Anterior pituitary function in Rathke's cleft cysts versus nonfunctioning pituitary adenomas.

Although Rathke's cleft cysts (RCCs) are common sellar/parasellar lesions, studies examining pituitary function in patients with nonsurgical RCC are limited. This study aimed to clarify the importance of RCCs, including small nonsurgical ones, as a cause of hypopituitarism by determining the prevalence of pituitary hormone secretion impairment and its relationship to cyst/tumor size in patients with RCC and in those with nonfunctioning pituitary adenoma (NFA). We retrospectively investigated the basal levels of each anterior pituitary hormone, its responses in the stimulation test(s), and cyst/tumor size in patients with RCC (n = 67) and NFA (n = 111) who were consecutively admitted to our hospital for endocrinological evaluation. RCCs were much smaller than NFAs (median height, 12 vs. 26 mm). The prevalence of gonadotropin, PRL, and GH secretion impairment in RCC was lower in comparison to NFA (19% vs. 44%, 34% vs. 61%, and 24% vs. 46%, respectively), whereas the prevalence of TSH and ACTH secretion impairment was comparable (21-27% and 17-24%, respectively). A significant positive relationship between cyst/tumor size and number of impaired hormones was observed in both groups, but smaller cysts could cause hormone secretion impairment in RCC. Stimulation tests suggested that most hormone secretion impairment was attributable to the interrupted hypothalamic-pituitary axis in both groups. Therefore, RCC, even small ones, can cause pituitary dysfunction. Different mechanisms may underlie hypothalamic-pituitary interruption in RCC and NFA.

Dysregulation of hypothalamic-pituitary estrogen receptor α-mediated signaling causes episodic LH secretion and cystic ovary.

Polycystic ovary syndrome (PCOS) is a hypothalamic-pituitary-gonadal (HPG) axis disorder. PCOS symptoms most likely result from a disturbance in the complex feedback regulation system of the HPG axis, which involves gonadotrophic hormones and ovarian steroid hormones. However, the nature of this complex and interconnecting feedback regulation makes it difficult to dissect the molecular mechanisms responsible for PCOS phenotypes. Global estrogen receptor α (ERα) knockout (KO) mice exhibit a disruption of the HPG axis, resulting in hormonal dysregulation in which female ERα KO mice have elevated levels of serum estradiol (E2), testosterone, and LH. The ERα KO females are anovulatory and develop cystic hemorrhagic ovaries that are thought to be due to persistently high circulating levels of LH from the pituitary. However, the role of ERα in the pituitary is still controversial because of the varied phenotypes reported in pituitary-specific ERα KO mouse models. Therefore, we developed a mouse model where ERα is reintroduced to be exclusively expressed in the pituitary on the background of a global ERα-null (PitERtgKO) mouse. Serum E2 and LH levels were normalized in PitERtgKO females and were comparable to wild-type serum levels. However, the ovaries of PitERtgKO adult mice displayed a more overt cystic and hemorrhagic phenotype when compared with ERα KO littermates. We determined that anomalous sporadic LH secretion caused the severe ovarian phenotype of PitERtgKO females. Our observations suggest that pituitary ERα is involved in the estrogen negative feedback regulation, whereas hypothalamic ERα is necessary for the precise control of LH secretion. Uncontrolled, irregular LH secretion may be the root cause of the cystic ovarian phenotype with similarities to PCOS.-Arao, Y., Hamilton, K. J., Wu, S.-P., Tsai, M.-J., DeMayo, F. J., Korach, K. S. Dysregulation of hypothalamic-pituitary estrogen receptor α-mediated signaling causes episodic LH secretion and cystic ovary.

Evaluation of a Novel General Pituitary Hormone Score to Evaluate the Function of the Residual Anterior Pituitary (Adenohypophysis) in Patients Following Surgery for Pituitary Adenoma.

BACKGROUND The aim was to develop and assess a general pituitary hormone score to evaluate the function of the anterior pituitary (adenohypophysis) in patients following resection of pituitary adenomas. MATERIAL AND METHODS Sixty-six patients with pituitary null cell macroadenoma (1-3 cm diameter) (N=38) and pituitary null cell giant adenoma (≥3 cm diameter) (N=28) had preoperative and postoperative data including magnetic resonance imaging (MRI) and measurement of six pituitary hormones levels, adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The postoperative general pituitary hormone score, for 57 patients who underwent subtotal resection (>60%) and nine patients who underwent partial resection (≤60%), was 1-5 for each hormone level (score range, 6-30). RESULTS ACTH, GH, TSH, PRL, FSH, and LH levels in 38 patients with pituitary null cell macroadenoma were not statistically different from the 28 patients with pituitary null cell giant adenoma; the general pituitary hormone score in the former group was significantly increased compared with the latter group (P<0.05). ACTH, GH, TSH, PRL, FSH, and LH levels in the 57 patients with subtotal tumor resection were not significantly different from the nine patients with partial tumor resection; the general pituitary hormone score in the former group was significantly reduced compared with the latter group (P<0.05). CONCLUSIONS A general pituitary hormone score was developed that might be relevant to the evaluation of pituitary function following surgical resection of pituitary null cell macroadenoma and giant adenoma.

Evaluation of serum ferritin and thyroid function in the second trimester of pregnancy.

Ferritin is a universal intracellular protein that acts as an iron carrier. Several studies have indicated that iron deficiency affects thyroid function in non-pregnant women. Our objective was to assess the relationship between serum ferritin levels and thyroid function in pregnant women during the second trimester. Pregnant women with sufficient iodine intake and normal antithyroid antibodies during the second trimester were recruited from the obstetric outpatient department of the Fifth People's Hospital of Fudan University. Serum ferritin (SF) levels, thyroid function, anti-thyroid antibodies and vitamin B12 were determined by electrochemiluminescence immunoassay kit. Maternal serum iron (Fe), unsaturated iron binding capacity (UIBC), hemoglobin (Hb), creatinine (Cr), fasting blood glucose (FBG), and alanine aminotransferase (ALT) were also evaluated. Stepwise regressions performed to evaluate the associations between SF and other maternal parameters. In the second trimester, 11.4% pregnant women had a SF concentration less than 12 µg/L, and 7.6% pregnant women were anemic. SF levels were negatively correlated with serum TSH levels (r = -0.219, p < 0.05), and positively correlated with FT4 levels (r = 0.203, p < 0.05). Linear regression analysis showed only SF, age, week of gestation were significant predictors of regression with TSH as the dependent variable (ß: -0.007, -0.059, and 0.118 respectively; all p < 0.05). However consistent relation between the SF levels and FT4 was not observed in stepwise linear regression. Maternal iron status is a determinant of TSH concentrations during pregnancy in pregnant women during the second trimester.

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance.

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines.

Long-Term Follow-Up of Anterior Pituitary Deficiency after Aneurysmal Subarachnoid Hemorrhage: Prospective Cohort.

OBJECTIVE: The aim of this study was to evaluate the prevalence of hypopituitarism in the acute stage after aneurysmal subarachnoid hemorrhage (SAH) as well at the chronic stage, at least 1 year after bleeding, to assess its implications and correlation with clinical features of the studied population. PATIENTS AND METHODS: This was a prospective cohort study that evaluated patients admitted between December 2009 and May 2011 with a diagnosis of SAH secondary to cerebral aneurysm rupture. Clinical and endocrine assessment was performed during the acute stage after hospital admission and before treatment at a mean of 7.5 days (SD ± 3.8) following SAH, and also at the follow-up visit at a mean of 25.5 months (range: 12-55 months) after the bleeding. RESULTS: Out of the 119 patients initially assessed, 92 were enrolled for acute stage, 82 underwent hormonal levels analysis, and 68 (82.9%) were followed up in both acute and chronic phases. The mean age and median age were lower among patients with dysfunction in the acute phase compared to those without dysfunction (P < .05). The prevalence of dysfunction in the acute phase was higher among patients with hydrocephalus on admission computed tomography (57.9%) than among those without it (P < .05). At chronic phase, there was an association between dysfunction and Hunt & Hess scale score greater than 2 (P < .05). CONCLUSIONS: We believe that there is not enough literature evidence to incorporate routine endocrinological evaluation for patient victims of SAH, but we should always keep this differential diagnosis in mind when conducting long-term assessments of this population.

Relationship between pituitary stalk (PS) visibility and the severity of hormone deficiencies: PS interruption syndrome revisited.

CONTEXT: Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been evaluated due to the visibility of pituitary stalk (PS) in imaging findings. OBJECTIVE: The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS. METHODS: This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared. RESULTS: Of the 74 patients with PSIS, age at diagnosis was 25 (22-28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin-releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24-h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups. CONCLUSIONS: The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.

Pituitary dysfunction after aneurysmal subarachnoid haemorrhage: course and clinical predictors­the HIPS study.

OBJECTIVE: We describe the occurrence and course of anterior pituitary dysfunction (PD) after aneurysmal subarachnoid haemorrhage (SAH), and identify clinical determinants for PD in patients with recent SAH. METHODS: We prospectively collected demographic and clinical parameters of consecutive survivors of SAH and measured fasting state endocrine function at baseline, 6 and 14 months. We included dynamic tests for growth-hormone function. We used logistic regression analysis to compare demographic and clinical characteristics of patients with SAH with and without PD. RESULTS: 84 patients with a mean age of 55.8 (±11.9) were included. Thirty-three patients (39%) had PD in one or more axes at baseline, 22 (26%) after 6 months and 6 (7%) after 14 months. Gonadotropin deficiency in 29 (34%) patients and growth hormone deficiency (GHD) in 26 (31%) patients were the most common deficiencies. PD persisted until 14 months in 6 (8%) patients: GHD in 5 (6%) patients and gonadotropin deficiency in 4 (5%). Occurrence of a SAH-related complication was associated with PD at baseline (OR 2.6, CI 2.2 to 3.0). Hydrocephalus was an independent predictor of PD 6 months after SAH (OR 3.3 CI 2.7 to 3.8). PD was associated with a lower score on health-related quality of life at baseline (p=0.06), but not at 6 and 14 months. CONCLUSIONS: Almost 40% of SAH survivors have PD. In a small but substantial proportion of patients GHD or gonadotropin deficiency persists over time. Hydrocephalus is independently associated with PD 6 months after SAH. TRIAL REGISTRATION NUMBER: NTR 2085.

[Sheehan's syndrome--a forgotten disease with 100 years' history]. / Zespól Sheehana--zapomniana choroba ze stuletnia historia.

Although named after Harold Sheehan, postpartum ischemic pituitary necrosis was reported for the first time 100 years ago in Przeglad Lekarski by Leon Konrad Glinski. In the majority of cases, the syndrome is a consequence of severe postpartum bleeding episode resulting in severe hypotension or hemorrhagic shock. The frequency of Sheehan's syndrome has decreased in developed countries as a result of improved obstetrical care, but this clinical entity remains a common cause of hypopituitarism in developing countries. The syndrome is characterized by varying degrees of anterior pituitary dysfunction resulting from the deficiency of multiple pituitary hormones. The order of frequency of hormone loss has generally been found to be growth hormone and prolactin, gonadotropins, ACTH and thyrotropin. Women with Sheehan's syndrome exhibit a variety of signs and symptoms including failure to lactate or resume menses, loss of genital and axillary hair, and often occurring long after delivery clinical manifestations of central hypothyroidism and secondary adrenal insufficiency. Diagnosis is based on laboratory studies, including hormone levels and hormone stimulation tests. Treatment of Sheehan's syndrome involves hormone replacement therapy. The aim of this study is to review current knowledge on clinically relevant aspects of this clinical entity and to provide the reader with recommendations concerning its diagnosis and treatment.

A novel hook-shaped enhancement on contrast-enhanced sagittal magnetic resonance image in acute Sheehan's syndrome: a case report.

We report characteristic magnetic resonance (MR) image findings in a case of Sheehan's syndrome. A 37-year-old woman experienced complications of retained placenta and massive bleeding (3600 g) during delivery of a full-term baby. A pituitary function test demonstrated panhypopituitarism. MR image of the pituitary gland on postpartum day 10 revealed swelling of the anterior lobe. A hook-shaped enhancement was demonstrated on a sagittal image. The pituitary stalk, majority of the marginal zone of the anterior lobe, the anterior lobe just in front of the posterior lobe, and posterior lobe were well enhanced. In contrast, the central portion and the superior margin, just in front of the stalk insertion of the anterior lobe, were not enhanced. Anatomically, blood supply to these unenhanced portions of the anterior lobe was via the hypophyseal long portal vein and trabecular artery, which are tributaries of the superior hypophyseal artery that originate far from the internal carotid artery. Based on clinical history and MR image findings, the patient was diagnosed with Sheehan's syndrome and treated with hydrocortisone and levothyroxine. Follow-up MR image revealed marked atrophy of the anterior lobe. The characteristic hook-shaped enhancement in Sheehan's syndrome well reflected the vulnerability to massive bleeding based on the complex pituitary vasculature, which has not been reported previously. MR image with contrast enhancement is useful in the diagnosis of the acute phase of Sheehan's syndrome and in evaluating infarction of the anterior lobe.

Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients.

Polycystic ovary syndrome (PCOS) is a common endocrine condition that affects fertility through oligo-ovulation, hyperandrogenism and polycystic morphology of the ovaries. Since it has been demonstrated a high incidence of insulin resistance in PCOS patients, our study aimed to evaluate the efficacy of the integrative treatment with D-chiro-inositol (DCI) (500 mg die, per os, for 12 weeks) on hormonal parameters and insulin sensitivity in a group of overweight/obese PCOS patients (body mass index; BMI > 26). After the treatment, interval several endocrine parameters improved (luteinizing hormone [LH], LH/follicle stimulating hormone [FSH], androstenedione and insulin), insulin response to oral glucose tolerance test reported the significant improvement of insulin sensitivity as well as the gonadotropin-releasing hormone (GnRH)-induced (10 µg, in bolus) LH response. BMI decreased, though no lifestyle modification was requested. When data were analyzed according to the presence or absence of first-grade diabetic relatives, PCOS patients with diabetic relatives showed greater improvement after DCI administration. In conclusion DCI administration is effective in restoring better insulin sensitivity and an improved hormonal pattern in obese hyperinsulinemic PCOS patients, in particular, in hyperinsulinemic PCOS patients who have diabetic relatives.

[Antipsychotic-drug-induced hyperprolactinemia: physiopathology, clinical features and guidance]. / Hyperprolactinémies induites par les antipsychotiques : physiopathologie, clinique et surveillance.

BACKGROUND: Hyperprolactinemia is a frequent but neglected adverse effect observed in patients treated with antipsychotic-drugs. In this review, we summarize its physiopathogenetic mechanism, its clinical manifestations in men and women, and the way to manage it. LITERATURE FINDINGS: Prolactin is a hormone secreted by lactotroph cells in the anterior pituitary. Its synthesis and release are under the control of peptides, steroids and neurotransmitters. The main inhibitory regulation is made by dopamine, which binds dopamine receptors D2 on the membrane of lactotroph cells. Antipsychotic-drugs block these receptors and thus remove the inhibitory effect of dopamine on prolactin secretion. All antipsychotic-drugs block D2 receptors and all can induce hyperprolactinemia. Nonetheless, it seems that the faster the antipsychotic-drug dissociates from D2 receptors, the lesser the increase of prolactin in the plasma. Another way to explain hyperprolactinemia is the ability of antipsychotic-drugs to cross the blood-brain barrier. The role of their metabolites should also be considered. For these reasons, one can distinguish prolactin-raising (conventional neuroleptics, amisulpride, risperidone) and prolactin-sparing (clozapine, aripiprazole, olanzapine) antipsychotics. An English study showed that 18% of men and 47% of women treated with antipsychotics for severe mental illness had a prolactin level above the normal range. Hyperprolactinemia is in fact more frequent in women than in men. Sometimes it is asymptomatic, but the higher the prolactin level is, the more patients have clinical manifestations. Some symptoms are due to the hypogonadism caused by prolactin, which disturbs hypothalamic-pituitary axis function, and others are due to direct effects on target tissues. Consequently, patients can suffer from sexual dysfunction, infertility, amenorrhea, gynecomastia or galactorrhoea. Data suggest that these symptoms are common, but patients don't mention them spontaneously and clinicians underestimate their prevalence. In the long-term, hypogonadism involves a premature bone loss in men and women. Klibanski and colleagues showed that this loss is significant only in women with hyperprolactinemia associated with amenorrhea. That suggests that prolactin is not directly responsible for this clinical feature. Nevertheless, prolactin seems to be involved in the development of breast cancer, but its role is unclear for prostate cancer. DISCUSSION: Our review promotes a check-up before beginning a treatment with antipsychotic agents. First, a baseline prolactin level should be measured. It should also include the research on previous treatment with antipsychotic-drugs and the assessment of adverse effects suggestive of hyperprolactinemia. Questioning should finally look for any contra-indication to antipsychotics. Monitoring during antipsychotic treatment has been studied by a group of international experts in psychiatry, medicine, toxicology and pharmacy who made a critical review of clinical guidance on hyperprolactinemia. Experts notify that it is important to check whether patients have any sexual dysfunction, such as loss of libido or menstrual irregularity, and galactorrhoea. Prolactin level should also be controlled after three months of stable dose treatment, or if any clinical feature of hyperprolactinemia appears. If a patient prescribed antipsychotic-drugs has a confirmed prolactin level above the normal range, it is necessary to exclude other causes of hyperprolactinemia. If antipsychotics are really involved, the management should be adapted with the prolactin level and the patient him/herself. To summarize, clinicians can decrease the dose of the antipsychotic or switch to a prolactin-sparing drug. Oral contraceptives can be added whether to prevent pregnancy or to prevent bone loss and osteoporosis. Finally, experts recommend reserving dopamine agonists to treat antipsychotic-induced hyperprolactinemia in very exceptional circumstances as it can worsen the mental illness.

Anterior Pituitary Dysfunction After Traumatic Brain Injury: A Prospective Study.

OBJECTIVE: Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases. METHODS: This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase). RESULTS: At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months. CONCLUSIONS: Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients.

Pituitary function in patients with hereditary haemochromatosis.

Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1 ± 7.9 years; age at study inclusion 50.7 ± 7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 µg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4-3.0 µg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below -2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients.

Differential patterns of regional neuroadrenergic cardiovascular drive in acromegalic disease.

It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat-to-beat mean arterial pressure, heart rate and efferent post-ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30 min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.

Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) has been linked with rare abnormalities in genes encoding transcription factors necessary for pituitary development. We have isolated LHX3, a gene involved in a new syndrome, using a candidate-gene approach developed on the basis of documented pituitary abnormalities of a recessive lethal mutation in mice generated by targeted disruption of Lhx3 (ref. 2). LHX3, encoding a member of the LIM class of homeodomain proteins, consists of at least six exons located at 9q34. We identified a homozygous LHX3 defect in patients of two unrelated consanguineous families displaying a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. Two of these patients also displayed a severe pituitary hypoplasia, whereas one patient presented secondarily with an enlarged anterior pituitary. These LHX3 mutations consist of a missense mutation (Y116C) in the LIM2 domain at a phylogenetically conserved residue and an intragenic deletion predicting a severely truncated protein lacking the entire homeodomain. These data are consistent with function of LHX3 in the proper development of all anterior pituitary cell types, except corticotropes, and extrapituitary structures.

ACTH-secreting pituitary microadenomas are associated with a higher prevalence of central hypothyroidism compared to other microadenoma types.

CONTEXT: Unlike pituitary macroadenomas, microadenomas (micros) are not commonly associated with hypopituitarism. In clinical practice, we have observed that patients with ACTH-secreting micros have a higher than expected prevalence of central hypothyroidism (HT), and we speculated that this effect might be because of glucocorticoid-induced suppression of the hypothalamic-pituitary-thyroid axis. OBJECTIVE: To determine whether there is a difference in the prevalence of central HT among ACTH micros compared to other types of microadenoma, and if so, to investigate whether this is directly related to the degree of hypercortisolism. DESIGN, SETTING AND PATIENTS: Retrospective study of 149 newly diagnosed patients with pituitary micros: 34 ACTH-secreting, 72 prolactin-secreting (PRLomas) and 43 clinically nonfunctioning adenomas (NFAs). MAIN OUTCOMES MEASURES: Prevalence of central HT, correlation between normalized free T4 or TSH vs normalized urinary free cortisol (UFC) or salivary cortisol. RESULTS: The prevalence of central HT was significantly higher in the ACTH compared to the non-ACTH adenomas: 18% (ACTH), 1% (PRL) and 0% (NFAs). The mean normalized free T4 was lower in the ACTH micros compared to the non-ACTH micros (1·29 ± 0·06 vs 1·50 ± 0·23, P = 0·0001). There was no correlation between the degree of hypercortisolism, as reflected by 24-h urine free cortisol and salivary cortisol, and free T4 or TSH levels among the ACTH adenomas. Similarly, there were no differences in mean UFC or salivary cortisol between ACTH adenomas with and without central HT. Following transsphenoidal adenomectomy, central HT recovered in three of six patients with ACTH micros. CONCLUSIONS: These findings suggest that patients with ACTH-secreting microadenomas should always, at a minimum, undergo testing for central HT. However, given the potential for recovery of thyroid function following cure of Cushing disease, we recommend withholding thyroid hormone replacement until after pituitary surgery.

Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey.

AIM: The aim of this study is to evaluate the clinical, anthropometric, hormonal, and radiological characteristics of children with central diabetes insipidus (DI). METHODS: Case records of 34 children (22 boys and 12 girls) with documented central DI referred to the Pediatric Endocrinology and Adolescent Clinic of Dokuz Eylul University Faculty of Medicine were reviewed. The mean age at diagnosis was 6.4 +/- 5.6 years (range, 0.08-16 years). All patients underwent anterior pituitary function assessment and magnetic resonance imaging of pituitary at diagnosis. The median duration of follow-up was 7.9 +/- 4.5 years. RESULTS: The etiology of central DI was organic in 22 (64.7%) patients, trauma in 2 (5.9%) patients, and idiopathic in 10 (29.4%) patients. Organic causes consisted of craniopharyngioma in 7 patients, Langerhans cell histiocytosis in 4 patients, germinoma in 4 patients, holoprosencephaly in 3 patients, astrocytoma in 1 patient, cavernous hemangioma in 1 patient, Rathke's cleft cyst in 1 patient, and autoimmune polyendocrinopathy in 1 patient. Anterior pituitary hormone deficiencies were documented in 18 (53%) patients. Organic central DI group had a greater prevalence of anterior pituitary hormone deficiency when compared with the idiopathic group (66% and 10%, respectively; p = 0.007). The final height of patients with organic etiology were significantly lower than the idiopathic group (155 and 178, cm respectively; p = 0.021). CONCLUSIONS: Etiological diagnosis is possible in a significant proportion (70.6%) of children with central DI. Findings of this study suggest that accompanying anterior pituitary hormone deficiencies and short stature may be considered as indicators of organic etiology.

Evaluation of the anterior pituitary function in the acute phase after spontaneous subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a potential cause of hypopituitarism. Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH. AIM: To prospectively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters. METHODS: Pituitary function was tested in 60 patients within 72 h after spontaneous SAH. RESULTS: 56.9% of the patients showed at least one anterior pituitary hormone deficiency: gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies (33.3 and 22.0%, respectively), whereas ACTH and TSH deficiency was less frequent (7.1 and 1.8%, respectively). With the exception of secondary hypogonadism, the prevalence of other pituitary hormone deficiencies is in agreement with previous studies, which evaluated pituitary function on longterm follow up after SAH. No correlation was found between hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma Scales. Moreover, no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher's scale. CONCLUSIONS: We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself, the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism. Therefore, an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow-up.

A retrospective study of pituitary-thyroid interaction in patients with first-episode of bipolar disorder type I in Mania State.

ABSTRACT: Bipolar disorder (BD)-mania is related to the dysfunction of anterior pituitary gland, but the pituitary-thyroid interaction on the acute stage of BD has been controversial. In order to rule out the effects of drugs, we aimed to determine the upstream interaction of first-episode of BD type I in mania state, and tried to find the relationship between thyroid-stimulating-hormone (TSH) and Prolactin (PRL)This study included 70 real-world patients diagnosed with first-episode BD-mania recuited and 70 healthy controls (HC) matched for age and sex from 2016 to 2017 in the same district of Shanghai. We compared the levels of thyroid hormones and prolactin between the two groups, and linear regression and curve estimation were used for the correlation analysis of TSH and PRLThere were differences in triiodothyronine (TT3), total thyroxin (TT4), and free thyroxine (FT4) concentrations between the groups (P's < .05). After being grouped by sex, higher PRL in the male and female BD-mania subgroup were observed compared to each isosexual HC [(P's < .01, Cohen's d = 0.82/1.08, 95%CI (0.33, 1.31)/(0.58, 1.58)]. Higher FT4 in the male BD-mania group was observed compared to the HC males [(P's  < .01, Cohen's d = 0.90, 95%CI (0.41, 1.39)] while the female BD-mania group showed lower TT3 and TT4 compared to the HC females [(P's  < .01, Cohen's d = 0.93/0.88, 95%CI (0.43, 1.42)/(0.39, 1.37)]. In the female BD-mania group, correlation analysis established an inverse relationship between PRL and TSH (r2 = 0.25, F = 11.11, P < .01).The findings demonstrate that sex impacts the concentration of hormones secreted by the anterior pituitary of patients with first-episode BD-mania. The increased PRL may be a putative mechanism that underlies the onset in female patients with a moderate inverse relationship between TSH and PRL. Thyroid hormones and prolactin levels may be developed as potential markers for identifying BD-manic.