Cause Of Hypopituitarism Research Articles

Abstract #994705: The High Prevalence of Coronary Calcification and Increased Risk for Coronary Heart Disease in Patients with Sheehan’s Syndrome

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 pro-inflammatory 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). The present study was designed to evaluate the prevalence of coronary calcium deposits in patients with SS appropriately replaced for pituitary hormones deficiencies but untreated for GHD.

A Clinical Audit on Diagnosis and Management of Hypopituitarism in Scarborough General Hospital

Objectives: The main objective was to evaluate the use and compliance to the guidelines issued by the Endocrine Society in diagnosis and management of hypopituitarism and their impact on the clinical practice in Scarborough General Hospital (SGH). Design: A retrospective review of secondary data of patients with a diagnosis of hypopituitarism in SGH. Methodology: The data was collected from both patients’ case notes and electronic medical records. Data analysis was performed using Microsoft excel. Results: 18 patients with the diagnosis of Hypopituitarism were identified. 5 patients were females and 13 were males. 11 patients aged between 60-80 years, 4 patients were between 51-60 years and 3 patients were between 31-50 years. All the patients had low cortisol levels; however, cortisol was checked at 9AM in only 4 patients. All the patients had their thyroid stimulating hormone levels checked, which were low in all of them. Free T4 levels were normal in 2 patients, and low in 16 patients. 17 patients had low follicular stimulating hormone levels, whereas 15 had low luteinising hormone levels. Testosterone levels were checked in 9 male patients out of which 7 had low levels. Insulin-like growth factor-1(IGF1) was done in all patients and levels were low in 10 patients. All those with low IGF1 had glucagon stimulation test. Serum sodium levels were low in 3 patients and high in 5 patients. Plasma osmolality was only checked in 8 patients (was high in 5 patients). Urine osmolality was checked in 10 patients, and it was low in 5 patients. Brain MRI was performed in 16 patients, and 2 patients had brain CT. The most common cause of hypopituitarism was non-functioning pituitary adenoma (44.4%), and the least common causes were empty Sella syndrome (5.6%) and craniopharyngioma (5.6%). All patients received glucocorticoid replacement therapy, 17 received thyroid hormone replacement therapy, 8 received testosterone replacement therapy, 3 received desmopressin (DDAVP) treatment, and one patient received growth hormone replacement therapy. Conclusion: This Audit shows that our practice in diagnosis and management of hypopituitarism is mostly in line with the recommendation of the Endocrine Society. However, cortisol levels were not always measured at 9:00 am and we are not compliant with performing Growth Hormone stimulation test in every patient.

Identification of FOXA2 and PNPLA6 Among Other Genes, as a Potential Risk for Pituitary Hormone Deficiency

Abstract Pituitary hormone deficiency or hypopituitarism is characterized by a malformed or underdeveloped pituitary gland resulting in an impaired pituitary hormone secretion. Several transcription factors have been described in its etiology, but defects in known genes account for only a small proportion of cases. We sought to identify the cause of hypopituitarism in 171 unrelated patients diagnosed with or without extra-pituitary manifestations that were recruited from several Argentinean medical centers. We conducted panel sequencing, and identified among other genes and variants, de novo heterozygous mutations in FOXA2 and PNPLA6. FOXA2 is a transcription factor member of the forkhead class of DNA-binding proteins, involved in the early development of multiple tissues. FOXA2 is highly expressed throughout the developing hypothalamic-pituitary axis, and regulates GLI2, SHH and NKX2-2 expression. Mutations of FOXA2 have been linked to combined pituitary hormone deficiency (CPHD) in some cases with extra-pituitary phenotypes including hyperinsulinism or gastrointestinal malformations. We found two patients with CPHD and rare FOXA2 variants. Case 1 had GHD, anterior pituitary hypoplasia, mammary hypertelorism and digital anomalies and a heterozygous variant FOXA2 p.Arg228Ser, predicted to be pathogenic. Case 2 had GH and TSH deficiency, craniofacial anomalies and neurodevelopmental delay, and a novel, stop codon mutation FOXA2 p.Ser229* and an heterozygous GLI1 variant (p.Asp1048Asn). Both FOXA2 variants are located within the forkhead domain which may affect the DNA binding ability. We suspect they are likely damaging based on the literature, the in-silico prediction, and their absence in GnomAD. PNPLA6 is a conserved lysophospholipase involved in maintaining nervous system integrity. Mutations in PNPLA6 have been identified in a broad spectrum from pure ataxia to rare neuroendocrine conditions including Gordon Holmes and Oliver McFarlane syndromes. Here, we identified two de novo heterozygous variants in PNPLA6 in children with CPHD. Variant p.W1039R was found in a patient with CPHD, intellectual disability and visual problems. A second variant (p.T1115P) was identified in a 10-year-old girl with CPHD, retinitis pigmentosa and neurodevelopmental delay. According to modelling studies of the protein structure, both variants are expected to be critical for the activity of the NTE as they are located in close proximity to the protein’s catalytic pocket. It is likely that these variants may contribute to our patient’s phenotype. However, as most reported PNPLA6 variants in the literature were found in homozygosity or compound heterozygosity, additional studies are necessary to draw more definitive genotype-phenotype correlations. In summary, in this work we were able to expand our knowledge of pituitary target genes for genetic diagnosis for CH.

Classic cardiovascular risk factors improve in very elderly hypopituitary patients treated on standard hormone replacement in long term follow- up

BackgroundHypopituitarism in the elderly population is an underdiagnosed condition and may increase comorbidities related to glucose metabolism, dyslipidemia, and cardiovascular risk factors. Optimization of hormone replacement that considers alterations in clearance rates of hormones, interaction with other medications, and evaluation of the risk-benefit ratio of treatment is a big challenge for clinical practice.ObjectivesThis study aimed to evaluate classic cardiovascular risk factors in hypopituitary septuagenarians and octagenarians by diagnosis and after long-term hormone replacement.MethodsThis is a retrospective observational study, with patients recruited and selected from a registry in a tertiary medical center. We included patients aged 70–99 years with hypopituitarism, evaluated hormonal and biochemical parameters, and cardiovascular risk scores were calculated by diagnosis and compared after long-term follow-up. All patients gave informed consent. Patient data were compared to a sex and age-matched control group, with long-term geriatric follow-up, without endocrine diseases.ResultsThirty-five patients were included, 16 patients aged 70–75 years (72.61), 12 patients 76–80 years (72.28), 7 patients 81–99 years (89.28). Pituitary macroadenomas were the main cause of hypopituitarism, mean maximal diameter 3.4 cm (2.9–4.3), and invasive craniopharyngiomas. At the moment of diagnosis, most patients were overweight, and abdominal adiposity was observed in 76.9% of women and 36.4% of men, primarily in octagenarians and nonagenarians. Comorbidities were frequent; 85.7% presented hypertension, 37.1% diabetes, 53.1% low HDL, 51.5% hypertriglyceridemia. Most patients presented more than two combined pituitary deficiencies; hypogonadism in 88.6%, central hypothyroidism in 82.9%, GH deficiency in 65.7%, and adrenal insufficiency in 25.7%. Analysis of cardiovascular risk prediction in the total cohort showed that 57.1% of patients presented a reduction in the General Cardiovascular Disease (CVD) Risk Prediction Score and 45.7% in atherosclerotic CVD risk estimated by ACC/AHA 2013 Pooled Cohort Equation, despite being submitted to conventional hormone replacement, during the mean follow-up of 14.5 years. This reduction was not observed in the control group.Discussion and conclusionIn this study, aged hypopituitary patients presented a reduction in estimated general CVD risk during long-term follow-up, despite replacement with corticosteroids, levothyroxine, or gonadal steroids. Early diagnosis and treatment of hypopituitarism in the elderly remain challenging. Larger studies should be performed to assess the risk-benefit ratio of hormone replacement on the metabolic profile in septuagenarian and octogenarian patients.

Pituitary Stalk Interruption Syndrome: A Case Report

Panhypopituitarism occurs as a result of the insufficiency of all hormones produced in the anterior pituitary gland. Pituitary Stalk Interruption Syndrome (PSIS) is a rare congenital syndrome leading to hypopituitarism. The anterior pituitary hormones should be evaluated in patients with the signs and symptoms of hormone insufficiency and magnetic resonance imaging of the pituitary should be performed for the etiology. Although PSIS is a rare cause of hypopituitarism, it must be treated with the replacement of the insufficient hormones. In this case report, we evaluated a PSIS case presented with panhypopituitarism

Chapter 14 - Antibodies against the pituitary and hypothalamus in boxers

Traumatic brain injury (TBI), a growing public health problem worldwide, has recently been recognized as one of the leading causes of hypopituitarism. The main causes of TBI-induced pituitary dysfunction are car accidents, falls, violence, sports-related brain injury, and war accidents, including blast-related brain injuries. Car accidents and falls are the most common causes of TBI and pituitary dysfunction among the younger generation and elderly population, respectively. The prevalence of hypopituitarism after TBI is about 30%. GH is the most common hormone lost. The mechanisms underlying hypopituitarism are still unclear; however, recent studies have demonstrated that hypoxic insult, increased intracranial pressure, axonal injury, genetic predisposition, neuroinflammation, and autoimmunity may be responsible for the development of pituitary dysfunction. Neuroendocrine abnormalities are recently described in athletes dealing with contact sports, including boxing and kickboxing, which are characterized by chronic repetitive head trauma. Mild TBI and concussion are accepted in boxing and kickboxing. The positivity of antipituitary and antihypothalamic antibodies is also a significant risk factor in the development of neuroendocrine abnormalities. Autoimmune reaction may also be responsible for the reduction in pituitary volume in boxers with hypopituitarism. In this chapter, the role of autoimmunity in the occurrence of pituitary dysfunction among boxers is discussed.

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.

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.

Slow Developing Sheehan Syndrome with Spontaneous Pregnancies: A Case Report and Literature Review

Sheehan's syndrome (SS) is known as pituitary insufficiency that develops after bleeding and hypovolemia at birth or after birth. The pathological and clinical findings of SS were first described by Harold L. Sheehan. Due to improvements in obstetric care, the frequency of the disease has declined worldwide. Sheehan syndrome is a rare cause of hypopituitarism in developed countries.. However, it is more common in underdeveloped and developing countries. Small sella size enlargement of the pituitary gland, autoimmunity also play a role in the pathogenesis of the disease. Depending on the pituitary damage, symptoms may appear immediately or years later. It may be presented as isolated hormone deficiency or pan hypopituitarism. For diagnosis, it is important to have a history of excessive hemorrhage at birth, amenorrhea and inability to breastfeed. Lymphocytic hypophysitis should be remembered in differential diagnosis. In this review, a patient with serious post-partum hemorrhage, followed by a history of 3 pregnancies is presented with a slow developing and pan hypopituitarism-causing SS and current physio pathological data in SS are presented.

Characteristics of NAFLD Based on Hypopituitarism.

Background Hypopituitarism and hypothalamic disorders, which induce central obesity and appetite disorder, are associated with nonalcoholic fatty liver disease (NAFLD). We retrospectively analyzed the clinical features of NAFLD patients with hypopituitarism. Patients. We examined the cases of 15 NAFLD patients with hypopituitarism (mean age, 39.4 years; males/females, 11/4). The causes of hypopituitarism were surgical in eight cases (six with craniopharyngioma and two with prolactinoma) and nonsurgical in seven cases, including unexplained hypopituitarism in five cases, Sheehan syndrome in one case, and one case that occurred after the radiation therapy. Serum adiponectin, soluble tumor necrosis factor receptor-2 (TNFR-2), and leptin levels were measured. Results We compared the cases of the eight patients who underwent cranial surgery due to craniopharyngioma or prolactinoma and seven nonsurgical cases. The body mass index (surgery group, 30.2 ± 4.1; nonsurgery group, 29.2 ± 14.2) and the rate of diabetes (75% in surgery group, 14.3% in nonsurgery group) tended to be higher in the surgery group, and the hepatic fibrosis grade (surgery group, 3.75 ± 0.38; nonsurgery group, 1.64 ± 1.07) was significantly higher in the surgery group. The levels of adipocytokines, serum adiponectin, and serum soluble TNFR-2 showed no correlation with hepatic fibrosis, whereas the serum leptin levels were significantly correlated with liver fibrosis (R = 0.696). Conclusion The hepatic fibrosis grade rapidly progressed in the cranial surgery cases of NAFLD patients with hypopituitarism, possibly in association with BMI, diabetes mellitus, and leptin. In such cranial surgery patients, strong interventions should be considered from the early stage, including diet education, hormone replacement, and more.

Lipid profile and response to statin therapy in patients with hypopituitarism.

Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

SAT-315 CircVPS13c Promotes Tumor Growth and Invasiveness in Pituitary Adenoma by Downregulating IFITM1

Background and objectivesInvasive nonfunctioning pituitary adenoma (NFPA) remains the major cause of hypopituitarism and infertility. Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression in a wide range of tumors. The present study was designed to explore the role of circRNAs in proliferation and invasion of NFPAs.MethodsThe expression profile of circRNAs was compared with circRNA array between NFPA (n=10) and normal pituitary tissues (n=4), invasive (n=5) and noninvasive (n=5) NFPA samples. A total of 249 circRNAs were shown to be significantly upregulated in human invasive NFPA tissues, comparing to the noninvasive ones. CircVPS13C was identified for further study, whose oncogenic effect were explored with in vitro and in vivo experiments.ResultsCircVPS13C was markedly upregulated in NFPA samples and positively correlated with NFPA invasiveness. Silencing of circVPS13C effectively suppressed NFPA cell proliferation, invasiveness and promoted apoptosis, in vitro, and suppressed tumor growth, in vivo. The oncogenic effects were significantly enhanced when circVPS13C was overexpressed. By whole exome sequencing, interferon induced transmembrane protein 1 (IFITM1) was found significantly increased in cells with circVPS13C knockout. Decreased level of IFITM1 protein was confirmed in NFPAs samples, and negatively correlated with the level of circVPS13C and tumor invasiveness. Upregulation of IFITM1 could partly reverse the effect of IFITM1 on tumor cells, and IFITM1 downregulating enhanced the oncogenic effect of circVPS13C. CHIRP analysis suggested that circVPS13C may inhibit the IFITM1 transcription by competitively binding the RNA-associated proteins.ConclusionsCircVPS13C promotes NFPA growth and invasiveness by regulating tumor suppressor IFITM1, revealing a therapeutic target in preventing the tumorigenesis of NFPA.

SAT-245 A Rare Case of Clival Primary Diffuse Large B-Cell Lymphoma Presenting with Panhypopituitarism and Unmasked Diabetes Insipidus

Background: Central adrenal insufficiency (AI) is known to conceal diabetes insipidus (DI) by impairing free water clearance from the renal system and inhibiting polyuria, which is later unmasked by the initiation of glucocorticoids. The instances of masked DI in the literature are confined to case reports - the actual incidence is unclear. There have been no documented cases of masked DI secondary to a clival tumor, which remains a rare cause of hypopituitarism. Here we discuss a case of primary diffuse large B-cell lymphoma (DLBCL) of the clivus presenting with panhypopituitarism and the development of DI upon glucocorticoid initiation. Clinical Case: A 60-year-old man with DLBCL initially presented to an outside institution with headache, diplopia, and right eye ptosis. Brain MRI showed enhancement of the clivus without obvious pituitary gland involvement. He underwent biopsy with partial resection of the tumor and pathology confirmed DLBCL. His course was complicated by persistent fevers. Extensive work-up was unrevealing and he was transferred to our institution for further management. On admission, infectious work-up was positive for C. Difficile. He later developed septic shock requiring vasopressors and broad-spectrum antibiotics. Despite prolonged antibiotics, he remained hypotensive. Due to proximity of the clivus and sella, there was concern for pituitary involvement. A random cortisol was 9.1 [3.7-19.4 ug/dL], subsequent 250ug cosyntropin stimulation test yielded 13.1 and 14.9 at 30- and 60-minutes, respectively. Given inadequate stimulation and persistent hypotension in this critically ill patient, he was then started on stress dose hydrocortisone (HC) with prompt resolution of hypotension. Further work-up of the pituitary axes was consistent with anterior hypopituitarism: ACTH 5 [6-50 pg/mL], TSH 0.336 [0.350-4.940 uIU/mL], free T4 0.5 [0.7-1.5 ng/dL], FSH 0.3/LH 0.1 [1-10 mIU/mL], IGF-1 <16 [41-279 ng/mL], prolactin <1 [3-16 ng/mL]. On day two of HC stress dosing, he developed hypernatremia and polyuria. Urine studies were consistent with DI and desmopressin was started with subsequent improvement. Conclusion:This is the first documented case of DLBCL of the clivus leading to panhypopituitarism. For tumors in close proximity to the pituitary, there should be a low threshold for pituitary axes evaluation. In addition, masked DI from central AI remains rare and requires close attention by the Endocrinologist following initiation of glucocorticoids.

MON-256 A Late-Onset Case of Sheehan’s Syndrome Presenting as Life Threatening Adrenal Insufficiency

OBJECTIVESheehan’s syndrome or postpartum pituitary necrosis, is an important but rare cause of hypopituitarism, caused due to severe postpartum hemorrhage. Seen more commonly in the developing world, it is less common in developed countries due to advanced obstetric practices. It can present acutely but more frequently has an insidious course (onset 10-20 years later) with variable hormonal deficiencies. Here, we report a late-onset case of Sheehan’s syndrome, 24 years after the incident event, presenting as life threatening adrenal failure.CASE PRESENTATIONA 48-year-old female with no significant past medical history was admitted to the hospital after being found unresponsive at home. She had not seen a physician for many years. She complained of weakness and lethargy for a week and recently established care with a primary care physician. The patient was severely hypotensive in the emergency department and had an elevated temperature of 101°F. Physical examination showed no significant abnormalities. CBC and metabolic panel were not significantly altered. CSF analysis and CSF/blood cultures were negative for any infection. TSH was 4.29 mIU/mL (0.27-4.20) but the total and free T4 (fT4) were severely low at 1.1 mcg/mL (4.6-12) and 0.24 ng/dL (0.93-1.70) respectively. On further questioning, patient reported severe postpartum hemorrhage 24 years ago, needing multiple units of blood transfusion. This was followed by inability to lactate and menstruate but was never worked up as she had not seen any physician all these years. Pituitary hormonal panel was obtained, demonstrating multiple hormonal deficiencies with fT4 severely low at 0.24 ng/dL, ACTH of 2.6 pg/mL (7.2-63.3), prolactin (PRL) 1 ng/mL (4.8-23.3) and insulin like growth factor-1 (IGF-1) low at 10 ng/mL (56-194). Cortisol level was elevated in the hospital due to administration of high dose IV steroids but a morning cortisol level obtained 1 week prior by her primary was 1.5 mcg/dL (10-20). Estradiol levels were low with FSH and LH levels inappropriately normal. MRI of the pituitary was obtained which showed an empty sella turcica. Patient was diagnosed as late-onset Sheehan’s syndrome. She was started on hormone replacement with hydrocortisone followed by levothyroxine and had marked improvement in her symptoms. She continues to do well.CONCLUSIONOur patient presented late due to lack of medical care and awareness. A great number of patients with Sheehan’s diseasae go undiagnosed due to subtle clinical presentations, thus delaying treatment. It is imperative to diagnose this condition timely with appropriate obstetric/gynecological history and clinical suspicion to avoid late manifestations of the disease, especially adrenal crisis. Patients at risk need long term follow-up. Early treatment is necessary to improve quality of life and reduce morbidity and mortality associated with this condition.

Spontaneous Conception, Pericardial Effusion, and Pseudohypertrophic Myopathy Mimicking Muscular Dystrophy in Delayed Presentation of Sheehan Syndrome

Sheehan syndrome, characterized by postpartum pituitary necrosis, is an important cause of hypopituitarism in developing countries. We report the case of a 50-year-old female with Sheehan syndrome, who had two spontaneous conceptions following severe postpartum hemorrhage in her first delivery and presented 27 years later with moderate pericardial effusion and features of pseudohypertrophic myopathy mimicking muscular dystrophy.

Genetic causes of hypopituitarism.

Hypopituitarism in neonates is rare, but has life-threatening complications if untreated. This review describes the features of hypopituitarism and the evidence for which infants in whom a genetic cause should be suspected. Importantly, neonates are often asymptomatic or present with non-specific symptoms. Hypopituitarism can be due to abnormal gland development as a result of genetic defects, which result from mutations in gene coding for transcription factors which regulate pituitary development. The mutations can be divided into those causing isolated hypopituitarism or those causing syndromes with associated hypopituitarism. The latter involve mutations in transcription factors which regulate pituitary, as well as extra-pituitary development. There is a paucity of evidence as to which patients should be investigated for genetic mutations, but detailed clinical and biochemical phenotyping with magnetic resonance imaging of the pituitary gland could help target those in whom genetic investigations would be most appropriate.

Growth hormone secretion, fatigue and quality of life after childhood traumatic brain injury.

Traumatic brain injury (TBI) is a recognised cause of hypopituitarism in adults but the prevalence after childhood TBI remains controversial. To investigate long-term endocrine outcomes and quality of life (PedsQL and QoL-AGHDA (Quality of Life in Adult Growth Hormone Deficiency Assessment)) following childhood TBI. Prospective study. Participants with moderate/severe TBI (n = 31) and controls (n = 17). Mean (range) age: 19.8 ± 4.2 (11-26), time post TBI: 9 (7-11) years. Detailed endocrine evaluation of stimulated (insulin tolerance test (ITT)) and spontaneous GH secretion (overnight profile) was undertaken in the TBI group; QoL and neuroimaging in both groups. No participant had seizures, short stature, precocious puberty or hypothyroidism. In 6/25 the ITT GH response was below age-defined cut-offs and cortisol <500 nmol/L in 2/25. Mean spontaneous GH secretion was <3.1 µg/L in 16/22 but peak GH was low only in 1/22 profiles. One patient had abnormal spontaneous and stimulated GH secretion and hypogonadism. Fatigue and depression scores were higher in TBI patients (P = .011 and P = .020). Fatigue correlated with measures of spontaneous but not stimulated GH secretion. Overall QoL (PedsQL) did not differ between groups but specific attributes of health state (cognition, memory) were impaired in TBI patients. Pituitary neuroimaging was normal in all participants. Fatigue and depression were common 8-10 years post childhood TBI. One individual had GHD (1/22) using rigorous diagnostic criteria. A single ITT potentially over-diagnosed GHD in 25% (6/25) without clear correlation with symptoms underlying the importance of using two diagnostic tests in TBI survivors.

Autoimmune phenomena involving the pituitary gland in children: New developing data about diagnosis and treatment.

The contribution of autoimmune phenomena to dysfunction of hypophysis or hypothalamus is far to be unraveled and also the specific pathways of hypophysitis are poorly understood until now, mostly for the pediatric population. Primary hypophysitis is rare in children and often regarded as an autoimmune disorder, following the evidence of lymphoplasmacytic infiltration in the pituitary gland, detection of anti-pituitary antibodies (APA) and anti-hypotalamus antibodies (AHA) by indirect immunofluorescence on cryostatic sections of human or primate hypophysis and hypothalamus, and coexistence with other autoimmune disorders. The rarity of this condition and the lack of ad hoc studies make hard any assessment of the real incidence of hypophysitis in pediatric patients, and also the role of APA and AHA has been poorly investigated in children with idiopathic hypopituitarism. Potential target autoantigens studied in autoimmune hypophysitis have been various pituitary-specific factors, chaperone proteins, alpha-enolase, secretogranins, chorionic somatomammotropin and intracellular transcription factors. Many clinical features both endocrine and neurologic or systemic can herald the onset of autoimmune hypophysitis. Antidiuretic hormone deficiency with central diabetes insipidus and growth retardation are the most significant presenting symptoms in children with hypophysitis, requiring a careful differential diagnosis with other causes of hypopituitarism, including tumors of the sellar region, differently from adults in whom adrenal insufficiency, hypogonadism, headache or diplopia might be the leading manifestations. Growth hormone deficiency is found in 3/4 of pediatric cases. Five histologic variants of primary hypophysitis have been described: lymphocytic, granulomatous, xanthomatous, IgG4-related and necrotizing: lymphocytic hypophysitis is the most frequent variant in the pediatric sceneries. Children with diagnosis of hypophysitis are also at risk of developing germinomas later in life, and require an extended follow-up in the long-term. Therapeutic options should be differentiated according to the rapidity of disease progression and modality of clinical onset, as acute pictures might require corticosteroids or immunosuppressant agents, while chronic forms may need a conservative management or appropriate hormone replacement therapies. This review updates and summarizes the most recent information related to the autoimmune involvement of hypophysis and hypothalamus in children, discusses the correlations between APA, AHA and disease activity, as well as the recommendations for treatment of primary hypophysitis from the pediatric perspective.

Giant cerebral aneurysm a rare cause of hypopituitarism: a case report

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

SUN-434 Simultaneously Occurring Suprasellar Tumor and Meningitis: A Rare Cause of Hypopituitarism

Background: The most common cause of hypopituitarism is pituitary adenoma. In recent years there is increased reporting of rare causes of hypopituitarism acquired in adulthood, such as other sellar and parasellar masses, brain damage, vascular lesions, infiltrative/immunological/inflammatory diseases and infectious diseases. We report an unusual case of hypopituitarism associated with simultaneously occurring suprasellar tumor and meningitis. Clinical case: A 45-year-old man was brought to the Emergency Department after being found collapsed at his home with a reduced level of consciousness. About 1 week ago, the patient was complaint headache, nausea and vomiting. He had no significant medical history. His initial assessment showed a blood pressure of 130/70 mmHg, heart rate 133/min, and body temperature 38.5 ºC. Initial laboratory finding revealed serum sodium level of 149 mmol/L (135-150), potassium level of 4.3 mmol/L (3.5-5.5), serum osmolality 292 mOsm/Kg (275-295) and urine osmolality 504 mOsm/Kg (400-800). His random cortisol level was 31.8 ug/dl, TSH 0.568 uIu/ml (0.55-4.78), and free T4 10.75 pmol/L (11.5-22.7). From clinical examination and initial investigations, he was diagnosed as having meningitis or encephalitis and was promptly commenced on empirical i.v. antibiotics. The magnetic resonance imaging (MRI) of the brain revealed diffuse leptomeningeal enhancement in both cerebral hemisphere and 1.8*1.5*1.1cm sized, oval-shaped mass in suprasellar portion, which combined peripheral edema. Examination of the cerebrospinal fluid (CSF) following lumbar puncture confirmed meningitis, antibiotics and antiviral agent were continued. After 2 weeks, he suddenly underwent hypotension and polyuria, despite inflammatory markers of blood were improved. Laboratory finding showed serum osmolality 337 mOsm/Kg, urine osmolality 271 mOsm/Kg, serum sodium 153 mmol/L, random cortisol 1.3 ug/dl, and free T4 5.19 uIu/ml. When coupled with the initial results of the brain imaging, this result helped to confirm a hypopituitarism associated with suprasellar tumor and meningitis. The patient's clinical status promptly improved with intravenous hydrocortisone and desmopressin. After that, levothyroxine supplement was started. He had good response to hormone replacement. Conclusion: Hypopituitarism may develop rapidly or slowly depending on the underlying etiology and may involve one, multiple, or all of the pituitary hormones. The clinical presentations of hypopituitarism are usually nonspecific and the recognition of these patients remains the challenge. We emphasize the importance of careful clinical assessment and focused investigations, including cranial imaging and pituitary hormone profiling to establish the underlying diagnosis.