Luteal phase hyperprolactinemia.

PubMed

Falk, R J; Anderson, L

1994-01-01

To determine the incidence of both isolated and repetitive prolactin elevations in the luteal phase of otherwise normoprolactinemic women. To see if sporadic luteal-phase hyperprolactinemia is associated with progesterone deficiency, and to explore a possible physiological basis for sporadic hyperprolactinemia by TRH challenge. Hospital-based reproductive endocrinology/infertility service. Prospective measurement of luteal phase serum progesterone and prolactin in normoprolactinemic ovulatory women. TRH stimulation testing in volunteers with repetitive luteal phase hyperprolactinemia and normoprolactinemic controls. 133 sequentially selected infertile, ovulatory women with normal prolactin levels in the proliferative phase of the cycle. Measurement of serum progesterone and prolactin during the luteal phase, based on the day of the LH surge. TRH testing in the midluteal phase of the cycle in patients with two or more luteal phase prolactin elevations, and in five normoprolactinemic volunteers in both the preovulatory and midluteal phase. Of 133 subjects, 85 (64%) had no prolactin level exceeding 20 ng/mL in the luteal phase. Thirty-three (25%) had two or more elevated levels, and were considered to have repetitive luteal phase hyperprolactinemia (LPH). TRH testing in control subjects resulted in a greater prolactin response in the preovulatory phase. The group with LPH demonstrated an initial elevation of prolactin greater than that of the normoprolactinemic controls, but a subsequent drop to levels lower than both preovulatory and midluteal normoprolactinemic controls by 45 minutes. Sporadic luteal-phase hyperprolactinemia is a relatively common event (36% of 133 subjects in the present series). Of these 48 women, 33 (69%) had repetitive elevations, suggesting the elevation in these subjects to be more than a random event. The physiological validity of this observation is further demonstrated by an abnormal response to TRH stimulation, but the normal levels of luteal phase progesterone leave questions as to its pathological importance.

A case of sibutramine-induced hyperprolactinemia.

PubMed

Soares Leaes, Carolina Garcia; Pereira-Lima, Júlia Fernanda Semmelmann; da Costa Oliveira, Miriam

2011-01-01

Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels. The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia. A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome. sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia.

Is chronic nipple piercing associated with hyperprolactinemia?

PubMed

Sun, Grace E Ching; Pantalone, Kevin M; Gupta, Manjula; Kennedy, Laurence; Nasr, Christian; Constantiner, Marigel; Hamrahian, Amir H; Hatipoglu, Betul

2013-09-01

Literature on hyperprolactinemia in the setting of a nipple piercing is limited to individuals with concomitant breast/chest wall infection. It is unclear if chronic nipple stimulation from a piercing alone can cause sustained elevations of serum prolactin. Nipple piercing is emerging as a more mainstream societal form of body art, and the answer to this clinical question would potentially alter patient management. Our aim was to assess serum prolactin levels in subjects with nipple piercing. Inclusion criteria were as follows: men and women ≥ 18 years old with nipple piercing(s) present > 6 months. Exclusion criteria included: women who are pregnant, lactating or < 6 months postpartum; subjects on medications known to increase prolactin levels; chest wall/breast infection at the time of phlebotomy or conditions known to be associated with hyperprolactinemia. Three men and eight women were enrolled. Median (range) ages for men and women were 33 (24-42) and 27 years (23-42), respectively. All except one subject had bilateral piercings. The median interval from nipple piercing to blood draw was 4.0 (2.0-12.0) years. None of the subjects had hyperprolactinemia. Median (range) prolactin levels for men and women were 5.6 ng/mL (3.8-7.4) and 8.0 ng/mL (2.8-10.9), respectively. Our results suggest that in the absence of any concomitant infection, chronic nipple piercing is not associated with hyperprolactinemia.

Rethinking the Stalk Effect: A New Hypothesis Explaining Suprasellar Tumor-Induced Hyperprolactinemia

PubMed Central

Skinner, Donal C.

2009-01-01

The pars tuberalis is a distinct subdivision of the pituitary gland but its function remains poorly understood. Suprasellar tumors in this pars tuberalis region are frequently accompanied by hyperprolactinemia. As these tumors do not immunoreact for any of the established pituitary hormones, they are classified as non-secretory. It has been postulated that these suprasellar tumors induce hyperprolactinemia by compressing the pituitary stalk, resulting in impaired dopamine delivery to the pituitary and, consequently, disinhibition of the lactotropes. An alternative hypothesis proposed is that suprasellar tumors secrete a specific pars tuberalis factor that stimulates prolactin secretion. Hypothesized candidates are the preprotachykinin A derived tachykinins, substance P and/or neurokinin A. PMID:19028420

[Macroprolactinemia identification in patients with hyperprolactinemia].

PubMed

Sandoval, Carolina; González, Baldomero; Cheng, Sonia; Esquenazi, Yoshua; Mercado, Moisés

2007-08-01

Macroprolactinemia is defined as hyperprolactinemia with predominance of the big-big prolactine isoform. Its frequency has not been clearly established due to technical difficulties to identify it. This method used to detect it is gel filtration chromatography, an expensive and complicated procedure that could not be used routinely. To validate the PEG precipitation technique, to identify the presence of macroprolactinemia and to correlate it with the clinical characteristics in a group of pre-selected patients with elevated serum PRL levels from different causes. There were studied 14 patients non pre-selected with high PRL serum levels. Prolactine levels were determined with commercial immunometric quimioluminescence essays. All the essays were duplicated, and healthy patients serum (without hyperprolactinemia) were used. Technique consists on mixing 250 microL of serum with the same volume of polyethylene glycol. Later it was centrifugated at 3000 rpm during 30 minutes at 4 degrees C. Prolactine level was measured in supernatant. Within patients 7 to 14 macroprolactinemia was ruled out and confirmed truth hyperprolactinemia, some times slight and nontumoral, some times mild, and some times due to prolactin-producer hypophysial macroadenomas. Polyethylene glycol precipitation technique is reliable to detect macroprolactinemia.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

PubMed

Andereggen, Lukas; Frey, Janine; Andres, Robert H; El-Koussy, Marwan; Beck, Jürgen; Seiler, Rolf W; Christ, Emanuel

2017-01-01

In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

Improvement of psoriatic arthritis in a patient treated with bromocriptine for hyperprolactinemia.

PubMed

Buskila, D; Sukenik, S; Holcberg, G; Horowitz, J

1991-04-01

We describe a woman with psoriatic arthritis who experienced a remarkable improvement of her skin and joint disease while only taking bromocriptine therapy. She was treated with bromocriptine for primary infertility due to hyperprolactinemia. The improvement in joint symptoms appeared to parallel that of the skin. More studies are required to determine the reproducibility of this observation.

Breastfeeding a baby with mother on Bromocripine.

PubMed

Verma, Sanjay; Shah, Dheeraj; Faridi, M M A

2006-05-01

Prolactinomas, the most common pituitary adenomas, are important causes of infertility. Bromocriptine remains the treatment of choice for managing hyperprolactinemia in most of these cases. Breastfeeding in mothers receiving bromocriptine is often doubtful and matter of concern for most people. Here we report a case, where by timely intervention and skilled counseling, exclusive breastfeeding could be established in a mother receiving bromocriptine for the treatment of hyperprolactinemia.

LIV-1 and Zn Transporters: Establishing a Link Between Hyperprolactinemia and Breast Cancer

DTIC Science & Technology

2008-10-14

depression (e.g. dopamine antagonists) secondarily increase prolactin levels, potentially increasing breast cancer risk in an extraordinary number of...this relationship lies in the fact that drugs which induce hyperprolactinemia secondarily to the principal mode of action (e.g. dopamine antagonists...developmental disorders, mood disorders and autism . In many cases, these drugs are prescribed for patients as young as 3 years of age and are chronically

Add-on effects of a low-dose aripiprazole in resolving hyperprolactinemia induced by risperidone or paliperidone.

PubMed

Qiao, Ying; Yang, Fuzhong; Li, Chunbo; Guo, Qian; Wen, Hui; Zhu, Suoyu; Ouyang, Qiong; Shen, Weidi; Sheng, Jianhua

2016-03-30

This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event. Copyright © 2016. Published by Elsevier Ireland Ltd.

One-Year Follow-Up of Serum Prolactin Level in Schizophrenia Patients Treated with Blonanserin: A Case Series.

PubMed

Takahashi, Sakae; Suzuki, Masahiro; Uchiyama, Makoto

2015-10-01

In our previous study, a prolactin elevation was more frequently in risperidone than in blonanserin; however, it was more often in blonanserin than in olanzapine. Therefore, while a rate of PRL rising is low to moderate, hyperprolactinemia is a considerable adverse effect in the blonanserin treatment. In this study, to examine detailed characteristics of hyperprolactinemia of blonanserin, we analyzed the prolactin data in six schizophrenic patients who were switched to blonanserin from other antipsychotics and followed for one year. As a result, blonanserin dose was clearly associated with serum prolactin level. The average prolactin level was almost normal when the mean blonanserin dosage was 8.0 mg/day. Regardless of the dose decrease of blonanserin, there were no remarkable changes in symptoms and social functions. Based on our findings, we conclude that low dose blonanserin medication may be useful for schizophrenia maintenance treatment without hyperprolactinemia and a high rate of relapse.

One-Year Follow-Up of Serum Prolactin Level in Schizophrenia Patients Treated with Blonanserin: A Case Series

PubMed Central

Suzuki, Masahiro; Uchiyama, Makoto

2015-01-01

In our previous study, a prolactin elevation was more frequently in risperidone than in blonanserin; however, it was more often in blonanserin than in olanzapine. Therefore, while a rate of PRL rising is low to moderate, hyperprolactinemia is a considerable adverse effect in the blonanserin treatment. In this study, to examine detailed characteristics of hyperprolactinemia of blonanserin, we analyzed the prolactin data in six schizophrenic patients who were switched to blonanserin from other antipsychotics and followed for one year. As a result, blonanserin dose was clearly associated with serum prolactin level. The average prolactin level was almost normal when the mean blonanserin dosage was 8.0 mg/day. Regardless of the dose decrease of blonanserin, there were no remarkable changes in symptoms and social functions. Based on our findings, we conclude that low dose blonanserin medication may be useful for schizophrenia maintenance treatment without hyperprolactinemia and a high rate of relapse. PMID:26508971

Polycystic ovary syndrome and prolactinoma association.

PubMed

Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

2009-01-01

Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma.

Primary Amenorrhea Associated with Hyperprolactinemia in Polyglandular Autoimmune Syndrome Type II: A Case Report.

PubMed

Cottas, Luiza Tizziotti; Borges, Maria de Fátima; Oliveira, Lívia Prata Santos; Resende, Ana Luísa Mantovani; Ataíde, Meire Soares; Resende, Elisabete Aparecida Mantovani Rodrigues

2018-06-27

Polyglandular autoimmune syndrome type II (PGA-II) is a rare immunoendocrinopathy syndrome characterized by the occurrence of autoimmune Addison disease along with diabetes mellitus type 1 and/or autoimmune thyroid disease. Here, we report the case of a 23-year-old female with PGA-II who was followed up at the dermatology and endocrinology clinics of the Universidade Federal do Triângulo Mineiro, located in the state of Minas Gerais, Brazil. First, the patient presented diffuse skin hyperpigmentation, vitiligo; and in sequence, due to vomiting, appetite and weight loss, hypoglycemia, amenorrhea, and galactorrhea, the patient was then diagnosed with PGA-II. The patient also presented intense hyperprolactinemia due to primary hypothyroidism. The late diagnosis of PGA-II is frequent because the disorder is uncommon and has non-specific clinical manifestations. This report emphasizes the significance of a timely diagnosis and appropriate treatment to reduce morbidity and mortality associated with these diseases, especially Addison disease. The present study reports a rare case of a patient with PGA-II with primary amenorrhea associated with hyperprolactinemia. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Blonanserin, a novel antipsychotic, is suitable for treating schizophrenia associated with hyperprolactinemia: a case series.

PubMed

Kawabe, Kentaro; Horiuchi, Fumie; Ueno, Shu-ichi

2013-01-01

Recently, atypical antipsychotic agents have primarily been used in pharmacological treatment of schizophrenia because of the fewer associated adverse effects. Blonanserin is a novel atypical antipsychotic recently introduced to treat patients with schizophrenia in Japan and South Korea. In this study, we examined the efficacy of switching antipsychotic medications to blonanserin monotherapy in patients with chronic schizophrenia with associated hyperprolactinemia. Ten schizophrenic patients (5 males and 5 females) with hyperprolactinemia were recruited. Clinical data before (baseline) and 12 weeks after (end point) switching to blonanserin monotherapy were assessed using the Brief Psychiatric Rating Scale score, Drug-Induced Extrapyramidal Symptoms Scale, and serum prolactin levels. The mean (SD) blonanserin dosage was 14.8 (3.8) mg/d. After switching to blonanserin, there were significant improvements in the Brief Psychiatric Rating Scale in the patients from both sexes. Moreover, serum prolactin levels in the female patients significantly decreased to within reference range. There were no additional adverse effects observed with the blonanserin treatment. Switching to blonanserin can reverse medication-induced prolactin elevations found in female patients- and blonanserin is a suitable antipsychotic for schizophrenic patients.

Adjunctive Aripiprazole Versus Placebo for Antipsychotic-Induced Hyperprolactinemia: Meta-Analysis of Randomized Controlled Trials

PubMed Central

Li, Xianbin; Tang, Yilang; Wang, Chuanyue

2013-01-01

Objective To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. Methods Population: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. Interventions: adjunctive aripiprazole vs. adjunctive placebo. Outcome measures: adverse events and efficacy of treatment. Studies: randomized controlled trials. Results Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo) met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158) prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed) −0.05 to 0.04 (95% confidence interval −0.13 to 0.16); I2 = 0% to 68%, P = 0.20 to 0.70). However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random) 0.76 (95% confidence interval 0.67 to 0.85); I2 = 43%, P<0.00001). The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. Conclusion Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day. PMID:23936389

Transient hyperprolactinemia in infertile women with luteal phase deficiency.

PubMed

Huang, K E; Bonfiglio, T A; Muechler, E K

1991-10-01

This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Concomitant occurrence of macroprolactin, exercise-induced amenorrhea, and a pituitary lesion: a diagnostic pitfall. Case report.

PubMed

Cattaneo, F A; Fahie-Wilson, M N

2001-08-01

The authors report the case of a 37-year-old woman who presented with amenorrhea and an increased level of serum prolactin. Magnetic resonance images of the pituitary revealed a lesion with characteristics consistent with those of a microadenoma. Transsphenoidal exploration was performed, but a prolactinoma was not found. After endocrinological review, the patient's hyperprolactinemia was found to be caused by the presence of macroprolactin and her amenorrhea was due to intense exercise and low body weight. Macroprolactin is an isoform of prolactin that is variably reactive in assays for prolactin, but displays minimum bioactivity in vivo. Patients with macroprolactin are mostly asymptomatic. This phenomenon may cause elevated prolactin values, which the authors view as apparent hyperprolactinemia. The presence of macroprolactin is an underrecognized problem, occurring in as many as 15 to 20% of patients with elevated prolactin values and often leading to unnecessary, expensive diagnostic procedures and inappropriate treatment. The presence of macroprolactin should always be suspected when the patient's clinical history or clinical or radiological data are incompatible with the prolactin value. Physicians dealing with diagnosis and treatment of hyperprolactinemia (general practitioners, gynecologists, neurosurgeons, endocrinologists, and biochemists) should be aware of the potentially misleading nature of macroprolactin.

TSH and prolactin responses to thyrotropin releasing hormone (TRH) and domperidone in patients with empty sella syndrome.

PubMed

Valensi, P; Combes, M E; Perret, G; Attali, J R

1996-05-01

The aim of this study was to investigate TSH and PRL response to TRH and domperidone, an antidopaminergic drug which does not cross the blood-brain barrier, in 16 patients with primary empty sella (PES) and either normal or elevated plasma PRL level and to compare it with the response observed in 8 patients with prolactinoma. In the patients with PES and hyperprolactinemia, the PRL response to TRH was significantly lower than in the controls and the patients with PES and normal PRL, which suggests there is impaired PRL synthesis and release in cases of PES with hyperprolactinemia. The TSH response to domperidone was significantly elevated in patients with PES and either normal or elevated PRL, as in patients with prolactinoma. The PRL response to domperidone was significantly reduced in patients with PES and hyperprolactinemia as in patients with prolactionoma. These results suggestthat in PES with prolactinoma the inhibiting dopaminergic tone is increased on the thyrotropic cells and reduced on the lactotropic cells in PES with elevated PRL and that some patients with PES might bear a microprolactinoma in the bottom of the sella which remained undetected by the CT scan.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans.

PubMed

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H; Konrad, Robert J; Angelin, Bo

2016-01-01

Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

PubMed Central

Lehtihet, Mikael; Bonde, Ylva; Beckman, Lena; Berinder, Katarina; Hoybye, Charlotte; Rudling, Mats; Sloan, John H.; Konrad, Robert J.; Angelin, Bo

2016-01-01

Objective Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. Research design and methods We used a sensitive and specific dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. Results In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. Conclusions In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID:26866603

Hyperprolactinemia following chronic alcohol administration.

PubMed

Sarkar, Dipak K

2010-01-01

There are several reports showing evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Alcohol-induced hyperprolactinemia has also been demonstrated in nonhuman primates and laboratory animals. Therefore, the clinical data as well as animal data suggest that ethanol consumption is a positive risk factor for hyperprolactinemia. In animal studies, it was found that chronic ethanol administration not only elevates plasma levels of PRL but also increases proliferation of pituitary lactotropes. Ethanol action on lactotropes involves crosstalk with estradiol-responsive signaling cascade or estradiol-regulated cell-cell communication. Additionally, it involves suppression of dopamine D2 receptors inhibition of G proteins and intracellular cyclic adenosine monophosphate (cAMP), modulation of transforming growth factor-beta (TGF-beta) isoforms and their receptors (TbetaRII), as well as factors secondary to TGF-beta actions, including production of beta-fibroblast growth factor (bFGF) from follicular-stellate cells. The downstream signaling that governs b-FGF production and secretion involves activation of the MAP kinase p44/42-dependent pathway. A coordinated suppression of D2 receptor- and TbetaRII receptor-mediated signaling as well as enhancement of bFGF activity might be critical for ethanol action on PRL production and cell proliferation in lactotropes. Copyright (c) 2010 S. Karger AG, Basel.

[Influence of hyperprolactinemia and tumoral size in the postoperative pituitary function in clinically nonfunctioning pituitary macroadenomas].

PubMed

Fonseca, Ana Luiza Vidal; Chimelli, Leila; Santos, Mario José C Felippe; Santos, Alair Augusto S M Damas dos; Violante, Alice Helena Dutra

2002-09-01

To study the influence of hyperprolactinemia and tumoral size in the pituitary function in clinically nonfunctioning pituitary macroadenomas. Twenty three patients with clinically nonfunctioning pituitary macroadenomas were evaluated by image studies (computed tomography or magnetic resonance) and basal hormonal level; 16 had preoperative hypothalamus-hypophysial function tests (megatests). All tumors had histological diagnosis and in seventeen immunohistochemical study for adenohypophysial hormones was also performed. Student's t test, chi square test, exact test of Fisher and Mc Neman test were used for the statistics analysis. The level of significance adopted was 5% (p<0.05). Tumoral diameter varied of 1.1 to 4.7 cm (average=2.99 cm +/- 1.04). In the preoperative, 5 (21.7%) patients did not show laboratorial hormonal deficit, 9 (39.1%) developed hyperprolactinemia, 13 (56,5%) normal levels of prolactin (PRL) and 1 (4.3%) subnormal; 18 (78.3%) patients developed hypopituitarism (4 pan-hypopituitarism). Nineteen patients (82.6%) underwent transsfenoidal approach, 3 (13%) craniotomy and 1 (4.4%) combined access. Only 6 patients had total tumoral resection. Of the 17 immunohistochemical studies, 5 tumours were immunonegatives, 1 compound, 1 LH+, 1 FSH +, 1 alpha sub-unit and 8 focal or isolated immunorreactivity for one of the pituitary hormones or sub-units; of the other six tumours, 5 were chromophobe and 1 chromophobe/acidophile. No significant statistic difference was noted between tumoral size and preoperative PRL levels (p=0.82), nor between tumoral size and postoperative hormonal state, except in the GH and gonadal axis. Significant statistic was noted: between tumoral size and preoperative hormonal state (except in the gonadal axis); between normal PRL levels, associated to none or little preoperative hypophysial disfunction, and recovery of postoperative pituitary function. Isolated preoperative hyperprolactinemia and tumoral size have not been predictable for the recovery of postoperative pituitary function.

Hyperprolactinemia Diagnosis and Treatment

MedlinePlus

... excess prolactin. One cause is an underactive thyroid ( hypothyroidism ), so you may have a blood test to ... with estrogen (for women) or testosterone (for men). Hypothyroidism. An underactive thyroid most often needs treatment with ...

Partial regimen replacement with aripiprazole reduces serum prolactin in patients with a long history of schizophrenia: A case series.

PubMed

Naono-Nagatomo, Keiko; Naono, Hisao; Abe, Hiroshi; Takeda, Ryuichiro; Funahashi, Hideki; Uchimura, Daisuke; Ishida, Yasushi

2017-02-01

Aripiprazole (ARP) is a popular antipsychotic drug that has demonstrated ameliorative effects on hyperprolactinemia. However, no study to date has studied the utility of ARP in patients with a long history of schizophrenia and antipsychotic treatment. We therefore examined the effect of partial antipsychotic regimen replacement with ARP on hyperprolactinemia induced by chronic antipsychotic use in patients with schizophrenia. Sixteen patients with a schizophrenia diagnosis (F2) based on the International Classification of Diseases (version 10) were recruited. At months 0, 1, 3, and 6 of the study, serum prolactin, body weight, and blood glucose were measured, and QOL and psychotic symptoms were assessed using Global Assessment of Functioning scores and Clinical Global Impressions of Improvement (CGI-I) scores. Nine patients with an average age of 46.7±9.6 years and mean disease duration of 15.9±10.4 years were included in the final analysis. Serum prolactin levels significantly decreased and GAF and CGI-I scores improved significantly over the 6-month period after partial replacement with ARP. Additionally, no changes were observed in body weight or blood glucose over the 6-month period. Partial antipsychotic regimen replacement with ARP improves hyperprolactinemia, and may improve the QOL of patients with a long history of schizophrenia. Japan Medical Association, Center for clinical trials D: JMA-IIA00245. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperprolactinemia (Prolactin Excess)

MedlinePlus

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Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

PubMed

Felix, I A; Horvath, E; Kovacs, K; Smyth, H S; Killinger, D W; Vale, J

1986-01-01

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

Endometrioid endometrial carcinoma indirectly caused by pituitary prolactinoma: a case report.

PubMed

Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-01-01

We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential.

Endometrioid Endometrial Carcinoma Indirectly Caused by Pituitary Prolactinoma: A Case Report

PubMed Central

Nishino, Kimihiro; Niwa, Yuri; Mizutani, Teruyuki; Shimizu, Ken; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-01-01

We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential. PMID:23467393

A randomized cross-over study comparing cabergoline and quinagolide in the treatment of hyperprolactinemic patients.

PubMed

De Luis, D A; Becerra, A; Lahera, M; Botella, J I; Valero; Varela, C

2000-01-01

Quinagolide (QUI) and cabergoline (CAB) are dopamine agonists recently introduced for the treatment of hyperprolactinemia. In the present study, these drugs have been compared in terms of effectiveness and tolerability. Twenty patients (18 females and 2 males) with hyperprolactinemia (8 with microprolactinomas, 6 with idiopathic hyperprolactinemia and 6 with empty sella turcica syndrome) were treated with oral QUI (75 microg once daily) and CAB (0,5 mg twice weekly), in a randomized cross-over trial with placebo between both drugs. Each drug was administered for 12 weeks, separated by other 12 weeks with placebo. PRL levels decreased with both drugs at 2 or 4 weeks of starting the treatment, without differences between both drugs at weeks 4, 8 and 12. At week 12, normal PRL levels (<20 ng/ml) were attained in 90% patients with CAB and only in 75% patients with QUI (p<0.05). After discontinuation of treatment, significant increase in serum PRL was higher after QUI withdrawal than after CAB. Clinical efficacy of both treatments was similar in terms of improvement amenorrhea, oligomenorrhea, galactorrhea, and impotence. All patients completed both cycles of treatment, and the most frequent side-effects were nausea, headache and dizziness, without significant differences between CAB (30%) and QUI (55%). Our study indicates that, at the doses employed here, CAB showed a high percentage of patients with normal PRL at the end of treatment and long-lasting efficacy in the levels of PRL. Clinical response and side-effects were similar in both drugs.

Hair loss and hyperprolactinemia in women

PubMed Central

2012-01-01

In the literature of the past 30 years there are only some publications concerned with hair loss and hyperprolactinemia in women. Therefore, the relevance of hyperprolactinemia was evaluated in 40 women with diffuse alopecia. Hair loss was assessed by clinical appearance and the pluck trichogram. 82.5% of the female patients had diffuse hair loss and 17.5% had androgenetic alopecia. The highest prolactin values measured were 1390 ng/ml and 255 ng/ml. Six patients had values between 150–80.4 ng/ml and 10 between 79.1–51.7 ng/ml. All others had prolactin values below 50 ng/ml. Fifteen untreated patients with elevated prolactin levels could be followed up. Without any prolactin-inhibiting drugs, reductions and normalizations beside moderate fluctuations could be detected. Thyroid-specific diagnostics showed in 95% of the patients a normal thyroid function. 2.5% had a slight hyperthyreoidism and 2.5% had a slight hypothyreoidism. No female patient had clinical signs of androgenization and the determined androgens testosterone, androstendione and dihydroepiandrostendione were in the normal range. According to these results, moderate elevated prolactin levels in association with diffuse or androgenetic hair loss can be neglected as causative for the hair loss, because there is no evidence that they have an influence to the pattern, the extent or the duration of the hair loss. These results are supported by investigations of other authors who described only in high doses of prolactin an inhibiting effect on human hair follicles in vitro. Nevertheless, moderate constantly elevated prolactin levels should induce further diagnostics to exclude a prolactin-producing tumor of the pituitary gland. PMID:22870355

Mucuna pruriens (L.) DC chemo sensitize human breast cancer cells via downregulation of prolactin-mediated JAK2/STAT5A signaling.

PubMed

Sinha, Sonam; Sharma, Sonal; Vora, Jaykant; Shah, Heta; Srivastava, Anshu; Shrivastava, Neeta

2018-05-10

Mucuna pruriens (L.) DC (MP) is an ancient Indian medicinal plant traditionally used to treat Parkinson's disease. L-Dopa (LD), precursor of dopamine is abundantly found in the seeds of MP. L-dopa is a natural inhibitor of prolactin (PRL) hormone which is required to maintain lactation in women but it's over production (hyperprolactinemia) plays critical role in advancement of breast cancer. We aim to examine the pharmacological effect of LD and MP on this hyperprolactinemia associated breast cancer and related signaling for effective management of the disease. We also investigated chemo-sensitizing effect of MP on hyperprolactinemia-mediated cisplatin resistance. Methanolic seed extract of MP were prepared and analysed using HPLC. Effect of LD and MP on the cellular viability of breast cancer cells (T47D, MCF-7, MDA-MB-468 and MDA-MB-231) were evaluated using MTT assay. Further, effect of LD and MP on colony forming potential, DNA damage, cell cycle distribution and apoptosis was determined using agar/agarose method, comet assay and annexin and PI method followed by FACS analysis. To reveal the molecular mechanism involved in the anti-cancer activity of MP, transcriptional and translational level analysis of the key proteins involved in the PRL-mediated signaling, was performed using RT-PCR and western blot analysis. The effect of MP extract on PRL-mediated signaling was validated using dopaminergic agonist bromocriptine. MP extract and cisplatin was given in different combination with appropriate controls to check their effect on chemo-resistivity of breast cancer cells. Our results demonstrated that MP seed extract has the potential to inhibit cellular proliferation of PRL expressing T47D and MCF-7 breast cancer cells via induction of DNA damage, G1 phase of cell cycle arrest and apoptosis more effectively as compare to LD. Further, MP-mediated anti-cancerous effect was associated with the downregulation of PRL expression, further suppressing the JAK2/STAT5A/Cyclin D1 signaling pathway which has been validated using dopaminergic agonist bromocriptine. Cancer-related hyperprolactinemia confers cisplatin resistance, we observed that MP via PRL inhibition, enhances cisplatin efficacy after their combinatorial treatment in breast cancer cells. Collectively, our study suggests that MP could be recommended as dietary supplement along with the chemotherapeutic agents against breast cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

Pathologic hyperprolactinemia.

PubMed

Molitch, M E

1992-12-01

Unlike other pituitary hormones, PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, dopamine. GAP and GABA may also be inhibitory. PRL-releasing factors include TRH and VIP and possibly others. Circulating PRL is predominantly monomeric, although some patients with hyperprolactinemia appear to have increased quantities of the less biologically active polymeric forms. PRL is secreted episodically, with an increase in the amplitude of the secretory pulses with sleep. A transitory increase also occurs in response to the protein component of meals. Basal PRL levels increase in response to the hormonal milieu of pregnancy, and suckling postpartum triggers PRL release. Pathologic increases of PRL owing to hypothalamic dysregulation occur with a variety of medications, including the neuroleptics, metoclopramide, antidepressants, methyldopa, reserpine and verapamil, abuse of opiates and cocaine, renal insufficiency, cirrhosis, hypothyroidism, adrenal insufficiency, neurogenic stimulation, and idiopathically. Hyperprolactinemia also may occur from structural lesions of the stalk and hypothalamus, which cause disinhibition with or without maintenance of PRF activity, ectopic neoplasm production, and, most commonly, from prolactinomas. Diagnostic testing consists of routine chemistry and thyroid testing and imaging with MRI or CT. Dopamine agonists are the treatment of choice of prolactinomas of all sizes. Transsphenoidal surgery is an alternative for the patient who does not respond to medical therapy or who wishes definitive tumor removal, realizing that long-term cure is achieved in only 50% to 60% of patients with microadenomas and a much lower number in those with macroadenomas. Radiotherapy is reserved for patients who do respond to either medical or surgical treatment. Patients wishing to become pregnant usually are treated with bromocriptine, although prepregnancy surgical debulking may be advisable for those with large macroadenomas to reduce problems with tumor enlargement.

HYPERTHYROIDISM AND HYPERPROLACTINEMIA: IS THERE ANY ASSOCIATION?

PubMed

Sanjari, Mojgan; Safi, Zohreh; Tahroodi, Khatereh Mohammadi

2016-12-01

To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism. Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age. The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001). The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism. PRL = prolactin T4 = thyroxine TRH = thyrotropin-releasing hormone TSH = thyroid-stimulating hormone.

The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients.

PubMed

Lee, Bun-Hee; Kim, Yong-Ku

2006-06-01

Hyperprolactinemia can be induced by dopamine D2 receptor-binding drugs such as antipsychotic drugs. The author investigated the relationship between changes in prolactin (PRL) and clinical efficacy of risperidone. In this study, 27 acute psychotic inpatients completed a 12-week trial of risperidone. At baseline and at 2, 4, 8, and 12 weeks after beginning medication, the author measured PRL, assessed hyperprolactinemia-related symptoms, and administered the Brief Psychotic Rating Scale (BPRS). Risperidone treatment significantly elevated serum PRL level (range: 26.9 ng/ml-320.0 ng/ml). The increases of PRL in females were higher than males. The changes in serum PRL levels were not significantly correlated with the improvements in total BPRS scores. PRL-related symptoms such as irregular menstruation, galactorrhea, or erectile dysfunction occurred in nine subjects (7 females and 2 males) whose serum PRL levels increase very highly after 2 weeks of risperidone. In conclusion, our study suggests that the changes in serum PRL levels were not significantly correlated with clinical efficacy of risperidone.

Role of Na+/K+-ATPase in Natriuretic Effect of Prolactin in a Model of Cholestasis of Pregnancy.

PubMed

Abramicheva, P A; Balakina, T A; Bulaeva, O A; Guseva, A A; Lopina, O D; Smirnova, O V

2017-05-01

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

[Early recurrent miscarriage: Evaluation and management].

PubMed

Gallot, V; Nedellec, S; Capmas, P; Legendre, G; Lejeune-Saada, V; Subtil, D; Nizard, J; Levêque, J; Deffieux, X; Hervé, B; Vialard, F

2014-12-01

To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). Literature review, establishing levels of evidence and recommendations for grades of clinical practice. Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). These recommendations should improve the management of couples faced with early recurrent miscarriages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana)

PubMed Central

Meehan, Cheryl L.; Hogan, Jennifer N.; Morfeld, Kari A.; Carlstead, Kathy

2016-01-01

As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8–55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status. PMID:27416141

Reproductive Health Assessment of Female Elephants in North American Zoos and Association of Husbandry Practices with Reproductive Dysfunction in African Elephants (Loxodonta africana).

PubMed

Brown, Janine L; Paris, Stephen; Prado-Oviedo, Natalia A; Meehan, Cheryl L; Hogan, Jennifer N; Morfeld, Kari A; Carlstead, Kathy

2016-01-01

As part of a multi-institutional study of zoo elephant welfare, we evaluated female elephants managed by zoos accredited by the Association of Zoos and Aquariums and applied epidemiological methods to determine what factors in the zoo environment are associated with reproductive problems, including ovarian acyclicity and hyperprolactinemia. Bi-weekly blood samples were collected from 95 African (Loxodonta africana) and 75 Asian (Elephas maximus) (8-55 years of age) elephants over a 12-month period for analysis of serum progestogens and prolactin. Females were categorized as normal cycling (regular 13- to 17-week cycles), irregular cycling (cycles longer or shorter than normal) or acyclic (baseline progestogens, <0.1 ng/ml throughout), and having Low/Normal (<14 or 18 ng/ml) or High (≥14 or 18 ng/ml) prolactin for Asian and African elephants, respectively. Rates of normal cycling, acyclicity and irregular cycling were 73.2, 22.5 and 4.2% for Asian, and 48.4, 37.9 and 13.7% for African elephants, respectively, all of which differed between species (P < 0.05). For African elephants, univariate assessment found that social isolation decreased and higher enrichment diversity increased the chance a female would cycle normally. The strongest multi-variable models included Age (positive) and Enrichment Diversity (negative) as important factors of acyclicity among African elephants. The Asian elephant data set was not robust enough to support multi-variable analyses of cyclicity status. Additionally, only 3% of Asian elephants were found to be hyperprolactinemic as compared to 28% of Africans, so predictive analyses of prolactin status were conducted on African elephants only. The strongest multi-variable model included Age (positive), Enrichment Diversity (negative), Alternate Feeding Methods (negative) and Social Group Contact (positive) as predictors of hyperprolactinemia. In summary, the incidence of ovarian cycle problems and hyperprolactinemia predominantly affects African elephants, and increases in social stability and feeding and enrichment diversity may have positive influences on hormone status.

Recurrence of hyperprolactinemia and continuation of ovarian acyclicity in captive African elephants (Loxodonta africana) treated with cabergoline.

PubMed

Morfeld, Kari A; Ball, Ray L; Brown, Janine L

2014-09-01

Hyperprolactinemia is associated with reproductive acyclicity in zoo African elephants (Loxodonta africana) and may contribute to the non-self-sustainability of the captive population in North America. It is a common cause of infertility in women and other mammals and can be treated with the dopamine agonist cabergoline. The objectives of this study were to assess prolactin responses to cabergoline treatment in hyperprolactinemic, acyclic African elephants and to determine the subsequent impact on ovarian cyclic activity. Five elephants, diagnosed as hyperprolactinemic (>11 ng/ml prolactin) and acyclic (maintenance of baseline progestagens for at least 1 yr), were treated with 1-2 mg cabergoline orally twice weekly for 16-82 wk. Cabergoline reduced (P < 0.05) serum prolactin concentrations during the treatment period compared to pretreatment levels in four of five elephants (11.5 +/- 3.2 vs. 9.1 +/- 3.4 ng/ml; 20.3 +/- 16.7 vs. 7.9 +/- 9.8 ng/ml; 26.4 +/- 15.0 vs. 6.8 +/- 1.5 ng/ml; 42.2 +/- 22.6 vs. 18.6 +/- 8.9 ng/ml). However, none of the females resumed ovarian cyclicity based on serum progestagen analyses up to 1 yr posttreatment. In addition, within 1 to 6 wk after cessation of oral cabergoline, serum prolactin concentrations returned to concentrations that were as high as or higher than before treatment (P < 0.05). One elephant that exhibited the highest pretreatment prolactin concentration (75.2 +/- 10.5 ng/ml) did not respond to cabergoline and maintained elevated levels throughout the study. Thus, oral cabergoline administration reduced prolactin concentrations in elephants with hyperprolactinemia, but there was no resumption of ovarian cyclicity, and a significant prolactin rebound effect was observed. It is possible that higher doses or longer treatment intervals may be required for cabergoline treatment to result in permanent suppression of prolactin secretion and to mitigate associated ovarian cycle problems.

Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

PubMed

Maggi, Mario; Buvat, Jaques; Corona, Giovanni; Guay, André; Torres, Luiz Otavio

2013-03-01

Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning. © 2012 International Society for Sexual Medicine.

Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial

PubMed Central

Zhao, Jingyuan; Song, Xueqin; Ai, Xiaoqing; Gu, Xiaojing; Huang, Guangbiao; Li, Xue; Pang, Lijuan; Ding, Minli; Ding, Shuang; Lv, Luxian

2015-01-01

Objective The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. Results One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusions Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. Trial Registration chictr.org ChiCTR-IOR-15006278 PMID:26448615

One-year follow-up study of psychotic patients treated with blonanserin: a case series.

PubMed

Takahashi, Sakae; Suzuki, Masahiro; Uchiyama, Makoto

2013-09-01

Blonanserin is a relatively new atypical antipsychotic drug, and has been used in Korea and Japan for 1 and 3 years, respectively. Therefore, the clinical characteristics of blonanserin remain unclear. In this study, to clarify the features of blonanserin, we performed prospective and long-term comparative investigations of patients treated with blonanserin. We followed 10 psychiatric patients who were switched to blonanserin from other antipsychotics for 1 year (schizophrenia: 8; mental retardation: 2). In the light of quality of life, we focused on adverse effects of patients during the follow-up. In the long-term follow-up, (i) hyperprolactinemia is more frequently in risperidone than in blonanserin; however, it is more often in blonanserin than in olanzapine; and (ii) weight gain is more common in olanzapine than in blonanserin. We switched to blonanserin from other antipsychotic drugs within the same case, and then followed the case for 1 year. We consider that long-term observations within the same case lead to obvious comparisons among drugs. On the basis of our findings, we conclude that blonanserin may be useful for the maintenance treatment of schizophrenia without inducing hyperprolactinemia and weight gain. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Hand-Schüller-Christian Disease and Erdheim-Chester Disease: Coexistence and Discrepancy

PubMed Central

Yin, Jun; Zhang, Feng; Zhang, Huizhen; Shen, Li; Li, Qing; Hu, Shundong; Tian, Qinghua; Bao, Yuqian

2013-01-01

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) share similar clinical features and mechanisms. In very rare circumstances, the two diseases coexist in the same patient. Here we report such a patient, who was first diagnosed with Hand-Schüller-Christian disease (HSC), a type of LCH. Several years later, the patient presented with severe exophthalmos and osteosclerosis on radiograph. New biopsy revealed ECD. We also analyze 54 cases of LCH and 6 cases of ECD diagnosed in our hospital, as well as their progression during a follow-up period of 8 years. In five cases of HSC (9.3% of LCH), a triad of central diabetes insipidus, hyperprolactinemia, and pituitary stalk thickening on magnetic resonance imaging (MRI) preceded the typical bone lesions by 4–9 years. In addition, LCH was featured as elevated plasma alkaline phosphatase (ALP), which was normal in ECD. Combined with a literature review, several features are summarized to differentiate ECD from HSC. In patients with diabetes insipidus, concomitant hyperprolactinemia and pituitary stalk thickening on MRI indicate a possible HSC. Additionally, if osteosclerosis is observed in a patient with LCH, the coexistence of ECD should be considered. PMID:23299772

Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age.

PubMed

Tzeng, Chii-Ruey; Chang, Yuan-chin Ivan; Chang, Yu-chia; Wang, Chia-Woei; Chen, Chi-Huang; Hsu, Ming-I

2014-05-01

To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care. Retrospective study, cluster analysis. Outpatient clinic, university medical center. 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease. None. Cardiovascular and metabolic parameters and clinical and biochemical characteristics. Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk. Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases. NCT01826357. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Diagnostic usefulness of 3 tesla MRI of the brain for cushing disease in a child.

PubMed

Ono, Erina; Ozawa, Ayako; Matoba, Kaori; Motoki, Takanori; Tajima, Asako; Miyata, Ichiro; Ito, Junko; Inoshita, Naoko; Yamada, Syozo; Ida, Hiroyuki

2011-10-01

It is sometimes difficult to confirm the location of a microadenoma in Cushing disease. Recently, we experienced an 11-yr-old female case of Cushing disease with hyperprolactinemia. She was referred to our hospital because of decrease of height velocity with body weight gain. On admission, she had typical symptoms of Cushing syndrome. Although no pituitary microadenomas were detected on 1.5 Tesla MRI of the brain, endocrinological examinations including IPS and CS sampling were consistent with Cushing disease with hyperprolactinemia. Oral administration of methyrapone instead of neurosurgery was started after discharge, but subsequent 3 Tesla MRI of the brain clearly demonstrated a 3-mm less-enhanced lesion in the left side of the pituitary gland. Finally, transsphenoidal surgery was performed, and a 3.5-mm left-sided microadenoma was resected. Compared with 1.5 Tesla MRI, 3 Tesla MRI offers the advantage of a higher signal to noise ratio (SNR), which provides higher resolution and proper image quality. Therefore, 3 Tesla MRI is a very useful tool to localize microadenomas in Cushing disease in children as well as in adults. It will be the first choice of radiological examinations in suspected cases of Cushing disease.

Risperidone-induced symptomatic hyperprolactinaemia in adolescents.

PubMed

Holzer, Laurent; Eap, Chin B

2006-04-01

Studies performed in adult patients unambiguously demonstrate a marked effect of risperidone on prolactin blood levels, with possible clinical effects related to hyperprolactinemia, such as gynecomastia and galactorrhea. However, the largest study performed in children and adolescents showed a weak effect of risperidone on prolactin concentrations during short-term treatment and a negligible effect during long-term treatment, which was probably because of the relatively low dosages of risperidone used [approximately 0.04 mg/(kg x d)]. Among the 10 psychotic adolescents treated with risperidone in our unit, we had 3 cases of gynecomastia in 3 male patients and 2 cases of galactorrhea in 2 female patients. The prolactin blood levels in these cases and in 3 other patients without apparent prolactin-related side effects were all above the normal range (median, 59 ng/mL; range, 30-123 ng/mL). Thus, risperidone administered to adolescents at doses commonly used for the treatment of psychotic symptoms can strongly increase prolactin levels, with clinical consequences such as gynecomastia and/or galactorrhea. Given that the long-term effects of antipsychotic drug-induced hyperprolactinemia are not well documented, especially regarding osteopenia, infertility, growth, and pubertal delay, risperidone should be administered with caution to children and adolescents.

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

PubMed Central

Chin, Sang Ouk; Hwang, Jin-Kyung; Rhee, Sang Youl; Chon, Suk; Oh, Seungjoon; Lee, Misu; Pellegata, Natalia S.

2015-01-01

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor. PMID:25559714

ROHHAD Syndrome: The Girl who Forgets to Breathe.

PubMed

Sanklecha, Mukesh; Sundaresan, Suba; Udani, Vrajesh

2016-04-01

ROHHAD syndrome is an exceedingly rare cause of central hypoventilation. A 7-year-old girl with ROHHAD syndrome who had central hypoventilation, rapid weight gain, multiple cardiac arrests and hyperprolactinemia. She required prolonged and repeated ventilation, and finally died due to complications of ventilation. ROHHAD Syndrome should be suspected in any child who presents with obesity, behavioral changes or autonomic instability following a neural crest tumor.

Gynecomastia.

PubMed

Leung, A K

1989-04-01

Gynecomastia may be physiologic, familial, pathologic, drug-induced or, in many cases, of unknown etiology. Breast enlargement is usually unilateral and asymptomatic. Mechanisms of gynecomastia involve increased estrogen stimulation, decreased testosterone levels or a decreased androgen/estrogen ratio. Hyperprolactinemia is not a cause. Treatment of gynecomastia should be directed at the underlying cause when one can be identified. Most cases are benign and can be managed by explanation, reassurance and observation.

Euprolactinemic Gynecomastia and Galactorrhea with Risperidone-Fluvoxamine Combination

PubMed Central

P.J., Pratheesh; Praharaj, Samir Kumar; Srivastava, Ashish

2011-01-01

Risperidone is associated with hyperprolactinemia and its consequent symptoms such as gynnecomastia, galactorrhea and sexual dysfunction in adults, and less so in adolescents. Rarely, serotonin reuptake inhibitors are also associated with such adverse effects. We report a case of gynecomastia and galactorrhea in an adolescent male while on a combination of risperidone and fluvoxamine, although the serum prolactin was within normal range. PMID:22506441

Acute Onset Polymyositis after Prolactinoma Extirpation

PubMed Central

Jakez-Ocampo, Juan; Atisha-Fregoso, Yemil; Llorente, Luis

2014-01-01

Hyperprolactinemia has been related to autoimmune diseases. Herein, we describe a case of a female with a prolactin producer pituitary macroadenoma who developed severe polymyositis one month after its removal. The patient had very high levels of CPK and muscle biopsy showed remarkable inflammatory infiltration. Steroid therapy was followed with total recovery. To the best of our knowledge, this is the first case reported of acute polymyositis after pituitary macroadenoma exeresis. PMID:25431724

Psychosomatic symptoms as biomarkers: transcending the psyche-soma dichotomy.

PubMed

Neuman, Yair

2010-01-01

Following the advancement in understanding dynamical systems, the author presents a novel metaphor of psychosomatic symptoms as low-dimensional biomarkers. This metaphor, which transcends the old binary of psyche-soma, resonates with classical psychoanalytic concepts and with Matte-Blanco's idea of repetition as indicative of dimensionality reduction. The relevance of this metaphor for explanation, diagnosis, and treatment is illustrated through a case study of a male patient suffering from hyperprolactinemia.

Reversibility of dopamine receptor antagonist-induced hyperprolactinemia and associated histological changes in Tg RasH2 wild-type mice.

PubMed

Krishna, Gopala; Ganiger, Shivaputhrappa; Kannan, Kamala; Gopalakrishnan, Gopa; Goel, Saryu

2015-12-01

The purpose of this study was to better understand the biological effects of increased prolactin levels induced in mice by dopamine D2 receptor antagonist molindone treatment. Toxicokinetics, prolactin levels, and reproductive tissue histology were evaluated in Tg rasH2 wild-type mice treated orally with molindone at 0, 5, 15, and 50mg/kg/day for 6 months, followed by a 2-month posttreatment recovery period. A greater than dose-proportional increase in molindone exposure ([AUC]0‒24) was observed on Day 180 for both sexes. Statistically significant (P<0.01) increases in prolactin levels were observed in most treatment groups compared with controls at 0.5h postdose on Days 1 and 180. Prolactin levels returned to baseline levels during the recovery period. Microscopic changes attributable to hyperprolactinemia, including corpora lutea enlargement and interstitial cell atrophy in the ovaries, and atrophy of the uterus and vagina were observed on Day 180. These changes were reversed during the recovery period in the 5- and 15-mg/kg/day treatment groups. Mice receiving molindone at 50mg/kg/day also showed signs of reversal on histologic examination. Copyright © 2015 Elsevier Inc. All rights reserved.

Macroprolactin, big-prolactin and potential effects on the misdiagnosis of hyperprolactinemia using the Beckman Coulter Access Prolactin assay.

PubMed

Ellis, M Jane; Livesey, John H; Soule, Steven G

2006-10-01

To examine whether use of the Beckman Coulter Access Prolactin (PRL) assay, which has low reactivity with macro-PRL, obviates the need for screening hyperprolactinemic samples. Samples from 1020 hyperprolactinemic individuals and 401 healthy volunteers were treated with polyethylene glycol (PEG). Macro-PRL was assessed from (1) percent PRL recovery, using cut-off values derived by gel filtration chromatography (GFC) and (2) significant (p<0.05) normalisation of PRL following PEG. PRL recovery was similar in volunteer and hyperprolactinemic samples (mean+/-SD 101+/-13% and 101+/-19%, respectively). In hyperprolactinemic samples, macro-PRL was identified from PRL recovery in 9.7%, although levels were moderate to high in only 3.9%. The total PRL normalised following PEG in 7.4%. Correlations of PRL recovery with the proportions of macro-, big- and monomeric PRL following GFC (n=30 samples, range of PRL and macro-PRL levels) were -0.89, -0.20 and 0.92, respectively. The big-PRL content was 0-28%. Regression analysis suggested that PEG precipitated both macro-PRL and big-PRL. Using the Access assay, macro-PRL can cause apparent hyperprolactinemia and big-PRL may cause misclassification of individuals. Screening using PEG is applicable to assays with low macro-PRL reactivity provided specific reference values are derived.

18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.

PubMed

Wang, Di; Zhang, Yongfeng; Wang, Chunyue; Jia, Dongxu; Cai, Guangsheng; Lu, Jiahui; Wang, Di; Zhang, Zhang-Jin

2016-09-01

The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.

Interactions between prolactin and kisspeptin to control reproduction.

PubMed

Donato, Jose; Frazão, Renata

2016-01-01

Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin's functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin's actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

Management of prolactinomas.

PubMed

Molitch, M E

1989-01-01

Prolactinomas are the most common of the hormone-secreting pituitary tumors and must be distinguished from nonsecreting tumors causing hyperprolactinemia by hypothalamic or stalk dysfunction. For both micro- and macroadenomas, dopamine agonists appear to be the treatment of choice, transsphenoidal surgery being reserved for nonresponders. For women desiring pregnancy, dopamine agonists are safe when there is a microadenoma or an intrasellar macroadenoma. However, in women with large macroadenomas desiring pregnancy, limited transsphenoidal decompression followed by bromocriptine appears to be the safest mode of treatment.

Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

PubMed

Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

1986-08-01

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

Flaxseed bioactive compounds change milk, hormonal and biochemical parameters of dams and offspring during lactation.

PubMed

Troina, A A; Figueiredo, M S; Passos, M C F; Reis, A M; Oliveira, E; Lisboa, P C; Moura, E G

2012-07-01

We evaluated maternal intake of SDG (secoisolariciresinol diglucoside), a compound from flaxseed, and flaxseed oil+SDG on biochemical and hormonal parameters of dams and male and female offspring during lactation. Dams were fed a standard diet (C); diet added 40 mg of SDG/100g diet (SDG) or diet added 40 mg of SDG/100g diet and 7% of flaxseed oil (OLSDG). SDG and OLSDG dams showed hyperprolactinemia. The OLSDG milk had lower lactose and protein, while the SDG milk had lower protein on the 14th day of lactation. At 14 days, OLSDG male and female pups showed lower body mass, SDG and OLSDG male pups had hypoprolactinemia and lower body fat mass, but higher visceral fat mass (VFM) and hypertriglyceridemia. At 21 days, male SDG and OLSDG presented hypotriglyceridemia. At 14 days, SDG and OLSDG female offspring showed higher serum 17-β estradiol (E2); OLSDG presented hypercholesterolemia and SDG presented hypertriglyceridemia. At 21 days, SDG and OLSDG female pups showed hypotriglyceridemia and OLSDG shower lower E2. Both maternal treatments changes maternal metabolism as well as hormonal and biochemical parameters of the offspring, which are gender-dependent. Maternal hyperprolactinemia may act as an imprint factor responsible for the hormonal and metabolic changes observed in the pups. Copyright © 2012 Elsevier Ltd. All rights reserved.

McCune-Albright syndrome associated with pituitary microadenoma: patient report.

PubMed

Chen, Chun-Jung; Liu, Jah-Yao; Cheng, Shin-Nan; Chang, Fung-Wei; Yuh, Yeong-Seng

2004-03-01

McCune-Albright syndrome (MAS) is a rare disorder characterized by the classic triad of precocious puberty, polyostotic fibrous dysplasia and café-au-lait spots. Additional endocrine abnormalities may also be present, including hyperthyroidism, growth hormone excess and hyperprolactinemia. The most commonly encountered endocrine dysfunction is gonadal hyperfunction. Gonadotropin-independent precocious puberty is typically the initial manifestation of MAS in girls. Ovarian cysts may be detected on pelvic ultrasound. Our patient was also found to have pituitary microadenoma, evidenced by dynamic magnetic resonance imaging.

Drug-induced gynecomastia.

PubMed

Eckman, Ari; Dobs, Adrian

2008-11-01

Gynecomastia is caused by drugs in 10 - 25% of all cases. The pathophysiologic mechanism for some drugs includes exogenous estrogens exposure, medications that cause hypogonadism, anti-androgenic effects and hyperprolactinemia. This manuscript reviews common examples of drug-induced gynecomastia, discussing the mechanisms and possible treatments. Discontinuing the medication is always the best choice; however, if this is not possible, then testosterone replacement therapy may be needed for hypogonadism. When a man is euogonadal, a trial of the anti-estrogen, tamoxifen or an aromatase inhibitor may be an option.

Adenohypophyseal function in dogs with primary hypothyroidism and nonthyroidal illness.

PubMed

Diaz-Espiñeira, M M; Mol, J A; Rijnberk, A; Kooistra, H S

2009-01-01

A recent study of dogs with induced primary hypothyroidism (PH) demonstrated that thyroid hormone deficiency leads to loss of thyrotropin (TSH) hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with large vacuolated "thyroid deficiency" cells that double-stained for growth hormone (GH) and TSH, indicative of transdifferentiation of somatotropes to thyrosomatropes. Similar functional changes in adenohypophyseal function occur in dogs with spontaneous PH as do in dogs with induced PH, but not in dogs with nonthyroidal illness (NTI). Fourteen dogs with spontaneous PH and 13 dogs with NTI. Adenohypophyseal function was investigated by combined intravenous administration of 4 hypophysiotropic releasing hormones (4RH test), followed by measurement of plasma concentrations of ACTH, GH, luteinizing hormone (LH), prolactin (PRL), and TSH. In the PH dogs this test was repeated after 4 and 12 weeks of thyroxine treatment. In 6 PH dogs, the basal TSH concentration was within the reference range. In the PH dogs, the TSH concentrations did not increase with the 4RH test. However, TSH concentrations increased significantly in the NTI dogs. Basal and stimulated GH and PRL concentrations indicated reversible hypersomatotropism and hyperprolactinemia in the PH dogs, but not in the NTI dogs. Basal and stimulated LH and ACTH concentrations did not differ between groups. Dogs with spontaneous PH hypersecrete GH but have little or no TSH hypersecretion. Development of hyperprolactinemia (and possible galactorrhea) in dogs with PH seems to occur only in sexually intact bitches. In this group of dogs with NTI, basal and stimulated plasma adenohypophyseal hormone concentrations were not altered.

Emotional aspects of hyperprolactinemia.

PubMed

Sobrinho, L G

1998-01-01

Patients with hyperprolactinemia often present with emotional difficulties. These occasionally persist even after successful treatment. Insight into the roots of their diseased state makes a difference in the handling of all cases, but becomes crucial in the not-so-rare situations in which the normalization of hormonal levels is not followed by a feeling of cure. This chapter attempts to provide details, discuss and situate in context the following blocks of pertinent information: (1) prolactin acts upon the central nervous system and variations in its concentrations do affect mood, emotions and behavior; (2) most actions of prolactin are directed to metabolical and behavioral adaptation to pregnancy and the care of the young; (3) even in the absence of pregnancy prolactin secretion responds to environmental stimuli under specific conditions. Whether adaptive, as in the case of surrogate maternity, or pathological, as in the case of pseudopregnancy, prolactin responds to a perceived need to take care of a child; (4) the facts that the clinical onset of prolactinomas often follows life-events and that these tumors occur preferentially in women brought up under specific conditions suggest the possibility that psychological factors may predispose to prolactinomas; (5) dealing with individual cases requires the perception that the relations between prolactin, emotions and feelings are circular, i.e., prolactin affects the brain and mood but, on the other hand, personality traits and environmental factors may stimulate the secretion of prolactin and may play a role in the genesis of the disease.

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

PubMed

Nota, N M; Dekker, M J H J; Klaver, M; Wiepjes, C M; van Trotsenburg, M A; Heijboer, A C; den Heijer, M

2017-08-01

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L -1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. © 2016 Blackwell Verlag GmbH.

Sex-specific factors for bone density in patients with schizophrenia.

PubMed

Lin, Chieh-Hsin; Lin, Chun-Yuan; Huang, Tiao-Lai; Wang, Hong-Song; Chang, Yue-Cune; Lane, Hsien-Yuan

2015-03-01

Patients with schizophrenia are susceptible to low bone mineral density (BMD). Many risk factors have been suggested. However, it remains uncertain whether the risk factors differ between men and women. In addition, the study of bone density in men is neglected more often than that in women. This study aims to examine specific risk factors of low BMD in different sexes. Men (n=80) and women (n=115) with schizophrenia, similar in demographic and clinical characteristics, were enrolled in three centers. Clinical and laboratory variables (including blood levels of prolactin, sex and thyroid hormones, cortisol, calcium, and alkaline phosphatase) were collected. BMD was measured using a dual-energy X-ray absorptiometer. Men had lower BMD than women. Predictors for BMD in men included hyperprolactinemia (B=-0.821, P=0.009), body weight (B=0.024, P=0.046), and Global Assessment of Functioning score (B=0.027, P=0.043); in women, BMD was associated with menopause (B=-1.070, P<0.001), body weight (B=0.027, P=0.003), and positive symptoms (B=0.094, P<0.001). In terms of the effect of psychotic symptoms, positive symptoms were related positively to BMD in women, but not in men. The findings suggest that sex-specific risk factors should be considered for an individualized intervention of bone loss in patients with schizophrenia. Physicians should pay particular attention to bone density in men with hyperprolactinemia and postmenopausal women. Further prospective studies in other populations are warranted to confirm these findings.

Hypopituitarism induced by traumatic brain injury in the transition phase.

PubMed

Aimaretti, G; Ambrosio, M R; Di Somma, C; Gasperi, M; Cannavò, S; Scaroni, C; De Marinis, L; Baldelli, R; Bona, G; Giordano, G; Ghigo, E

2005-12-01

Traumatic brain injury (TBI) has been associated with hypopituitarism in general and GH deficiency (GHD) in particular; the consequences of this on growth and development are likely to be critical in children and adolescents in the so-called "transition phase". In order to verify the consequences of TBI on pituitary function in the transition phase, we studied a population of adolescents and young adults 3 and 12 months after brain injury [no. = 23, 9 females, 14 males; age: 16-25 yr; body mass index (BMI): 21.9 +/- 0.6 kg/m2]. At 3 months, hypopituitarism was present in 34.6%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 21.7%, respectively. Diabetes insipidus (DI) was present in 8.6% patients and mild hyperprolactinemia in 4.3%. At 12 months, hypopituitarism was present in 30.3%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 17.4%, respectively. DI was present in 4.3% of patients and mild hyperprolactinemia in 4.3%. Total hypopituitarism was always confirmed at retesting. Multiple and isolated hypopituitarism were confirmed in 0/1 and 2/5, respectively. Two/23 patients showed isolated hypopituitarism at 12 months only; 1 patient with isolated at 3 months showed multiple hypopituitarism at retesting. GHD and secondary hypogonadism were the most common acquired pituitary deficits. These results show the high risk of TBI-induced hypopituitarism also in the transition age. Thus it is recommended that pediatric endocrinologists follow-up pituitary function of children and adolescents after brain injuries.

NUTRITIONAL AND METABOLIC ASSESSMENT IN OVERWEIGHT PATIENTS WITH AND WITHOUT HYPERPROLACTINEMIA CAUSED BY PROLACTINOMA.

PubMed

Breyer Freitas, Bruna; Rothen, Renata Elisabeth; Zeni, Débora; Garcia Soares Leães, Carolina; Costa Oliveira, Miriam; Michielin Busnello, Fernanda; Fernanda Semmelmann Pereira-Lima, Júlia

2015-11-01

prolactinomas are pituitary adenomas that express and secrete prolactin. These patients are overweight and the mechanisms are being studied. assess nutritional and metabolic status of overweight patients with and without hyperprolactinemia caused by prolactinoma and compare them. cross-sectional study, patients with body mass index (BMI) ≥ 25 kg/m2 with and without prolactinoma: 1) 20 normoprolactinemic (NPrl) with prolactinoma; 2) 23 hyperprolactinemic (HPrl) with prolactinoma; 3) 28 controls without prolactinoma or alterations in prolactin levels. Evaluated through anthropometric, dietetics, and biochemical assessment. of the 71 patients evaluated, most were obese women with macroprolactinomas. All three groups had diets with low caloric and monounsaturated fatty acid (MUFA) intake, the NPrl group had low carbohydrate (CHO) intake and high lipid (LIP) and saturated fatty acid (SFA) intake, and the NPrl and HPrl groups had appropriate intake of polyunsaturated fatty acids (PUFA). The HPrl group had elevated total cholesterol. HDL cholesterol was below the recommended threshold for most patients. No statistically significant differences were found in anthropometric and biochemical variables among the groups. most patients with prolactinomas and controls are obese and metabolically similar regardless of prolactin levels. All groups presented low caloric and MUFA intake. Protein, LIP, SFA, and cholesterol were significantly different among the groups, the NPrl group ingested less amount of protein and greater of fat. Snacking between meals and changes of food consumption on weekends was reported by most patients. This is the first study comparing patients with prolactinomas and controls, both with overweight, regarding food consumption and feeding behavior. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Bilateral Mastectomy as Radical Treatment of Gynecomastia Secondary to Antiretroviral Therapy in a Low-Income Setting: A Case Report.

PubMed

Antunes, Mario; Schiavone, Marcella; Pizzol, Damiano; Di Gennaro, Francesco; Ludovico, Rossana; De Palma, Angela

2018-05-11

Gynecomastia is a common finding in males, with an incidence that varies widely globally. In 10-25% of cases, it is caused by drugs. Its pathophysiologic mechanism includes exposure to exogenous estrogens and medications that cause hypogonadism, antiandrogenic effects and hyperprolactinemia. Gynecomastia is associated with exposure to antiretroviral therapy (ART), particularly efavirenz. Sometimes surgery may be required as treatment. We report a case of a 46-year-old man receiving ART presenting with a marked bilateral breast enlargement who underwent bilateral mastectomy as the only successful treatment in a low-income setting.

Pituitary adenoma associated with gigantism and hyperprolactinemia.

PubMed

Alikasifoglu, A; Kandemir, N; Akalan, N; Yordam, N

2001-12-01

An 11-year-old girl presented with excessive growth, headache, left visual loss and seizures. Her growth hormone (GH) and prolactin (PRL) levels were high and magnetic resonance imaging findings showed an invasive macroadenoma. Gross total tumor removal was performed and then radiotherapy and medical therapy were given. During the follow-up, she developed ACTH deficiency, secondary hypothyroidism and hypogonadism requiring replacement therapy. It is still unclear whether the biological characteristics of GH- and PRL-secreting tumors are different in children from those in adults. More data are needed before a definitive conclusion can be established. Copyright 2001 S. Karger AG, Basel

[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

PubMed

Haefliger, T; Bonsack, C

2006-01-01

Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case-reports describe the occurrence of retrograde ejaculation associated with risperidone but the exact prevalence is unknown. Retrograde ejaculation is thought to be related to the strong adrenolytic activity of risperidone. Alberto refused his medication because the ejaculatory dysfunction was unbearable for him. A switch to haloperidol depot was eventually well tolerated, without any sexual complaints. His case emphasizes the importance of sexual function for self-esteem and how this may amplify the intolerance to side-effects. David is on depot-risperidone in a setting of a legally forced treatment. Though he - reluctantly - accepts his medication, this side effect exacerbates his pre-existing delusions, strongly focused on sexual themes. His case illustrates how intolerance to sexual side-effects may be amplified by nature of delusions. Mireille is a 58 year old psychotic female patient, whose 2 mg risperidone treatment produced a unilateral galactorrhea. This sign became problematic because potentially visible at a time when Mireille started an activity in a sheltered occupation in town. Lowering dosage of antipsychotic allowed disappearance of the problem. Subjective responses to galactorrhea have been reported to be highly individual. Apart being a potentially visible side-effect, it may be misinterpreted as evidence of pregnancy or of a tumoral process. The cases of Ermina and Denise illustrate two contrasted situations in terms of subjective tolerability of reproductive function side-effects. Both were pre-menopausal patients with hyperprolactinemia secondary to risperidone treatment, resulting in amenorrhea. This was unbearable for Ermina. A switch to olanzapine allowed, one month later, the menses to resume. For Denise, on the other hand, the amenorrhea was a positive event, freeing her of unpleasant menses. Amenorrhea occurs in about 30% of pre-menopausal women treated with risperidone. It is a consequence of hyperprolactinemia, which, although often silent, is not devoid of potential negative consequences (ie increased risk of osteoporosis or neoplasia, worsening of psychopathology) (34). When hyperprolactinemia is symptomatic, lowering of the dose of the antipsychotic, or switching to a prolactin-sparing agent (olanzapine, quetiapine, aripiprazole and clozapine) is recommended. Before this, women with amenorrhea secondary to antipsychotic-induced hyperprolactinemia should be advised that menses may resume. Especially after long-standing amenorrhea they may assume being menopaused, hence may believe birth control measures are no longer required. The prevalence of antipsychotic-induced sexual and reproductive function side-effects is high. Clinicians should be aware of them, because they are often badly tolerated, are associated with a low satisfaction and may therefore result in low adherence with treatment. This implies for the clinician to overtly discuss with the patient of his sexuality and the potential negative impact of antipsychotic treatment on it. The recognition of these problems allows the searching together for a solution. The described cases indicate that solving the problem is often possible, provided that individual preferences and subjective impact are taken in account. Antipsychotic treatment is often prescribed for very long periods. A better knowledge of - and attention to - the associated side effects, particularly on the sexual and reproductive functions, is necessary in order to reduce some potentially negative long-term effects and to improve the adherence to treatment of our patients.

Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia.

PubMed

Overgaard, Martin; Pedersen, Susanne Møller

2017-10-26

Hyperprolactinemia diagnosis and treatment is often compromised by the presence of biologically inactive and clinically irrelevant higher-molecular-weight complexes of prolactin, macroprolactin. The objective of this study was to evaluate the performance of two macroprolactin screening regimes across commonly used automated immunoassay platforms. Parametric total and monomeric gender-specific reference intervals were determined for six immunoassay methods using female (n=96) and male sera (n=127) from healthy donors. The reference intervals were validated using 27 hyperprolactinemic and macroprolactinemic sera, whose presence of monomeric and macroforms of prolactin were determined using gel filtration chromatography (GFC). Normative data for six prolactin assays included the range of values (2.5th-97.5th percentiles). Validation sera (hyperprolactinemic and macroprolactinemic; n=27) showed higher discordant classification [mean=2.8; 95% confidence interval (CI) 1.2-4.4] for the monomer reference interval method compared to the post-polyethylene glycol (PEG) recovery cutoff method (mean=1.8; 95% CI 0.8-2.8). The two monomer/macroprolactin discrimination methods did not differ significantly (p=0.089). Among macroprolactinemic sera evaluated by both discrimination methods, the Cobas and Architect/Kryptor prolactin assays showed the lowest and the highest number of misclassifications, respectively. Current automated immunoassays for prolactin testing require macroprolactin screening methods based on PEG precipitation in order to discriminate truly from falsely elevated serum prolactin. While the recovery cutoff and monomeric reference interval macroprolactin screening methods demonstrate similar discriminative ability, the latter method also provides the clinician with an easy interpretable monomeric prolactin concentration along with a monomeric reference interval.

Psychiatrists' judgments about antipsychotic benefit and risk outcomes and formulation in schizophrenia treatment.

PubMed

Markowitz, Michael A; Levitan, Bennett S; Mohamed, Ateesha F; Johnson, F R; Bridges, John F P; Alphs, Larry; Citrome, Leslie

2014-09-01

The objectives were to quantify psychiatrists' judgments of the benefits and risks of antipsychotic treatments of patients with schizophrenia and to evaluate how patient adherence history affects these judgments. Weights assigned by respondents to risks, benefits, and alternative drug formulations in the treatment of schizophrenia were assessed via a Web-based survey by using a discrete-choice experiment. Respondents in the United States and the United Kingdom chose among alternative scenarios characterized by various levels of improvement in positive symptoms, negative symptoms, social functioning, weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia and by formulation. The effect of patient adherence history on respondents' judgments was also assessed. Random-parameters logit and bivariate probit models were estimated. The sample included 394 psychiatrists. Improvement in positive symptoms from "no improvement" to "very much improved" was the most preferred outcome over the range of improvements included and was assigned a relative importance score of 10. Other outcomes, in decreasing order of importance, were improvement in negative symptoms from "no improvement" to "very much improved" (5.2; 95% confidence interval [CI]=4.2-6.2), social functioning from "severe problems" to "mild problems" (4.6, CI=3.8-5.4), no hyperglycemia (1.9, CI=1.5-2.4), <15% weight gain (1.5, CI=.9-2.0), no hyperprolactinemia (1.3, CI=.8-1.6), and no EPS (1.1, CI=.7-1.5). As adherence decreased, formulation became more important than modest efficacy changes and injections were preferred to daily pills (p<.05). Psychiatrists favored treatments that primarily improve positive symptoms. Choice of formulation became more important as likely adherence declined.

Time Course of Resolution of Hyperprolactinemia After Transsphenoidal Surgery Among Patients Presenting with Pituitary Stalk Compression.

PubMed

Zaidi, Hasan A; Cote, David J; Castlen, Joseph P; Burke, William T; Liu, Yong-Hui; Smith, Timothy R; Laws, Edward R

2017-01-01

Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect-related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery. Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014. Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (≥23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P < 0.01) and galactorrhea (11.1% vs. 2.1%; P < 0.01). Patients with lactotroph disinhibition were more likely to harbor macroadenomas than were patients who did not show lactotroph disinhibition (81.9% vs. 70.2%; P = 0.06). Among patients with increased preoperative prolactin, 77.8% experienced normalization of serum prolactin postoperatively, galactorrhea improved in 100%, sexual dysfunction resolved in 66.6%, and menstrual dysfunction among premenopausal females normalized in 73.3% at last follow-up (mean, 5.35 years; range, 0.1-10 years). Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

Patients' Preferences Related to Benefits, Risks, and Formulations of Schizophrenia Treatment.

PubMed

Levitan, Bennett; Markowitz, Michael; Mohamed, Ateesha F; Johnson, F Reed; Alphs, Larry; Citrome, Leslie; Bridges, John F P

2015-07-01

The objective of this study was to quantify patients' preferences related to benefits and risks of antipsychotic treatments for schizophrenia and to assess the relative importance of treatment attributes and adherence. Treatment-related preferences among U.S. residents with a self-reported physician diagnosis of schizophrenia were assessed via a discrete-choice experiment. Patients chose between competing hypothetical scenarios characterized by improvements in positive symptoms, negative symptoms, and social functioning; incidence of weight gain, extrapyramidal symptoms (EPS), hyperprolactinemia, and hyperglycemia; and medication formulation. Preferences were estimated by using a random-parameters logit model, and the impact of adherence was estimated with conditional logit models. The final sample consisted of 271 patients. Complete improvement in positive symptoms was the most preferred outcome (relative importance score of 10.0), followed by elimination of hyperglycemia (3.6, 95% confidence interval [CI]=2.6-4.6), improvement in negative symptoms (3.0, CI=1.6-4.3), reduced weight gain (2.6, CI=1.2-4.0), avoidance of hyperprolactinemia (1.7, CI=.9-2.6), improved social functioning (1.5, CI=.4-2.5), and avoidance of EPS (1.0, CI=.3-1.8). Patients judged a daily pill superior to monthly injections (p<.01) and monthly injections superior to injections every three months (p<.01) for adherent patients and monthly injections superior to a daily pill for nonadherent patients (p=.01). Persons who self-identified as having schizophrenia judged improvement in positive symptoms as the most important treatment benefit. Hyperglycemia was identified as the most important adverse event. Patients judged oral formulations to be better than monthly injections for adherent patients and monthly injections to be a better choice for nonadherent patients.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report.

PubMed

Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases. We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine. The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects. Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain.

Evaluation of prolactin levels in patients with newly diagnosed pemphigus vulgaris and its correlation with pemphigus disease area index.

PubMed

Lajevardi, Vahideh; Hallaji, Zahra; Daneshpazhooh, Maryam; Ghandi, Narges; Shekari, Peyman; Khani, Sepideh

2016-06-01

Prolactin is a hormone; in addition to it known roles, it has immunomodulatory effects on lymphocytes maturation and immunoglobulins production. Hyperprolactinemia has been demonstrated in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes mellitus, and Graves' disease. In view of the prolactin immunomodulatory roles, studying prolactin levels in pemphigus as an autoimmune blistering disease may introduce new ways of understanding disease etiology and developing treatment strategies. Our purpose was to determine the prolactin levels in patients with newly diagnosed pemphigus vulgaris and study its correlation with pemphigus disease area index. Our study was limited by the lack of a control group. In this cross-sectional study, prolactin and anti-desmoglein 1 and 3 autoantibodies levels were measured in 50 patients with newly diagnosed pemphigus vulgaris in Razi Dermatology Hospital. Pemphigus severity and extent was estimated using the Pemphigus Disease Area Index. Of the 50 patients, 18 were male and 32 were female with a mean age of 41.56 ± 13.66 years. Mean prolactin (PRL) level was 15.60 ± 11.72 ng/ml (10.68 in males and 18.37 in females). Mean anti-desmoglein 1 and 3 autoantibodies were 135.8 ± 119.8 and 245.8 ± 157.4 U/ml, respectively. Eleven out of 50 patients had a higher than normal prolactin range. No relation was found between prolactin level and disease activity ( p = .982). Also, correlation studies show no relation between prolactin and anti-desmoglein 1 and 3 autoantibodies levels (respectively, p = .771 and .738). In comparing the extent of the disease between the two groups with normal and high prolactin, paired t-test showed no significance ( p = .204). In our study, 22% of patients had hyperprolactinemia, which was greater among females. The highest PRL level was detected in mucocutaneous group. Although serum PRL levels were higher in patients with a greater Pemphigus Disease Area Index, it did not reach statistical significance.

[The premenstrual syndrome: effectiveness of Vitex agnus castus].

PubMed

Döll, Michaela

2009-05-01

Premenstrual syndrome (PMS) is a complex combination of a variety of symptoms including mood swings, anxiety, depression, tender breasts and food cravings. For some women the physical pain and emotional stress are severe enough to affect their daily routines and activities. The causes of the premenstrual syndrome have not yet been understood clearly, but have been attributed to hormonal and neuronal dysbalance, diet and lifestyle. Hyperprolactinemia seems to be an important factor which is considered to be part of the endocrine disorder. Different clinical investigations and double blind trials have shown that preparations containing Vitex agnus castus fruit extract are a useful tool to decrease pathophysiologicaly increased prolactin serum levels and though could be an effective treatment for women suffering from premenstrual syndrome.

Drug-induced sexual dysfunction.

PubMed

Aldridge, S A

1982-01-01

Commonly used drugs that may cause sexual dysfunction are reviewed. The anatomy and physiology of the normal sexual response are reviewed. The influence of drugs on neurogenic, hormonal, and vascular mechanisms may result in diminished libido, impotence, ejaculatory and orgasmic difficulties, inhibited vaginal lubrication, menstrual irregularities, and gynecomastia in men or painful breast enlargement in women. Parasympatholytic agents, which interfere with cholinergic transmission, may affect erectile potency, while adrenergic inhibiting agents may interfere with ejaculatory control. Central nervous system depressants or sedating drugs, drugs producing hyperprolactinemia, and antiandrogenic drugs also may affect the normal sexual response. Drugs such as antihypertensive and antipsychotic agents may induce sexual dysfunction that can result in patient noncompliance. Usually, drug-induced side effects are reversible with discontinuation of the offending agent.

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.

Role of Prolactin in the Regulation of Bicarbonates Biodynamics in Female Rat Model of Cholestasis of Pregnancy.

PubMed

Bulaeva, O A; Abramicheva, P A; Balakina, T A; Smirnova, O V

2017-03-01

We studied possible involvement of prolactin in the regulation of bicarbonate biodynamics using female rat model of cholestasis of pregnancy induced by transplantation of the donor pituitary under the renal capsule of a recipient (hyperprolactinemia) and bile duct ligation (cholestasis). The concentration of bicarbonates in the bile and blood, their excretion, clearance, and reabsorption, as well as glomerular filtration rate and excretion of sodium ions were assessed. It was found that the main effect of prolactin was directed to the kidney-regulated pool of bicarbonates and consisted in stimulation of their clearance and inhibition of reabsorption, which led to a decrease in bicarbonate blood concentration. Parallel influence of prolactin on the clearance of bicarbonates and sodium ions was observed.

A case of atypical McCune-Albright syndrome requiring optic nerve decompression.

PubMed

Yavuzer, R; Khilnani, R; Jackson, I T; Audet, B

1999-10-01

McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of café-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented.

Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro

PubMed Central

Ye, Qi; Zhang, Qiao-yan; Zheng, Cheng-jian; Wang, Yang; Qin, Lu-ping

2010-01-01

Aim: To investigate the anti-hyperprolactinemia activity of casticin, a flavonoid isolated from Vitex rotundifolia, and elucidate its molecular mechanism. Methods: Hyperprolactinemia (MIHP) was induced by administration of metoclopramide dihydrochloride (50 mg/kg, tid, ip, for 10 d) in SD rats and the primary pituitary cells were prepared from the pituitary glands of the SD rats. Prolactin concentrations were measured using a radioimmunoassay. Cell viability was measured using an MTT assay. The mRNA expression of estrogen receptor alpha and beta in rat pituitary cells was measured using semi-quantitative RT-PCR analysis. Results: The level of serum prolactin in the MIHP model group was 2.1 fold higher than that in the untreated control group (P<0.01). Casticin (10, 20, and 40 mg/kg, ip, for 7 d) reduced serum prolactin levels by 33.9%, 54.3%, and 64.7%, respectively (P<0.01). The positive control drug bromocriptine 1 mg/kg decreased the serum prolactin concentration in MIHP rats by 44.9%. 17β-Estradiol (E2) significantly increased the proliferation of pituitary cells and casticin (1 and 10 μmol/L) markedly inhibited E2-induced pituitary cell proliferation by 27.7% and 42.1%, respectively. Stimulation of pituitary cells with E2 increased prolactin secretion into the cell culture supernatants, and casticin (0.1, 1, and 10 μmol/L) significantly inhibited the prolactin release stimulated by E2 in a concentration-dependent manner. Casticin (1 and 10 μmol/L) significantly inhibited ERα mRNA expression in pituitary cells stimulated with E2 (P<0.01) but increased ERβ mRNA expression at a concentration of 10 μmol/L (P<0.01). However, casticin had no effects on proliferation and prolectin release of the unstimulated primary pituitary cells in vitro. Conclusion: Casticin inhibited the release of prolactin from pituitary cells of SD rats stimulated with E2 in vivo and in vitro. These effects might be related with inhibiting the ERα mRNA expression and increasing the ERβ mRNA expression. PMID:21042288

SERUM LEVELS OF FIBROBLAST GROWTH FACTOR-23, OSTEOPROTEGERIN, AND RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B LIGAND IN PATIENTS WITH PROLACTINOMA.

PubMed

Arslan, Muyesser Sayki; Sahin, Mustafa; Karakose, Melia; Tutal, Esra; Topaloglu, Oya; Ucan, Bekir; Demirci, Taner; Caliskan, Mustafa; Ozdemir, Seyda; Ozbek, Mustafa; Cakal, Erman

2017-03-01

The aim of this study to was to evaluate the effect of fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), receptor activator nuclear κB ligand (RANKL), and vitamin D hormones on bone loss in patients with hyperprolactinemia due to pituitary prolactinoma. We recruited 46 premenopausal female patients with prolactinoma and age and sex-matched healthy controls (Group 3, n = 20) for this cross-sectional study. Prolactinoma patients were divided into 2 groups as patients newly diagnosed (Group 1, n = 26) and those under cabergoline treatment (Group 2, n = 20). Anthropometric and metabolic variables; hormonal profiles; and osteocalcin, deoxypyridinoline (DOP), and bone mineral density measurements were performed for all participants. FGF-23, OPG, and RANKL levels were analyzed in all groups. FGF-23, OPG, calcium, phosphorus, and parathormone levels were similar between all groups despite significantly higher levels in the control group in terms of vitamin D and RANKL levels than in patients. Bone loss was found more in Group 2, particularly observed in Z scores of femur and spinal bone (P<.05). Correlation analysis revealed a negative correlation between FGF-23 and femur neck T score (r = -0.0433, P = .05) in patients with active prolactinoma. A positive correlation was also observed between parameters of DOP and OPG (r = 0.673, P = .02). In patients with remission there were a negative correlation between prolactin and luteinizing hormone (r = -600, P = .08). Additionally, a negative correlation was found between osteocalcin and osteoprotegerin in patients in remission (r = -0.73, P = .01). Our data indicated that FGF-23 and OPG levels do not play a critical role on the development of bone decrease in patients with hyperprolactinemia. However, further prospective studies in larger numbers of participants should be designed to clarify this issue. BFP = body fat percentage BMD = bone mineral density BMI = body mass index CV = coefficient of variation DOP = deoxypyridinoline ELISA = enzyme-linked immunosorbent assay FGF-23 = fibroblast growth factor-23 HOMA-IR = homeostatic model assessment of insulin resistance OPG = osteoprotegerin RANKL = receptor activator nuclear κB ligand.

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

PubMed

Mete, Ozgur; Gomez-Hernandez, Karen; Kucharczyk, Walter; Ridout, Rowena; Zadeh, Gelareh; Gentili, Fred; Ezzat, Shereen; Asa, Sylvia L

2016-02-01

Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 μg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our findings argue against the use of the nomenclature 'silent' for these tumors. To better reflect the characteristics of these tumors, we propose that they be classified as 'poorly differentiated Pit-1 lineage adenomas'.

Pyodermia chronica glutealis complicated by acromegalic gigantism.

PubMed

Nishijima, S; Kasahara, M; Suzuki, K; Kondoh, M; Tsubura, A

1998-04-01

We report a case of pyodermia chronica glutealis complicated by acromegalic gigantism associated with hyperprolactinemia. The serum prolactin, growth hormone, adrenocorticotropic hormone, and 11-deoxycortisol levels were elevated, but the estradiol and dehydroepiandrosterone-sulphate levels were within normal limits. However, the testosterone level was very low. Histopathologically, we found sinus tracts and scarring in a specimen from the buttocks. We could not immunohistochemically detect clear androgen, growth hormone, or prolactin receptors at any site. The patient was a man with a height of 197 cm and weight of 140 kg, he had clinical features of active acromegaly such as excessive sweating and increased thickness of soft tissue. He was also diagnosed with diabetes mellitus. Under such conditions, bacteria could easily grow and lesions might have been aggravated by the heavy pressure from his weight, a possible causes of his pyodermia chronica glutealis.

Neuroendocrine Causes of Amenorrhea—An Update

PubMed Central

Fourman, Lindsay T.

2015-01-01

Context: Secondary amenorrhea—the absence of menses for three consecutive cycles—affects approximately 3–4% of reproductive age women, and infertility—the failure to conceive after 12 months of regular intercourse—affects approximately 6–10%. Neuroendocrine causes of amenorrhea and infertility, including functional hypothalamic amenorrhea and hyperprolactinemia, constitute a majority of these cases. Objective: In this review, we discuss the physiologic, pathologic, and iatrogenic causes of amenorrhea and infertility arising from perturbations in the hypothalamic-pituitary-adrenal axis, including potential genetic causes. We focus extensively on the hormonal mechanisms involved in disrupting the hypothalamic-pituitary-ovarian axis. Conclusions: A thorough understanding of the neuroendocrine causes of amenorrhea and infertility is critical for properly assessing patients presenting with these complaints. Prompt evaluation and treatment are essential to prevent loss of bone mass due to hypoestrogenemia and/or to achieve the time-sensitive treatment goal of conception. PMID:25581597

A Rare Cause of Hypothalamic Obesity, Rohhad Syndrome: 2 Cases.

PubMed

Şiraz, Ülkü Gül; Okdemir, Deniz; Direk, Gül; Akın, Leyla; Hatipoğlu, Nihal; Kendırcı, Mustafa; Kurtoğlu, Selim

2018-03-19

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) syndrome is a rare disease that is difficult to diagnosis and distinguish from genetic obesity syndromes. The underlying causes of the disease has not been fully explained. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction and autonomic alterations. There are around 80 reported patients due to lack of recognition. We present two female patient suspected of ROHHAD due to weight gain since early childhood. The presented symptoms, respiratory and circulatory dysfunction, hypothalamic hypernatremia, hypothalamo-pituitary hormonal disorders such as santral hypothyrodism, hyperprolactinemia and santral early puberty are completely matched the criteria of ROHHAD syndrome. ROHHAD syndrome should be considered in differential diagnosis since it is difficult to distinguish from causes of monogenic obesity. Early identification of the disease reduces morbidity of the syndrome and patients require regular follow-up by a multidisciplinary approach.

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity

PubMed Central

Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih

2014-01-01

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction. PMID:25541898

ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity.

PubMed

Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih

2014-12-01

A very rare syndrome of rapid-onset obesity with hypoventilation, hypothalamic dysfunction and autonomic dysregulation (ROHHAD) has been recently described as causing morbidity due to hypothalamic dysfunction and respiratory arrest. Its prognosis is poor and often cardiac arrest occurs due to alveolar hypoventilation. This disorder can mimic genetic obesity syndromes and several endocrine disorders. We present a 13-year-old female patient who was reported to be healthy until the age of 3 years. She was admitted to our emergency department, presenting with respiratory distress. Features matching ROHHAD syndrome such as rapid-onset obesity, alveolar hypoventilation, central hypothyroidism, hyperprolactinemia, Raynaud phenomenon and hypothalamic hypernatremia were detected in the patient. In addition to these features, the patient was found to have hypergonadotropic hypogonadism and megaloblastic anemia. Because of its high mortality and morbidity, the possibility of ROHHAD syndrome needs to be considered in all pediatric cases of early- and rapid-onset obesity associated with hypothalamic-pituitary endocrine dysfunction.

Zero gravity and cardiovascular homeostasis. The relationship between endogenous hyperprolactinemia and plasma aldosterone

NASA Technical Reports Server (NTRS)

Haber, E.; Re, R. N.; Kourides, I. A.; Weihl, A. C.; Maloof, F.

1978-01-01

Prolactin, thyrotropin and aldosterone were measured by radioimmunoassay and plasma renin activity by the radioimmunoassay of angiotensin I in normal women before and after the intravenous injection of 200 micrograms of thyrotropin releasing hormone. Prolactin increased at 15 minutes following thyrotropin releasing hormone. Plasma renin activity was not different from control levels during the first hour following the administration of thyrotropin releasing hormone, nor did the plasma aldosterone concentration differ significantly from the control levels during this period. However, with upright posture, an increase in aldosterone and in plasma renin activity was noted, demonstrating a normal capacity to secrete aldosterone. Similarly, no change in aldosterone was seen in 9 patients with primary hypothyroidism given thyrotropin releasing hormone, despite the fact that the increase in prolactin was greater than normal. These data demonstrate that acutely or chronically elevated serum prolactin levels do not result in increased plasma aldosterone levels in humans.

Endocrinology of recurrent pregnancy loss.

PubMed

Arredondo, Francisco; Noble, Luis S

2006-02-01

Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. Although the great majority of pregnant women have no pre-existing endocrine abnormalities, a small number of women can have certain endocrine alterations that could potentially lead to recurrent pregnancy losses. It is estimated that approximately 8 to 12% of all pregnancy losses are the result of endocrine factors. During the preimplantation period, the uterus undergoes important developmental changes stimulated by estrogen, and more importantly, progesterone. Progesterone is essential for the successful implantation and maintenance of pregnancy. Therefore, disorders related to inadequate progesterone secretion by the corpus luteum are likely to affect the outcome of the pregnancy. Luteal phase deficiency, hyperprolactinemia, and polycystic ovarian syndrome are some examples. Several other endocrinological abnormalities such as thyroid disease, hypoparathyroidism, uncontrolled diabetes, and decreased ovarian reserve have been implicated as etiologic factors for recurrent pregnancy loss.

The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

PubMed

Arnold, Edith; Thebault, Stéphanie; Baeza-Cruz, German; Arredondo Zamarripa, David; Adán, Norma; Quintanar-Stéphano, Andrés; Condés-Lara, Miguel; Rojas-Piloni, Gerardo; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2014-01-29

Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

PubMed

Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

A review of dopamine agonist therapy in type 2 diabetes and effects on cardio-metabolic parameters.

PubMed

Lamos, E M; Levitt, D L; Munir, K M

2016-02-01

Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long-acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Endocrine dysfunction and recurrent spontaneous abortion: An overview

PubMed Central

Kaur, Ramandeep; Gupta, Kapil

2016-01-01

Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15–20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20th week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus. PMID:27127734

Cystic Mammary Adenocarcinoma Associated with a Prolactin-secreting Pituitary Adenoma in a New Zealand White Rabbit (Oryctolagus cuniculus)

PubMed Central

Sikoski, Paul; Trybus, James; Cline, J Mark; Muhammad, F Salih; Eckhoff, Andrew; Tan, Josh; Lockard, Mandy; Jolley, Tammy; Britt, Susan; Kock, Nancy D

2008-01-01

A 44-mo-old, female, nulliparous New Zealand White Rabbit (Oryctolagus cuniculus) presented with bilaterally diffusely enlarged mammary glands with enlarged, discolored teats that exuded brown, mucoid discharge. The complete blood count and serum chemistry panels were within normal limits, bacteria were not isolated from a culture of the discharge, and the clinical signs did not resolve with antibiotic treatment. Computed tomography and serum prolactin levels supported the diagnosis of mammary gland dysplasia, possibly due to a prolactin-secreting pituitary adenoma. Histologic evaluation confirmed the presence of a pituitary adenoma, mammary hyperplasia, dysplasia, and cystic mammary adenocarcinoma. Immunohistochemical staining confirmed the presence of abundant prolactin secreting cells in the pituitary adenoma. This is the second report of hyperprolactinemia with mammary dysplasia in rabbits, and the first report of cystic mammary adenocarcinoma associated with a prolactin-secreting pituitary adenoma in a rabbit. PMID:18589874

Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg.

PubMed

Ipekci, S H; Cakir, M; Kiyici, A; Koc, O; Artac, M

2015-07-01

Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

[Hormones and hair growth].

PubMed

Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

PubMed

Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

2007-02-01

Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

[Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress].

PubMed

Strizhkov, V V

1991-01-01

A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.

A Rare Case of Gestational Gigantomastia with Hypercalcemia: The Challenges of Management and Follow up

PubMed Central

Moazzami, Bahram; Chaichian, Shahla; Farahvash, Mohammad Reza; Taheri, Saeedeh; Ahmadi, Seyed Ali; Mokhtari, Majid; Sheibani, Kourosh

2016-01-01

Background: Gigantomastia is a breast disorder marked by exaggerated rapid growth of the breasts, generally bilaterally. Since this disorder is very rare and has been reported only in sparse case reports its etiology has yet to be fully established. Treatment is aimed at improving the clinical and psychological symptoms and reducing the treatment side effects; however, the best therapeutic option varies from case to case. Case Presentation: The present report described a case of gestational gigantomastia in a 30-year-old woman, gravida 2, parity 1, 17 week pregnant admitted to Pars Hospital, Tehran, Iran, on May 2014. The patient was admitted to hospital at week 17 of pregnancy, although her breasts initially had begun to enlarge from the first trimester. The patient developed hypercalcemia in her 32nd week of pregnancy. The present report followed this patient from diagnosis until the completion of treatment. Conclusion: Although gestational gigantomastia is a rare condition, its timely prognosis and careful examination of some conditions like hyperprolactinemia and hypercalcemia is essential in successful management of this condition. PMID:27921004

Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence?

PubMed Central

2008-01-01

There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia. PMID:18830450

Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence?

PubMed

Carmichael, A R

2008-09-01

There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.

The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity

PubMed Central

2014-01-01

Bisphenol A (BPA) is a monomer found in commonly used consumer plastic goods. Although much attention in recent years has been placed on BPA's impact as an endocrine disruptor, it also appears to activate many immune pathways involved in both autoimmune disease development and autoimmune reactivity provocation. The current scientific literature is void of research papers linking BPA directly to human or animal onset of autoimmunity. This paper explores the impact of BPA on immune reactivity and the potential roles these mechanisms may have on the development or provocation of autoimmune diseases. Potential mechanisms by which BPA may be a contributing risk factor to autoimmune disease development and progression include its impact on hyperprolactinemia, estrogenic immune signaling, cytochrome P450 enzyme disruption, immune signal transduction pathway alteration, cytokine polarization, aryl hydrocarbon activation of Th-17 receptors, molecular mimicry, macrophage activation, lipopolysaccharide activation, and immunoglobulin pathophysiology. In this paper a review of these known autoimmune triggering mechanisms will be correlated with BPA exposure, thereby suggesting that BPA has a role in the pathogenesis of autoimmunity. PMID:24804084

Granulomatous Lobular Mastitis Following Drug-Induced Galactorrhea and Blunt Trauma.

PubMed

Cserni, Gábor; Szajki, Károly

1999-11-01

We report a single case of chronic granulomatous lobular mastitis following metoclopramide-related galactorrhea and a blunt trauma in a young parous woman who underwent two conservative operations before becoming symptom-free. We have found only two other literature cases associated with hyperprolactinemia, and our case could be another of this etiologic group. The absence of well-formed granulomas in the first histology specimen in the present case was misleading; it was reinterpreted as granulomatous mastitis only after the second specimen was examined. Reinterpretation was based on the lobular distribution of a lymphoplasmocytic infiltrate (nonspecific chronic lobulitis) and the presence of epithelioid cell sheets and neutrophils in the absence of well-formed granulomas. The case lends further support to the theory of a local immune response initiated by the secreted material or by one of its components in the formation of granulomas. However, contributory factors such as the trauma in this case (a blow from a shovel handle) or systemic disease in others may play a role in the development of the disease, which in some instances may represent a pattern of tissue reactions to different noxious agents.

From Folklore to Scientific Evidence: Breast-Feeding and Wet-Nursing in Islam and the Case of Non-Puerperal Lactation

PubMed Central

Moran, Lia; Gilad, Jacob

2007-01-01

Breast-feeding practice has an important medical and socio-cultural role. It has many anthropological aspects concerning the “power structures” that find their expression in breast-feeding and the practices that formed around it, both socially, scientifically, and legally-speaking. Breast-feeding has been given much attention by religions and taboos, folklore, and misconception abound around it making it a topic of genuine curiosity. This paper aims at expanding the spectrum of folklore associated with breast-feeding. The paper deals with historical, religious, and folkloristic aspects of breast-feeding, especially wet-nursing, in Islam and focuses on an intriguing Islamic tale on breast-feeding - lactation by non-pregnant women (or non-puerperal lactation). Apparently, accounts of non-puerperal lactation are not restricted to Islam but have been documented in various societies and religions throughout centuries. Two medical situations - hyperprolactinemia and induced lactation, appear as possible explanations for this phenomenon. This serves as an excellent example for the value of utilizing contemporary scientific knowledge in order to elucidate the origin, anthropology and evolvement of ancient myth and superstition. PMID:23675050

Endocrinology and physiology of pseudocyesis

PubMed Central

2013-01-01

This literature review on pseudocyesis or false pregnancy aims to find epidemiological, psychiatric/psychologic, gynecological and endocrine traits associated with this condition in order to propose neuroendocrine/endocrine mechanisms leading to the emergence of pseudocyetic traits. Ten women from 5 selected studies were analyzed after applying stringent criteria to discriminate between cases of true pseudocyesis (pseudocyesis vera) versus delusional, simulated or erroneous pseudocyesis. The analysis of the reviewed studies evidenced that pseudocyesis shares many endocrine traits with both polycystic ovarian syndrome and major depressive disorder, although the endocrine traits are more akin to polycystic ovarian syndrome than to major depressive disorder. Data support the notion that pseudocyetic women may have increased sympathetic nervous system activity, dysfunction of central nervous system catecholaminergic pathways and decreased steroid feedback inhibition of gonadotropin-releasing hormone. Although other neuroendocrine/endocrine pathways may be involved, the neuroendocrine/endocrine mechanisms proposed in this review may lead to the development of pseudocyetic traits including hypomenorrhea or amenorrhea, galactorrhea, diurnal and/or nocturnal hyperprolactinemia, abdominal distension and apparent fetal movements and labor pains at the expected date of delivery. PMID:23672289

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

Estrogen action and prostate cancer

PubMed Central

Nelles, Jason L; Hu, Wen-Yang; Prins, Gail S

2011-01-01

Early work on the hormonal basis of prostate cancer focused on the role of androgens, but more recently estrogens have been implicated as potential agents in the development and progression of prostate cancer. In this article, we review the epidemiological, laboratory and clinical evidence that estrogen may play a causative role in human prostate cancer, as well as rodent and grafted in vivo models. We then review recent literature highlighting potential mechanisms by which estrogen may contribute to prostate cancer, including estrogenic imprinting and epigenetic modifications, direct genotoxicity, hyperprolactinemia, inflammation and immunologic changes, and receptor-mediated actions. We discuss the work performed so far separating the actions of the different known estrogen receptors (ERs), ERα and ERβ, as well as G-protein-coupled receptor 30 and their specific roles in prostate disease. Finally, we predict that future work in this field will involve more investigations into epigenetic changes, experiments using new models of hormonal dysregulation in developing human prostate tissue, and continued delineation of the roles of the different ER subtypes, as well as their downstream signaling pathways that may serve as therapeutic targets. PMID:21765856

Efficacy, Tolerability, and Safety of Blonanserin in Schizophrenia: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Kishi, Taro; Matsui, Yuki; Matsuda, Yuki; Katsuki, Asuka; Hori, Hikaru; Yanagimoto, Hiroko; Sanada, Kenji; Morita, Kiichiro; Yoshimura, Reiji; Shoji, Yoshihisa; Hagi, Katsuhiko; Iwata, Nakao

2018-03-07

We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. Ten RCTs (n = 1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD = -10.62, 95% CI = -17.67 to -3.560, p = 0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR = 1.373, 95% CI = 1.088-1.734, p = 0.008, NNH = 11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated. © Georg Thieme Verlag KG Stuttgart · New York.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

The prevalence of endocrinopathies among Lebanese women presenting with hirsutism to an endocrine clinic.

PubMed

Zreik, R S; Nasrallah, Mona P

2014-01-01

Hirsutism is a common condition in women characterized by excessive growth of terminal hair in a male pattern distribution. It may be a manifestation of underlying pathologies. Since there is no data published about the prevalence of endocrinopathies among hirsute women in Lebanon, this study's aim was to reveal the most common etiologies of hirsutism in this population. The study is a descriptive review of cases of 160 females with hirsutism presenting to a single endocrinologist clinic. Data about history, physical exam, blood tests and imaging results were collected after review of medical charts. Out of the 160 cases reviewed, 14 females (8.8%) were left undiagnosed. Out of 146 subjects diagnosed, 72.6% were found to have polycystic ovary syndrome (PCOS), 18.5% idiopathic hirsutism (IH), 4.6% non-classic congenital adrenal hyperplasia, 2.6% hyperprolactinemia, 0.6% Cushing's syndrome and 0.6% hypothyroidism. A higher percentage of irregular menses and a trend for overweight were found among the PCOS group. PCOS remains the most common cause of hirsutism in an endocrine referral clinic, similar to other populations. A low threshold for diagnostic workup is in order, especially when there is associated menstrual irregularity or overweight.

[Impact of end-stage renal disease and kidney transplantation on the reproductive system].

PubMed

Delesalle, A-S; Robin, G; Provôt, F; Dewailly, D; Leroy-Billiard, M; Peigné, M

2015-01-01

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pituitary Tumors in Childhood: an update in their diagnosis, treatment and molecular genetics

PubMed Central

Keil, Margaret F.; Stratakis, Constantine A.

2009-01-01

Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 - 6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments. PMID:18416659

Ovulation disorders: part I anovulation associated with estrogen deficiency.

PubMed

Check, J H

2007-01-01

To describe the diagnosis and treatment of anovulatory disorders associated with estrogen deficiency. Anovulation with estrogen deficiency was divided into two types: association with low vs. high serum gonadotropin levels. Treatments included bromocriptine or cabergoline for hyperprolactinemia and gonadotropins for normal prolactin levels. When gonadotropins were low, lowering the elevated serum FSH to restore down-regulated FSH receptors in the few remaining follicles with either ethinyl estradiol or GnRH agonists or antagonists was used. High serum FSH was followed by either close observation for spontaneous follicular maturation or low dose gonadotropin stimulation. Progesterone supplementation, especially by vaginal use, was given in the luteal phase. Though success in ovulation induction and pregnancies was greater in women with low FSH than high FSH, pregnancies following ovulation induction were nevertheless achieved even in women in apparent menopause. The use of ethinyl estradiol as opposed to other estrogen drugs has the advantage of not being able to be measured by most serum assays for estradiol allowing the physician to detect endogenous follicular development and thus determining when follicular maturation has been achieved. Even in the presence of marked diminished ovarian egg reserve, eggs from chronically younger women are superior in quality to women aged > or = 45.

Early effects of cranial irradiation on hypothalamic-pituitary function

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

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

Polycystic ovarian disease: contribution of vaginal endosonography and reassessment of ultrasonic diagnosis.

PubMed

Ardaens, Y; Robert, Y; Lemaitre, L; Fossati, P; Dewailly, D

1991-06-01

We evaluated the superiority of vaginal ultrasonography (US) on the abdominal US for the diagnosis of polycystic ovarian disease (PCOD). The US pattern of ovaries was prospectively investigated by abdominal US and, whenever possible, by vaginal US. Primary care, institutional. One hundred forty-four women in whom PCOD was suspected on endocrine grounds and 62 other patients presenting with primary hyperprolactinemia (n = 23) or hypothalamic anovulation (n = 39). Vaginal US allowed a better analysis of the ovarian stroma. The external ovarian features of PCOD were observed by both routes in less than one third of the 144 patients with PCOD. The internal ovarian features of PCOD were much more frequently observed by vaginal US than by abdominal US (polycystic pattern: 66.7% versus 38.1%, P less than 0.05; increased ovarian stroma: 57.1% versus 4.8%, P less than 0.001). In the 62 patients without PCOD, US features of PCOD were observed in less than 10% of them, except for the uterine width/ovarian length ratio less than 1 and the polycystic pattern (abdominal US: 17% and 34%; vaginal US: 11% and 50%, respectively). An increased ovarian stroma seems to be the most sensitive and specific US sign of PCOD, providing that it can be investigated by vaginal US.

Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies.

PubMed

Hull, M G

1987-09-01

The frequency of polycystic ovarian disease (PCOD) as a cause of oligo-amenorrhea and infertility was determined, first by characterizing clinically occult PCOD using endocrinological methods, and secondly by estimating the frequency of overt and occult PCOD amongst infertile women residing in a particular area. Four groups of infertile women with oligo-amenorrhea due to 'functional' disorder were compared. The results show that by contrast with the groups having hyperprolactinemia or hypothalamic disorder the group with hirsutism (and therefore presumed PCOD) was closely resembled by a non-hirsute group in terms of estrogenization, LH level, LH/FSH ratio, prolactin level, body mass and responsiveness to clomiphene. The last group was therefore concluded to have a mild occult form of PCOD. The population studies revealed, first, that overt and occult PCOD accounted for 90% of patients with oligomenorrhea and 37% with amenorrhea, or 73% with oligo- or amenorrhea. Oligo- or amenorrhea accounted for 21% of couples with infertility and the annual incidence was 247 patients per million of the general population. The annual incidence of infertility due to PCOD per million was 41 with overt PCOD and 139 with occult PCOD (total 180). Of those, 140 appeared to respond well to clomiphene (78%) but 40 (22%) failed, requiring alternative therapy.

Prolactin and breast cancer: The need to avoid undertreatment of serious psychiatric illnesses in breast cancer patients: A review.

PubMed

Froes Brandao, Denise; Strasser-Weippl, Kathrin; Goss, Paul E

2016-01-15

Hyperprolactinemia, defined as a sustained elevation of prolactin (PRL) levels greater than 530 mIU/L in women and greater than 424 mIU/L in men, has been implicated for a long time in breast cancer etiology and prognosis. Elevated PRL values (approximately 2-3 times higher than the reference values) are a common adverse effect of antipsychotic medications, especially with first-generation drugs, and most antipsychotics carry a standard warning regarding PRL elevations on their US product labels. These associations foster undertreatment of serious psychiatric illnesses in both otherwise healthy patients and cancer patients. This review assesses both the preclinical and clinical evidence that has led to the hypothesis of PRL's role in breast cancer risk or breast cancer progression. It is concluded that taken together, the published data are unconvincing and insufficient to deprive cancer patients in general and breast cancer patients specifically of potentially effective antipsychotic or antidepressant medications for serious psychiatric indications. We thus call on revised medication guidelines to avoid the existing undertreatment of serious psychiatric illnesses among cancer patients based on an unproven contraindication to psychiatric medications. Cancer 2016;122:184-188. © 2015 American Cancer Society. © 2015 American Cancer Society.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

PubMed

Zajdel, Paweł; Kos, Tomasz; Marciniec, Krzysztof; Satała, Grzegorz; Canale, Vittorio; Kamiński, Krzysztof; Hołuj, Małgorzata; Lenda, Tomasz; Koralewski, Robert; Bednarski, Marek; Nowiński, Leszek; Wójcikowski, Jacek; Daniel, Władysława A; Nikiforuk, Agnieszka; Nalepa, Irena; Chmielarz, Piotr; Kuśmierczyk, Justyna; Bojarski, Andrzej J; Popik, Piotr

2018-02-10

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D 2 receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT 1A R agonism, 5-HT 2A /5-HT 7 /D 2 /D 3 R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A functional thyrotropin- and growth hormone-secreting pituitary adenoma with a ultrastructurally monomorphic feature: a case study.

PubMed

Ozawa, Y; Kameya, T; Kasuga, A; Naritaka, H; Kanda, N; Maruyama, H; Saruta, T

1998-04-01

A 38-yr-old female with a TSH- and GH-secreting pituitary adenoma is described, who had both overt symptoms, hyperthyroidism and acromegaly. Her serum TSH was not suppressed despite high concentrations of free T3 and free T4, and her alpha-subunit/TSH molar ratio was high. Her serum GH was consistently high, and was not suppressed by an oral glucose tolerance test. Preoperative testing revealed that, although the TSH response was impaired, TSH, alpha-subunit and GH were increased by TRH injection, and that these hormones were reduced by bromocriptine or somatostatin analog. Although she did not have hyperprolactinemia, the in vitro culture and immunohistochemical studies revealed that the adenoma cells produced and released PRL, in addition to TSH, alpha-subunit and GH. Immunohistochemical studies showed the presence of GH in the cytoplasm of many adenoma cells. TSH beta-positive adenoma cells were less frequently seen than GH-positive adenoma cells. No cells showed the coexistence of GH and TSH beta, and a few cells were positive for PRL. By electron microscopy, the adenoma was found to be composed of a single cell type resembling thyrotrophs, and did not have any characteristics of somatotrophs. This case was considered to be of interest, because the adenoma was ultrastructurally monomorphous, but immunohistochemically polymorphous.

Xanthomatous Hypophysitis Presenting with Diabetes Insipidus Completely Cured Through Transsphenoidal Surgery: Case Report and Literature Review.

PubMed

Lin, Wei; Gao, Lu; Guo, Xiaopeng; Wang, Wenze; Xing, Bing

2017-08-01

Xanthomatous hypophysitis (XH) is extremely rare. Only 27 cases have been reported in the literature. No XH patient presenting with diabetes insipidus (DI) has been completely cured through surgery. Here, we describe the first XH case of a DI patient whose pituitary function was normalized postoperatively, without hormone replacement therapy. A 41-year-old woman suffered from polydipsia, DI, headache, and breast discharge. Laboratory investigation revealed hyperprolactinemia. Pituitary magnetic resonance imaging showed a 2.0-cm × 1.4-cm × 1.6-cm lesion that demonstrated heterogeneous intensity on T1-weighted imaging and peripheral ring enhancement following contrast; the lesion was totally removed through transsphenoidal surgery. Histopathologic and immunohistochemical examinations confirmed the diagnosis of XH. At the 4- and 15-month follow-up visits, all pituitary-related hormones were normal, and the patient was not taking medication. A repeat pituitary magnetic resonance imaging showed no evidence of recurrence. To the best of our knowledge, this case is the first documented occurrence of XH with DI completely cured through surgery. If XH is suspected, total surgical resection of the lesion is recommended and normal pituitary tissue should be carefully protected intraoperatively. Copyright © 2017 Elsevier Inc. All rights reserved.

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

PubMed

Horvath, E; Kovacs, K; Smyth, H S; Cusimano, M; Singer, W

2005-01-01

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

Prolactin and Autoimmunity

PubMed Central

Borba, Vânia Vieira; Zandman-Goddard, Gisele; Shoenfeld, Yehuda

2018-01-01

The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood. PMID:29483903

Prolactin and Autoimmunity.

PubMed

Borba, Vânia Vieira; Zandman-Goddard, Gisele; Shoenfeld, Yehuda

2018-01-01

The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood.

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes

PubMed Central

Cristina, Carolina; Díaz-Torga, Graciela S; Goya, Rodolfo G; Kakar, Sham S; Perez-Millán, María I; Passos, Vanessa Q; Giannella-Neto, Daniel; Bronstein, Marcello D; Becu-Villalobos, Damasia

2007-01-01

Background Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis. PMID:17222350

Intrasellar cysticercosis: a systematic review.

PubMed

Del Brutto, Oscar H; Del Brutto, Victor J

2013-09-01

The objective of this study was to review patients with intrasellar cysticercosis to outline the features of this form of neurocysticercosis. A MEDLINE and manual search of patients with intrasellar cysticercosis were done. Abstracted data included clinical manifestations, neuroimaging findings, therapy, and outcome. Twenty-three patients were reviewed. Ophthalmological disturbances, including diminution of visual acuity and visual field defects following a chiasmatic pattern, were recorded in 67 % of cases. Endocrine abnormalities were found in 56 % of patients (panhypopituitarism, hyperprolactinemia, diabetes insipidus, and isolated hypothyroidism). In addition, some patients complained of seizures or chronic headaches. Neuroimaging studies showed lesions confined to the sellar region in 47 % of cases. The remaining patients also had subarachnoid cysts associated or not with hydrocephalus, parenchymal brain cysts, or parenchymal brain calcifications. Thirteen patients underwent surgical resection of the sellar cyst through a craniotomy in nine cases and by the transsphenoidal approach in four. Visual acuity or visual field defects improved in only two of these patients. Five patients were treated with cysticidal drugs without improvement. Intrasellar cysticercosis is rare and probably under-recognized. Clinical manifestations resemble those caused by pituitary tumors, cysts, or other granulomatous lesions. Neuroimaging findings are of more value when intrasellar cysts are associated with other forms of neurocysticercosis, such as basal subarachnoid cysts or hydrocephalus. Prompt surgical resection is mandatory to reduce the risk of permanent loss of visual function. There seems to be no role for cysticidal drug therapy in these cases.

PROLACTIN LEVELS DO NOT RISE AMONG TRANSGENDER WOMEN TREATED WITH ESTRADIOL AND SPIRONOLACTONE.

PubMed

Bisson, Jason R; Chan, Kelly J; Safer, Joshua D

2018-04-30

Existing transgender treatment guidelines suggest that for transfeminine hormone treatment there is a need to monitor prolactin levels. Also, recent studies suggest that use of cyproterone acetate as an adjunctive anti-androgen during transgender hormone treatment may elevate serum prolactin. We sought to determine whether the reported relationship between transfeminine estradiol treatment and hyperprolactinemia would be evident when the regimen used spironolactone as the adjunctive anti-androgen. Estradiol levels, testosterone levels, prolactin levels, and BMI as well as prescribed spironolactone dosage were extracted from the electronic medical records of 98 de-identified transgender women treated with estrogen therapy at the Endocrinology Clinic at Boston Medical Center. Up to 6 years of data were available for some patients. We found no statistically significant relationship between prolactin and any of the other measures. No estrogen dose associated elevations in prolactin were found. None of the patients were diagnosed with prolactinoma. Our data suggest that there may be no significant rise in prolactin when transgender women are treated with estrogen along with spironolactone as the adjunct anti-androgen, and that it may be unnecessary to monitor prolactin in women on this treatment combination. BMI = body mass index; BMC = Boston Medical Center; HT = hormone therapy; ENIGI = European Network for the Investigation of Gender Incongruence; E2 = estradiol; LCMS/MS = liquid chromatography tandem mass spectrometry; T = testosterone.

Toxicological assessment of drugs that affect the endocrine system in puberty-related disorders.

PubMed

Maranghi, Francesca; Tassinari, Roberta; Mantovani, Alberto

2013-10-01

Toxicologists must ensure that clinical risk-to-benefit analysis should be made both for genders and age groups, with any treatment. Puberty concerns physiological changes leading to organism's maturation. Pubertal growth disorders are increasing in last decades: besides causing physical and psychological distress, they may signal underlying endocrine-metabolic abnormalities with serious health consequences later on. Therapeutic approaches for some health conditions in childhood and adolescence are considered. The authors discuss how some diseases and treatments can impact pubertal growth. The authors look at particular immunological disorders such as asthma and how both the disease and treatment affects pubertal growth. They also discuss how the provision of available data can help to assess the dose-response of the drug, in these cases, and minimize the chance of side effects. The authors also discuss pediatric inflammatory bowel disease and how both the disease and treatment can mitigate the growth delay. Last, but not least, the authors discuss how the effects of the drugs used in the treatment of psychiatric disorders may accentuate endocrine issues in juvenile patients. Hyperprolactinemia induction by some antipsychotics is highlighted as an example. Appropriate risk-benefit analysis of drugs prescribed during childhood and adolescence and intended to be used in the long term is required. Furthermore, future treatment strategies and safer compounds development should be supported by the knowledge of mechanisms underlying adverse side effects in pubertal growth and development.

Prolactin-Producing Pituitary Carcinoma, Hypopituitarism, and Graves' Disease-Report of a Challenging Case and Literature Review.

PubMed

Bettencourt-Silva, Rita; Pereira, Josué; Belo, Sandra; Magalhães, Daniela; Queirós, Joana; Carvalho, Davide

2018-01-01

The diagnosis of pituitary carcinoma is very rare, requires the evidence of metastatic disease, and has a poor overall survival. Malignant prolactinoma frequently requires dopamine agonist therapy, pituitary surgery, radiotherapy, and even chemotherapy. A 19-year-old female presented with galactorrhea, primary amenorrhea, and left hemianopsia. Complementary study detected hyperprolactinemia and a pituitary macroadenoma with cavernous sinus invasion and suprasellar growth. She was treated with cabergoline and bromocriptine without clinical or analytical improvement. Resection of the pituitary lesion was programmed and a non-contiguous lesion of the nasal mucosa was detected during the approach. This metastasis led to the diagnosis of prolactin-producing pituitary carcinoma. After partial resection, the patient was submitted to radiotherapy for residual disease with persistent symptoms. She developed growth hormone deficiency, central hypothyroidism, hypogonadism, and permanent diabetes insipidus. Six years later she was admitted for the suspicion of secondary adrenal insufficiency and thyrotoxicosis. Physical findings, laboratory data, thyroid ultrasound, and scintigraphy achieved the diagnosis of Graves' disease and hypocortisolism. She was treated with hydrocortisone and methimazole, but central hypothyroidism recurred after antithyroid drug withdrawal. Nine years after the diagnosis of a pituitary carcinoma, she maintains treatment with bromocriptine, has a locally stable disease, with no metastases. This report highlights an unusual presentation of a prolactin-producing pituitary carcinoma in a young female. The patient had multiple hormone deficiencies due to a pituitary lesion and treatments. The posterior development of hyperthyroidism and adrenal insufficiency brought an additional difficulty to the approach.

[Reproduction, endocrine disorders and celiac disease: risk factors of osteoporosis].

PubMed

Stazi, A V; Trinti, B

2006-04-01

In genetically predisposed individuals, celiac disease (CD) is permanent intolerance to gluten. Besides the overt enteropathy, there are clinical and subclinical forms which appear later in life; target organs include liver, thyroid, skin and reproductive systems. CD interference is related to the different concurrent genetic-environmental factors, showing multifactorial nature. CD induces malabsorption with consequent deficiencies of micronutrients essential for organogenesis, spermatogenesis and bone structure, such as vitamin D and calcium. In fact, among extraintestinal manifestations of CD, osteoporosis deserves attention because it can be a sign of silent CD. In celiac patients' serum, cytochinic imbalance related to bone loss is present; in vitro these sera act on the osteoblastic activity. The IL-1b is also present in celiac patients' relatives, confirming the genetic predisposition to its etiopathogenesis which is also regulated by endocrine-environmental factors. In females, CD acts indirectly on the bone, determining early menopause and amenorrhea. Even frequent pregnancies and long periods of lactation can bring to bone loss; in such periods, silent CD can appear, suggesting the presence of endocrine-immunology factors. In celiac males, osteoporosis presence, besides calcium and vitamin D deficiencies, is associated to growth hormone deficit and hypogonadism, which is related to hyperprolactinemia, endocrine factors which affect the reproduction. Osteoporosis is relevant among the elderly and vitamin D and calcium supplementations are important to people diagnosed with CD later in life. Thus, to prevent damages such as osteoporosis, early CD screening among people with reproductive problems is necessary.

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma

PubMed Central

Khare, Shruti; Lila, Anurag R.; Patil, Rishikesh; Phadke, Milind; Kerkar, Prafulla; Bandgar, Tushar; Shah, Nalini S.

2017-01-01

Background: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. Objective: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. Design: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. Results: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. Conclusion: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure. PMID:28217516

Circulating Prolactin Associates With Diabetes and Impaired Glucose Regulation

PubMed Central

Wang, Tiange; Lu, Jieli; Xu, Yu; Li, Mian; Sun, Jichao; Zhang, Jie; Xu, Baihui; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Ning, Guang

2013-01-01

OBJECTIVE Prolactin is a major stimulus for the β-cell adaptation during gestation and guards postpartum women against gestational diabetes. Most studies of the role of prolactin on glucose metabolism have been conducted in humans and animals during pregnancy. However, little is known concerning the association between circulating prolactin and glucose metabolism outside pregnancy in epidemiological studies. We aimed to determine whether the variation of circulating prolactin concentration associates with diabetes and impaired glucose regulation (IGR) in a cross-sectional study. RESEARCH DESIGN AND METHODS We recruited 2,377 participants (1,034 men and 1,343 postmenopausal women) without hyperprolactinemia, aged 40 years and older, in Shanghai, China. Diabetes and IGR were determined by an oral glucose tolerance test. Multinomial logit analyses were performed to evaluate the relationship of prolactin with diabetes and IGR. RESULTS Prolactin levels decreased from normal glucose regulation to IGR to diabetes. Multinomial logit analyses, adjusted for potential confounding factors, showed that high circulating prolactin was associated with lower prevalence of diabetes and IGR. The adjusted odds ratios (95% CI) for IGR and diabetes for the highest compared with the lowest quartile of prolactin were 0.54 (95% CI 0.33–0.89) and 0.38 (0.24–0.59) in men and 0.54 (0.36–0.81) and 0.47 (0.32–0.70) in women. CONCLUSIONS High circulating prolactin associates with lower prevalence of diabetes and IGR in the current study. Further studies are warranted to confirm this association. PMID:23340889

[Andrologic consequences of chronic renal failure: State of the art for the yearly scientific report of the French National Association of Urology].

PubMed

Neuzillet, Y; Thuret, R; Kleinclauss, F; Timsit, M-O

2016-11-01

To describe the state of the art of current knowledge regarding gonadal consequences of end-stage chronic kidney disease (CKD) and renal transplantation. A systematic review of the literature search was performed from the databases Medline (NLM, Pubmed) and Embase, focused on the following keywords: "chronic kidney disease"; "chronic renal failure"; "hypogonadism"; "kidney transplantation"; "testicular dysfunction"; "testosterone". Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 383 articles. After reading titles and abstracts, 51 were included in the text, based on their relevance. The prevalence of hypogonadism in CKD is reported between 24 % and 66 %, and decreases partially after renal transplantation. This is a hypogonadotropic hypogonadism whose pathophysiology is multifactorial, involving mainly a primitive testicular deficit, a hypothalamic-pituitary dysregulation, and an hyperprolactinemia. The consequences of this hypogonadism are not only sexual but also contribute to anemia, sarcopenia, atherosclerosis, and potentially in the progression of CKD. Hypogonadism is an independent risk factor for mortality in CKD patients. CKD is frequently associated with an hypogonadism whose correction is validated only in the setting of erectile dysfunction treatment. The other benefits of the correction of hypogonadism in the CKD patients, including overall survival, needs to be evaluated. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation and management of abnormal uterine bleeding in premenopausal women.

PubMed

Sweet, Mary Gayle; Schmidt-Dalton, Tarin A; Weiss, Patrice M; Madsen, Keith P

2012-01-01

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

[Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study].

PubMed

Milewicz, A; Gejdel, E; Sworen, H; Sienkiewicz, K; Jedrzejak, J; Teucher, T; Schmitz, H

1993-07-01

The efficacy of a Vitex agnus castus preparation (Strotan capsules) was investigated in a randomized double blind study vs. placebo. This clinical study involved 52 women with luteal phase defects due to latent hyperprolactinaemia. The daily dose was one capsule (20 mg) Vitex agnus castus preparation and placebo, respectively. Aim of the study was to prove whether the elevated pituitary prolactin reserve can be reduced and deficits in luteal phase length and luteal phase progesterone synthesis be normalized. Blood for hormonal analysis was taken at days 5-8 and day 20 of the menstrual cycle before and after three month of therapy. Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after i.v. injection of 200 micrograms TRH. 37 complete case reports (placebo: n = 20, verum: n = 17) after 3 month of therapy were statistically evaluated. The prolactin release was reduced after 3 months, shortened luteal phases were normalised and deficits in the luteal progesterone synthesis were eliminated. These changes were significant and occurred only in the verum group. All other hormonal parameters did not change with the exception of 17 beta-estradiol which rouse up in the luteal phase in patients receiving verum. Side effects were not seen, two women treated with the Vitex agnus castus preparation got pregnant. The tested preparation is thought to be an efficient medication in the treatment of luteal phase defects due to latent hyperprolactinaemia.

Reproductive disturbances in multiple neuroendocrine tumor syndromes.

PubMed

Lytras, Aristides; Tolis, George

2009-12-01

In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

Statin Medications and the Risk of Gynecomastia.

PubMed

Skeldon, Sean C; Carleton, Bruce; Brophy, James; Sodhi, Mohit; Etminan, Mahyar

2018-06-19

Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (i.e. statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. Case control study. A cohort of patients from a random sample of 9,053,240 US subjects from the PharMetrics Plus ™ health claims database from 2006 to 2016 was created. New cases of gynecomastia requiring at least two ICD-9 codes were identified from the cohort and matched to 10 controls by follow-up time and age using density-based sampling. Rate ratios (RRs) for past users of statins were computed using conditional logistic regression adjusting for alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, obesity, hypogonadism, hyperprolactinemia and use of spironolactone, ketoconazole, H 2 receptor antagonists (H 2 blockers), risperidone, testosterone and androgen deprivation therapy. Our cohort included 6,147 cases of gynecomastia and 61,470 corresponding matched controls. The adjusted RR for current, recent and past statin use with respect to gynecomastia was 1.19 (1.04-1.36), 1.38 (1.15-1.65) and 1.20 (1.03-1.40) respectively. Statin use is associated with an increased risk of developing gynecomastia. Clinicians should be cognizant of this effect and educate patients accordingly. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Convenience clinic redefine polycystic ovary syndrome (Stein-Leventhal)].

PubMed

Zárate-Treviño, Arturo; Hernández-Valencia, Marcelino; Morán, Carlos; Manuel, Leticia; Saucedo, Renata

2014-04-01

In 1935 during a medical meeting behalf in New Orleans was presents a study that included seven cases of women that suffered menstrual dysfunctions, hirsutism and sterility, for laparotomy the description of the ovaries had a pearly white color and it was hypertrophic, the cuneiform resection in both ovaries resulted in correction of the menstrual dysfunction and two of them got pregnancy later on, receiving the name of polycystic ovary syndrome (PCOS). The technological advance facilitates the hormonal analyses demonstrating the hyperandrogenism existence and the mechanism of the anovulation, the PCOS showed to be heterogeneous, reason why it was hindered to define it, this advanced the current trend to question the existence of the PCOS and to accept the convenience, either to change the name or to redefine it, leaving it as a simple syndrome with several phenotypes. The endocrine component includes abnormal secretion of insulin and consequently outlying resistance to this hormone, likewise is hyperandrogenism, dislipoproteinemia and obesity. The hormonal exams are unnecessary for the diagnostic and treatment; it is convenient to demonstrate for sonography the ovarian growth. Other dysfunctions like the congenital suprarenal hyperplasia, hyperprolactinemia and hypotiroidism should be discarded. The treatment should be individualized with relationship to the reason of the consultation and the patients age. It has not been demonstrated that the sensibilitizers use to the insulin avoids long term cardiovascular illness and diabetes. Therefore, the phenotype is heterogeneous with a fickle metabolic component and for it has arisen the restlessness of a better definition of the SPO.

[A not very essential obesity: the Rohhad syndrome. Description of two cases and review of the literature].

PubMed

Ramistella, V; Wasniewska, M; Valenzise, M; Corica, D; Cantucci, S; Pitrolo, E; Romeo, M; De Luca, F

2013-01-01

Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Children typically show ROHHAD after the first years of life with rapid weight gain and subsequently autonomic nervous system dysregulation (altered pain perception, pupillary dysfunction, hypothermia and bradycardia); alveolar hypoventilation with risk of cardiorespiratory arrest and hypothalamic dysfunction (central diabetes insipidus, hypothyroidism, growth hormone and corticotrophin deficiency). Tumours of neural crest origin, such as ganglioneuroblastoma and ganglioneuronoma, are reported in 33% of the patients and may be found in the chest or abdomen. Here we describe two girls who presented with rapid weight gain, at the age of 5 and 9 years respectively. The first was admitted due to obesity and central hypothyroidism. After two months she rapidly developed a clinical picture characterized by thermal dysregulation, hypodipsia and severe hypernatriemia, hypertrigliceridemia, alveolar hypoventilation supported by mechanical ventilation. The second presented with rapid-onset obesity and a mild hyperprolactinemia. After three months of follow-up she was admitted due to a clinical picture of hypothermia, seizures and hyponatremia. Subsequentely she developed altered water balance (severe hypernatremia) and severe hypoventilation. Chest CT and MR imaging showed a posterior mediastinal mass. Endocrinological investigation showed corticotrophin deficiency and central hypothyroidism treated with specific replacement therapies. On the basis of our experiences we can infer that it is necessary perform specific further investigations of hypothalamic function in all the children with rapid onset obesity in order to early prevent the catastrophic consequences that may occur in this syndrome.

Ept7 influences estrogen action in the pituitary gland and body weight of rats.

PubMed

Kurz, Scott G; Dennison, Kirsten L; Samanas, Nyssa Becker; Hickman, Maureen Peters; Eckert, Quincy A; Walker, Tiffany L; Cupp, Andrea S; Shull, James D

2014-06-01

Estrogens control many aspects of pituitary gland biology, including regulation of lactotroph homeostasis and synthesis and secretion of prolactin. In rat models, these actions are strain specific and heritable, and multiple quantitative trait loci (QTL) have been mapped that impact the responsiveness of the lactotroph to estrogens. One such QTL, Ept7, was mapped to RNO7 in female progeny generated in an intercross between BN rats, in which the lactotroph population is insensitive to estrogens, and ACI rats, which develop lactotroph hyperplasia/adenoma and associated hyperprolactinemia in response to estrogen treatment. The primary objective of this study was to confirm the existence of Ept7 and to quantify the impact of this QTL on responsiveness of the pituitary gland of female and male rats to 17β-estradiol (E2) and diethylstilbestrol (DES), respectively. Secondary objectives were to determine if Ept7 influences the responsiveness of the male reproductive tract to DES and to identify other discernible phenotypes influenced by Ept7. To achieve these objectives, a congenic rat strain that harbors BN alleles across the Ept7 interval on the genetic background of the ACI strain was generated and characterized to define the effect of administered estrogens on the anterior pituitary gland and male reproductive tissues. Data presented herein indicate Ept7 exerts a marked effect on development of lactotroph hyperplasia in response to estrogen treatment, but does not affect atrophy of the male reproductive tissues in response to hormone treatment. Ept7 was also observed to exert gender specific effects on body weight in young adult rats.

Ectopic prolactin secretion from a perivascular epithelioid cell tumor (PEComa).

PubMed

Korytnaya, Evgenia; Liu, Jiayan; Camelo-Piragua, Sandra; Sullivan, Stephen; Auchus, Richard J; Barkan, Ariel

2014-11-01

The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor, and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far. A 47-year-old woman presented with amenorrhea and galactorrhea of 3-year duration. Serum prolactin ranged from 300 to > 900 ng/mL, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary magnetic resonance imaging revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/mL), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 × 13 × 8-cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/mL. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor. Between 5 and 10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract, confirming the diagnosis of ectopic prolactin synthesis and secretion. We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/mL and negative sellar MRI.

Preoperative preparation of patients with pituitary gland disorders.

PubMed

Malenković, Vesna; Gvozdenović, Ljiljana; Milaković, Branko; Sabljak, Vera; Ladjević, Nebojsa; Zivaljević, Vladan

2011-01-01

This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.

Three Cases of Hair Loss Analyzed by the Point of View of the Analytical Psychology

PubMed Central

Leite Júnior, Ademir Carvalho; Katzer, Tatiele; Ramos, Denise Gimenez

2017-01-01

Psychotrichology is the science, which covers the psychosomatics applied to hair problems, i.e., body-psyche phenomena involving scalp and hair disorders. The approaches involving psychotricology are varied and may include psychiatric,[1] psychoanalytical,[23] and those involving knowledge related to analytical psychology.[4] An analysis from the analytical psychology point of view, a theory developed by the physician Carl Gustav Jung, favors a symbolic view to the disease, providing it attributions and meanings that go beyond those related to physical body signs and symptoms only. This paper aims to describe and analyze, under the analytical psychology view, three cases the psychic and clinical demonstrations of which relate to symbolic and historic aspects concerning life of patients as possibilities of cause and maintenance of hair problems. The first of them is related to an 8-year-old girl who witnessed a scene of physical aggression by her father against her mother and developed a case of total alopecia. The second case is related to a 43-year-old woman who developed self-inflicted scalp dermatitis due to severe anxiety; and at last, the case of a telogen effluvium in a 23-year-old woman who developed hyperprolactinemia after the death of her mother, having to substitute her in the care about her husband and brothers. Looking at the clinical history and symbolic matters of scalp and hair diseases enabled, in the aforementioned cases, a better understanding of patients' psychoemotional disorders that may be related to the beginning and maintenance of clinical cases presented by them. PMID:29118523

Three Cases of Hair Loss Analyzed by the Point of View of the Analytical Psychology.

PubMed

Leite Júnior, Ademir Carvalho; Katzer, Tatiele; Ramos, Denise Gimenez

2017-01-01

Psychotrichology is the science, which covers the psychosomatics applied to hair problems, i.e., body-psyche phenomena involving scalp and hair disorders. The approaches involving psychotricology are varied and may include psychiatric,[1] psychoanalytical,[23] and those involving knowledge related to analytical psychology.[4] An analysis from the analytical psychology point of view, a theory developed by the physician Carl Gustav Jung, favors a symbolic view to the disease, providing it attributions and meanings that go beyond those related to physical body signs and symptoms only. This paper aims to describe and analyze, under the analytical psychology view, three cases the psychic and clinical demonstrations of which relate to symbolic and historic aspects concerning life of patients as possibilities of cause and maintenance of hair problems. The first of them is related to an 8-year-old girl who witnessed a scene of physical aggression by her father against her mother and developed a case of total alopecia. The second case is related to a 43-year-old woman who developed self-inflicted scalp dermatitis due to severe anxiety; and at last, the case of a telogen effluvium in a 23-year-old woman who developed hyperprolactinemia after the death of her mother, having to substitute her in the care about her husband and brothers. Looking at the clinical history and symbolic matters of scalp and hair diseases enabled, in the aforementioned cases, a better understanding of patients' psychoemotional disorders that may be related to the beginning and maintenance of clinical cases presented by them.

Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis.

PubMed

Montefusco, L; Harari, S; Elia, D; Rossi, A; Specchia, C; Torre, O; Adda, G; Arosio, M

2018-05-01

Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet. Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH. Observational cross-sectional study on 18 adults (7 M/11 F, 42±12years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism. Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO - ) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung + ). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient. The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported. Copyright © 2017. Published by Elsevier B.V.

LH pulses and the corpus luteum: the luteal phase deficiency LPD).

PubMed

Wuttke, W; Pitzel, L; Seidlová-Wuttke, D; Hinney, B

2001-01-01

The proper function of the GnRH pulse generator in the hypothalamus is essential for normal ovarian function, hence also for proper function of the corpus luteum. During the luteal phase LH pulses stimulate progesterone release, which is essential for normal endometrial transformation. Approximately one-half of all luteal phase deficiencies (LPD) are due to improper function of the GnRH pulse generator. Obviously, following ovulation the increased serum progesterone levels oversuppress the GnRH pulse generator, resulting in too few LH pulses and therefore improper luteal function. Also, latent hyperprolactinemia may lead to an LPD which can be effectively treated with plant extracts containing dopaminergic (prolactin-suppressing) compounds. Our increasing knowledge of auto- and paracrine mechanisms between nonsteroidogenic and steroidogenic cells now allow subclassification of LPDs of ovarian origin. The so-called small luteal cells are LH-responsive. If they develop improperly the regularly occurring LH pulses are unable to stimulate progesterone secretion from the small luteal cells, which results in what we call the small luteal cell defect. In addition, there is also evidence that the large luteal cells may function improperly. Hence, basal progesterone release is too low while LH-stimulated progesterone release from the small luteal cells appears to be intact. This subclassification of luteal phase deficiency results in the suggestion of different treatments. In cases where the corpus luteum is LH-responsive, such as the hypothalamic corpus luteum insufficiency and the large luteal cell defect, HCG treatment or pulsatile treatment with GnRH is advisable. In the case of LH/hCG-unresponsive small luteal cell defect a progesterone substitution is suggested.

Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function.

PubMed

Zayour, Dany H; Selman, Warren R; Arafah, Baha M

2004-11-01

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats.

PubMed

Krishna, Gopala; Gopalakrishnan, Gopa; Goel, Saryu

2017-06-01

Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60 mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75 mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.

Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications.

PubMed

Wuttke, W; Jarry, H; Christoffel, V; Spengler, B; Seidlová-Wuttke, D

2003-05-01

Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.

A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines.

PubMed

Weisskopf, M; Schaffner, W; Jundt, G; Sulser, T; Wyler, S; Tullberg-Reinert, H

2005-10-01

Extracts of Vitex agnus-castus fruits (VACF) are described to have beneficial effects on disorders related to hyperprolactinemia (cycle disorders, premenstrual syndrome). A VACF extract has recently been shown to exhibit antitumor activities in different human cancer cell lines. In the present study, we explored the antiproliferative effects of a VACF extract with a particular focus on apoptosis-inducing and potential cytotoxic effects. Three different human prostate epithelial cell lines (BPH-1, LNCaP, PC-3) representing different disease stages and androgen responsiveness were chosen. The action of VACF on cell viability was assessed using the WST-8-tetrazolium assay. Cell proliferation in cells receiving VACF alone or in combination with a pan-caspase inhibitor (Z-VAD-fmk) was quantified using a Crystal Violet assay. Flow cytometric cell cycle analysis and measurement of DNA fragmentation using an ELISA method were used for studying the induction of apoptosis. Lactate dehydrogenase (LDH) activity was determined as a marker of cytotoxicity. The extract inhibited proliferation of all three cell lines in a concentration-dependent manner with IC (50) values below 10 microg/mL after treatment for 48 h. Cell cycle analysis and DNA fragmentation assays suggest that part of the cells were undergoing apoptosis. The VACF-induced decrease in cell number was partially inhibited by Z-VAD-fmk, indicating a caspase-dependent apoptotic cell death. However, the concentration-dependent LDH activity of VACF treated cells indicated cytotoxic effects as well. These data suggest that VACF contains components that inhibit proliferation and induce apoptosis in human prostate epithelial cell lines. The extract may be useful for the prevention and/or treatment not only of benign prostatic hyperplasia but also of human prostate cancer.

Hypothalamic-pituitary sarcoidosis with vision loss and hypopituitarism: case series and literature review.

PubMed

Anthony, Jeremy; Esper, Gregory J; Ioachimescu, Adriana

2016-02-01

Hypothalamic-pituitary (HP) neurosarcoidosis (NS) accounts for 0.5 % cases of sarcoidosis and 1 % of HP masses. Correlative data on endocrine and neurological outcomes is lacking. Retrospective case series and literature review of presentation, treatment and outcome of HP NS. Our series includes 4 men, ages 34-59, followed for a median of 7.3 years (range 1.5-17). All had optic neuropathy, multiple pituitary hormone abnormalities (PHAs) and other organ involvement by sarcoidosis (lung, sino-nasal, brain/spine and facial nerve). Two patients had central diabetes insipidus and one impaired thirst with polydipsia. After treatment with high-dose glucocorticoids, optic neuropathy improved in one case and stabilized in the others. After treatment, HP lesions improved radiologically, but PHAs persisted in all cases. Review of four published series on HP NS in addition to ours yielded 46 patients, age 37 ± 11.8 years, 65 % male. PHAs consisted of anterior hypopituitarism (LH/FSH 88.8 %, TSH 67.4 %, GH 50.0 %, ACTH 48.8 %), hyperprolactinemia (48.8 %) and diabetes insipidus (65.2 %). PHAs were the first sign of disease in 54.3 % patients. Vision problems occurred in 28.3 % patients, but optic neuropathy was not well documented in previous series. Most patients (93.5 %) received high-dose glucocorticoids followed by taper; 50 % also received other immunomodulators, including methotrexate, mycophenolate mofetil, cyclosporine, azathioprine, infliximab and hydrochloroquine. Only 13 % patients showed improvement in PHAs. All-cause mortality was 8.7 %. HP NS is a serious disease requiring multidisciplinary treatment and lifelong follow-up. Prospective multicentric studies are needed to determine a more standardized approach to HP NS and outline predictors of disease outcome.

Hypopituitarism patterns and prevalence among men with macroprolactinomas.

PubMed

Tirosh, Amit; Benbassat, Carlos; Lifshitz, Avner; Shimon, Ilan

2015-02-01

Men with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas. A retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10-19 mm (group A), 20-39 mm (group B), and ≥40 mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment. Eighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9% (p = 0.046; A vs B and C), central hypocortisolism - 0, 6.9 and 33.3% (p = 0.005), and central hypothyroidism - 6.7, 17.9 and 26.1% (NS) in groups A, B and C, respectively. Only 26.7% of all patients presented with hypocortisolism and/or hypothyroidism (42.9% in group C). Anemia (Hb < 13.5 g%) was detected in 31.3, 57.1 and 80.0% in groups A, B and C, respectively (p = 0.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (r = -0.42, p = 0.043). Macroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.

Hypothalamic IGF-I Gene Therapy Prolongs Estrous Cyclicity and Protects Ovarian Structure in Middle-Aged Female Rats

PubMed Central

Rodríguez, Silvia S.; Schwerdt, José I.; Barbeito, Claudio G.; Flamini, Mirta A.; Han, Ye; Bohn, Martha C.

2013-01-01

There is substantial evidence that age-related ovarian failure in rats is preceded by abnormal responsiveness of the neuroendocrine axis to estrogen positive feedback. Because IGF-I seems to act as a permissive factor for proper GnRH neuronal response to estrogen positive feedback and considering that the hypothalamic content of IGF-I declines in middle-aged (M-A) rats, we assessed the effectiveness of long-term IGF-I gene therapy in the mediobasal hypothalamus (MBH) of M-A female rats to extend regular cyclicity and preserve ovarian structure. We used 3 groups of M-A rats: 1 group of intact animals and 2 groups injected, at 36.2 weeks of age, in the MBH with either a bicistronic recombinant adeno-associated virus (rAAV) harboring the genes for IGF-I and the red fluorescent protein DsRed2, or a control rAAV expressing only DsRed2. Daily vaginal smears were taken throughout the study, which ended at 49.5 weeks of age. We measured serum levels of reproductive hormones and assessed ovarian histology at the end of the study. Although most of the rats injected with the IGF-I rAAV had, on the average, well-preserved estrous cyclicity as well as a generally normal ovarian histology, the intact and control rAAV groups showed a high percentage of acyclic rats at the end of the study and ovaries with numerous enlarged cysts and scarce corpora lutea. Serum LH was higher and hyperprolactinemia lower in the treated animals. These results suggest that overexpression of IGF-I in the MBH prolongs normal ovarian function in M-A female rats. PMID:23584855

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population.

PubMed

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding.

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population

PubMed Central

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

Background The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Methods Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Results Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Conclusion Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding. PMID:28553116

Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

PubMed

Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

2013-04-01

Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

PubMed

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Serum Levels of Tryptophan, 5-Hydroxytryptophan and Serotonin in Patients Affected with Different Forms of Amenorrhea

PubMed Central

Comai, S.; Bertazzo, A.; Carretti, N.; Podfigurna-Stopa, A.; Luisi, S.; Costa, C.V.L.

2010-01-01

Tryptophan (Trp) is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT) through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5-hydroxytryptophan (5-HTP) in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P ≤ 0.05) lower in the anorexic (11.64 ± 0.53 μg/ml, mean ± S.E.) than in the control (12.98 ± 0.37 μg/ml) groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed. This study shows that women affected by various forms of amenorrhea present an altered metabolism of tryptophan via serotonin and, in particular, markedly high differences are observed between the two subgroups of anorexic patients. PMID:22084589

Pituitary Magnetic Resonance Imaging for Sellar and Parasellar Masses: Ten-Year Experience in 2598 Patients

PubMed Central

Famini, Pouyan; Maya, Marcel M.

2011-01-01

Context: Sellar and parasellar masses present with overlapping clinical and radiological features ranging from asymptomatic incidental presentations and hormonal effects to compressive local mass effects. Pituitary masses are diagnosed with increased frequency with magnetic resonance imaging (MRI) advancements and availability, but indications and diagnostic outcomes of MRI screening for sellar lesions are not defined. Although pituitary adenomas are the most frequently encountered sellar mass lesions, other etiologies should be considered in the differential diagnosis of a sellar mass. Setting: The study was conducted at a tertiary pituitary center. Patients: This study was a retrospective review of 2598 subjects undergoing at least one pituitary MRI scan from 1999 to 2009. Main Outcome Measure: Prevalence and diagnosis of specific sellar and parasellar masses as screened by pituitary MRI. Results: The most common indications for pituitary imaging, excluding known mass follow-up, were for evaluation of hyperprolactinemia or hypogonadism. A normal pituitary gland was reported in 47% of subjects undergoing pituitary MRI. The most common pituitary adenomas initially identified by MRI included prolactinoma (40%), nonfunctioning adenoma (37%), and GH adenoma (13%). Nonadenomatous sellar masses accounted for 18% of visible lesions, of which the most common were Rathke's cleft cyst (19%), craniopharyngioma (15%), and meningioma (15%). Metastases accounted for 5% of nonpituitary lesions and breast cancer was the most common primary source. Conclusions: Half of all pituitary MRI scans performed in a large patient population yielded no visible lesion. Nonadenomatous pituitary lesions should be considered in the diagnosis of sellar masses observed on MRI, and a high clinical suspicion is required to exclude the presence of a nonfunctioning pituitary adenoma. PMID:21470998

Endocrine disrupting pesticides impair the neuroendocrine regulation of reproductive behaviors and secondary sexual characters of red munia (Amandava amandava).

PubMed

Pandey, Surya Prakash; Tsutsui, Kazuyoshi; Mohanty, Banalata

2017-05-01

The exposure effects of two endocrine disrupting pesticides (EDPs), mancozeb/MCZ and imidacloprid/IMI of the group dithiocarbamate and neonicotinoid respectively, on reproductive behaviors and secondary sexual characters have been studied in a seasonally breeding wildlife bird, red munia (Amandava amandava). Adult male birds were exposed to both the pesticides individually (0.25% LD 50 of each) as well as co-exposed (MIX-I: 0.25% LD 50 of each and MIX-II: 0.5% LD 50 of each) through food for 30d in preparatory (July-August) and breeding (September-October) phase of reproductive cycle. Singing and pairing patterns started decreasing from 2nd week to complete disappearance during 4th week of pesticides exposures at both the phases of reproductive cycles. Similar trend was observed in the disappearance of spots on the plumage as well as color of both plumage and beak which turned black/gray from red. Pesticides caused impairment of the lactotropic as well as hypothalamic-pituitary-testicular (HPT) axes as there was increased plasma PRL and decreased LH, FSH and testosterone levels. Testicular expressions of GnRH and androgen receptor/AR were significantly decreased but that of GnIH significantly increased as compared to control. Significant differences among individually- and co-exposed groups were also present. Abnormalities in sexual behaviors and secondary sexual characteristics could be linked to inhibition of HPT axis and/or direct toxicity at the level of hypothalamus, pituitary and testis. In addition, pesticide-induced hyperprolactinemia as well as impaired thyroid hormones might have also affected maintenance of reproductive behaviors. On co-exposures, the more distinct impairments might be due to cumulative toxicity of pesticides. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of cabergoline on metabolism in prolactinomas.

PubMed

Auriemma, Renata S; Granieri, Luciana; Galdiero, Mariano; Simeoli, Chiara; Perone, Ylenia; Vitale, Pasquale; Pivonello, Claudia; Negri, Mariarosaria; Mannarino, Teresa; Giordano, Carla; Gasperi, Maurizio; Colao, Annamaria; Pivonello, Rosario

2013-01-01

Hyperprolactinemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of 12- and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS) in patients with prolactinomas. 61 patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, prolactin (PRL) and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after the 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations the lipid profile significantly improved compared to baseline. Fasting insulin and homeostatic model assessment of insulin resistance significantly decreased after 1 year of CAB (p = 0.012 and p = 0.002, respectively) and further improved after 60 months (p = 0.000). The visceral adiposity index significantly decreased after the 60-month treatment (p = 0.000) compared to baseline. At the 5-year evaluation CAB dose was the best predictor of percent decrease in fasting insulin (t = 2.35, p = 0.022). CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB. © 2013 S. Karger AG, Basel.

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

PubMed

Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

2017-10-01

Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Accurate Diagnosis as a Prognostic Factor in Intrauterine Insemination Treatment of Infertile Saudi Patients

PubMed Central

Isa, Ahmed Mostafa; Abu-Rafea, Basim; Alasiri, Saleh Ahmed; Al-Mutawa, Johara; Binsaleh, Saleh; Al-Saif, Sameera; Al-Saqer, Aisha

2014-01-01

Background The study meant to define the prognostic factors that help in prescribing intrauterine insemination (IUI) for infertility treatment which remains an area of continuous improvements. Methods The diagnostic indications of a cohort of IUI-treated patients and their corresponding pregnancy rates (PRs) were randomly and prospectively studied among Saudi cohort of 303 patients for a period of 20 months. The indications of IUI cases were statistically analyzed for those eligible patients over a period of twenty months (January 2010 till August 2011), and the PR that corresponded to each group was investigated as well. P-value less than 0.05 was considered significant. Results The highest PR, 18.87%, of the polycystic ovarian syndrome (PCOS)-only diagnosed patients, was significantly higher than the average PR of all other indications combined, 7.22%, (p = 0.011, compared to all other groups combined). The second highest PR, 14.0%, of the tubal factor (TF)-only indication, was double the PR average of all other indications combined, though it did not reach significance. However, PCOS and TF accompanied by other indications caused the PR to drop to 5.88% and 5.56%, respectively. However, a group of some hormonal-imbalance based indications had the least PR (0.0% to 2.70%). Those indications were elevated serum FSH, hyperprolactinemia, hypogonadotrophy, hypothyroidism and endometriosis. The rest of the indications had an average PR (8.33% to 11.11%). Conclusion There is a reasonable chance of conception after IUI treatment for female factor infertility except in cases with sever hormonal imbalance. The PCOS cases having the best success chances. PMID:25473626

Extended Endoscopic Endonasal Approach for Suprasellar Craniopharyngioma.

PubMed

Locatelli, D; Pozzi, F; Agresta, G; Padovan, S; Karligkiotis, A; Castelnuovo, P

2018-02-01

Objectives  We illustrate a suprasellar craniopharyngiomas treated with an extended endoscopic endonasal approach (EEEA). Design  Case report of a 43-year-old male affected by cerebral lesion located in suprasellar region involving the third ventricle and compressing the neurovascular structures, causing an anterosuperior dislocation of the chiasma. There is a complete disruption of the pituitary stalk that can explain the clinical finding of partial anterior hypopituitarism and hyperprolactinemia. The lesion is characterized by a solid and cystic component. Considering the absence of lateral extension and the suprasellar location of the lesion, an EEEA is preferred. Setting  University Hospital "Ospedale di Circolo," Department of Neurosurgery, Varese, Italy. Participants  Neurosurgical and ENT Skull Base Team. Main Outcome Measures  A bilateral parasagittal approach is performed using a four-hand technique. The first step of the surgery is the preparation of the Hadad's flap. The approach is extended to the planum sphenoidalis to expose the suprasellar region. The lesion is completely removed employing also an ultrasound aspirator. Skull base reconstruction is performed with three-layer technique: graft of fat tissue, fascia lata, and nasoseptal flap. Results  No postoperative complications occurred. In the post-op, the patient presents a panhypopituitarism and an improvement in neurological status. The visual deficit remains stable. Post-op magnetic resonance imaging at 1 year documents the complete absence of pathological contrast enhancement. Conclusions  EEEA is a feasible approach in treating craniopharyngioma with suprasellar extension. The advantages include optimal visualization, good resection rate, and absence of brain retraction. The link to the video can be found at: https://youtu.be/IYm-8P1jbBo .

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Management of nonfunctioning pituitary incidentaloma.

PubMed

Galland, Françoise; Vantyghem, Marie-Christine; Cazabat, Laure; Boulin, Anne; Cotton, François; Bonneville, Jean-François; Jouanneau, Emmanuel; Vidal-Trécan, Gwénaelle; Chanson, Philippe

2015-07-01

Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Prolactin promotes normal liver growth, survival, and regeneration in rodents: effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis.

PubMed

Moreno-Carranza, Bibiana; Goya-Arce, Maite; Vega, Claudia; Adán, Norma; Triebel, Jakob; López-Barrera, Fernando; Quintanar-Stéphano, Andrés; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2013-10-01

Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the effect of PRL on liver growth and angiogenesis before and after partial hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal endothelial cell (SEC) proliferation, and hepatic expression of VEGF were measured before and after PH in hyperprolactinemic rats, generated by placing two anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic expression. Also, liver regeneration was increased in AP-grafted rats and was accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression compared with nongrafted controls. Lowering circulating PRL levels with CB-154, an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and soon after PH, they displayed an approximately twofold increased mortality and elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However, liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates normal liver growth, promotes survival, and regulates liver regeneration by mechanisms that may include hepatic downregulation of IL-6 and upregulation of SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to physiological liver growth and has potential clinical utility for ensuring survival and regulating liver mass in diseases, injuries, or surgery of the liver.

Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice.

PubMed

Bhaskar, Rakesh; Mohanty, Banalata

2014-09-01

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight. Copyright © 2014 Elsevier Inc. All rights reserved.

PITUITARY GIGANTISM--EXPERIENCE OF A SINGLE CENTER FROM WESTERN INDIA.

PubMed

Patt, Hiren P; Bothra, Nikita; Goel, Atul H; Kasaliwal, Rajeev; Lila, Anurag R; Bandgar, Tushar R; Shah, Nalini S

2015-06-01

Limited data are available on pituitary gigantism, as it is a rare disorder. This study was carried out to assess the clinical, hormonal, and radiologic profiles and management outcomes of patients with pituitary gigantism. We conduced a retrospective analysis of 14 patients with pituitary gigantism who presented to a single tertiary care institute from 1990 to 2014. Thirteen patients were male, and 1 was female. The mean age at diagnosis was 21.9 ± 6.1 years, with a mean lag period of 6.5 ± 5.6 years. The mean height SD score at the time of diagnosis was 3.2 ± 0.6. Symptoms of tumor mass effect were the chief presenting complaint in the majority (50%) of patients, while 2 patients were asymptomatic. Six patients had hyperprolactinemia. At presentation, the nadir PGGH (postglucose GH) and insulin-like growth factor (IGF 1)-ULN (× upper limit of normal) were 63.2 ± 94.9 ng/mL and 1.98 ± 0.5, respectively. All (except 1 with mild pituitary hyperplasia) had pituitary macroadenoma. Six patients had invasive pituitary adenoma. Transsphenoidal surgery (TSS) was the primary modality of treatment in 13/14 patients, and it achieved remission in 4/13 (30.76%) patients without recurrence over a median follow-up of 7 years. Post-TSS radiotherapy (RT) achieved remission in 3/5 (60%) patients over a median follow-up of 3.5 years. None of the patients received medical management at any point of time. Gigantism is more common in males, and remission can be achieved in the majority of the patients with the help of multimodality treatment (TSS and RT).

Double pituitary adenomas: six surgical cases.

PubMed

Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

1999-05-01

While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

Chronic hyperprolactinemia evoked by disruption of lactotrope dopamine D2 receptors impacts on liver and adipocyte genes related to glucose and insulin balance.

PubMed

Luque, Guillermina María; Lopez-Vicchi, Felicitas; Ornstein, Ana María; Brie, Belén; De Winne, Catalina; Fiore, Esteban; Perez-Millan, Maria Inés; Mazzolini, Guillermo; Rubinstein, Marcelo; Becu-Villalobos, Damasia

2016-12-01

We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose and insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice that selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), which have chronic high prolactin levels associated with increased body weight, marked increments in fat depots, adipocyte size, and serum lipids, and a metabolic phenotype that intensifies with age. LacDrd2KO mice of two developmental ages, 5 and 10 mo, were used. In the first time point, obesity and increased body weight are marginal, although mice are hyperprolactinemic, whereas at 10 mo there is marked adiposity with a 136% increase in gonadal fat and a 36% increase in liver weight due to lipid accumulation. LacDrd2KO mice had glucose intolerance, hyperinsulinemia, and impaired insulin response to glucose already in the early stages of obesity, but changes in liver and adipose tissue transcription factors were time and tissue dependent. In chronic hyperprolactinemic mice liver Prlr were upregulated, there was liver steatosis, altered expression of the lipogenic transcription factor Chrebp, and blunted response of Srebp-1c to refeeding at 5 mo of age, whereas no effect was observed in the glycogenesis pathway. On the other hand, in adipose tissue a marked decrease in lipogenic transcription factor expression was observed when morbid obesity was already settled. These adaptive changes underscore the role of prolactin signaling in different tissues to promote energy storage. Copyright © 2016 the American Physiological Society.

An open-label tolerability study of BL-1020 antipsychotic: a novel gamma aminobutyric acid ester of perphenazine.

PubMed

Anand, Ravi; Geffen, Yona; Vasile, Daniel; Dan, Irina

2010-01-01

BL-1020, a novel gamma aminobutyric acid (GABA) ester of perphenazine, is a new oral antipsychotic with a strong affinity for dopamine and serotonin receptors. Unlike first- and second-generation antipsychotics, it has agonist activity at GABA(A). This is the first study to examine tolerability and safety of BL-1020 in schizophrenia. This was a phase-II, open-label, multicenter, 6-week study treating patients (n = 36) with chronic schizophrenia. Dosing started at 20 mg/d and increased over 7 days to 40 mg/d. Weekly assessments were conducted. All but 1 patient was titrated to 30 mg/d at day 4; on day 7, 30 were titrated to 40 mg/d. Four patients discontinued the study prematurely. There was no clinically relevant increase in vital signs, sedation, dizziness, or other central nervous system effects or electrocardiogram or laboratory abnormalities and a small increase in weight. Ten patients experienced extrapyramidal symptoms (EPS) requiring treatment with an anticholinergic; 4 patients were unable to reach maximum dose because of EPS. Extrapyramidal Symptom Rating Scale did not indicate clinically significant changes in EPS. The most common adverse event was insomnia (6 patients); other frequent adverse effects (all n = 3) were extrapyramidal disorder, headache, parkinsonism, tremor, and hyperprolactinemia. There was improvement on Positive and Negative Syndrome Scale and Clinical Global Impression of Change with 22 patients showing at least 20% decrease by end point on Positive and Negative Syndrome Scale and 31 patients showing at least minimal improvement on Clinical Global Impression of Change. These data suggest that 20 to 40 mg/d of BL-1020 is associated with clinically relevant improvement of psychosis with no worsening of EPS and support further testing in randomized controlled trials.

Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil.

PubMed

Freire, Carmen; Koifman, Rosalina Jorge; Sarcinelli, Paula Novaes; Rosa, Ana Cristina Simões; Clapauch, Ruth; Koifman, Sergio

2014-03-01

Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones. To examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides. A cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models. Prevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p'-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'-DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin. Premenopausal women (N=210) did not show statistically significant associations between OC pesticides and sex hormones. Inverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population. Copyright © 2013. Published by Elsevier GmbH.

Acromegaly and McCune-Albright Syndrome

PubMed Central

Salenave, Sylvie; Boyce, Alison M.; Collins, Michael T.

2014-01-01

Background: McCune-Albright syndrome (MAS) includes the triad of poly/monostotic fibrous dysplasia, café-au-lait spots, and hyperfunctioning endocrinopathies. Acromegaly affects around 20% of MAS patients. Aims: The objective was to review all reported cases of acromegaly associated with MAS. Methods: All studies and case reports of acromegaly in patients with MAS were systematically sought in the world literature up to January 2013. We also included new data (from three unreported cases) and updated data on 23 previously reported patients from our two centers. Results: We reviewed the cases of 112 patients (65 males). Mean age at diagnosis of acromegaly was 24.4 years (range, 3–64). Among the 40 pediatric patients, 23 (57%) had precocious puberty. GH/IGF-1 excess was suggested by accelerated growth in 85% of pediatric cases. Acromegaly was almost always associated with skull base fibrous dysplasia. Modern imaging techniques (computed tomography or magnetic resonance imaging) revealed an adenoma in 54% of the patients (macroadenoma in more than two-thirds). Median GH levels and mean IGF-1 SD score at diagnosis were 57 μg/L (2.8 to 291 μg/L) and 8 (2.3 to 24), respectively. Hyperprolactinemia was present in 81% (mean, 149 μg/L; range, 21–600). Pituitary surgery, performed in 25 cases, very rarely cured the GH/IGF-1 excess. Somatostatin analogs improved GH/IGF-1 levels in most patients but achieved control of acromegaly in only 17 (30%) of 56 patients. Pegvisomant achieved normal IGF-1 levels in 10 of 13 cases. Conclusion: Acromegaly, which is present in 20–30% of patients with MAS, raises particular diagnostic and therapeutic issues. PMID:24517150

McCune-Albright syndrome: a detailed pathological and genetic analysis of disease effects in an adult patient.

PubMed

Vasilev, Vladimir; Daly, Adrian F; Thiry, Albert; Petrossians, Patrick; Fina, Frederic; Rostomyan, Liliya; Silvy, Monique; Enjalbert, Alain; Barlier, Anne; Beckers, Albert

2014-10-01

McCune Albright syndrome (MAS) is a clinical association of endocrine and nonendocrine anomalies caused by postzygotic mutation of the GNAS1 gene, leading to somatic activation of the stimulatory α-subunit of G protein (Gsα). Important advances have been made recently in describing pathological characteristics of many MAS-affected tissues, particularly pituitary, testicular, and adrenal disease. Other rarer disease related features are emerging. The objective of the investigation was to study the pathological and genetic findings of MAS on a tissue-by-tissue basis in classically and nonclassically affected tissues. This was a comprehensive autopsy and genetic analysis. The study was conducted at a tertiary referral university hospital. An adult male patient with MAS and severe disease burden including gigantism was the subject of the study. Interventions included clinical, hormonal, and radiographic studies and gross and microscopic pathology analyses, conventional PCR, and droplet digital PCR analyses of affected and nonaffected tissues. Pathological findings and the presence of GNAS1 mutations were measured. The patient was diagnosed with MAS syndrome at 6 years of age based on the association of café-au-lait spots and radiological signs of polyostotic fibrous dysplasia. Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism, and hyperparathyroidism were diagnosed throughout the adult period. The patient died at the age of 39 years from a pulmonary embolism. A detailed study revealed mosaiscism for the p.R201C GNAS1 mutation distributed across many endocrine and nonendocrine tissues. These genetically implicated tissues included rare or previously undescribed disease associations including primary hyperparathyroidism and hyperplasia of the thymus and endocrine pancreas. This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1-related pathology across a wide range of affected organs.

Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from an endocrinologist and a psychiatrist

PubMed Central

Athanasoulia-Kaspar, Anastasia P; Popp, Kathrin H; Stalla, Gunter Karl

2018-01-01

The dopaminergic treatment represents the primary treatment in prolactinomas, which are the most common pituitary adenomas and account for about 40% of all pituitary tumours with an annual incidence of six to ten cases per million population. The dopaminergic treatment includes ergot and non-ergot derivatives with high affinity for the dopamine receptors D1 or/and D2. Through the activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine agonists inhibit the prolactin synthesis and secretion, therefore normalizing the prolactin levels and restoring eugonadism, but they also lead to tumour shrinkage. Treatment with dopamine agonists has been associated – apart from the common side effects such as gastrointestinal symptoms, dizziness and hypotension – with neuropsychiatric side effects such as impulse control disorders (e.g. pathological gambling, compulsive shopping, hypersexuality and binge eating) and also with behavioral changes from low mood, irritability and verbal aggressiveness up to psychotic and manic symptoms and paranoid delusions not only in patients with prolactinomas but also in patients with Parkinson’s disease and restless leg syndrome. They usually have de novo onset after initiation of the dopaminergic treatment and have been mainly reported in patients with Parkinson’s disease, who are being treated with higher doses of dopamine agonists. Moreover, dopamine and prolactin seem to play an essential role in the metabolic pathway. Patients with hyperprolactinemia tend to have increased body weight and an altered metabolic profile with hyperinsulinemia and increased prevalence of diabetes mellitus in comparison to healthy individuals and patients with non-functioning pituitary adenomas. Treatment with dopamine agonists in these patients in short-term studies seems to lead to weight loss and amelioration of the metabolic changes. Together these observations provide evidence that dopamine and prolactin have a crucial role both in the regard and metabolic system, findings that merit further investigation in long-term studies. PMID:29378769

Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials.

PubMed

Kishi, Taro; Matsuda, Yuki; Nakamura, Hiroshi; Iwata, Nakao

2013-02-01

There is uncertainty about the efficacy and tolerability of blonanserin in schizophrenia. PubMed, the Cochrane Library databases, PsycINFO, and Google Scholar were searched up to September 2012. A systematic review and meta-analysis of individual patient data from randomized, controlled trials comparing blonanserin with other antipsychotics were conducted. The risk ratio (RR), 95% confidence intervals (CI), numbers-needed-to-harm (NNH), and weighted mean difference (WMD) were calculated. Four studies (total n = 1080) were identified (vs. risperidone studies [n = 508], vs. haloperidol studies [n = 572]). Comparing blonanserin with other pooled antipsychotics, there were no significant differences in the Positive and Negative Syndrome Scale (PANSS) total score (p = 0.75), PANSS positive (p = 0.41), PANSS negative (p = 0.09), and PANSS general psychopathology subscale scores (p = 0.96), and response rate (p = 0.72). However, blonanserin showed greater efficacy in PANSS negative subscale scores compared with haloperidol (WMD = -1.29, CI = -2.29 to -0.30, p = 0.01, I(2) = 0%). No significant differences were found in discontinuation rates between blonanserin and other pooled antipsychotics (due to any cause: p = 0.29, inefficacy: p = 0.32, adverse events: p = 0.56). Blonanserin had a 0.31 lower risk of hyperprolactinemia than the other pooled antipsychotics (CI = 0.20-0.49, NNH = not significant). While dizziness (RR = 0.47, CI = 0.23-0.93, NNH = not significant) and akathisia (RR = 0.54, CI = 0.32-0.90, NNH = 7) occurred significantly less often with blonanserin than with haloperidol, blonanserin had a 1.62 higher risk of akathisia than risperidone (CI = 1.18-2.22, NNH = 8) [corrected]. Our results suggest that although blonanserin has a more beneficial effect on negative symptoms than haloperidol, there was a significant difference in the adverse events profile between blonanserin and other antipsychotics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Each Individual Isoform of the Dopamine D2 Receptor Protects from Lactotroph Hyperplasia

PubMed Central

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna

2013-01-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R−/− mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states. PMID:23608643

Each individual isoform of the dopamine D2 receptor protects from lactotroph hyperplasia.

PubMed

Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna; Borrelli, Emiliana

2013-06-01

Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and their comparison with D2L-null animals. These mice represent a valuable tool with which to investigate dopamine-dependent isoform-specific signaling in the pituitary gland. We sought to assess the existence of a more prominent role of D2L or D2S in controlling PRL expression and lactotroph hyperplasia. Importantly, we found that D2L and D2S are specifically linked to independent transduction pathways in the pituitary. D2L-mediated signaling inhibits the AKT/protein kinase B kinase activity whereas D2S, in contrast, is required for the activation of the ERK 1/2 pathway. Under normal conditions, presence of only 1 of the 2 D2R isoforms in vivo prevents hyperprolactinemia, formation of lactotroph's hyperplasia, and tumorigenesis that is observed when both isoforms are deleted as in D2R-/- mice. However, the protective function of the single D2R isoforms is overridden when single isoform-knockout mice are challenged by chronic estrogen treatments as they show increased PRL production and lactotroph hyperplasia. Our study indicates that signaling from each of the D2R isoforms is sufficient to maintain lactotroph homeostasis in physiologic conditions; however, signaling from both is necessary in conditions simulating pathologic states.

Endoscopic Endonasal Transsphenoidal Approach

PubMed Central

Cappabianca, Paolo; Alfieri, Alessandra; Colao, Annamaria; Ferone, Diego; Lombardi, Gaetano; de Divitiis, Enrico

1999-01-01

The outcome of endoscopic endonasal transsphenoidal surgery in 10 patients with pituitary adenomas was compared with that of traditional transnasal transsphenoidal approach (TTA) in 20 subjects. Among the 10 individuals subjected to “pure endoscopy,” 2 had a microadenoma, 1 an intrasellar macroadenoma, 4 had a macroadenoma with suprasellar expansion, 2 had a macroadenoma with supra-parasellar expansion, and 1 a residual tumor; 5 had acromegaly and 5 had a nonfunctioning adenoma (NFA). Among the patients subjected to TTA, 4 had a microadenoma, 2 had an intrasellar macroadenoma, 6 had a macroadenoma with suprasellar expansion, 4 had a macroadenoma with supra-parasellar expansion, and 4 had a residual tumor; 9 patients had acromegaly, 1 hyperprolactinemia, 1 Cushing's disease, and 9 a NFA. At the macroscopic evaluation, tumor removal was total (100%) after endoscopy in 9 patients and after TTA in 14 patients. Six months after surgery, magnetic resonance imaging (MRI) confirmed the total tumor removal in 21 of 23 patients (91.3%). Circulating growth hormone (GH) and insulin-like growth factor-I (IGF-I) significantly decreased 6 months after surgery in all 14 acromegalic patients: normalization of plasma IGF-I levels was obtained in 4 of 5 patients after the endoscopic procedure and in 4 of 9 patients after TTA. Before surgery, pituitary hormone deficiency was present in 14 out of 30 patients: pituitary function improved in 4 patients, remaining unchanged in the other 10 patients. Visual field defects were present before surgery in 4 patients, and improved in all. Early surgical results in the group of 10 patients who underwent endoscopic pituitary tumor removal were at least equivalent to those of standard TTA, with excellent postoperative course. Postsurgical hospital stay was significantly shorter (3.1 ± 0.4 vs. 6.2 ± 0.3 days, p < 0.001) after endoscopy as compared to TTA. ImagesFigure 1Figure 2 PMID:17171126

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice.

PubMed

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone ( GnRH ) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

PubMed Central

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function. PMID:29403355

Relation of RANKL and OPG Levels with Bone Resorption in Patients with Acromegaly and Prolactinoma.

PubMed

Ozer, Firuzan Firat; Dagdelen, Selcuk; Erbas, Tomris

2018-06-12

The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=-0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=-0.384, p=0.036 and r=-0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=-0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton. © Georg Thieme Verlag KG Stuttgart · New York.

Hypogonadotropic hypogonadism revisited.

PubMed

Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

2013-01-01

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

Food safety involving ingestion of foods and beverages prepared with phthalate-plasticizer-containing clouding agents.

PubMed

Yen, Tzung-Hai; Lin-Tan, Dan-Tzu; Lin, Ja-Liang

2011-11-01

In May 2011, the illegal use of the phthalate plasticizer di(2-ethylhexyl) phthalate in clouding agents for use in foods and beverages was reported in Taiwan. This food scandal has caused shock and panic among the majority of Taiwanese people and has attracted international attention. Phthalate exposure is assessed by ambient monitoring or human biomonitoring. Ambient monitoring relies on measuring chemicals in environmental media, foodstuff and consumer products. Human biomonitoring determines body burden by measuring the chemicals, their metabolites or specific reaction products in human specimens. In mammalian development, the fetus is set to develop into a female. Because the female phenotype is the default, impairment of testosterone production or action before the late phase may lead to feminizing characteristics. Phthalates disrupt the development of androgen-dependent structures by inhibiting fetal testicular testosterone biosynthesis. The spectrum of effects obtained following perinatal exposure of male rats to phthalates has remarkable similarities with the human testicular dysgenesis syndrome. Epidemiological studies have suggested associations between phthalate exposure and shorter gestational age, shorter anogenital distance, shorter penis, incomplete testicular descent, sex hormone alteration, precocious puberty, pubertal gynecomastia, premature thelarche, rhinitis, eczema, asthma, low birth weight, attention deficit hyperactivity disorder, low intelligence quotient, thyroid hormone alteration, and hypospadias in infants and children. Furthermore, many studies have suggested associations between phthalate exposure and increased sperm DNA damage, decreased proportion of sperm with normal morphology, decreased sperm concentration, decreased sperm morphology, sex hormone alteration, decreased pulmonary function, endometriosis, uterine leiomyomas, breast cancer, obesity, hyperprolactinemia, and thyroid hormone alteration in adults. Finally, the number of phthalate-related scientific publications from Taiwan has increased greatly over the past 5 years, which may reflect the health effects from the illegal addition of phthalate plasticizer to clouding agent in foodstuff over the past two decades. Copyright © 2011. Published by Elsevier B.V.

Psychosocial approach to endocrine disease.

PubMed

Sonino, Nicoletta; Tomba, Elena; Fava, Giovanni A

2007-01-01

In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment. In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability. After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). Indeed, in a population study, the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood, demoralization, persistent somatization. In particular, irritable mood was found to occur in 46% of 146 patients successfully treated for endocrine conditions, a rate similar to that found in cardiology and higher than in oncology and gastroenterology. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. In patients who showed persistence or even worsening of psychological distress upon proper endocrine treatment, the value of appropriate psychiatric interventions was underscored. As it happened in other fields of clinical medicine, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary for improving effectiveness in endocrinology. The DCPR have been demonstrated to be a valuable tool for psychological assessment in the various phases of endocrine disease from diagnostic to follow-up periods.

Inhibitory action of methadone and its metabolites on erg-mediated K+ current in GH₃ pituitary tumor cells.

PubMed

Huang, Mei-Han; Shen, Ai-Yu; Wang, Trey-Shy; Wu, Hui-Ming; Kang, Ya-Fei; Chen, Chia-Tai; Hsu, Tai-I; Chen, Bing-Shuo; Wu, Sheng-Nan

2011-02-04

Methadone (Mtd) is a widely used opioid drug associated with the side effect of hyperprolactinemia. The mechanism of how Mtd induces prolactin secretion remains unclear. The effects of Mtd and its two main metabolites (EDDP: (±)-2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium percholarate and EMDP: 2-ethyl-5-methyl-3,3-dipnehyl-1-pyrroline) on ion currents were investigated in GH₃ pituitary tumor cells. Hyperpolarization-elicited K+ currents in GH₃ cells bathed in a high-K(+), Ca(2+)-free solution were studied to evaluate the effects of Mtd and other related compounds on the ether-à-go-go-related-gene (erg) K(+) current (I(K(erg))). Mtd suppressed the amplitude of I(K(erg)) in a concentration-dependent manner with an IC(50) value of 10.4 μM. With the aid of a minimal binding scheme, the inhibitory action of Mtd on I(K(erg)) was estimated with a dissociation constant of 8.2 μM. Mtd tended to increase the rate of I(K(erg)) deactivation in a voltage-dependent fashion. EDDP (10 μM) had no effect on I(K(erg)), while EMDP (10μM) slightly suppressed it. In GH₃ cells incubated with naloxone (30 μM), the Mtd-induced inhibition of I(K(erg)) remained unaltered. Under cell-attached voltage-clamp recordings, Mtd increased the frequency of spontaneous action currents with no change in current amplitude. Similarly, Mtd can suppress I(K(erg)) in differentiated NG108-15 cells; dynorphin A(1-13) did not reverse Mtd-induced inhibition of I(K(erg)). This study shows that Mtd has a depressant effect on I(K(erg)), and suggests its ability to affect membrane excitability and prolactin secretion. The cyclization of Mtd, in which EDDP and EMDP are formed, tends to be critical in removal of the Mtd binding to erg K+ channel. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

PubMed

Abe, T; Tara, L A; Lüdecke, D K

1999-07-01

Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.

Pituitary Dysfunction in Adult Patients after Cranial Radiotherapy: Systematic Review and Meta-Analysis

PubMed Central

Kokshoorn, Nieke E.; Dekkers, Olaf M.; Neelis, Karen J.; Biermasz, Nienke R.; Romijn, Johannes A.; Smit, Johannes W. A.; Pereira, Alberto M.

2011-01-01

Context: Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. Objective: We conducted a systematic review and meta-analysis of reported prevalences of hypopituitarism in adults radiated for nonpituitary tumors. Data Sources: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library to identify potentially relevant studies. Study Selection: Studies were eligible for inclusion with the following criteria: 1) cranial radiotherapy for nonpituitary tumors and/or total body irradiation for hematological malignancies; 2) adult population (>18 yr old); and 3) report on endocrine evaluation. Data Extraction: Data review was done by two independent reviewers. Besides extraction of baseline and treatment characteristics, also endocrine tests, definitions, and cutoff values used to define pituitary insufficiency were extracted. Results: Eighteen studies with a total of 813 patients were included. These included 608 patients treated for nasopharyngeal cancer (75%) and 205 for intracerebral tumors. The total radiation dose ranged from 14 to 83 and 40 to 97 Gy for nasopharyngeal and intracerebral tumors, respectively. The point prevalence of any degree of hypopituitarism was 0.66 [95% confidence interval (CI), 0.55–0.76]. The prevalence of GH deficiency was 0.45 (95% CI, 0.33–0.57); of LH and FSH, 0.3 (95% CI, 0.23–0.37); of TSH, 0.25 (95% CI, 0.16–0.37); and of ACTH, 0.22 (95% CI, 0.15–0.3), respectively. The prevalence of hyperprolactinemia was 0.34 (95% CI, 0.15–0.6). There were no differences between the effects of radiotherapy for nasopharyngeal vs. for intracerebral tumors. Conclusion: Hypopituitarism is prevalent in adult patients after cranial radiotherapy for nonpituitary tumors. Therefore, all patients treated by cranial radiotherapy should have structured periodical assessment of pituitary functions. PMID:21613351

Hypogonadotropic Hypogonadism Revisited

PubMed Central

Fraietta, Renato; Zylberstejn, Daniel Suslik; Esteves, Sandro C

2013-01-01

Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic). Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively. Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb. Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility. When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm. PMID:23503957

Risk factors for medication-induced amenorrhea in first-episode female Chinese patients with schizophrenia treated with risperidone

PubMed Central

Chen, Haizhi; Qian, Mincai; Shen, Xinhua; Yang, Shengliang; Yang, Jianhong; Song, Juanfang; Fei, Xiaocong; Tao, Baiping; Song, Baohua; Ren, Lihua; Shen, Zhongxia

2013-01-01

Background Amenorrhea is a common adverse effect of treatment with antipsychotic medications that influences both fertility and adherence to medication regimens. Most research suggests that medication-induced prolactinemia is the main cause of amenorrhea but few prospective studies have assessed this hypothesis. Aim Identify risk factors for amenorrhea following treatment with antipsychotic medication. Methods The study used a prospective, nested case-control design. First-episode, drug naïve female patients with schizophrenia who were in the middle of their menstrual cycle at the time of admission were enrolled. Serum levels of six reproductive hormones were assessed before and after a 12-week course of treatment with risperidone: progesterone, estradiol, prolactin, follicular stimulating hormone, luteinizing hormone, and testosterone. The hormone levels of 31 patients who had no menstruation during the entire 12 weeks of treatment (the amenorrhea group) were compared to those of 31 age-matched subjects who had normal menstrual periods over the 12 weeks of treatment (the control group). Results We found a dramatic 4-fold increase in prolactin levels in women of childbearing age treated with risperidone, but the pretreatment and posttreatment levels of prolactin were not different between patients who did and did not develop amenorrhea with treatment. However, there were significantly lower pretreatment levels of estradiol and progesterone in patients who subsequently developed amenorrhea with risperidone treatment than in patients who did not develop amenorrhea. A conditional logistic regression analysis found that pretreatment levels of estradiol remained significantly associated with the development of amenorrhea during treatment even when adjusting for the pretreatment levels of the other five reproductive hormones assessed. Conclusion These findings do not support the suggestion that amenorrhea associated with the use of antipsychotic medication is the result of hyperprolactinemia. If our finding of the predictive power of pretreatment levels of estradiol is confirmed in larger studies, this information would be of use to clinicians in selecting antipsychotic medications for female patients with schizophrenia; patients at highest risk of developing amenorrhea could be preferentially treated with the medications that are at lowest risk of inducing amenorrhea. PMID:24991131

Reports of pathological gambling, hypersexuality, and compulsive shopping associated with dopamine receptor agonist drugs.

PubMed

Moore, Thomas J; Glenmullen, Joseph; Mattison, Donald R

2014-12-01

Severe impulse control disorders involving pathological gambling, hypersexuality, and compulsive shopping have been reported in association with the use of dopamine receptor agonist drugs in case series and retrospective patient surveys. These agents are used to treat Parkinson disease, restless leg syndrome, and hyperprolactinemia. To analyze serious adverse drug event reports about these impulse control disorders received by the US Food and Drug Administration (FDA) and to assess the relationship of these case reports with the 6 FDA-approved dopamine receptor agonist drugs. We conducted a retrospective disproportionality analysis based on the 2.7 million serious domestic and foreign adverse drug event reports from 2003 to 2012 extracted from the FDA Adverse Event Reporting System. Cases were selected if they contained any of 10 preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA) that described the abnormal behaviors. We used the proportional reporting ratio (PRR) to compare the proportion of target events to all serious events for the study drugs with a similar proportion for all other drugs. We identified 1580 events indicating impulse control disorders from the United States and 21 other countries:710 fordopamine receptor agonist drugs and 870 for other drugs. The dopamine receptor agonist drugs had a strong signal associated with these impulse control disorders (n = 710; PRR = 277.6, P < .001). The association was strongest for the dopamine agonists pramipexole (n = 410; PRR = 455.9, P < .001) and ropinirole (n = 188; PRR = 152.5, P < .001), with preferential affinity for the dopamine D3 receptor. A signal was also seen for aripiprazole, an antipsychotic classified as a partial agonist of the D3 receptor (n = 37; PRR = 8.6, P < .001). Our findings confirm and extend the evidence that dopamine receptor agonist drugs are associated with these specific impulse control disorders. At present, none of the dopamine receptor agonist drugs approved by the FDA have boxed warnings as part of their prescribing information. Our data, and data from prior studies, show the need for more prominent warnings.

Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury.

PubMed

Zheng, Ping; He, Bin; Guo, Yijun; Zeng, Jingsong; Tong, Wusong

2015-07-01

The relationship between microstructural abnormality in patients with traumatic brain injury (TBI) and hormone-secreting status remains unknown. In this study, the authors aimed to identify the role of the apparent diffusion coefficient (ADC) using a diffusion-weighted imaging (DWI) technique and to evaluate the association of such changes with hypopituitarism in patients with TBI. Diffusion-weighted images were obtained in 164 consecutive patients with TBI within 2 weeks after injury to generate the pituitary ADC as a measure of microstructural change. Patients with TBI were further grouped into those with and those without hypopituitarism based on the secretion status of pituitary hormones at 6 months postinjury. Thirty healthy individuals were enrolled in the study and underwent MRI examinations for comparison. Mean ADC values were compared between this control group, the patients with TBI and hypopituitarism, and the patients with TBI without hypopituitarism; correlational studies were also performed. Neurological outcome was assessed with the Glasgow Outcome Scale (GOS) for all TBI patients 6 months postinjury. In the TBI group, 84 patients had hypopituitarism and 80 had normal pituitary function. The pituitary ADC in TBI patients was significantly less than that in controls (1.83 ± 0.16 vs 4.13 ± 0.33, p < 0.01). Furthermore, the mean ADC was much lower in TBI patients with hypopituitarism than in those without pituitary dysfunction (1.32 ± 0.09 vs 2.28 ± 0.17, p < 0.05). There was also a significant difference in ADC values between patients with hyperprolactinemia and those with normal prolactin levels (p < 0.05). Additionally, the receiver operating characteristic curve analysis showed that the pituitary ADC could predict hypopituitarism with a sensitivity of 90.0% and a specificity of 90.1% at the level of 1.720 (ADC value). Finally, the ADC value was positively correlated with neurological outcome at 6 months following TBI (r = 0.602, p < 0.05). Use of DWI demonstrated that the pituitary ADC is correlated with hormone-secreting status in TBI patients. The authors suggest that pituitary ADC may be a useful biomarker to predict pituitary function in patients with TBI.

Neuroendocrine abnormalities in patients with traumatic brain injury

NASA Technical Reports Server (NTRS)

Yuan, X. Q.; Wade, C. E.

1991-01-01

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture. Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

Limited endoscopic transsphenoidal approach for cavernous sinus biopsy: illustration of 3 cases and discussion.

PubMed

Graillon, T; Fuentes, S; Metellus, P; Adetchessi, T; Gras, R; Dufour, H

2014-01-01

Advances in transsphenoidal surgery and endoscopic techniques have opened new perspectives for cavernous sinus (CS) approaches. The aim of this study was to assess the advantages and disadvantages of limited endoscopic transsphenoidal approach, as performed in pituitary adenoma surgery, for CS tumor biopsy illustrated with three clinical cases. The first case was a 46-year-old woman with a prior medical history of parotid adenocarcinoma successfully treated 10 years previously. The cavernous sinus tumor was revealed by right third and sixth nerve palsy and increased over the past three years. A tumor biopsy using a limited endoscopic transsphenoidal approach revealed an adenocarcinoma metastasis. Complementary radiosurgery was performed. The second case was a 36-year-old woman who consulted for diplopia with right sixth nerve palsy and amenorrhea with hyperprolactinemia. Dopamine agonist treatment was used to restore the patient's menstrual cycle. Cerebral magnetic resonance imaging (MRI) revealed a right sided CS tumor. CS biopsy, via a limited endoscopic transsphenoidal approach, confirmed a meningothelial grade 1 meningioma. Complementary radiosurgery was performed. The third case was a 63-year-old woman with progressive installation of left third nerve palsy and visual acuity loss, revealing a left cavernous sinus tumor invading the optic canal. Surgical biopsy was performed using an enlarged endoscopic transsphenoidal approach to the decompress optic nerve. Biopsy results revealed a meningothelial grade 1 meningioma. Complementary radiotherapy was performed. In these three cases, no complications were observed. Mean hospitalization duration was 4 days. Reported anatomical studies and clinical series have shown the feasibility of reaching the cavernous sinus using an endoscopic endonasal approach. Trans-foramen ovale CS percutaneous biopsy is an interesting procedure but only provides cell analysis results, and not tissue analysis. However, radiotherapy and radiosurgery have proven effective for SC meningiomas. When histological diagnosis is required, limited endoscopic transsphenoidal approach appears as a safe, fast, and useful alternative to the classical endocranial approach. Also, a tailored enlargement of the approach could be performed if optic nerve decompression is required. The feasibility of CS endoscopic transsphenoidal biopsy has prompted us to consider CS biopsy when the diagnosis of CS meningioma is uncertain. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Possible factors influencing the duration of hospital stay in patients with psychiatric disorders attempting suicide by jumping.

PubMed

Omi, Tsubasa; Ito, Hiroshi; Riku, Keisen; Kanai, Koji; Takada, Hiromune; Fujimi, Satoshi; Matsunaga, Hidenori; Ohi, Kazutaka

2017-03-20

Patients with psychiatric disorders have a high rate of suicide. The present study investigated factors influencing hospital stays for Japanese patients with psychiatric disorders attempting suicide by jumping. We diagnosed all suicide attempts (n = 113) by jumping based on the International Classification of Diseases 10th Revision (ICD-10) and investigated the mean hospital stays of patients with each diagnosis based on the ICD-10 code. We then analyzed differences in the demographic and clinical characteristics between the diagnostic groups to identify factors influencing the duration of hospital stay. Patients diagnosed with schizophrenia (F2 code) were the most frequent (32.7%) of all diagnoses; therefore, we divided the diagnostic groups into schizophrenia group (n = 37) and other psychiatric diagnoses group (n = 76). The patients with schizophrenia showed a significantly longer hospital stay (125.7 ± 63.9 days) compared with the patients with other psychiatric diagnoses (83.6 ± 63.2) (β ± SE = 42.1 ± 12.7, p = 0.0013), whereas there was no difference in the jump height between the two groups (the average was the 3rd to 4th floor; p > 0.05). The number of injured parts, particularly lower-limb fractures, was significantly higher (p = 0.017) in patients with schizophrenia than in patients with other psychiatric diagnoses. The duration of psychiatric treatment in patients with schizophrenia were significantly longer (z = 3.4, p = 0.001) than in patients with other psychiatric diagnoses. Our findings indicate that the number of injuries and the body parts injured in patients with schizophrenia are associated with a longer duration of hospital stay following a suicide attempt by jumping. The current use of antipsychotics and a longer duration of taking antipsychotics might contribute to the risk of bone fracture via hyperprolactinemia. Further cognitive impairment in patients with schizophrenia might prevent rehabilitation for the management of lower-limb fractures. From these results, we suggest that clinicians should monitor the level of prolactin and cognitive function in patients with schizophrenia in future studies on managing of lower-limb fractures.

The diagnosis of luteal phase deficiency: a critical review.

PubMed

McNeely, M J; Soules, M R

1988-07-01

Luteal phase deficiency is an ovulatory dysfunction problem that is subtle but real. It may be the most common ovulatory problem in women. Luteal phase deficiency has been clearly demonstrated in the research setting (1) in spontaneous cycles, (2) when follicular maturation has been impeded, and (3) when luteotrophic influences have been suppressed. The diagnosis of LPD in the clinical setting remains problematic and controversial primarily because there is no practical diagnostic method that has been validated. This article has reviewed the methods that have been used to diagnose LPD. BBT charts are insensitive; these charts reliably diagnose LPD only when there are persistent short luteal phases. There is disagreement whether ovarian follicular size, as determined by ultrasonography, is decreased in LPD; however, ultrasonographic diagnosis of LPD would require daily scans through ovulation, which makes this approach impractical. Mild hyperprolactinemia is a probable cause of LPD in a minority of patients; a physician should obtain a PRL level in LPD women with the realization that there is considerable sampling variability. Determination of serum gonadotropin levels (LH or FSH or both) is not practical for the clinical diagnosis of LPD. Random serum P levels, whether single or multiple, are not helpful in the diagnosis of LPD in individual patients. The secretory pattern of P results in such wide confidence limits that P samples from individuals cannot be compared to normal in a useful manner. Most of the controversy about the diagnosis of LPD has centered around the use of individual serum P levels. The timed endometrial biopsy relies on the endometrium as a bioassay of P over time. The endometrial biopsy has not been carefully validated in terms of its sensitivity or accuracy for the diagnosis of LPD. However, it remains the best current method for the diagnosis of LPD when the standard guidelines for its use are followed. As opposed to the other tests for LPD, awareness of the usefulness of the biopsy has increased as we have learned more about CL physiology. No current research method for the diagnosis of LPD appears to be a practical method that could be applied in the clinical setting. Specific secretory proteins from the endometrium and methods to measure hormone secretion that circumvent the secretory pattern hold promise for improved methods to diagnose LPD in the future.

The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation.

PubMed

Kurtulmus, Neslihan; Mert, Meral; Tanakol, Refik; Yarman, Sema

2015-04-01

Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11%) exhibited single organ involvement, while eight patients (89%) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44%) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78%), a thalamic mass in one patient (11%), and the absence of the bright spot in all patients. A single patient (11%) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT+CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1%) developed anterior pituitary hormone deficiency, three (43%) were diagnosed with GH deficiency, and one (14%) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.

Medicinal plants of the genus Anthocleista--A review of their ethnobotany, phytochemistry and pharmacology.

PubMed

Anyanwu, Gabriel O; Nisar-ur-Rehman; Onyeneke, Chukwu E; Rauf, Khalid

2015-12-04

The genus Anthocleista of the Gentianaceae family contains 14 species of trees and shrub-like plants distributed in tropical Africa, in Madagascar and on the Comoros. Traditionally, they are commonly used in the treatment of diabetes, hypertension, malaria, typhoid fever, obesity, diarrhea, dysentery, hyperprolactinemia, abdominal pain, ulcer, jaundice, asthma, hemorrhoids, hernia, cancer, wounds, chest pains, inflammations, rheumatism, STDs, infertility and skin diseases. They serve as an anthelmintic, laxative, diuretic and contraceptive. This review aims to provide for the first time a repository of ethnopharmacological information while critically evaluating the relation between the traditional medicinal uses, chemical constituents and pharmacological activities of the Anthocleista species so as to unveil opportunities for future research. A search for relevant information on Anthocleista species was performed on scientific databases (Pubmed, Google Scholar, SciFinder, Web of Science, Scopus, PubChem and other web sources such as The Plant List, Kew Botanical Garden and PROTA) and books, PhD and MSc dissertations for un-published resources. Out of the 14 species of Anthocleista, 6 have been reported in literature to be widely used in traditional medicine for the treatment of various ailments. The six species include: A. djalonensis, A. vogelii, A. nobilis, A. grandiflora, A. schweinfurthii, and A. liebrechtsiana. The chemical compounds isolated from Anthocleista species fall into the class of phytochemicals such as secoiridoids, nor-secoiridoids, xanthones, phytosterols, triterpenes, alkaloids, and others of which majority of the compounds were isolated from A. djalonensis and A. vogelii. The in vitro and in vivo pharmacological studies on the crude extracts, fractions and few isolated compounds of Anthocleista species showed antidiabetic, antiplasmodial, antimicrobial, hypotensive, spasmogenic, anti-obesity, antiulcerogenic, analgesic, anti-inflammatory, antioxidant, antitrypanosomal, anthelmintic, fertility, diuretic and laxative activities which supports most of their uses in traditional medicine. However, the bulk of the studies where centered on the antidiabetic, antiplasmodial and antimicrobial activities of Anthocleista species, although the evidence of its antiplasmodial effect was not convincing enough due to the discrepancies between the in vitro and in vivo results. A. djalonensis and A. vogelii are potential antidiabetic and antibacterial agents. The antibacterial potency relates to infections or diseases caused by E. coli, S. typhi and S. aureus such as urinary tract infections, typhoid, diarrhea, skin diseases, and food poisoning. Pharmacological research on this genus is quite elementary and limited, thus, more advanced research is necessary to isolate and determine the activities of bioactive compounds in vitro and in vivo, establish their mechanisms of action and commence the process of clinical research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Estimation of Somatomedin-C Levels in Normals and Patients with Pituitary Disease by Radioimmunoassay

PubMed Central

Furlanetto, Richard W.; Underwood, Louis E.; Van Wyk, Judson J.; D'Ercole, A. Joseph

1977-01-01

The development of a radioimmunoassay for somatomedin-C has for the first time made it possible to discriminate between serum concentrations of a single peptide or closely related group of peptides and the net somatomedin activity measured by less specific bioassay and radioreceptor techniques. Antibodies to human somatomedin-C were raised in rabbits using a somatomedin-C ovalbumin complex as the antigen. A variety of peptide hormones at concentrations up to 1 μM are not recognized by the antibody. Insulin at concentrations >0.1 μM cross reacts in a non-parallel fashion; purified somatomedin-A is only 3% as active as somatomedin-C; and radiolabeled cloned rat liver multiplication stimulating activity does not bind to the antibody. Immunoreactive somatomedin-C can also be quantitated in the sera of a variety of subhuman species. Unusual assay kinetics, which are manifest when reactants are incubated under classic “equilibrium” assay conditions, appear to result from the failure of 125I-somatomedin-C to readily equilibrate with the somatomedin-C serum binding protein complex. It is, therefore, necessary to use nonequilibrium assay conditions to quantitate somatomedin-C in serum. With this assay it is possible to detect somatomedin-C in normal subjects using as little as 0.25 μl of unextracted serum. Serum somatomedin-C concentrations in normal subjects were lowest in cord blood and rose rapidly during the first 4 yr of life to near adult levels. In 23 normal adult volunteers, the mean serum somatomedin-C concentration was 1.50±0.10 U/ml (SEM) when compared to a pooled adult serum standard. 19 children with hypopituitary dwarfism had concentrations below 0.20 U/ml. 17 of these were below 0.1 U/ml, the lower limit of sensitivity of the assay. The mean concentration in 14 adults with active acromegaly was 6.28±0.37 U/ml (SEM), five times greater than the normal volunteers. Significant increases in serum somatomedin-C concentrations were observed in 8 of 10 hypopituitary children within 72 h after the parenteral administration of human growth hormone. Three patients with Cushing's disease had elevated serum somatomedin-C concentrations (2.61±0.14 U/ml [SEM]). Three patients with hyperprolactinemia had normal concentrations (1.74±0.11 U/ml [SEM]). The important new discovery brought to light by quantitation of immunoassayable somatomedin in patient sera is that all previously used assays detect, in addition to somatomedin-C, serum substances that are not under as stringent growth hormone control. PMID:893668

[Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

PubMed

Lu, Hong-Lei; Wang, Tao; Xu, Hao; Chen, Li-Ping; Rao, Ke; Yang, Jun; Yuan, Hui-Xing; Liu, Ji-Hong

2016-08-01

To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (［2.35±0.71］ vs ［1.83±0.36］ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (［0.78±0.40］ vs ［2.71±0.70］ ng/ml with Andriol; ［0.93±0.44］ vs ［3.07±0.67］ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (［11.5±2.3］ vs ［7.5±2.3］ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

[Aripiprazole, gambling disorder and compulsive sexuality].

PubMed

Mété, D; Dafreville, C; Paitel, V; Wind, P

2016-06-01

Aripiprazole, an atypical or second-generation antipsychotic, is usually well tolerated. It is an approved treatment for schizophrenia and mania in bipolar disorder type 1. Unlike the other antipsychotics, it has high affinity agonist properties for dopamine D2 and D3 receptors. It has also 5-HT1A partial agonist and 5-HT2A antagonist properties. Aripiprazole is a first or second line treatment frequently used because it has reduced side effects such as weight gain, sleepiness, dyslipidemia, insulin resistance, hyperprolactinemia and extrapyramidal symptoms. We report the case of a 28-year-old male patient diagnosed with schizoid personality disorder. He was a moderate smoker with occasional social gambling habits. After several psychotic episodes, he was first treated with risperidone, but he experienced excessive sedation, decreased libido, erectile dysfunction and was switched to 15 mg aripiprazole. He developed an addiction habit for gambling at casino slot machines. Due to large gambling debts, he requested placement on a voluntary self-exclusion list. Thereafter, he turned his attention towards scratch card gambling. The patient described his experience of gambling as a "hypnotic state". He got several personal loans to obtain money to continue gambling. He was then referred to an addiction unit. Before being treated with aripiprazole, he was an exclusive heterosexual with a poor sexual activity. Under treatment, he switched to a homosexual behavior with hypersexuality, unprotected sex and sadomasochistic practices. The craving for gambling and compulsive sexual behavior ceased two weeks after aripiprazole was discontinued and he was switched to amisulpride. Thereafter, he reported a return to a heterosexual orientation. Compulsive behaviors such as gambling, hypersexuality and new sexual orientation are common in patients with Parkinson's disease treated with dopaminergic agonists. These behaviors involve the reward system, with an enhanced dopaminergic activity in the mesolimbic pathways and occur more frequently in young subjects, males with previous gambling habits and tobacco use. A few cases of aripiprazole-induced pathological gambling as well as aripiprazole-induced hypersexuality have been reported. To our knowledge, we are the first to report a case of gambling disorder associated with hypersexuality and change of sexuality orientation. Aripiprazole is the only antipsychotic with agonist properties for the D2 dopamine receptor. It may also act as an enhancer in the mesolimbic dopaminergic pathways. Aripiprazole also has 5-HT1A partial agonist and 5-HT2A antagonist properties that may promote sexual activity. Aripiprazole is an antipsychotic associated with reduced side effects compared to other antipsychotics. We report the case of a patient who experienced gambling disorder, hypersexuality and a new sexual orientation under treatment. These side effects are little known. They are usually difficult for patients to mention due to feelings of guilt. The consequences on social life, family and health may be serious. Clinicians and patients should be aware about the possible issue of these behavior disorders with aripiprazole. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases.

PubMed

Yamada, Shozo; Fukuhara, Noriaki; Horiguchi, Kentaro; Yamaguchi-Okada, Mitsuo; Nishioka, Hiroshi; Takeshita, Akira; Takeuchi, Yasuhiro; Ito, Junko; Inoshita, Naoko

2014-12-01

The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.

[Non-structural abnormalities of CNS function resulting in coincidence of endocrinopathies, epilepsy and psychoneurologic disorders in children and adolescents].

PubMed

Starzyk, Jerzy; Pituch-Noworolska, Anna; Pietrzyk, Jacek A; Urbanik, Andrzej; Kroczka, Sławomir; Drozdz, Ryszard; Wójcik, Małgorzata

2010-01-01

In the population of children and adolescents, epilepsy affects approximately 1% of cases, nonepileptic seizures are seen in approximately 3%, and endocrine disorders are several times more common. For this reason, coincidence of endocrine disorders and epilepsy and psychoneurologic disorders is frequent. Much less common are structural abnormalities (tumors, developmental abnormalities), and especially non-structural CNS abnormalities, resulting in coincidence of both disorders. There are no reports available in the literature that would address the problem. 1) Assessment of the frequency of coincidental epilepsy and endocrine disorders in patients without structural CSN abnormalities treated as outpatients and inpatients of Department of Endocrinology University Children's Hospital of Krakow. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining the common etiology of both disorders. On the basis of ICD code patients with coincidance of endocrine disorders, epilepsy and psychoneurologic disorders were selected from several thousands of children treated between 2000 and 2009 in Pediatric Endocrinology Department. The neurologic disorders were diagnosed and treated in Chair and Department of Children's and Adolescents Neurology or in another pediatric neurology center. Various forms of epilepsy (symptomatic or idiopathic) and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, autoaggression, or hypothalamic obesity) coincident with one or more endocrine disorders, such as growth disorders, disorders of pubertal development, obesity, thyroid diseases, adrenal diseases, hyperprolactinemia, hypoparathyroidism and ion metabolism disorders were diagnosed in 49 patients. The group included: i) children after cranial irradiation and chemotherapy due to medulloblastoma (3 patients), oligodenroglioma (1 patient), ependymoma (1 patient), optic chiasm glioma (2 patients), suprasellar germinal tumor (1 patient), ii) children with Hashimoto encephalopathy (2 patients), iii) children with Prader-Willi syndrome (20 patients), with Klinefelter syndrome (10 patients), with Albright syndrome (9 patients). Of the 49 patients, a group of 6 children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common, and the diagnosis was usually delayed. 1. Cranial irradiation and chemotherapy, encephalopathy associated with Hashimoto disease and some of the syndromes with the chromosomal and genetic background are the causes of non-structural CNS abnormalities and coincidence of endocrinopathies, epilepsy and psychoneurologic disorders. 2. MR/CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy or seizures, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future. 3. Excluding structural CNS abnormalities allows for forming suspicions associated with diseases resulting in non-structural disorders of the CNS function, predisposing to coincidence of endocrine and neurological disorders. 4. In the diagnosis of Hashimoto's encephalopathy, a decisive factor is exclusion of structural, infectious, traumatic and metabolic causes, intoxications, epilepsy and presence of neuropsychiatric symptoms in patients with high level of against TPO antibodies. In cases of steroids resistance, a good therapeutic effect may be achieved by plasmapheresis, Rituximab therapy and progestagene inhibition of the menstrual cycle.

[Guidelines for the prescription of mood stabilizers for adolescents: A literature review].

PubMed

Munch, G; Godart, N

2017-10-01

Adolescence is a unique phase of the human developmental process. In adolescents, psychotropic medications may have different efficacy and tolerance profiles compared to those at other stages of the lifespan. Mood stabilizers are a complex pharmacological category including lithium, some anticonvulsants, and some second generation antipsychotics. Focusing on this class of pharmacological agents, we aim to answer the following questions: in which indications and according to which modalities should mood stabilizers be prescribed during adolescence? Information was sought from the websites of the French Haute Autorité de santé (HAS) and Agence nationale de sécurité du médicament et des produits de santé (ANSM), the American Food and Drug Administration (FDA) and the British National Institute for Health and Clinical Excellence (NICE). Guidelines from the American Academy of Child and Adolescent Psychiatry (AACAP) were also reviewed. Additional articles were found using PubMed and Google Scholar. We assumed that guidelines published by a national institute were the most relevant, second information from medical academies, then literature reviews, and finally single studies. Practical prescription data were also sought from the French Vidal Drug Dictionary. For bipolar disorder in adolescents, lithium has been the first drug licensed in France (from the age of 16) and in the USA (from the age of 12), with indications for acute mania and preventive treatment. Benefits for impulsive and self-aggressive behaviour disorders (especially relevant in case of borderline personality disorder) have also been documented, although lithium has not been licensed in any country for those indications. Extended-release tablets are usually used, at doses targeting for a lithiemia between 0.8 and 1.2mEq/L 12hours after last intake. Because of a narrow therapeutic window and potential side effects (especially nephrotoxicity), lithium prescription requires regular blood tests and good treatment compliance. None of the anticonvulsants has been licensed by a national drug administration as a mood stabilizer in adolescents. However, the AACAP recommends valproate as a first line treatment for mania, even though the NICE and the ANSM caution that valproate should not be used by women of child bearing age. Besides its teratogenic and endocrine side effects, valproate exposes one to the risk of hepatic toxicity. That is why regular liver function tests should be prescribed when valproate is chosen. According to the AACAP, carbamazepine (which is licensed for the treatment of mania in adults) is not a first line treatment for adolescents. Indeed, no clinical study has demonstrated its efficacy on manic episodes in adolescents. Moreover, carbamazepine exposes one to the risk of agranulocytosis. Lamotrigine has not been approved for adolescents, but some studies suggest its efficacy for bipolar depression (often a treatment-resistant phase) in this age group. Major side effects are the risk of Lyell or Stevens-Johnsons syndrome (which usually occur within the first eight weeks of treatment). There is no need for biological tests, just clinical monitoring. Pharmacological interactions between lamotrigine and oral contraceptives require caution. Finally, the use of some second generation antipsychotics for bipolar disorder in adolescents has been approved by national drug administrations. In France, only aripiprazole is licensed for acute mania (from the age of 13). In the USA, aripiprazole is licensed from the age of 10 for acute mania and preventive treatment, while risperidone and quetiapine are licensed from the age of 10 for acute mania, and olanzapine is licensed from the age of 13 for acute mania. The AACAP recommends second generation antipsychotics as a first line treatment for bipolar disorder. Moreover, the AACAP and the NICE recommend second generation antipsychotics for behavioural disorders in adolescents. Recommended doses are usually lower and titration slower than for adults. As in adults, adverse effects are metabolic, motor and cognitive disorders. Moreover, hyperprolactinemia, sedation and weight gain are more frequent than in adults. Epidemiologic data for prescription of mood stabilizers in adolescents only partially concord with recommendations from drug administrations and scientific societies. On the one hand, there is a trend toward preferential prescription of second generation antipsychotics, on the other hand lithium is hardly prescribed to adolescents, less often than anticonvulsants. Thus, without approval from any drug administration, the anticonvulsants are often preferred to lithium (because of lithium's potential risks due to noncompliance or voluntary poisoning) and to second generation antipsychotics (because of their tolerance profile). Nevertheless, for prescribers it is a complex matter to compare side effects: the frequency and intensity of adverse effects is quite variable from one mood stabilizer to another, and such a thing as an expected value is therefore hard to define. Regardless of the medication chosen, compliance and therapeutic alliance are major issues. Compliance is especially low during adolescence (less than 40% according to a study on bipolar disorder). This lack of compliance has multiple determinants: poor acceptance or misunderstanding of the psychiatric disorder, indirect effects of bad relationships with parents and more generally adults, but also reckless behaviour or death wishes. Improving therapeutic alliance appears as a major challenge for health practitioners dealing with youth. One interesting path of research could be the therapeutic education programs using humanistic communication techniques (addressing both adolescents and their parents) which have already produced encouraging results. Copyright © 2016. Published by Elsevier Masson SAS.