-17 family was investigated during sepsis in C57BL/6 mice. The concentrations in plasma of IL-17A, IL-17F, and the IL-17AF heterodimer all were increased greatly in mice after endotoxemia or cecal ligation and puncture as compared with sham mice. Surprisingly, when compared with IL-17A (487 pg/mL), the concentrations of IL-17F (2361 pg/mL) and the heterodimer, IL-17AF (5116 pg/mL), were much higher 12 hours after endotoxemia. After surgical removal of the adrenal glands, mice had much higher mortality after endotoxemia or cecal ligation and puncture. The absence of endogenous adrenal gland hormones (cortical and medullary) was associated with 3- to 10-fold higher concentrations of IL-17A, IL-17F, IL-17AF, and IL-23. The addition of adrenaline, noradrenaline, hydrocortisone, or dexamethasone to lipopolysaccharide-activated peritoneal macrophages dose-dependently suppressed the expression and release of IL-17s. The production of IL-17s required activation of c-Jun-N-terminal kinase, which was antagonized by both catecholamines and glucocorticoids. These data provide novel insights into the molecular mechanisms of immune modulation by catecholamines and glucocorticoids during acute inflammation. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Repressor of Estrogen Receptor Activity (REA) Is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice

PubMed Central

Park, Sunghee; Zhao, Yuechao; Yoon, Sangyeon; Xu, Jianming; Liao, Lan; Lydon, John; DeMayo, Franco; O'Malley, Bert W.

2011-01-01

Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland. PMID:21862609

Morphology and function of lacrimal gland acinar cells in primary culture.

PubMed

Hann, L E; Tatro, J B; Sullivan, D A

1989-01-01

The objectives of the current investigation were fourfold: (1) to establish an effective procedure for the isolation of acinar cells from the rat lacrimal gland; (2) to evaluate the functional capacity of freshly isolated cells; (3) to determine defined culture conditions which permit maintenance of viable, differentiated cells, as well as secretory component (SC) production, during long-term culture; and (4) to characterize the morphological features of cultured cells. Acinar cells were isolated by serial incubation of gland fragments in chelating and enzymatic solutions, followed by centrifugation through a Ficoll gradient. The yield of viable cells/gland appeared to be age-dependent: cell recovery was inversely proportional to the age of the animals. Immunofluorescence analysis of freshly isolated cells showed the presence of SC, the IgA antibody receptor, within isolated cells. In addition, experiments with a labeled analog (Nle4-D-Phe7-alpha MSH) of alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrated specific binding sites on freshly isolated cells; alpha-MSH is a known modulator of acinar protein secretion. Maximum binding of the alpha-MSH analog occurred within 30 min, was dependent upon cell density and was reduced by coincubation with unlabeled alpha-MSH. To determine the culture requirements of acinar cells, cells were cultured on a variety of substrates (plastic or modified plastic [Primaria], coated with or without extracellular matrix [Matrigel]) in the presence or absence of various supplements and/or fetal calf serum (FCS) for 0.7 to 3.5 weeks. Cell attachment, function and long-term viability required an extracellular matrix. Moreover, in long term cultures (25 days), acinar cell attachment was enhanced by the inclusion of supplements to media containing 10% FCS. Replacement of serum with fibroblast growth factor, high-density lipoprotein and an increased concentration of epidermal growth factor resulted in a distinct "cobblestone

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

Parental management of adrenal crisis in children with congenital adrenal hyperplasia

PubMed Central

Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

2018-01-01

Purpose Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydro-cortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents’ perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents’ perceived management ability and the impact CAH has on the family. Methods In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents’ experiences in managing crises. Results There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Practice

Parental management of adrenal crisis in children with congenital adrenal hyperplasia.

PubMed

Fleming, Louise; Knafl, Kathleen; Knafl, George; Van Riper, Marcia

2017-10-01

Congenital adrenal hyperplasia (CAH) requires parents to inject their child with hydrocortisone intramuscularly during times of illness and adrenal crisis. The purpose of this study was to describe circumstances surrounding adrenal crisis events in children with CAH; to explore parents' perceptions of the consequences of having a child with a life-threatening condition; and to examine a relationship between parents' perceived management ability and the impact CAH has on the family. In Phase 1 of this mixed-methods, cross-sectional study, 77 parents were asked to complete questionnaires comprising measures of family life in the context of childhood illness. Descriptive statistics were computed with four separate analyses using linear mixed models allowing for correlation between responses from parents of the same family and for the variance to be different for fathers and mothers. The following relationships were examined: (1) parental management ability and type of provider instruction on how to manage adrenal crises; (2) parental management ability and child age; (3) the perceived impact of the condition on the family and management ability; and (4) the age of the child and number of adrenal crisis events. In Phase 2, 16 semi-structured interviews were conducted to elicit detailed descriptions of parents' experiences in managing crises. There was a significant, positive relationship between detailed provider instruction to parents on adrenal crisis management and perceived management ability (p = .02), additionally the stronger the perceived management ability, the less impact CAH had on the family (p < .001). From birth to age 5, parents reported more frequent crisis events and less perceived ability to manage the condition when compared with parents of older children (p = .009). The threat of an adrenal crisis event is a pervasive concern for parents, especially when they are not being properly prepared by providers. Provider support is needed for these parents

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

PubMed Central

van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

2017-01-01

Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA

Adrenal hormones before and after venography during adrenal venous sampling: a self-controlled study.

PubMed

Koike, Yuya; Matsui, Seishi; Omura, Masao; Makita, Kohzoh; Obara, Alfonso W D; Moriya, Nobukazu; Nishikawa, Tetsuo

2017-03-01

A stress reaction involving increased adrenal hormone release occurs when starting adrenal venous sampling (AVS). The purpose of the present study was to investigate the effect of single shot venography on adrenal hormone production during AVS. This was a prospective self-controlled study. We enrolled 54 consecutive patients (21 men, 33 women; mean age 52 ± 11 years) with primary aldosteronism who underwent AVS from May 2014 to February 2015. Under non-stimulated conditions, blood samples were obtained from a common trunk of the left adrenal vein before and after single shot venography. The initial plasma aldosterone and cortisol concentration (PAC and PCC) were compared with those measured after venography for each patient. PAC and PCC were slightly but significantly decreased between before and after venography (after log transformation 2.12 ± 0.73 vs 2.07 ± 0.72, P = 0.00066, 1.89 ± 0.52 vs 1.83 ± 0.53, P = 0.00031, respectively). During non-stimulated left AVS, adrenal hormone secretion was slightly but significantly decreased after venography, similar to the normal time-related stress reaction. Venography did not increase the adrenal hormone secretion.

Proteomic Profiling of the Pituitary Gland in Studies of Psychiatric Disorders.

PubMed

Krishnamurthy, Divya; Rahmoune, Hassan; Guest, Paul C

2017-01-01

Psychiatric disorders have been associated with perturbations of the hypothalamic-pituitary-adrenal axis. Therefore, proteomic studies of the pituitary gland have the potential to provide new insights into the underlying pathways affected in these conditions as well as identify new biomarkers or targets for use in developing improved medications. This chapter describes a protocol for preparation of pituitary protein extracts followed by characterization of the pituitary proteome by label-free liquid chromatography-tandem mass spectrometry in expression mode (LC-MS E ). The main focus was on establishing a method for identifying the major pituitary hormones and accessory proteins as many of these have already been implicated in psychiatric diseases.