Cause Of Hypopituitarism Research Articles

7157 Unveiling PROP1 protein complex: NFIB as a key candidate in pituitary development

Abstract Disclosure: L.C. Iglesias García: None. M.F. Mercogliano: None. C. Schuster: None. L. Cheung: None. F. Brunello: None. V. Michan: None. M. Waldman: None. L. Defelipe: None. M. Martí: None. S.A. Camper: None. M.I. Perez-Millan: None. The transcription factor PROP1 is essential for pituitary development, and mutations in the gene are the most common cause of hypopituitarism in children. To understand PROP1 function, it is essential to identify the protein components of the PROP1 transcription complex. Rapid immunoprecipitation and mass spectrometry (RIME) experiments in GHFT1 cells, genetically engineered to express biotin-tagged PROP1, have revealed the association of PROP1 with 43 transcription factors (including β-CATENIN and the Nuclear Factor I/B). In silico analysis showed association between the armadillo domains of β-CATENIN and a predicted nuclear localization signal motif of PROP1. This interaction between PROP1 and β-CATENIN was confirmed in pituitary GHFT1 cells, where over-expression of PROP1 induces the translocation of β-CATENIN from the membrane and cytoplasm to the nucleus. Moreover, in pituitaries from Prop1df/df mutant embryos at e12.5, β-CATENIN was predominantly membrane-bound compared to wild-type embryos. These findings suggest that PROP1 is necessary for translocation of β-CATENIN to the nucleus during pituitary development.The association of PROP1 with NFIB is intriguing because PROP1 is necessary for the epithelial to mesenchymal-like transition of stem cells in pituitary development, and NFIB is associated with induction of EMT in several cancer models. We used immunohistochemistry to show that NFIB is expressed in embryonic pituitary glands from e12.5 to e16.5, and it co-localizes with the stem cell marker SOX2. To determine whether PROP1 and NFIB have common downstream targets, we performed CUT&RUN experiments for NFIB in GHFT-1 cells and compared the results with those from PROP1 ChIP-seq. Both PROP1 and NFIB bind to three sites in the NFIB gene, suggesting that NFIB is a downstream target of PROP1 and subject to autoregulation. Consistent with this idea, NFIB is reduced in pituitaries from Prop1df/df embryos at both e12.5 and e14.5 relative to normal littermates. Integration of the results from PROP1 ChIP-seq and RNA-seq (GHFT1 vs PROP1-GHFT1 cells) with NFIB CUT&RUN generated a list of 190 potential target genes. These genes are associated with cell migration, emphasizing their correlation with the EMT-like process orchestrated by PROP1 during pituitary development. In sum, we have identified an interesting set of PROP1 interacting proteins, including the transcription factor NFIB, which plays an important role in regulating stem cell differentiation in several organ systems. We have also cataloged the genome-wide set of binding sites for PROP1 and NFIB, which overlap at many genes regulating cell migration, a process that is important for pituitary stem cells to leave the niche and initiate differentiation. Presentation: 6/3/2024

8138 Pituitary Stalk Interruption Syndrome (PSIS) in a patient with Isolated Hypogonadotropic Hypogonadism

Abstract Disclosure: A. Thomson: None. R. Osman: None. Pituitary Stalk Interruption Syndrome in a Patient with Isolated Hypogonadotropic Hypogonadism Pituitary Stalk Interruption syndrome (PSIS) is a rare cause of hypopituitarism, characterized by a radiologic constellation of thin or interrupted pituitary stalk, hypoplasia, or aplasia of the anterior lobe and with the presence of an ectopic posterior pituitary (EPP). It is most commonly associated with isolated growth hormone deficiency (IGHD) and is often diagnosed in childhood. We present one case of a patient with isolated hypogonadotropic hypogonadism in adulthood, subsequently found to have an PSIS on MRI. A 45 year old male patient presented to our clinic with hypogonadism. He gradually started developing decreasing libido, fatigue, and loss of erections. He had normal puberty and childhood growth, and has fathered one child. He denied history of anosmia or visual symptoms. Subsequent hormonal testing showed: morning Total Testosterone: 145 ng/dl (normal 264-916 ng/dl), Free testosterone 1.5 pg/ml (normal 6.8-21.5 pg/ml), LH 1.1 mIU/ml (normal 1.7-8.6 mIU/ml) and FSH of 3.6 mIU/ml (normal 1.5-12.4 mIU/ml). Prolactin was minimally elevated at 21 ng/ml (normal 4.0 - 15.2 ng/ml). Thyroid, IGF-1, cortisol, and ferritin levels were within normal limits. Repeat levels showed similar findings. He denied ever taking any form of exogenous testosterone. His pituitary MRI revealed a small volume of anterior pituitary tissue, measuring 0.2cm x 0.7cm x 0.7cm, without discrete pituitary adenoma, a hypoplastic midline stalk measuring 1.3 mm in AP diameter (nl 2-3 mm), with a T1 hyperintense nodularity measuring 0.6cm x 0.4cm along the posterior aspect of the sella turcica consistent with EPP. No additional structural abnormality or any mass lesions were identified. He was subsequently started on replacement testosterone therapy and his symptoms resolved. PSIS usually presents in childhood with IGHD. Patients may have other pituitary hormone deficiencies and congenital central nervous system defects, although panhypopituitarism is rare. There have been reports in children with delayed puberty and isolated hypogonadotropic hypogonadism who have been found to have PSIS. Only one othercase of an adult female patient exhibiting hypogonadotropic hypogonadism as the only manifestation of PSIS has been documented in the literature. Our case highlights the potential for an adult male to present later in life with hypogonadotropic hypogonadism as a manifestation of PSIS. The marginally elevated prolactin level may be due to lack of inhibition of hypothalamic dopamine on lactotroph cells within the pituitary caused by the EPP, although it is doubtful that this has clinical significance. This is a rare presentation of PSIS, clinicians should be mindful ofthis radiological constellation and the potential for isolated hypogonadotropic hypogonadism presenting unusually in the adulthood. Presentation: 6/3/2024

7420 A Role for Glycoprotein Hormone Subunit Alpha 2 in Pituitary Development

Abstract Disclosure: L.T. Raetzman: None. X. Ge: None. K. Weis: None. Hypopituitarism results when the pituitary gland is not able to make one or more of its hormones. It is estimated that up to 80% of hypopituitarism detected at or near birth has no identifiable cause. We have created a mouse model of congenital hypopituitarism by conditionally deleting the gene Notch2 in the developing pituitary. NOTCH2 is expressed in pituitary stem cells and is necessary for stem cell maintenance, proliferation, and differentiation. However, the pathways NOTCH2 engages to affect pituitary development remain unclear. It is important to determine the mechanism of NOTCH2 action in the pituitary because it might help to reveal novel causes of hypopituitarism. In this study, we hypothesized that glycoprotein hormone subunit A2 (GPHA2), a corneal stem cell factor, is downstream of NOTCH2 signaling in the mouse pituitary. We found Gpha2 is expressed in a subset of quiescent Sox2-expressing pituitary stem cells by RNAscope in situ hybridization and scRNA seq analysis. A scRNA seq study in rats has also localized Gpha2 to Sox2-expressing folliculostellate cells. In Notch2 conditional knockout pituitaries, Gpha2 mRNA is reduced over 75% compared with control littermates. We then investigated the possible functions of GPHA2, hypothesizing it might have a role in stem cell maintenance and quiescence. However, pituitaries treated with a GPHA2 peptide do not have a change in proliferation or stem cell-related gene expression. Another role of GPHA2 may be as a paracrine signal to control lineage restricted cell fate. GPHA2 has been demonstrated to be a ligand for the thyroid stimulating hormone receptor (TSHR) and part of the hormone thyrostimulin. We demonstrated that, in dissociated adult pituitary cells, GPHA2 increased pCREB expression and this induction was reversed by co-treatment with a TSHR inhibitor. Our data show that TSHR is expressed in the rostral tip thyrotropes of the pars tuberalis and in isolated cells in the anterior lobe. These data suggest GPHA2 is a NOTCH2 related stem cell factor that activates TSHR signaling, potentially impacting pituitary development and maintenance as a paracrine signaling molecule. Presentation: 6/3/2024

OR13-03 Assessment Of Skeletal Health Including Bone Density, Turnover, Microarchitecture And Osteoporosis In Patients With Sheehan’s Syndrome: A Prospective, Multicentric Study In Asian Indians

Abstract Disclosure: L. Das: None. B. Laway: None. J. Sahoo: None. S.K. Bhadada: None. P. Dutta: None. Introduction: Sheehan’s syndrome (SS) is a rare cause of hypopituitarism. Evidence on skeletal health in patients with this condition is limited, and data on bone geometry, structure and volumetric bone mineral density (BMD) are lacking. We aimed to comprehensively explore skeletal fragility in a multicentric cohort of treated SS. Patients and Methods: Patients with SS were recruited for analysis of demographic, clinico-biochemical and hormonal profile including bone turnover markers. Areal BMD, T- and Z-scores and trabecular bone score (TBS) were evaluated using DXA. In a subset of patients (n=29) as well as age-and BMI-matched controls (n=34), high-resolution peripheral quantitative computed tomography (HRpQCT, XtremeCT II, Scanco Medical AG, Switzerland) was performed to assess bone geometry and microarchitecture. Results: There were a total of 105 patients with SS with a mean age 45.2 ± 10.5 years and a lag of 7.4 ± 5.5 years from disease onset to diagnosis. Regular levothyroxine replacement was ongoing in 91.2% and glucocorticoid replacement in 86.1% of the cohort. Past HRT replacement was done in 66.7% patients. Bone turnover markers (P1NP, CTX) were not significantly different between cases and controls. The T- score [-2.3 (-3.0 to -1.6) vs -1.5 (-3.0 to -0.7)] and Z-score [-1.4 (-2.1 to -1.2) vs -0.6 (-2.1 to -0.1)] at the lumbar spine (LS) and the T- score [-1.8 (-2.3 to -1.3) vs -0.8 (-2.1 to -0.1)] and Z-score [-1.1 (-1.7 to -0.4) vs -0.4 (-1.0 to 0.2)] at the femoral neck (FN) were lower in cases as compared to controls (trend towards significance). Osteopenia or osteoporosis was prevalent in significantly greater proportion of the cases as compared to controls, at LS (96.3% vs 64.7%), FN (91.7% vs 47%) and ultradistal radius (65.2% vs 11.8%). Bone microarchitectural assessment showed no significant differences between TBS, or bone geometry. However, trabecular volumetric bone mineral density was higher at both tibia (p<0.05) and radius (p>0.05) in cases as opposed to age-and BMI-matched controls. There was a weak negative correlation between glucocorticoid and levothyroxine replacement duration and BMD at both LS and FN (p<0.05), but not with replacement dose. Conclusion: Osteopenia-osteoporosis is highly prevalent in SS. BMD at both LS and FN is negatively correlated with duration of glucocorticoid and levothyroxine exposure. There are no significant differences in bone microarchitecture or geometry but tibial trabecular volumetric BMD is greater in treated SS. Presentation: Friday, June 16, 2023

Sella Turcica Size in Women with Sheehan Syndrome-A Case-Control Study.

Sheehan syndrome is a common cause of hypopituitarism in developing countries. Among risk factors, in addition to post-partum haemorrhage, a smaller sellar volume is also believed to predispose to pituitary necrosis. Some earlier studies have reported smaller sellar volume in these patients but involved a small number of patients and lacked matched controls. The main of the present study was to study the sellar volume in a large cohort of patients with Sheehan syndrome and compare it with age- and parity-matched controls. Fifty women with Sheehan syndrome and an equal number of age- and parity-matched controls were studied. Baseline investigations, relevant hormonal assay, and MRI of pituitary were studied in all. Sellar volume was significantly lower in patients with Sheehan syndrome (334.50 ± 129.08 mm3 in patients as against 456.64 ± 169.25 mm3 in controls, P = 0.000). Far more women with Sheehan syndrome than controls had decreased sellar volume (40% vs. 12%). Patients with Sheehan syndrome have a smaller sellar volume that may be a non-modifiable risk factor for the development of post-partum pituitary necrosis.

A RARE CASE OF SHEEHAN'S SYNDROME .

Sheehan's syndrome is postpartum hypopituitarism caused by necrosis of the pituitary gland.(1) It is rare complication which occurs in 1 out of every 100,000 births globally and is the most common cause of hypopituitarism in low- or middleincome countries [2, 3]. It is reported that Sheehan's syndrome accounts for 0.5% of all known cases of hypopituitarism in females [4]. The disease is deemed “rare” in industrialized nations, but in developing nations, due to a lack of access to sophisticated medical procedures, skilled professionals, and medical resources, which contributes to a higher prevalence of postpartum hemorrhage and subsequent Sheehan's syndrome, it is said to occur in 5 out of every 100,000 births [5, 6]. The prevalence is much higher in developing countries, with a prevalence as high as 3.1% in a state in India where more than half of the affected individuals had home deliveries [7]. The underlying process leading to Sheehan's syndrome is the infarction of the physiologically enlarged anterior pituitary lobe (due to hyperplasia of prolactin secreting cells as a result of elevated estrogen secretion) and secondary to the compression of the blood vessels supplying the gland by the enlarged gland itself or due to grossly decreased blood.

Approach to the Patient: A Case With an Unusual Cause of Hypopituitarism.

Hypopituitarism, which refers to insufficiency of one or more hormones of the pituitary, can be due to myriad causes. The clinical and radiological spectrum of the condition is heterogeneous, based on the patient's age, gender, clinical setting, and/or other past medical history. Hypopituitarism includes central hypocortisolism, hypothyroidism, hypogonadism, and growth hormone deficiency. Both hypo- and hyperprolactinemia can be associated with hypopituitarism, with low prolactin signifying more extensive pituitary damage. Posterior pituitary insufficiency (arginine vasopressin deficiency) occurs either in isolation or with anterior pituitary hormone deficiency. Clinical symptomatology of hypopituitarism is usually nonspecific and insidious in onset and progression. Overall, the most common cause of hypopituitarism is a pituitary adenoma and/or its management (surgery, radiotherapy, pharmacotherapy, or a combination of these). However, it is this subset of patients which is more likely to be identified and managed in a timely manner, possibly alleviating the premature mortality associated with hypopituitarism. What is more challenging is the recognition of hypopituitarism in less common settings, which may be either due to direct involvement of the pituitary (infection, traumatic brain injury, or infiltrative causes) or indirectly as a consequence of the primary process (thalassemia, vasculotoxic snakebite, subarachnoid hemorrhage). These entities are often under-recognized, and increased awareness can help in greater recognition of the burden. Further, pituitary insufficiency in most of these settings is dynamic and may progress, or rarely, show recovery of function. This renders complexity to the problem, but makes it even more imperative to suspect, screen, and appropriately manage patients with less common causes of hypopituitarism.

Partial Empty Sella Syndrome Presenting with Panhypopituitarism and Masked Central Diabetes Insipidus

Empty sella syndrome (ESS) is an uncommon cause of hypopituitarism. It is usually detected incidentally or with neurological symptoms whereas it is rare to present with symptomatic endocrine dysfunction. A 48-year old previously healthy man presented with generalized body weakness, lethargy, fatigue and pos­tural dizziness of one month with no headache or visual disturbance. He also had features suggestive of hypo­gonadism and hypothyroidism. Panhypopitutarism secondary to partial ESS was diagnosed based on pituitary hormone testing and MRI brain. After starting glucocorticoid (GC) replacement patient developed polyuria and polydipsia and was diagnosed to have partial central diabetes insipidus (DI). He was successfully treated with hydrocortisone, thyroxin, intranasal vasopressin and testosterone. ESS causes significant pituitary dysfunction in considerable proportion of patients.

ODP332 Maternal Central Diabetes Insipidus Immediately after Delivery, Owing to Vasospasm of the Internal Carotid Artery

Abstract Background Sheehan's syndrome is a cause of hypopituitarism during the postpartum period, but it rarely manifests immediately after birth. Clinical Case We report the case of a 30-year-old woman who delivered her second child, lost 1,050 mL of blood in the process, but did not receive a blood transfusion. A few hours after delivery, the patient complained of headache, nausea, and thirst, and her urine production increased to 9 L/day. No menstrual irregularities or abnormalities during pregnancy or childbirth had been reported. None of hypotension, external eye muscle paralysis, or visual impairment were identified on physical examination. The laboratory findings were low urine osmolality and high serum osmolality and sodium concentration. The concentrations of thyroid hormones, growth hormone (GH), and anti-diuretic hormone (ADH) were found to be low. The IgG4 concentration was not high (4.7 mg/dL; normal <105 mg/dL) and the patient was negative for anti rabphilin-3A antibody. Pituitary magnetic resonance imaging (MRI) on the day of admission showed enlargement of the pituitary gland and stalk, and magnetic resonance angiography showed stenosis of the left internal carotid artery. The patient showed a poor response to GH-releasing peptide 2 and thyroid releasing hormone stimulation. Hypertonic saline administration did not cause an increase in ADH concentration. We diagnosed adult growth hormone deficiency (aGHD), central hypothyroidism, and central diabetes insipidus (DI). The enlargement of the pituitary gland was slightly less marked and the stenosis of the left internal carotid artery improved 7 days after admission. After 6 months, the pituitary gland was almost normal in size, although the aGHD, central hypothyroidism, and central DI remained. Sheehan's syndrome or lymphocytic hypophysitis could have been responsible for the postpartum hypopituitarism. This case was not typical of lymphocytic hypophysitis with respect to the hormone deficiency pattern, the MRI findings, and the lack of anti rabphilin-3A antibody. Sheehan's syndrome is caused by ischemic necrosis of the anterior pituitary gland after severe postpartum hemorrhage. The prevalence of central DI is estimated to be 2%–3%. Typically, pituitary dysfunction progresses slowly and develops several years after childbirth. In contrast, in the present patient, stenosis of the left internal carotid artery developed and improved during short periods of time. The vasospasm of the internal carotid artery caused reductions in flow through the superior and inferior hypophysial arteries, which resulted in ischemia and necrosis of the pituitary gland, similar to Sheehan's syndrome. Clinical Lesson: Although rare, maternal central DI can be caused by ischemia and vasospasm immediately after the delivery of a child. The possibility of a pituitary stroke in the presence of neoplastic disease should not be ruled out, and imaging and pituitary gland function should be followed over the long term. Presentation: No date and time listed

An unusual cause of hypopituitarism with An even more unusual presentation - a case report

An unusual cause of hypopituitarism with An even more unusual presentation - a case report

A Challenging Diagnosis of Sheehan's Syndrome in Non-obstetric Critical Care and Emergency Settings: A Case Series of Five Patients with Varied Presentations.

Sheehan’s syndrome is a life-threatening endocrine emergency seen in postpartum females secondary to ischemic pituitary necrosis. It is a frequent cause of hypopituitarism in developing countries that occurs secondary to postpartum haemorrhage (PPH). Patients with Sheehan’s syndrome often present with organ dysfunctions in critical care settings, secondary to stressors precipitating the underlying hormonal deficiencies. The initial clinical picture of Sheehan’s syndrome may mimic some other disease, leading to misdiagnosis and diagnostic delay. Strict vigilance, timely diagnosis, and appropriate management are essential to avoid diagnostic delay and to improve the patient outcome. In this case series, we describe 5 cases of previously undiagnosed Sheehan’s syndrome (including young, middle aged and postmenopausal females) that presented to critical care and emergency settings with organ failures.

Neurosarcoidosis - an uncommon but important cause of hypopituitarism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Overview of Congenital Hypopituitarism for the Neonatologist.

Congenital hypopituitarism is the deficiency in 1 or more hormones produced by the anterior pituitary or released by the posterior pituitary and has an estimated incidence of 1 in 4,000 to 10,000. Due to the critical role the pituitary plays in growth, metabolic, and reproductive processes, early diagnosis is essential to prevent devastating and often preventable outcomes. However, in neonates with congenital hypopituitarism, symptoms are often nonspecific and tend to overlap with other disease processes, making diagnosis extremely challenging in the neonatal period. This review highlights the embryology and organogenesis of the pituitary gland, genetic causes of hypopituitarism, clinical presentations in the neonatal period, and methods to diagnose and treat select deficiencies with a focus on anterior pituitary hormones.

Abstract 56: Clinical profile of adult onset hypopituitarism in patients presenting to a tertiary care center in South Tamil Nadu

Background: The data regarding clinical profile of adult onset hypopituitarism in India is limited. Previous studies have shown that pituitary and sellar tumors are the most common cause of hypopituitarism.Aims and Objectives: To study the clinical profile of patients with adult onset hypopituitarism presenting to the Endocrinology Department to our tertiary care centre.Results: A total of seventeen patients were included in the analyses. The mean age of the patients was 39.55 +/-14 years. There were 8 (47%) males and 9 (53%) females included in the study. The most common presenting complaints were amenorrhea (52%), headache (35%), visual complaints (29%). 29%(n=5) patients were admitted with acute adrenal crises requiring intravenous steroids at diagnosis. 11%(n=2) of patients had pituitary apoplexy. 47%(n=8) patients had pituitary or sellar tumors, 35%(n=6) patients had postpartum pituitary necrosis, one patient each had history of snake bite and head trauma. 94 %( n=16) patients had secondary adrenal insufficiency, 88 %( n=15) patients had secondary hypothyroidism, 70 %( n=12) patients had hypogonadotrophic hypogonadism, and only 11% (n=2) had growth hormone deficiency. 88 %( n=15) patients had panhypopituitarism.Conclusion: The most common causes of hypopituitarism in our study were pituitary and sellar tumors. 88% patients had panhypopituitarism, 35% patients had deficiency of two pituitary hormones.

Secukinumab, Pituitary Enlargement and Panhypopituitarism: Are They Related?

Pituitary adenomas are the most common cause of hypopituitarism associated with pituitary enlargement, but other aetiologies have been emerging, namely immune checkpoint inhibitor-induced hypophysitis (ipilimumab, nivolumab and pembrolizumab). Secukinumab is a recently approved human monoclonal antibody used for the treatment of psoriasis, with no know reported cases of hypophysitis. We describe a challenging case of panhypopituitarism in a patient with a pituitary incidentaloma and a temporal relationship between secukinumab initiation and the manifestation of clinical features suggestive of hypopituitarism. In such intricate work-up, the differential diagnoses should be carefully considered, taking into account the therapeutic and prognostic implications.LEARNING POINTSPituitary adenomas are the leading cause of hypopituitarism associated with pituitary enlargement, but clinicians should be aware of non-tumoural causes such as hypophysitis.Drug-induced hypophysitis has been described with immune checkpoint inhibitors used for diverse types of malignancies, but there is no evidence of an association between hypophysitis and the novel antipsoriatic agent, secukinumab.The differential diagnosis of hypopituitarism requires careful investigation so that management is appropriate and prognosis is improved.

Hypopituitarism and pregnancy: clinical characteristics, management and pregnancy outcome

PurposeTo describe the clinical characteristics, management and pregnancy outcome of women with prepregnancy hypopituitarism (HYPO) that received care at our center.MethodsRetrospective study describing 12 pregnancies in women with prepregnancy HYPO (two or more pituitary hormonal deficiencies under replacement treatment) that received care during pregnancy at Hospital Santa Creu i Sant Pau. Clinical characteristics, management and pregnancy outcome were systematically collected.ResultsAverage patients’ age was 35 years and HYPO duration at the beginning of pregnancy was 19 years. The most frequent cause of HYPO was surgical treatment of a sellar mass (8 pregnancies). Eight pregnancies were in primigravid women and 10 required assisted reproductive techniques. The hormonal deficits before pregnancy were as follows: GH in 12 women, TSH in 10, gonadotropin in 9, ACTH in 5 and ADH in 2. All deficits were under hormonal substitution except for GH deficit in 4 pregnancies. During pregnancy, 4 new deficits were diagnosed. The dosage of replacement treatment for TSH, ACTH and ADH deficits was increased and GH was stopped. Average gestational age at birth was 40 weeks, gestational weight gain was excessive in 9 women, 8 patients required induction/elective delivery and cesarean section was performed in 6. Average birthweight was 3227 g. No major complications were observed. Five women were breastfeeding at discharge.ConclusionsIn this group of women with long-standing HYPO, with careful clinical management (including treatment of new-onset hormonal deficits) pregnancy outcome was satisfactory but with a high rate of excessive gestational weight gain and cesarean section.

Insights into non-classic and emerging causes of hypopituitarism

Hypopituitarism is defined as one or more partial or complete pituitary hormone deficiencies, which are related to the anterior and/or posterior gland and can have an onset in childhood or adulthood. The most common aetiology is a sellar or suprasellar lesion, often an adenoma, which causes hypopituitarism due to tumour mass effects, or the effects of surgery and/or radiation therapy. However, other clinical conditions, such as traumatic brain injury, and autoimmune and inflammatory diseases, can result in hypopituitarism, and there are also genetic causes of hypopituitarism. Furthermore, the use of immune checkpoint inhibitors to treat cancer is increasing the risk of hypopituitarism, with a pattern of hormone defects that is different from the classic patterns and depends on mechanisms that are specific for each drug. Moreover, autoantibody production against the pituitary and hypothalamus has been demonstrated in studies investigating the development or worsening of some cases of hypopituitarism. Finally, evidence suggests that posterior pituitary damage can affect oxytocin secretion. The aim of this Review is to summarize current knowledge on non-classic and emerging causes of hypopituitarism, so as to help clinicians improve early identification, avoid life-threatening events and improve the clinical care and quality of life of patients at risk of hypopituitarism. This Review summarizes current knowledge on non-classic and less common causes of hypopituitarism, such as traumatic brain injury, genetic causes, use of immune checkpoint inhibitors, autoimmune diseases and inflammatory diseases. Furthermore, emerging evidence that posterior pituitary damage can affect oxytocin secretion is highlighted.

Prevalence of coronary calcium deposits in Sheehan's syndrome patients on long term replacement treatment.

Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. The mean (± SD) age was 38.30 ± 10.73years and the diagnostic delay was 11.35 ± 4.74years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.

Sexual Dysfunction in Sheehan Syndrome

ObjectiveThe study was done to objectively document the sexual function in Sheehan syndrome (SS). SS is not an uncommon cause of hypopituitarism in developing countries. The lack of sex steroids from both ovaries and adrenal glands could lead to sexual dysfunction in SS. Sexual function is a neglected aspect of health in women in developing countries, although it greatly contributes toward the quality of life and feeling of well-being. Objective documentation of sexual function in SS is limited. MethodsThirty-two subjects with SS on conventional therapy (except growth hormone) were evaluated. SS was diagnosed as per standard criteria. Sexual function was assessed by validated questionnaires using the Female Sexual Function Index (FSFI). Thirty healthy women of a similar age range and socioeconomic background were included as comparators. ResultsThe mean age (±SD) of the study population and healthy controls was 39.9 (±8.6) years and 38.2 (±6.8) years, respectively. The median interval between inciting events and diagnosis of SS was 8.3 years (interquartile range, 5.2-13.5 years). Thirty subjects were sexually active. Of the 30 subjects, 28 (93%) had sexual dysfunction, that is, an FSFI score of ≤26.55. The median total FSFI scores of subjects with SS and controls were 20.8 and 29.05, respectively, (P = .001). There was a statistically significant difference for individual parameters of sexual function, including desire, arousal, lubrication, orgasm, and satisfaction, between those with SS and controls. However, the pain during intercourse was not different. FSFI score in subjects with SS was not correlated with any endocrine parameter or duration of the disease since diagnosis. ConclusionSexual dysfunction is very common, affecting >90% of subjects with SS.

Co-presentation of Acute Sheehan Syndrome with Raised Intracranial Pressure in a Post-partum Lady

Sheehan’s syndrome (SS) or necrosis of pituitary gland is a rare complication of severe postpartum hemorrhage. It may cause hypopituitarism immediately or several years later, depending on the degree of tissue destruction. Sheehan’s syndrome though rare is still one of the commonest causes of hypopituitarism in developing countries like ours. The presence of an intercurrent infection and administration of thyroxine exacerbated her corticosteroid insufficiency. Intracranial hypertension (IH) manifested as bilateral optic disc swelling with reduced visual acuity, bilateral sixth nerve palsies, and impaired consciousness. Intracranial hypertension (IH) has been associated with hypocortisolism caused by either primary adrenocortical insufficiency or corticosteroid withdrawal. The author describes a case of a young lady with IH with acute SS who presented on 3rd day postpartum after lower uterine cesarean section with acute severe symptomatic hyponatremia which was complicated by postpartum hemorrhage. The clinical manifestations of IH resolved with corticosteroid replacement