bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-911 Debilitating Neuropsychiatry Symptoms in Pancreatic Insulinoma Co-Secreting Serotonin and IGF-1
Authors: Azman Siti Sanaa Wan , Rajoo Subashini , Rahmatullah Ijaz Hallaj , Rahim Anilah Abdul , Bidin Mohamed Badrulnizam Long 
Published: May 2020

Abstract
Background:
Insulinoma is the most common type of functioning pancreatic neuroendocrine tumor (NET). Polyhormonal secretions from the NET, giving rise to distinct clinical symptoms such as carcinoid symptoms are rare. Clinical Case: We report a 68-year-old woman who presented with four months history of recurrent diaphoresis, palpitations, tremors and chest tightness. These were associated with episodic paroxysms of flushing and diarrhoea. The physical examination was unremarkable. She was a well-nourished woman with BMI of 28 kg/m2. Initial laboratory tests ruled out any renal, liver abnormalities with normal cortisol and thyroid function test. Further evaluation confirms insulin mediated hypoglycaemia with low random blood sugar 2.5 mmol/l (4.4-7.8) and failure to suppress C-peptide, 1092 pmol/L (298-2350) and insulin levels, 12.7 mU/L (3-25). Urine 5-HIAA was markedly elevated 2430.37 µmol/day (3.66-42.89) with borderline elevation of serum chromogranin A level 122 ng/mL (27-94). IGF-1 was also raised at 416 ug/L (91-282). Two months later she presented with new onset of delirium, incoherence, agitation and restlessness independent of her hypoglycaemic events. These symptoms deteriorated and fluctuates throughout the day with period of normalcy in between. This has led to requirement of a full time caregiver for her. Cranial CT excluded any brain pathology. We are faced with a diagnostic challenge to localize the primary lesion as radiological imaging so far were normal. GALLIUM-68 PET CT showed physiological uptake in the uncinate process of the pancreas (SUVmax 14.4). Endoscopic ultrasound of the pancreas was normal. An intra-arterial calcium stimulation test with hepatic venous sampling (ASVS) confirms a lesion at the head of pancreas with two times increment of insulin from baseline at the gastroduodenal artery distribution. Despite elimination of hypoglycaemic events with Diazoxide 100mg twice daily, her neuropsychiatric symptoms persisted. We postulate that this might be from excessive peripheral production of serotonin by the pancreatic carcinoid tumour or a niacin deficiency state because of metabolic diversion of its precursor, tryptophan. Conclusion:
This case highlights the occurrence of debilitating neuropsychiatry manifestations in a likely neuroendocrine tumour arising from the head of pancreas secreting insulin, serotonin and IGF-1.
OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency
Authors: Kumar Amit , Ghosh Maria , Jacob Jubbin Jagan 
Published: May 2020

Abstract
Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) &lt;135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na &gt;30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of &lt;18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.
MON-294 T2 MRI Signal Analysis of The Pituitary Gland Is Efficient in the Diagnosis of Acromegaly Due to GHRH Ectopic Secretion
Authors: Bonneville Jean Francois , Potorac Julia , Rohmer Vincent , Daly Adrian F , Beckers Albert M 
Published: May 2020

Abstract
Less than 1% of cases of acromegaly are secondary to ectopic secretion of Growth Hormone Releasing Hormone (GHRH), usually from a neuroendocrine tumor. Symptoms of ectopic acromegaly did not differ from classical acromegaly from pituitary origin. GH and IGF 1 values are in the same range. GHRH measurement only could make the correct diagnosis but is not routinely proposed in acromegaly. MRI of the pituitary gland is considered not very effective in ectopic acromegaly. In the literature (1), different patterns are described: pituitary enlargement (46%), adenoma (30%), empty sella (2%) or normal (20%). But T2MRI signal of the pituitary is never mentioned nor illustrated. Finally, in about 30 % of published cases, pituitary surgery, of course inefficient, was performed.
These data enhance the poor contribution of imaging studies in the published cases of ectopic acromegaly.
We have been able to obtain and read MRIs and particularly T2WI of 27 acromegalic patients- 20 female, 7 male- due to GHRH hypersecretion from a neuroendocrine tumor –principally bronchial carcinoid and pancreatic NET- which have been published or not. Remarquably, T2 sequences were available in only 27/61 cases we have collected. In all these 27 cases but two, the T2 signal was clearly hypointense if compared with the brain cortex, as it has been described in densely granulomated somatotropinomas (2). In one case with T2 hyperintensity, the pituitary mass presented the same imaging characters as multiple brain metastases from a bronchial carcinoïd. In one case, T2 signal was isointense. In 3 cases, tiny millimetric T2 hyperintense images were disseminated within pituitary hyperplasia. In several cases where pituitary MRI was considered as normal, correlation of the patient’age with pituitary size could make suspect an enlarged gland. In a case labeled empty sella, T2MRI signal of the pituitary remnant was hypointense. When coupling T2 and T1 gadolinium enhanced sequences, no pituitary adenoma was visualized and normal pituitary tissue was never identified along with pituitary hyperplasia.
In conclusion, T2 MRI hypointense signal of the pituitary gland is a better hallmark than pituitary hyperplasia for the diagnosis of acromegaly due to
GHRH ectopic secretion. Analysis of T2 MR signal in these cases is essential to avoid unnecessary interventions to the pituitary.
References
1 Ghazi A Endocrine 2013
2 Potorac J Endocr Relat Cancer 2015
SAT-451 Chronic Stress During Adolescence of Rats Shows Sex Dimorphism in the Thyroid Axis Response to Voluntary Exercise in Adulthood
Authors: Parra-Montes de Oca Marco Antonio , Gutiérrez-Mata Angélica , Charli Jean-Louis , Joseph-Bravo Patricia 
Published: May 2020

Abstract
Exposure to chronic stress during adolescence causes long-term effects on the response of Hypothalamus-Pituitary-Adrenal (HPA) axis, affecting behavior and energy homeostasis. Voluntary exercise activates the HP-Thyroid (HPT) axis allowing efficient fluxes of substrates to active target organs. Chronic stress in adult rats blunts HPT axis response to voluntary exercise in a sex-dependent manner (Front Endocrinol 10(418):1-13, 2019). As adolescents show sex-dependent responses to stress, we sought to evaluate the effect of chronic stress at this period in the response of HPT axis to voluntary exercise in adulthood. Wistar male and female rats were divided in an undisturbed group (Control, C) and one group exposed to chronic variable stress (CVS) where the rats were daily subjected to different stressors during postnatal day (PND) 30 to 60 for females and PND 30 to 70 for males. At adulthood (PND 74 for females and PND 84 for males) rats were exposed to running wheel following published protocol (Endocrinology 155:2020-2030, 2014). As females are more susceptible to stress during adolescence than males, additional independent experiments were performed with female rats kept in group or individual housing, since PND 30 (2 per cage or isolated (Iso)). At PND 64, Iso rats were housed in pairs and exposed to CVS every 3 days until PND 80; later, rats were exercised 26 days. Hormones were quantified by ELISA or RIA; mRNA expression was determined by RT-PCR. Voluntary exercise reduced fat mass in C groups, dependent on the amount of exercise performed; stressed rats exercised did not lose fat, indicating that adolescent stress avoids an appropriate energy distribution during exercise. The expression of Crh and Avp in hypothalamic paraventricular nucleus (PVN) decreased in stressed groups mainly in females, as reported. Exercise decreased corticosterone levels only in C rats, suggesting that CVS during adolescence modifies the HPA axis response to exercise. CVS inhibited Pomc expression induced by exercise and increased Npy expression in arcuate nucleus, decreased Trh expression in PVN for both sexes and in dorsomedial hypothalamus in males. Thyroid hormones were not altered in CVS males and Iso females; however, T3 and T4 levels were high in CVS females, so different stress exposures may modify the HPT axis state in females. The response to exercise of the target organs of thyroid hormones reveals with more accuracy the activity of HPT axis, exercise stimulated the expression of Adrb3 and Dio2 in brown adipose tissue of C females, and the expression of Dio2 and Pgc1a in skeletal muscle (gastrocnemius) of both sexes, changes attenuated by CVS. These results indicate that chronic stress during adolescence blunts the response of HPT axis to voluntary exercise, strongly in females than males.
MON-103 Pattern and Predictors of Thyroid Dysfunction Among Paediatric Endocrine Referrals at Tertiary Care Centre: A Longitudinal Study
Authors: Masoodi Shariq Rashid , Sood Mona , Peerzada Ovais Ahmed , Bhat Moomin , Vasudevan Vishnu 
Published: May 2020

Abstract
Background Post iodisation era has experienced gradual change in pattern of thyroid disorders among paediatric population with autoimmunity taking precedence over iodine deficiency disorders and subclinical hypothyroidism (SCH) now more frequently diagnosed but inappropriately managed. Aims This study was conducted to evaluate pattern of abnormal thyroid function among children referred to our tertiary care centre, to ascertain characteristics that influence treatment decisions and to follow them for various outcome measures. Design It was an observational longitudinal follow up study where all children less than 18 years, referred to our outpatient clinic for suspected thyroid disorder were recruited. Demographic data, personal and family history, clinical features were noted and laboratory tests including TT4, TT3, TSH, anti-thyroid peroxidase(antiTPO) and anti-thyroglobulin(antiTG) antibody were conducted in study subjects. Management was based on the clinical judgment of the attending endocrinologist. Patients were followed at 6 week, 3 months, 6 months and one year with clinical and laboratory work up at each visit. Results A total of 241 subjects aged 18 days to 17 years were included out of which 62.25% were females. Initial evaluation revealed SCH in 40% of refereed subjects, overt hypothyroidism (OH) in 33%, congenital hypothyroidism (CH) in 18% and overt thyrotoxicosis in 5%. Autoimmune thyroiditis constituted the major cause of hypothyroidism in the OH group with significantly higher prevalence of anti-TPO and antiTG antibody in comparison of SCH group (61% vs 31%; 45% vs 21.9%, p&lt;0.05) respectively. All subjects in OH group were treated whereas 76% subjects in SCH group were treated and the mean dose of L thyroxine required to treat OH was significantly higher (2.31+1.1ug/kg/day vs 1.76+1.07ug/kg/day; p&lt;0.001) in comparison of SCH group. A major independent predictor of treatment in SCH was initial TSH which was significantly higher in the treated group (11.65 + 3.80 uIU/ml vs 9.24 + 1.31 uIU/ml; p&lt;0.001). Subjects with congenital hypothyroid presented at a mean age of 6 months (18 days to 2 years) with most common aetiology being thyroid hypoplasia and dyshormonogenesis
(20% each). Graves’ disease was diagnosed in 11 out of 12 subjects with thyrotoxicosis and were treated with antithyroid drugs. Overall 85.5% of refereed subjects were treated and after one-year follow up management was found to be adequate in 81% subjects. Conclusions The evolving trend of diagnosing children having nonspecific symptoms with SCH is a matter of concern as many are subjected to the burden of unwanted prolonged treatment and frequent testing as highlighted in our study. Delayed presentation of CH in our study warrants active surveillance of children at birth for thyroid disorders to avoid long term adverse effects on mental development.
SUN-240 Female Mice Lacking Brain Insulin Production Exhibit Learning Deficits, Anxiety, and Reduced Hippocampal Cyclin D1 Expression
Authors: Baehring Stella Katharina , O’Leary Timothy P , Holenka Danae M , Li Hong , Kim Kyungchan , Mehran Arya E , Pavlidis Paul , Kim Eun-Kyoung , Bamji Shernaz X , Johnson James D 
Published: May 2020

Abstract
Insulin dysregulation independently underlies diabetes and Alzheimer’s Disease (AD) pathology. However, the former has also been shown to be a risk factor for the latter. The ancestral insulin gene (Ins2), but not the pancreas-specific Ins1gene, is transcribed locally within the brain in mice. We confirmed that neuronal expression of Ins2 is most prominent within the hippocampus, a brain region with established roles in learning and memory, and that it was reduced by a diet known to promote neuronal dysfunction. It is not yet clear, however, how insulin produced locally within the brain influences hippocampal function, learning and memory. To eliminate brain-derived insulin, we used young and old mice with germline Ins2knockout (Ins2-/-) and their normal complement of wildtype Ins1 alleles, which had equivalent pancreatic insulin and normal glucose homeostasis. Using the Morris water maze, we found that learning and memory performance of female Ins2-/-mice was significantly impaired relative to wild-type mice, whereas the performance of male Ins2-/-and wild-type mice did not differ. During acquisition training, the swim-speed in female Ins2-/-was faster than wild-type mice, suggesting increased stress reactivity and motivation to escape from water. Indeed, anxiety-like behavior was increased in female mice as assessed by the open-field test. Using RNA sequencing to profile isolated hippocampi, we found that femaleIns2-/-mice had a significant reduction in Cyclin D1 (Ccnd1) compared with littermate controls. This observation points to a possible defect in hippocampal neurogenesis, a physiological hallmark of impaired memory and emotionality implicated in both, diabetes and AD. Together these data suggest that Ins2plays sex- and brain region-specific roles in neuronal function and perhaps adult neurogenesis.
SUN-938 Rare Case of Ectopic Cushing Syndrome Caused by ACTH Secreting Thymic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1
Authors: Gorantla Yamuna , Moncada Jorge Soria , Sarmiento Juan , Amblee Ambika , Ganesh Malini 
Published: May 2020

Abstract
Introduction
Cushing syndrome (CS) represents an uncommon manifestation of MEN1 and can be caused by both ACTH dependent or independent etiologies. Among them, ectopic ACTH secretion from a Thymic neuroendocrine tumor (TNET) in MEN1 is rare, with very few cases reported so far in literature. We report a case of Ectopic Cushing syndrome (ECS) in a MEN1 patient (pt) with multiple tumors, secondary to ACTH-secreting TNET.
Case description:
A 44 year old male presented to our institution for nausea, vomiting, dizziness. He had initial workup which revealed multiple tumors (papillary thyroid cancer, thymic mass, parathyroid adenomas, bilateral adrenal nodules, macroprolactinoma, peripancreatic nodules). Given concern for MEN 1, genetic testing was performed which was confirmative. Hormonal workup at this time for adrenal nodules was negative including low dose dexamethasone suppression test(DST). The immobile thymic mass was found to be poorly differentiated NET on biopsy with Ki-67 &gt;50% with vascular invasion and adhesions to lung/chest wall on VATS, not amenable to surgery. The pt declined chemotherapy and radiotherapy due to poor social support. Six months later, he presented with complaints of shortness of breath, proximal muscle weakness, anasarca. Evaluation revealed AM cortisol &gt;60 ug/dL(range 6.7-22), high-dose DST Cortisol &gt;60 ug/dL, 24hr urine free cortisol: 8511mcg (range 4-50) and ACTH level: 278pg/mL(range 6-50) confirming ACTH-dependent CS. Special stains from the previous TNET biopsy demonstrated positive staining for ACTH confirming ectopic ACTH secretion. Ketoconazole and chemotherapy with Etoposide and Carboplatin was started, however he clinically deteriorated and expired a few weeks after diagnosed of ECS.
Discussion:
TNET in MEN 1 is rare, with a prevalence of 3-8%. TNET are unusual neoplasms that account for 2% to 7% of all mediastinal tumors. TNET in MEN1 rarely secrete functional hormones with very few reported Ectopic ACTH secretion. MEN1 associated ECS from TNET is an aggressive disease with local invasion of adjacent mediastinal structures or metastasis being common, resulting in poor prognosis as demonstrated in few case reports including our case. Radical surgery of involved adjacent structures and adjuvant local RT can provide local disease control.
Conclusion:
Our pt is a rare case of ECS from TNET in MEN1 with poor prognosis. A special feature of this case is that the patient had initial negative evaluation for hypercortisolemia, however 6 months later he presented with signs and symptoms of severe hypercortisolism, with evaluation confirming transformation into ACTH producing TNET. This conversion is very rarely found in literature and adds to the unique presentation of the case.
SUN-649 Metabolic and Functional Regulation of T Cells by Insulin and Insulin like Growth Factor 1
Authors: Kiernan Kaitlin , MacIver Nancie J 
Published: May 2020

Abstract
Obesity leads to altered immunity characterized by increased risk of autoimmunity, poor response to infection, and impaired vaccine response. T cells play an important role in this obesity-associated immune response; however, the mechanisms by which T cells are altered in obesity remain unknown. Our goal is to identify nutritionally regulated hormones and cytokines that link whole body nutrition and immunity, and to understand the mechanisms by which such factors can alter T cell response in obesity. To that end, we have identified the hormones insulin and insulin-like growth factor-1 (IGF-1) as potential links between nutritional status and T cell metabolism and function. Insulin is secreted from pancreatic beta cells in response to increasing blood glucose levels, and circulating insulin levels are elevated in obesity due to insulin resistance in metabolic tissues. IGF-1 levels are influenced by protein intake and nutrition status, and free (bioactive) levels of IGF-1 are elevated in obesity. To study the role of insulin and IGF-1 on T cell function and metabolism, we treated activated CD4 T cells with physiologic levels of insulin or IGF-1 in vitro for 24 hours. Treatment of CD4 T cells with insulin or IGF-1 increased glucose uptake, glycolytic metabolism, and mitochondrial metabolism while altering inflammatory cytokine production. In particular, both insulin and IGF-1 decreased IFN-γ production, whereas IGF-1 specifically increased IL-17 production from both bulk activated CD4 T cells and T cells skewed toward a T helper 17 (Th17) phenotype. Using a T cell-specific insulin receptor (IR) conditional knockout mouse, we found that loss of IR signaling decreased glucose uptake and mitochondrial metabolism and increased IFN-γ production by activated T cells. Moreover, IR appears to be required for both insulin and IGF-1 effects on T cells. Lastly, we investigated the CD4 T cell subset-specific expression of both IR and IGF-1 receptor (IGF-1R). We found that each CD4 T cell subset had its own unique expression of both IR and IGF-1R; however Th17 cells had a striking increase in IGF-1R expression compared to the other T cell subsets, indicating a specific role for IGF-1 in promoting inflammation. These findings underscore the ability of the nutritionally-regulated hormones insulin and IGF-1 to modulate CD4 T cell metabolism and function and thereby alter T cell immunity, which has direct clinical relevance in both normal physiology and in obesity.