bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-923 MENIN Gene Mutation: Unity Amidst Diversity
Authors: Rais Nadeem M , Kumar Anshul , Jain Swetha , Scaria Vinod , Prakash Savinitha , Mathur Sandeep Kumar , Joshi Apoorva 
Published: May 2020

Abstract
Introduction
The MEN 1 syndrome is an enigmatic disorder, manifesting a wide spectrum of disorders, in members of a family, harbouring the same gene mutation. We present one such family, with a MENIN gene mutation with marked diversity in the clinical presentation
Clinical cases
1992: RB (Age: 13) presented with accelerated puberty, galactorrhoea and a lactotroph adenoma. Treated with Bromocriptine, followed by hypophysectomy and radiotherapy. He was on hormone replacement for hypopituitarism.
1996: He gained 21 kg of weight and had recurrent episodes of convulsions with unconsciousness.He had hypoglycaemia (13mg/dl; N &gt;70), with hyperinsulinemia (58uIU/ml; N&lt;25). MRI abdomen showed a mass (3.4 x 3.0 cm) over the tail of the pancreas for which a distal pancreatectomy was done (HPE: Neuroendocrine tumour).
2013: He had pain in the lower limbs with hypercalcemia (11.4mg%; N: 8.5-10.5) and hyperparathyroidism (329 pg/ml; N: 10-61) (MIBG Scan: parathyroid adenomas treated by bilateral inferior parathyroidectomy).
2016: He had hypoglycaemia with hyperinsulinemia with multifocal pancreatic NETs. These were enucleated at surgery.
2017: He developed Zollinger Ellison syndrome with raised basal gastrin levels (Gastrin: &gt;200ng/ml; N&lt;180) and multiple duodenal ulcers (Treatment: Pantoprazole). He simultaneously had recurrent hyperparathyroidism and underwent a total parathyroidectomy with allograft. The allograft initially showed evidence of hyperparathyroidism followed by hypoparathyroidism.
His father VB (Age: 56) was seen by us in 1996 for skin lesions and a malignant thymic carcinoid, to which he succumbed to, shortly after the surgery. His aunt, SB (Age: 18), has a lactotroph adenoma with severe insulin resistance characterised by obesity, acanthosis nigricans and hyperandrogenism.
2009: His paternal uncle PB (Age: 54) had a pituitary macroadenoma. He underwent a hypophysectomy and was lost to follow up.
2018: PB had massive haemoptysis. A bronchoscopy showed nodules in the right lung which on biopsy revealed a NET. The whole body scan showed a hilar and mediastinal mass along with metastatic disease to the adrenals, liver, spine, skull and rectum. The histopathology examination revealed a malignant carcinoid
Clinical lesson
Whole exome sequencing of the two of the affected members showed mutations of the MENIN gene at exon 2 c.G2492T:p.G831V; g. chr10. This common mutation in the family was associated with a wide spectrum of diverse clinical manifestations which include the classic disease, malignant carcinoids of the lung and acromegaloid variant of Type A insulin resistance with hyperandrogenism. These observations suggest the unity amidst diversity in the enigmatic syndrome that encompasses MEN1.
SAT-004 Prevalence of Abnormalities of Glucose Metabolism in Teenage Indian Girls with PCOS
Authors: Talwar Vipan 
Published: May 2020

Abstract
Background:Polycystic ovary syndrome (PCOS) is one of the common endocrine disorders affecting young women and has been associated with an increased risk of impaired glucose tolerance and type 2 diabetes mellitus. However, there are very few studies on glucose abnormalities in Indian adolescent girls with PCOS. This study was conducted to determine the prevalence of abnormal glucose metabolism in this patient population. Method: Study group comprised of 106 young females aged 13–18 years. None of them were on metformin at the time of initial visit. Clinical examination along with Anthropometric evaluation was done and along with routine hormonal assessment they underwent a standard 75-g oral glucose tolerance test (OGTT). American Diabetes Association (ADA) criteria were used for diagnosis of diabetes (2 hr value&gt;200mg/dl), Impaired glucose tolerance (2 hour value &gt; 140 -199 mg/dl) and Impaired fasting glucose (blood glucose level of 100–125 mg/dl) Results:Out of 106 girls with PCOS diagnosis;1 girl met criteria for diagnosis of type 2 diabetes mellitus (0.9%).15 had impaired glucose tolerance (14.1%). In addition, 2 girls with impaired glucose tolerance were also noted to have impaired fasting glucose (1.9%).Abnormalities of glucose metabolism had significant correlation with BMI(p-0.02),Waist circumference (p-0.01) and testosterone levels (p-0.02). Conclusions:In our series of adolescent PCOS subjects, we report the prevalence of abnormal glucose metabolism to be 14.1% which is quite significant. Based on our results, we recommend that all adolescent girls with a diagnosis of PCOS should undergo formal oral glucose tolerance testing. Further studies are necessary in this field, so as to make guidelines regarding the timing and frequency of this testing, as well as its utility in the clinical management of these girls.
SAT-394 Concordant Parathyroid Imaging; Frequency and Predictors of Concordance and Its Impacts on Cure
Authors: Khine Aye Aye , Muhamad Hatta Sharifah Faradila Wan , Buch Harit , Yousuf Quratulain , Vydianath Sanjay , Strouhal Peter , Garnham Andrew 
Published: May 2020

Abstract
Introduction: Accurate pre-operative imaging of a parathyroid adenoma facilitates minimally invasive surgery for primary hyperparathyroidism, increases cure rate and reduces perioperative complications. The two most commonly deployed preoperative localization studies are ultrasonography (US) and parathyroid scintigraphy using 99m-techentium sestamibi (RN). Patients who have concordant results between the two studies (most studies report concordance rate of 60%) usually undergo minimally invasive surgery whilst those with non-concordance scan results often need bilateral open neck surgery.Objectives: We did a retrospective assessment of the clinical, biochemical and imaging parameters of patients who had parathyroid surgery in our hospital to assess (a) the sensitivity and positive predictive value (PPV) of US and RN scans (b) the frequency of concordance between the two imaging studies (c) the clinical and laboratory predictors of concordance and (d) the impact of concordance on the cure rate.Method: 155 patients who were operated for PHPT between January 2011 and January 2019 were included. All patients underwent preoperative localization with US and RN imaging. The sensitivity and PPV of the 2 imaging procedures in detecting a parathyroid adenoma were determined by correlating the imaging findings of both scans with the composite information obtained from surgical findings and post-operative biochemical results to indicate cure. The patients with concordant and non-concordant imaging findings were compared for surgical cure rate, serum calcium and parathormone level, and the volume and weight of the adenoma.Results: The sensitivity and PPV of US were 80.9% and 82.8% and for RN scan 78.7% and 87.8% respectively. There was no statistically significant difference in the accuracy between the two modalities. 93(60%) patients had concordant and 62(40%) patients had non-concordant scan results, which included true discordance and non-localization by one or both scans. Cure rate in concordant and non-concordant scans were 96.8% and 83.7% respectively (p=0.02, chi-square). In comparison to patients with non-concordant imaging, patients with concordant imaging had higher level of serum calcium (mean 3.02 vs 2.86, p=0.04), the resected adenoma was larger in volume (mean 3109mm3 vs 2083mm3, p=0.05) and was heavier (mean 1.59 vs 1.10 p=ns). However there was no difference in the age or serum PTH level between the 2 groups of patients.Conclusion: Both US and RN imaging have similarly high sensitivity and PPV in identifying a parathyroid adenoma and our figures were comparable to the published literature. When the two studies are concordant a significantly higher surgical success rate is obtained. Patients with higher serum calcium and larger adenomas are more likely to demonstrate concordant imaging.
SUN-216 Investigating the Role of the Liver X Receptor in Potentiating Mitotane Therapy in Adrenocortical Carcinoma
Authors: Warde Kate , Shoenmakers Erik , Leonard Maeve , Maunsells Rebecca , Hantel Constanze , Gurnell Mark , Dennedy Michael Conall 
Published: May 2020

Abstract
Introduction: Adrenocortical Carcinoma is a rare aggressive cancer which carries a poor prognosis. Adjuvant mitotane improves survival but is limited by a narrow therapeutic window and severe adverse effects. Liver X receptors (LXRs), part of the nuclear receptor superfamily are highly expressed in adrenal tissue and mediate transcellular and intracellular cholesterol homeostasis. We hypothesise that LXRα inhibition increases toxic lipid accumulation in adrenocortical cancer cells and potentiates the adrenolytic effect of mitotane. Methodology: ATCC-H295R and MUC1 ACC cells and were pre-treated with the LXRα inverse agonist SR9243 5µM and antagonist GSK2033 5µM followed by mitotane treatment (20, 40, 50μΜ) for 6 hours. Cholesterol-methyl-β-cyclodextrin treatment was carried out 1hr prior to mitotane. H295R cells were transfected with a LXR⍺ dominant negative construct using lipofectamine. Cell death was assessed using annexin/PI staining and proliferation using MTT assay. Free cholesterol (FC) levels were assayed using filipin staining and lipid droplets via BODIPY® and analysed on the Amnis ImageStream® imaging cytometer. Downstream targets ABCA1 and ABCG1 were evaluated by qRT-PCR. Lipid droplet associated proteins PLIN 1-4 and hormone sensitive lipase (HSL) expression were evaluated using western blotting. Results: Downstream reduction of ABCA1 and ABCG1 expression confirmed LXRα blockade. Mitotane effectively induced dose-dependent H295R apoptotic cell death which was potentiated pharmacologically and genetically by LXR⍺ inhibition. In line with these findings, cholesterol-methyl-β-cyclodextrin treatment increased cell death in H295R and MUC1 cells. In addition to inducing cell death, LXR⍺ inhibition decreased proliferation of both cell lines. An increase in FC and a decrease in cholesterol esters was observed following mitotane treatment in H295R cells. This was accompanied by decreased lipid droplet numbers confirmed by lower expression of lipid droplet associated proteins, PLIN1-3. These effects were potentiated when mitotane was combined with LXRα inhibition. We demonstrate increased HSL activity, which was associated with higher SOAT-1 expression and increasing toxic FC accumulation. Investigation of lipid droplet content BODIPY® of both cell lines showed H295R cells preferentially store cholesterol esters and MUC1 cells store triacylglycerides.Conclusion: We propose a mechanism for enhancing mitotane’s efficacy as an adrenolytic through increased free cholesterol via LXR⍺inhibition. Targeting the LXRα, its putative ligands, or associated lipid mediators may present a novel therapeutic approach in the setting of primary and metastatic ACC.
SUN-252 Rescue of Function of Inactivating Mutations in Human GPCRs in the Reproductive Hypothalamic-Pituitary-Gonadal Axis
Authors: Millar Robert Peter 
Published: May 2020

Abstract
Inactivating mutations have been described for human GPCRs at all levels of the reproductive hypothalamic-pituitary-gonadal (HPG) axis which results in reproductive incompetence. The majority of the mutations in GPCRs give rise to misfolding and a failure to traffick to the cell surface. We have interrogated data bases for cell-permeant small molecules which bind to and stabilise the GPCR as it emerges from the endoplasmic reticulum and hence facilitate trafficking of the mutant GPCR to the cell membrane and restoration of function. In this way we have successfully ‘rescued’ function of mutant Neurokinin B, GnRH, LH and FSH receptors using small molecule antagonists which bind orthosterically or agonists which bind allosterically. These discoveries represent an advance towards novel personalized medicine for GPCR deficiencies in the human HPG axis.
MON-697 Necrotising Fasciitis- Importance of Glycemic Control
Authors: Kasireddy Amulya Reddy , Farooq Umer 
Published: May 2020

Abstract
Introduction:
Necrotising fasciitis is an infection of the deep soft tissues characterised by fulminant tissue destruction, systemic toxicity and high mortality. We report a case where accurate diagnosis, timely surgical intervention and antibiotic therapy along with strict glycemic control resulted in a favourable outcome.
Case:
A 74 year old woman with a history of type 2 diabetes mellitus, hypertension and end stage renal disease(ESRD) on peritoneal dialysis(PD) presented to the emergency department with the complaint of pain in the right lower quadrant of abdomen, right pelvis and right groin since 4 days which acutely worsened overnight. Of note the patient has Peritoneal catheter for dialysis and was last dialysed last night without any difficulty. Other associated symptoms were chills, nausea. The patient denied fever, skin changes in the affected area.
On physical examination, the patient was awake, alert and oriented, in moderate distress. Abdomen was soft, non distended, PD catheter was in place with no surrounding skin erythema or tenderness. Genitourinary examination showed swelling of Mons Pubis with overlying erythema on the right side with extension to the right labia majora, exquisitely tender to palpation, no crepitus, no pustules, no palpable abscesses or visible wounds.
Initial labs showed elevated WBC count(36.4K/UL; n&lt;10.5K/UL) and Blood glucose of 361mg/dl(n 70-100mg/dl). CT scan of the abdomen and pelvis showed right anterior pelvic wall subcutaneous infiltration extending inferiorly into the mons pubis and right labial regions suspicious for cellulitis with no abscess. Broad spectrum intravenous antibiotics Meropenem, Vancomycin and Fluconazole were started and patient was taken to the operative room for debridement and approximately 25 cm long and 15 cm wide and 8 cm large abscess originating in the right labia extending up into her right groin was found along with necrotic skin, subcutaneous tissue and fat which was sharply excised. Peritoneal dialysis catheter site looked non infected and was left in place and fluid cultures were sent. Patient was switched to Hemodialysis while awaiting PD catheter fluid cultures. Hospital course was complicated by multiple debridements, severe septic shock requiring upto 4 pressors and intubation. She was started on insulin drip for glycemic control as the blood sugars were constantly ranging 300mg/dl(n 70-100mg/dl). HbA1C was 10.9% (n 5.7-6.4%). After 10days she was extubated and off pressors and was stable to be transferred to subacute rehab facility for diligent wound care for the next few weeks before she could go home.
Conclusion:
In patients with uncontrolled diabetes mellitus who present with critical illness like necrotising fasciitis, strict glycemic control with insulin drip yield favourable outcomes.
SUN-056 Long Term Outcomes in Patients with Disorders of Sex Development in Lucknow, North India
Authors: Bhatia Vijayalakshmi , Dominc Nibu 
Published: May 2020

Abstract
Due to the deviant genitalia and infertility, the ill effects of DSD are on sexual and psychosocial life. Our aim was to assess the self-reported psychosocial and sexual quality of life in older individuals who are living with a DSD. Quality of life in 31 patients with a DSD (age &gt;16 years, median [IQR] 23 [19-27] years, 16 males) was compared with age, sex and socioeconomic status matched normal (n = 46) and chronic disease controls (type 1 diabetes patients, n = 43) using SF-36v2 Health Survey. Another structured questionnaire was administered touching upon domains of sexual and psychosocial life. Eighteen patients reported history of persistent teasing, with no difference in prevalence between males and females. Eighteen reported suicidal thoughts (no association with being teased), 6 having attempted suicide. Gender identity (GI) of 30 patients was identical with their given sex of rearing, which had been decided by the caregiver in 19 families (including one who had gender change suggested by the parents at 4 years of age), and with physician assistance in 11. One patient had spontaneous change of GI at 16 years age. Sexual orientation was heterosexual in 25 of 29 who responded to this question, homosexual in 1 and bisexual in 3, including the 2 who had gender change. Romantic relationship was reported by 12 patients, sexual activity by 7, aversion to sex (due to fear of rejection) by 11 and abuse by 4. Seventeen patients thought the timing of genital surgery should be before age 5 years and another 10 before age 10 years. Only 2 of 31 patients thought decision for the timing and choice of surgery should rest with themselves, the remainder preferring a decision by parents in 25% and by the physician in 67%. The physical and mental quality of life scores (QOLS) were not different between patients and the controls. Mental QOLS were significantly lower for those with history of teasing. Physical QOLS in males correlated with external masculinisation score (r=0.55, p=0.04). Conclusion: Serious psychological stress is common in patients with DSD in our region. Despite early sex assignment, the absence of prominent gender dysphoria in adulthood, along with their stated preference for corrective genital surgery at an early age, favour an early sex assignment and genital reconstruction before the age of romantic relationships.
MON-474 Coexistence of Thyroid Dysgenesis and Premature Ovarian Failure: A Case Report
Authors: Calma Catherine P , Naranjo May U , Lima Valerie U , Tarongoy Jeannine Erika M 
Published: May 2020

Abstract
Background. Congenital hypothyroidism (CH) secondary to thyroid dysgenesis is rare. It may present with ascites and short stature. Primary ovarian failure (POF) is most commonly associated with autoimmune thyroid diseases1. However, there is no report of the association of POF with congenital hypothyroidism.
Clinical case. A 30 year old female presented with increasing abdominal girth, short stature and arrest of menstruation at 27 years old. Newborn screening was not done. Developmental milestones were at par. She had a low timber voice and was slow to respond. Her skin was rough and dry. Her hair was sparse, and she had thin eyebrows. Her tongue was not enlarged. Her abdomen was globular with a positive fluid wave test and shifting dullness. Initial tests indicated a hypothyroid state: elevated TSH (50.40 IU/mL, N=0.35-4.94 IU/mL), low FT4 (0 pmol/L, N=12-22 pmol/L). Ultrasound of the thyroid suggests thyroid dysgenesis (small right thyroid gland measuring 1.4 x 0.2 x 0.4 cm and an absent left thyroid gland). Karyotyping was 46, XX and insulin growth factor 1 was normal. Unexpectedly, further tests were consistent with a concomitant primary ovarian failure: low estradiol (5 pg/mL, N=12.4-233 pg/mL), high FSH (112.7 mIU/mL, N=3.5-12.5 mIU/mL) and LH (61.9 mIU/mL, N = 2.4-12.6 mIU/mL). Chest radiography showed left pleural effusion. Abdominal CT scan showed marked ascites with normal reproductive organs. Anti-TPO antibodies were normal (4.87 IU/mL, N=0-25 IU/mL). The patient was treated with Levothyroxine 50 mcg daily then gradually increased to 100 mcg daily. She was given Spironolactone 50 mg daily and paracentesis was also done to address ascites. The patient had improvement of symptoms after a month of treatment. However, the etiology of POF remains to be further elucidated.
Conclusion. This case report emphasizes the importance of the early detection of congenital hypothyroidism through newborn screening. Severe hypothyroidism is rarely seen due to the wide availability of the TSH assay and its diagnosis should instigate further work-up for its etiology. Concomitant premature ovarian failure in the absence of an autoimmune thyroid disorder should prompt further investigation for another etiology since premature ovarian failure is not commonly associated with congenital hypothyroidism.
Reference: (1) Ayesha, Jha V, Goswami D. Premature Ovarian Failure: An Association with Autoimmune Diseases. J Clin Diagn Res. 2016;10(10):QC10-QC12.
SUN-128 Impaired Fasting Glucose Is Associated with Insulin Resistance in Patients with Germline Mutations in the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene
Authors: Bansal Rashika , Armiyaw Latif , Lee Maya , Tepede Aisha , James Welch , Agarwal Sunita Kishore , Simonds William F , Weinstein Lee Scott , Muniyappa Ranganath , Blau Jenny 
Published: May 2020

Abstract
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by hyperparathyroidism, pituitary adenomas, and gastro-entero-pancreatic neuroendocrine tumors. Patients with MEN1 mutations have impaired glucose homeostasis, but the role of insulin resistance and beta-cell function is unclear.
METHODS: Using a case-control study design, a retrospective analysis of germline mutation-positive MEN 1 patients (n=289) seen at our institution between 1991-2019 was performed. Patients with diabetes and/or insulinoma were excluded. Subjects were age, BMI, sex and race matched 1:1 to unrelated, healthy controls. Fasting glucose, insulin, c-peptide, calcium, PTH, 25-OH vitamin D, cholesterol, LDL, HDL and triglycerides (TG) were compared between two groups. Homeostasis model assessment (HOMA-IR) and HOMA-beta cell function (HOMA-b) were used as surrogate measures of insulin resistance and beta-cell function, respectively. Data is presented as mean ± SD.
RESULTS: MEN1 subjects (n=40; age 41±11 years; BMI 29.2±7.2 kg/m2) were matched to healthy controls (age 41±11 years; BMI 29.1±7.5 kg/m2). Only 3 MEN1 patients had no evidence of pancreatic neuroendocrine tumors. Impaired fasting glucose was more prevalent in MEN1 compared with controls (53% vs 10%, p&lt;0.0001). HOMA-IR was positively associated with BMI, but not age, sex, calcium or vitamin D levels in either cohort. HOMA-IR adjusted for age, BMI, and sex was higher in patients with MEN1 compared with controls (4.01 vs. 2.44, adjusted ratio of means 1.54, 95% CI [1.14, 2.07], p=0.005). HOMA-b was not significantly different between the groups (177 vs. 129, adjusted ratio of means 1.17, 95% CI [0.86, 1.58], p=0.23). There were no significant differences in total cholesterol, LDL, HDL, and TG between the groups.
CONCLUSION: Lower insulin sensitivity, but not impaired beta cell function may contribute to the higher prevalence of impaired fasting glucose in MEN1 patients compared with controls. Mechanistic studies into the role of menin loss in glucose homeostasis are warranted.