Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

OBJECTIVES: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. DISCUSSION: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Case Report: A Rare Case of Coexisting of Autoimmune Polyglandular Syndrome Type 3 and Isolated Gonadotropin-Releasing Hormone Deficiency.

APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison's disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves' disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves' disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea.

Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report.

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.

Circulating profile of Activin-Follistatin-Inhibin Axis in women with hypothalamic amenorrhea in response to leptin treatment.

BACKGROUND: Chronic energy deficiency observed in women that exercise strenuously affects reproductive function, often leading to hypothalamic amenorrhea (HA). In such conditions, hypoleptinemia and robust changes in the Activin-Follistatin-Inhibin Axis (AFI) are observed. Treatment with leptin restores menstruation in many (60% responders) but not all (40% non-responders) women, suggesting that leptin is not the only regulator of reproductive function related to energy balance. In this work, we aimed to identify differences in hormonal profiles between leptin responders and non-responders among women with HA, with particular focus on the AFI axis. METHODS: AFI axis and reproductive hormones (LH, FSH, Estradiol, ΑΜΗ) were measured in blood in: a) An open-label interventional study, b) a randomized placebo-controlled trial, both investigating responders versus non-responders/women with HA treated with leptin. RESULTS: Women with HA that responded to leptin treatment have higher circulating levels/peak values of Inhibin A, Estradiol (E2), higher LH/FSH ratio and a trend to lower AMH compared with non-responders. CONCLUSIONS: Components of the AFI axis are associated with improvement of reproductive function in women with HA treated with leptin. ΑΜΗ may serve as a marker of ovarian recovery under HA treatment.

Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.

Anti-Müllerian Hormone and Ovarian Morphology in Women With Hypothalamic Hypogonadism.

CONTEXT: Different phenotypical features of women with hypothalamic hypogonadism (HH), also known as World Health Organization-1 anovulation, including ovarian morphology, have been scarcely described in large cohorts. Some studies have reported increased levels of anti-Müllerian hormone (AMH) in women with HH. OBJECTIVE: To assess whether women with HH, compared with healthy controls, have increased serum levels of AMH and what proportion of these women erroneously meet the Rotterdam Criteria for Polycystic Ovarian Syndrome (PCOS). DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study in a Dutch academic medical center including 83 women with neither anovulation nor menstrual cycle disorders (healthy controls), 159 women with HH and 3640 women with PCOS. Age matching was used between the HH and PCOS group (1:2 ratio) to create a second group consisting of 318 age-matched women with PCOS. INTERVENTION: None. MAIN OUTCOME MEASURES: AMH levels and ovarian morphology. RESULTS: Median AMH serum levels for the HH group were 3.8 (<0.1-19.8), compared with 7.5 (<0.1-81.0) in the PCOS group and 1.9 (<0.1-21.5) in the control group (P < 0.001). In the HH group, 58 (36%) erroneously met the Rotterdam Criteria for PCOS (meeting 2 of 3 criteria). CONCLUSIONS: AMH levels are increased in women with HH. We hypothesize that this increase, although there was no increase in follicle count, may be explained by the presence of a relatively large pool of antral follicles smaller than 2 mm in diameter, that are undetectable by transvaginal ultrasound. This study highlights the importance of measuring gonadotropins and estradiol before diagnosing a patient with PCOS.

Metabolic features and changes in glucose-induced serum glucagon-like peptide-1 levels in children with hypothalamic obesity.

Background Hypothalamic damage may alter glucagon-like peptide-1 (GLP-1) secretion and be involved in the pathogenesis of obesity. We aim to evaluate the metabolic features and the dynamic changes of GLP-1 levels during an oral glucose tolerance test (OGTT) in children with hypothalamic obesity (HO) compared with simple obesity controls. Methods Subjects included eight patients (six females, aged 9-16 years) with hypothalamo-pituitary tumors who later developed obesity and eight controls with simple obesity matched for age, body mass index (BMI), gender and puberty. We assessed the metabolic syndrome features, fat mass, severity of hyperphagia using a standardized questionnaire, and measured glucose, insulin and GLP-1 levels during a standard 75 g OGTT. Results Age, gender distribution, pubertal status and BMI-Z scores were not significantly different. Subjects with HO had higher fasting triglycerides (TG) than controls (128 vs. 94 mg/dL; p=0.05). Four HO subjects and three controls met the criteria for the metabolic syndrome. Fasting and 120 min post-glucose load GLP-1 levels were significantly higher in HO patients than in controls (21.9 vs. 19.7 pg/mL; p=0.025, 22.1 vs. 17.7 pg/mL; p=0.012). Patients with HO had significantly higher hyperphagia scores than in simple obese controls (13 vs. 2.5; p=0.012). Conclusions Patients with HO appear to have more metabolic complications and hyperphagia than controls with simple obesity. Impaired satiety may play an important role in HO. Fasting and glucose-induced serum GLP-1 concentrations seem to be altered in HO patients and could be a part of the pathogenesis of HO.

Sudden onset of sleep caused by hypothalamic infarction: a case report.

BACKGROUND: Hypothalamic lesions, such as tumors and demyelinating diseases, reportedly cause abnormal sleepiness. However, stroke involving the hypothalamus has rarely been described. Here, we report a patient with infarction restricted to the hypothalamus who presented with sudden onset of sleep. CASE PRESENTATION: A 42-year-old woman with a history of migraine without aura presented with irresistible sleepiness and developed several episodes of sudden onset of sleep. Neurological examinations were unremarkable except for partial left Horner syndrome. Brain magnetic resonance imaging (MRI) revealed a high-intensity lesion restricted to the left hypothalamus on diffusion-weighted and fluid-attenuated inversion recovery MRI images. Cerebrospinal fluid (CSF) orexin-A levels obtained on hospital day 3 after her sleepiness had resolved were normal (337 pg/mL; normal > 200 pg/mL). Serum anti-nuclear and anti-aquaporin 4 (AQP4) antibodies and CSF myelin basic protein and oligoclonal band were negative. A small hypothalamic infarction was suspected, and the patient was treated with intravenous edaravone and argatroban, as well as oral clopidogrel. Three months later, there had been no clinical relapse, and the hypothalamic lesion had almost disappeared on follow-up MRI. No new lesion suggestive of demyelinating disease or tumor was observed. CONCLUSION: Hypothalamic stroke should be considered a cause of sudden onset of sleep.

Anti-Hypothalamus and Anti-Pituitary Auto-antibodies in ROHHAD Syndrome: Additional Evidence Supporting an Autoimmune Etiopathogenesis.

BACKGROUND: Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a very rare and complex pediatric syndrome characterized by altered hypothalamic thermal regulation, pain threshold, and respiratory control, hyperphagia with rapid weight gain and, often, hypothalamic-pituitary dysfunction. Its etiopathogenesis remains undetermined. We investigated the presence of alterations to target genes and hypothalamic-pituitary autoimmunity in a patient with -ROHHAD syndrome. METHODS: A 3-year-old girl presenting with obesity after rapid weight gain was diagnosed with ROHHAD syndrome based on clinical features and abnormal biochemical and functional testing results. Because of worsening of rapid symptoms and demonstration of oligoclonal bands on cerebrospinal fluid (CSF) analysis, she was treated with plasmapheresis, methylprednisolone, anti-CD20 monoclonal antibodies, and azathioprine. Despite initial partial clinical improvement, the patient soon died of cardiorespiratory arrest. Post-mortem, whole exome sequencing, high-resolution comparative genomic hybridization array, and optimized indirect immunofluorescence (IIF) analysis were performed on blood and CSF. RESULTS: No putative causative genomic variants compatible with dominant or recessive inheritance nor clinically significant structural rearrangement were detected. IIF on serum and CSF demonstrated the presence of anti-pituitary and anti-hypothalamus autoantibodies. CONCLUSIONS: These findings support the involvement of autoimmunity in ROHHAD syndrome. However, response to immunosuppressive treatment was only transient and the patient died. Further cases are required to define the complex disease pathogenesis.

[Evaluation of nutrition, body composition and features of dietetic counseling for patients with functional hypothalamic amenorrhea].

The assessment of nutrition status, anthropometry, eating disorders, fat tissue and leptin levels in 48 patients with functional hypothalamic amenorrhea (FHA) was conducted. The study of nutrition status revealed a discrepancy between the caloric intake and energy expenditure in 50% of patients, inadequate daily intake of carbohydrates in 91.7%, increased protein intake in 70.8% of patients. The recommended ratio of proteins, fats, carbohydrates in patients of the study group was not observed (1:1:0.3). It was noted that the deficit of adipose tissue and the decrease in serum leptin concentration were observed not only in patients with low body mass index), but also in 70% of women with normal values. Using the questionnaire Eating Disorder Inventory 2 (EDI-2) revealed that 54.2% of patients had drive for thinness and 22.9% of patients had body dissatisfaction. The results indicate the need for an integrated approach to the management of patients with FHA, which provides consultation of a gynecologist, psychotherapist and nutritionist.

Hypothalamic and pituitary dysfunction is common in tubercular meningitis: A prospective study from a tertiary care center in Northern India.

INTRODUCTION: Current literature is poor with respect to well conducted prospective studies of hypothalamic pituitary axis (HPA) dysfunction in tubercular meningitis (TBM). As hormonal deficiencies are associated with poor clinical outcome in various neurological and non-neurological disorders, we prospectively evaluated the hypothalamic pituitary axis (HPA) dysfunction in TBM. PATIENTS AND METHODS: Present study included newly diagnosed drug naive TBM patients (n = 63) at a tertiary care centre in Northern India. All patients underwent detailed clinical, radiological evaluation (Gadolinium enhanced magnetic resonance imaging of brain) and HPA hormonal profiles (electrochemiluminescence assay) both at initial presentation and at six month follow up. All the data was recorded on a predesigned proforma. RESULTS: 77.8% patients had definite and 22.2% had highly probable TBM. 84.2% of patients had pituitary hormonal abnormalities at presentation. These included hyperprolactinemia (49.2%), secondary adrenal deficiency (42.9%), secondary hypogonadism (38.1%) and central hypothyroidism (9.5%). At follow up, 42.1% patients had HPA abnormalities [hyperprolactinemia (13.2%), secondary hypogonadism (15.8%), secondary adrenal deficiency (10.5%) and central hypothyroidism (10.5%)]. On multivariate logistic regression analysis, secondary hypocortisolism (Odd ratio: 4.042; 95% CI = 1.074-15.22; P = .039) was associated with poor outcome in TBM. CONCLUSION: Abnormalities of HPA are common in TBM. Patients with TBM should be evaluated for dysfunction of HPA and treated accordingly.

Changes in hormones of the hypothalamic-pituitary-gonadal axis in migraine patients.

The incidence of migraine is higher in women than in men. Abnormality of the hypothalamus-pituitary-gonadal (HPG) axis is believed to be implicated in the pathogenesis of migraine. The aim of this study was to detect serum hormone levels in the HPG axis of migraineurs and analyze the relationship between the hormone levels and migraine-related clinical characteristics. One hundred and nineteen migraineurs were enrolled. Serum FSH, LH, estradiol, progesterone, testosterone, prolactin and GnRH was detected. Pain intensity and migraine-related disability were evaluated using the visual analogue scale (VAS) and the Migraine Disability Assessment questionnaire (MIDAS). The relationships between sex hormone levels and the VAS score and the MIDAS score were also examined. Progesterone levels in male migraineurs were lower than those in healthy controls (P < .01). In female patients, in the follicular phase, testosterone levels were lower than in healthy controls (P < .01). In the luteal phase, estrogen and testosterone levels (P < .05) were lower than in healthy controls. Progesterone and testosterone levels (P < .01) were lower than in healthy controls in the postmenopausal phase. In male patients, estrogen levels were negatively associated with the MIDAS score (r = -0.602). In female patients, in the follicular phase, estrogen levels were positively correlated with headache duration and VAS score (r = 0.374, r = 0.331, respectively) and negatively related with MIDAS score (r = -0.334). In the luteal phase, estrogen and progesterone levels were negatively correlated with the MIDAS score (r = -0.772, r = -0.464, respectively). The levels of HPG axis hormones were abnormal in migraineurs and were associated with migraine-related clinical characteristics.

Heightened cortisol response to exercise challenge in women with functional hypothalamic amenorrhea.

BACKGROUND: Functional hypothalamic amenorrhea is characterized by anovulation caused by reduced gonadotropin-releasing hormone drive and is associated with hypercortisolemia that has been linked to heightened hypothalamic-pituitary-adrenal reactivity to common psychological and metabolic challenges. OBJECTIVE: We hypothesized that women with functional hypothalamic amenorrhea would display greater cortisol responses to exercise challenge than ovulatory women with eumenorrhea. STUDY DESIGN: We completed a cross-sectional comparison of 9 women with functional hypothalamic amenorrhea and 11 women with eumenorrhea who were of reproductive age, who weighed 90-110% ideal body weight, who did not exercise excessively, and who had no formal psychiatric diagnosis. Subjects completed a 20-minute submaximal exercise challenge using a cycle ergometer in a research exercise laboratory. Heart rate and circulatory cortisol, glucose, and lactate were measured at 10-minute intervals before, during, and after the exercise challenge. RESULTS: Baseline (t= -10 minutes) cortisol, glucose, lactate, and heart rate were comparable between groups. Glucose levels rose modestly during exercise by 2.9% in women with eumenorrhea (P=.4) but declined by 10.6% in functional hypothalamic amenorrhea (P<.03). The nadir in glucose levels in functional hypothalamic amenorrhea occurred at the end of the 20-minute exercise challenge (t= +20 min). Lactate levels rose comparably in both groups (P<.01). Heart rate increased significantly with exercise in both groups (P<.01), but the increase was smaller in subjects with functional hypothalamic amenorrhea (P<.01). Cortisol levels increased during the exercise challenge in both groups (P<.01) and peaked 10 minutes after the exercise ended (t= +30 min). At peak, subjects with functional hypothalamic amenorrhea displayed higher cortisol levels (147±22 [standard error of the mean] ng/mL) than women with eumenorrhea (96±12 ng/mL; P=.05). The mean percent increase over baseline was 62% in women with eumenorrhea and 92% in functional hypothalamic amenorrhea. CONCLUSION: The heightened cortisol response to exercise in women with functional hypothalamic amenorrhea was associated with a decline in blood glucose level that was not observed in women with eumenorrhea. Women with functional hypothalamic amenorrhea appear to be more reactive at the endocrine level to the metabolic demand of exercise. Submaximal challenge unmasks underlying stress sensitivity in women with functional hypothalamic amenorrhea and highlights the importance of the use of psychological interventions for stress reduction in this population.

Features of polycystic ovary syndrome (PCOS) in women with functional hypothalamic amenorrhea (FHA) may be reversible with recovery of menstrual function.

OBJECTIVE: Since features of polycystic ovary syndrome (PCOS) have been found to be prevalent in women with functional hypothalamic amenorrhea (FHA), we wished to determine what happens to these features after recovery of menstrual function in FHA Design: Prospective cohort study. Twenty-eight women with FHA and 30 age-matched ovulatory controls were studied. METHODS: Twenty-eight women with FHA and 30 age-matched ovulatory controls were studied. We measured serum estradiol, LH, FSH, testosterone, DHEAS, anti-Mullerian hormone (AMH), body mass index, and ovarian morphology on transvaginal ultrasound. RESULTS: At baseline, 12 of the 28 women (43%) had increased AMH (>4.7 ng/mL), and higher testosterone and larger ovaries compared to the other 16 women with normal AMH. One year after recovery of menstrual function, in the 12 women with increased AMH, serum AMH, testosterone and ovarian size decreased, while LH and estradiol increased. At one year, only one of the 12 women in the high AMH group developed clinical features of PCOS. CONCLUSIONS: In the majority of women with FHA who have PCOS-like features, these features may be due to the hypothalamic state and appear to be reversible. Few women may develop clinical PCOS after recovery.

Steroids, steroid precursors, and neuroactive steroids in critically ill equine neonates.

Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal survival score (Group 1: 3-18%; Group 2: 38-62%; Group 3: 82-97% likelihood of survival). Blood concentrations of adrenocorticotropic hormone (ACTH) and steroids were determined by immunoassays. ACTH-cortisol imbalance (ACI) was defined as a high ACTH/cortisol ratio. Septic foals had higher ACTH, cortisol, progesterone, 17α-OH-progesterone, pregnenolone, and androstenedione concentrations as well as higher ACTH/cortisol, ACTH/progesterone, ACTH/aldosterone, and ACTH/DHEAS ratios than SNS and healthy foals (P<0.01). Foals with DHEAS of 0.4-5.4ng/mL were more likely to have ACI (OR=2.5). Foals in Group 1 had higher ACTH, aldosterone, progesterone, and cortisol concentrations as well as ACTH/cortisol, ACTH/progesterone, and ACTH/DHEAS ratios than foals in Groups 2 and 3 (P<0.01). High progesterone concentrations were associated with non-survival and the cutoff value below which survival could be predicted was 23.5ng/mL, with 75% sensitivity and 72% specificity. In addition to cortisol, the response to the stress of illness in foals is characterised by the release of multiple adrenal steroids. DHEAS and progesterone were good predictors of HPAA dysfunction and outcome in hospitalised foals.

Investigation of the clinical significance of the growth hormone-releasing peptide-2 test for the diagnosis of secondary adrenal failure.

The aim of this study was to evaluate the ability of the growth hormone-releasing peptide-2 (GHRP-2) test to clinically diagnose hypothalamo-pituitary-adrenal (HPA) axis failure. We performed an insulin tolerance test (ITT), CRH stimulation test, and GHRP-2 test on 47 patients suspected of having a hypothalamo-pituitary disorder. Patients with pituitary disorders had significantly lower ACTH responses to the GHRP-2 test compared to patients with hypothalamic disorders and the control group. In contrast, peak cortisol levels in response to the GHRP-2 test were significantly lower in both hypothalamic and pituitary disorder cases compared with the control group. Assignment of a cut-off value of 11.6 µg/dL for the peak serum cortisol level demonstrated that the GHRP-2 test was able to predict secondary hypoadrenalism with 88.9% specificity and 89.7% sensitivity. The responses of ACTH and cortisol to the GHRP-2 test had no correlation to the CRH test, suggesting the involvement of a different mechanism of ACTH secretion. These results indicate that the GHRP-2 test may induce ACTH secretion from the pituitary gland through direct stimulation. Although the GHRP-2 test does not have the same predictive value as the insulin tolerance test (ITT), it has similar diagnostic potential as the CRH stimulation test for evaluating HPA axis failure.

[Functional hypothalamic amenorrhea]. / Funkcní hypotalamická amenorea.

Functional hypothalamic amenorrhea (FHA) besides pregnancy and syndrome of polycystic ovary is one of the most common causes of secondary amenorrhea. FHA results from the aberrations in pulsatile gonadotropin-releasing hormone (GnRH) secretion, which in turn causes impairment of the gonadotropins (follicle-stimulating hormone and luteinizing hormone). FHA is a form of the defence of organism in situations where life functions are more important than reproductive function. FHA is reversible; it can be normalized after ceasing the stress situation. There are three types of FHA: weight loss related, stress-related, and exercise-related amenorrhea. The final consequences are complex hormonal changes manifested by profound hypoestrogenism. Additionally, these patients present mild hypercortisolemia, low serum insulin levels, low insulin-like growth factor 1 (IGF-1) and low total triiodothyronine. Women health in this disorder is disturbed in several aspects including the skeletal system, cardiovascular system, and mental problems. Patients manifest a decrease in bone mass density, which is related to an increase in fracture risk. Therefore, osteopenia and osteoporosis are the main long-term complications of FHA. Cardiovascular complications include endothelial dysfunction and abnormal changes in the lipid profile. FHA patients present significantly higher depression and anxiety and also sexual problems compared to healthy subjects.

Headache and Depression in Patients with Hypothalamic-pituitary Disorders-etiology and Risk Factors.

INTRODUCTION: Headache and depression are common problems in patients with hypothalamic-pituitary disorders (HPD). AIM: To determine the prevalence of headache and depression in patients with HPD and the specific characteristics in affected individuals in comparison to patients with cardiovascular problems (CD). METHODS: Patients with HPD and CD were asked to complete a questionnaire regarding headache and depression. RESULTS: There were no significant differences between the HPD and the CD group. Prevalence of headache was not associated with the treatment modality of pituitary disease, hormone excess syndromes or any hormonal replacement therapy. However, ACTH, TSH and GH deficiency were associated with less headache when compared to patients with adequate secretion. Interestingly, patients who had prior surgery suffered significantly more often from depression. In addition, headache and depression were significantly more common in patients with microadenomas than in macroadenomas. DISCUSSION: The risk for headache and depression is mainly influenced by a combination of factors, but a specific pituitary hormone deficiency may decrease risk for headache.

Revised criteria for PCOS in WHO Group II anovulatory infertility - a revival of hypothalamic amenorrhoea?

OBJECTIVE: To evaluate revised criteria for polycystic ovarian morphology (PCOM) in the diagnosis of polycystic ovary syndrome (PCOS) in anovulatory infertility. DESIGN: Prospective cohort study. PATIENTS: WHO Group II anovulatory infertile women (n = 75). MEASUREMENTS: Clinical, sonographic and endocrine parameters, including anti-Müllerian hormone (AMH). RESULTS: The Rotterdam criteria for PCOM (antral follicle count (AFC) ≥12 and/or ovarian volume >10 ml) were fulfilled in 93% of the women. The PCOM prevalence was 68% when increasing the threshold to AFC >20 and 76% according to an AMH-based threshold of >35 pmol/l. The most recently proposed AFC ≥ 25 threshold reduced the PCOM prevalence to 52% (n = 39), leaving 48% (n = 36) without features of PCOM. Comparing the 36 women with non-PCOM with the 39 women in the PCOM group according to AFC ≥ 25, 22% vs 59% (P = 0·001) had serum LH >10 IU/l, 11% vs 41% (P = 0·003) had an LH/FSH ratio >2 and 19% vs 41% (P = 0·04) had hirsutism and/or elevated total testosterone, free testosterone, and/or androstenedione. The non-PCOM group included significantly more women with secondary infertility. The median AMH in the non-PCOM group was 47 pmol/l, which was twofold lower than in the PCOM group but above the upper limit of normo-ovulatory women. CONCLUSIONS: According to a revised threshold of 25 follicles, almost half the anovulatory infertile women do not have PCOM. The characteristics of these women may be compatible with hypothalamic anovulation, but according to AMH levels, the ovaries remain multifollicular. PERSPECTIVES: A better distinction between hypothalamic amenorrhoea and PCOS could improve treatment strategies for anovulatory infertility.

The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice.

GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles. Secondary complications of high-fat diet (HFD)-induced obesity are reported to be associated with hypothalamic inflammation and gliosis. Because GH and IGF-1 can modulate inflammatory processes, our objective was to evaluate the effect of HFD on hypothalamic inflammation/gliosis in the absence of GH signaling and determine how this correlates with changes in systemic metabolism. On normal chow, GHR-/- mice had a higher percentage of fat mass and increased circulating nonesterified free fatty acids levels compared with wild type (WT), and this was associated with increased hypothalamic TNF-α and phospho-JNK levels. After 7 weeks on a HFD, both WT and GHR-/- mice had increased weight gain, with GHR-/- mice having a greater rise in their percentage of body fat. In WT mice, HFD-induced weight gain was associated with increased hypothalamic levels of phospho-JNK and the microglial marker Iba-1 (ionized calcium-binding adapter molecule 1) but decreased cytokine production. Moreover, in GHR-/- mice, the HFD decreased hypothalamic inflammatory markers to WT levels with no indication of gliosis. Thus, the GH/IGF-1 axis is important in determining not only adipose tissue accrual but also the inflammatory response to HFD. However, how hypothalamic inflammation/gliosis is defined will determine whether it can be considered a common feature of HFD-induced obesity.