bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR24-05 Identifying Regulatory Elements Within a Novel Enhancer of FSHB Containing Two PCOS-Associated Single Nucleotide Polymorphisms
Authors: Bohaczuk Stephanie C , Thackray Varykina G , Mellon Pamela L 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is the most common cause of female infertility, affecting approximately 10 percent of women by Rotterdam criteria, and is comorbid with obesity, type II diabetes, hypertension, and non-alcoholic fatty liver disease. As twin studies reveal that genetics account for approximately 70% of PCOS risk, genome-wide association studies (GWAS) can provide powerful insight into PCOS etiology. PCOS GWAS studies from several populations identified a risk locus containing the FSHB gene, which encodes the beta subunit of follicle-stimulating hormone (FSH). As FSH supplementation can restore ovulation in some PCOS patients, deficient FSH signaling could be a causative factor of anovulation and potentially other facets of PCOS. Two of the lead single nucleotide polymorphisms (SNPs) in association with PCOS, rs11031005 and rs11031006, fall within a highly conserved genomic region in mammals. We hypothesized that the conserved region (~450 base pairs) enhances FSHB transcription, and that one or both PCOS-related SNPs alter its function. We have shown that the conserved region from both human and mouse can act as an enhancer of FSHB in LβT2 cells, an immortalized, mouse-derived, mature pituitary gonadotrope cell line, and that its function is altered by the rs11031006 minor allele through modification of an SF1 consensus site. As elimination of the SF1 site reduced but did not completely abolish the function of the enhancer, we continued our investigation to identify additional regulatory sites. Transient transfection of LβT2 cells revealed a possible role for the rs11031005 SNP in FSHB regulation, with the minor allele decreasing enhancer-mediated FSHB transcription. This effect may be due to decreased binding of an unidentified transcription factor, as gel shift revealed that the rs11031005 minor allele reduced the intensity of a binding complex. Using truncations and sliding deletions, we identified three additional putative transcription factor binding sites with consensus sequences for ZEB1, PTX1, and SMAD. To support a role for the conserved region as an enhancer in native chromatin, we assessed the histone status in LβT2 chromatin. Compared to the proximal Fshb promoter, the enhancer-specific marker, H3K4me1, was enriched near the conserved region. Neither promoter/enhancer markers of active (H3K27Ac) or repressed (H3K27me3) chromatin were enriched near the conserved region, although levels of both modifications were consistent with the Fshb proximal promoter. Overall, our data support the role of this conserved region as a novel regulator of FSHB/Fshb transcription and reveal a possible mechanism to explain the contribution of PCOS-associated SNPs through FSHB regulation.
MON-494 Quality of Life in Patients with Papillary Thyroid Microcarcinoma According to the Treatment: Total Thyroidectomy Versus Total Thyroidectomy with Radioactive Iodine Remnant Ablation
Authors: Ahn Jonghwa , Jeon Min Ji , Song Eyun , Kim Tae Yong , Kim Won Bae , Shong Young Kee , Kim Won Gu 
Published: May 2020

Abstract
Background: Recently, the role of radioactive iodine (RAI) ablation in the treatment of low risk differentiated thyroid carcinoma (DTC), especially for papillary thyroid microcarcinoma (PTMC), is controversial. This study aims to compare quality of life (QoL) parameters in patients with PTMC underwent total thyroidectomy (TT) versus TT with RAI ablation.
Methods: In this cross-sectional study, patients with PTMC who underwent TT with/without RAI remnant ablation were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: 12-item short-form health survey (SF-12), thyroid cancer specific quality of life (THYCA-QOL), and fear of progression (FoP).
Results: The TT and TT with RAI groups comprised 107 and 183 patients, respectively. The TT with RAI group had significantly lower serum TSH level than TT group. However, after matching of TSH level between the groups (TT with RAI = 100, TT = 100), there was no significant difference in baseline characteristics. According to the SF-12, the score for general health showed significantly lower in TT with RAI group than TT group (p = 0.047). The THYCA-QOL also showed statistically significant difference in felt chilly score between the groups (p = 0.023). No significant differences in FoP scores were seen between the groups.
Conclusion: Patients with PTMC underwent TT with RAI ablation experienced more health-related problems than those managed by TT alone. These findings support RAI ablation should be carefully determined in patients with low-risk DTCs.
SUN-297 Development of a Local Reference Range for Hypertonic Saline-Stimulated Copeptin
Authors: Brooks Emily K , Bachmeier Caroline , Vorster Juanita , Sorbello Jane , Peer Faseeha C , Chikani Viral P , Dimeski Goce , Ungerer Jacobus , Pretorius Carel , Inder Warrick John 
Published: May 2020

Abstract
Differentiating between primary polydipsia and central diabetes insipidus (DI) can be challenging. The water deprivation test has traditionally been used to diagnosis DI, however has poor diagnostic accuracy (1). Direct measurement of anti-diuretic hormone (ADH) is limited clinically. Copeptin is the C-terminal glycoprotein moiety of ADH prohormone, and correlates well with plasma ADH. Unlike ADH, copeptin is easy to measure (2).
Hypertonic saline stimulated copeptin measurements have recently been described for the diagnosis of central DI. A copeptin cut-off of &gt;4.9 pmol/L has a diagnostic accuracy of 96.5% for distinguishing primary polydipsia from central DI (3). A copeptin assay has recently been established in our laboratory. Validation of hypertonic saline-stimulated copeptin concentrations in our local population is needed before this test can be used with confidence in patients presenting to our institution with polyuria-polydipsia syndrome. The aim of this study was to develop a local reference range for hypertonic saline-stimulated copeptin in healthy volunteers.
Twenty healthy volunteers (10 male and 10 female) were recruited. Subjects underwent a hypertonic saline test, as previously described (3). Hypertonic saline (3%) was administered as an initial 250 mL bolus followed by 0.15 mL/kg/minute until a target serum sodium of ≥150 mmol/L was reached. At this time, blood was drawn for copeptin.
Twelve healthy volunteers (7 females; 5 males) have undergone the study to date. Median age was 28 years (range 26-50); median body weight 75.7 kg (range 57.9 -94.5); median baseline plasma sodium 138 mmol/L (range 136 - 140) and median serum osmolality 289.5 (range 281-297). Median peak sodium was 152 mmol/L (range 150-154) with osmolality 314.5 mmol/kg (range 306-320). Median volume of hypertonic saline infused was 1583 mL (1230-2177) and median hypertonic saline stimulated copeptin was 29.2 pmol/L (9.6-167.4). Overall symptom burden was 5/10 (range 3/10-9/10). There were no serious adverse events.
Development of a local reference range for hypertonic saline stimulated copeptin measurements will assist in interpretation of the test in our local population of patients presenting with polyuria-polydipsia syndrome.
References
1. Fenske W, Quinkler M, Lorenz D, Zopf K, Haagen U, Papassotiriou et al. Copeptin in the differential diagnosis of the polyuria-polydipsia syndrome- revisiting the direct and indirect water deprivation tests. JCEM. 2011;96:1506-1515
2. Timper K, Fenske W, Kuhn F, Frech N, Arici B, Rutishauser J et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. JCEM. 2015;100:2268-2274
3. Fenske, W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J. A copeptin-based approach in the diagnosis of diabetes insipidus. NEJM. 2018;379:428-439
SAT-657 The Gut Microbiome Regulates Host Glucose Homeostasis via Peripheral Serotonin
Authors: Keating Damien 
Published: May 2020

Abstract
The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find [1] that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.
[1] The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. Martin AM, Yabut JM, Choo JM, Page AJ, Sun EW, Jessup CF, Wesselingh SL, Khan WI, Rogers GB, Steinberg GR, Keating DJ.
SAT-664 Fluctuating Blood Glucose in an Infant with Newly Diagnosed IPEX Syndrome
Authors: Gottesman Bethany , Gottschalk Michael 
Published: May 2020

Abstract
Background: In the IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome, Type 1 diabetes mellitus is the most common endocrine complication and usually occurs with a variable presentation from immediately at birth to within the first few months of life.
Clinical case: A four-month-old male presented for evaluation of failure to thrive, eczema, and diarrhea. In the ED, his glucose value was 246 mg/dL with beta-hydroxybutyrate of 0.29 mmol/L (0.00-0.30). Within eight hours and without insulin, he became hypoglycemic and required dextrose-containing fluids to maintain euglycemia; he was quickly made NPO and started on TPN due to excessive stool output. For nearly two weeks he required no insulin while receiving 84g of dextrose per day (21 g/kg/day) in TPN. He developed bloody stools on the day that he started receiving Tacrolimus and IVIG and required transfer to the ICU, and an insulin need of 1 unit/kg/day developed with this worsening of his systemic illness. After the bloody stools resolved, immunosuppression with Rituximab was initiated. Once bowel function improved, Pedialyte and formula were slowly reintroduced and for three weeks his insulin requirement varied from 0.2-0.4 units/kg/day. In his seventh week of hospitalization his insulin was discontinued due to hypoglycemia, and at the time of discharge he had been without insulin for ten days on ad lib formula feeding.
Hemoglobin A1c on admission was 10.2%, and repeat was 10.3%. A fructosamine level was obtained to evaluate the discrepancy between the initial HgbA1c and being euglycemic. It was 269 umol/L (190-270), equivalent to an approximate HgbA1c of 6.5%, suggesting that hyperglycemia resulting in an elevated HgbA1c occurred early in his life and had improved in the days to weeks prior to admission. Further testing revealed an elevated GAD-65 antibody of &gt;250 IU/mL (&lt;5) but normal ICA 512 and insulin autoantibody.
His clinical picture was consistent with IPEX syndrome, confirmed with rapid whole genome sequencing showed a pathogenic hemizygous c.1010G&gt;A p.Arg337Gln variant in the FOXP3 gene.
A HgbA1c performed prior to discharge, eight weeks after the initial, was 6.6%. This spontaneous resolution of hyperglycemia in IPEX, with insulin needs developing only when he had worsening systemic illness as demonstrated by bloody stools, has yet to be described.
Conclusion: Hyperglycemia fluctuated in the first few months of life in a patient with IPEX syndrome, likely related to severity of systemic illness and control of enteropathy.
SUN-598 Phenotypic Study of Meso-Somatous (Roch-Leri) Lipomatosis
Authors: Lemaitre Madleen , Espiard Stéphanie , Humbert Linda , Boury Samuel , Lion Georges , Vantyghem Marie-Christine 
Published: May 2020

Abstract
Background: Lipomatosis is a condition in which multiple lipomas are present on the body. Different entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, MEN1, benign symmetric lipomatosis (Madelung or Launois-Bensaude disease), Dercum’s Disease, familial lipodystrophy, hibernomas, epidural lipomatosis, familial angiolipomatosis, and meso-somatous lipomatosis (LMS) still called Roch-Leri lipomatosis. LMS is characterized by the presence of many discrete, encapsulated lipomas of 2 to 5 cm, painless, at the level of the trunk and forearms. The aim of the present study was to determine the clinico-biological phenotype of LMS, as compared to controls. Patients and methods: In this single-center study (NCT01784289), 18 healthy controls (C) and 11 LMS were included after examining the cohort of 76 patients referred for suspected lipodystrophic syndrome between 2009 and 2019 in the Endocrinology Department of a University Hospital. Clinical (sex, age, weight, BMI, blood pressure (BP), alcohol consumption), metabolic (fasting blood glucose (FBG) and insulin levels, lipid balance, ASAT, ALAT, GammaGT, leptin), immuno-inflammatory (CBC, lymphocyte immunophenotyping), and anthropometric (% of body fat in DEXA, steatosis and intra-abdominal / total abdominal fat ratio (IAF / TAF) in MRI) were evaluated. Results: The following parameters, expressed as % or median, differed significantly between LMS vs. C groups, respectively: weight 100 vs. 69kg (p&lt;0.01), BMI 30.8 vs. 22.7 (p&lt;0.01), systolic BP 140 vs. 115 (p&lt;0.01) and diastolic BP 80 vs. 70 mmHg (p&lt;0.05), gammaGT 74 vs. 18 IU / L (p&lt;0.01), fasting insulin levels 7.3 vs. 4.7 microIU / mL (p&lt;0.05), leptin 28 vs. 5 ng / mL (p&lt;0.01), CD3 (867 vs. 1444 / mm3 (p&lt;0.01), CD4 499 vs 866 / mm3 (p&lt;0.05), CD8 227 vs. 546 (p&lt;0.05), fat mass 41 vs. 22 (p&lt;0.05). Three LMS patients had hepatic steatosis and 3 a first-degree family member with LMS. Percentage of men (63% vs. 52%, FBG, lipid levels, ASAT, ALT, CBC, IAF / TAF (0.25 vs 0.19) did not differ significantly. The number of lipomas was &gt; 5 in 82% of LMS patients and lipomas were localized first to the forearms (82%), then the thighs (73%) and the abdomen (55%). At diagnosis, the age of LMS patients was 20 years old; 55% of the LMS patients had a BMI above 30 and 45% above 25. No patient had excessive alcohol consumption. Five had a history of auto-immuneor inflammatory disease: 1 hyperthyroidism, 1 hypothyroidism, 1 multiple sclerosis, 1 vitiligo, 1 Raynaud syndrome. Conclusion: LMS mainly affects overweight men and is associated with hypertension, hyperinsulinism, increased gammaGT and a decrease in CD3, CD4 and CD8 lymphocytes, suggesting an immune dysregulation, all the more so that 45% had an associated auto-immune/inflammatory disease.
SAT-212 Management of VHL-Associated Pheochromocytoma in Pregnancy
Authors: Reikes Andrew Reed , Desai Ruchi 
Published: May 2020

Abstract
Background: The appropriate treatment of pheochromocytoma during pregnancy is crucial because, while its incidence is rare (0.007%), it is associated with increased maternal and fetal mortality1.
Clinical Case: A 32 year old Caucasian primigravida female presented with intrauterine pregnancy at 25 weeks for evaluation and management of a 9 mm left adrenal mass. The patient was previously diagnosed at age 10 with Von-Hippel Lindau (VHL) syndrome and genetic testing was positive for a VHL gene mutation (Type 2C VHL). At age 14, she underwent laparoscopic adrenalectomy to excise a right sided pheochromocytoma. At age 20, imaging revealed an enhancing left adrenal mass with imaging characteristics consistent with pheochromocytoma and with catecholaminergic labs that were normal or only mildy increased to 1.5 times upper normal range. Pre-partum the patient had been experiencing periodic episodes of headaches and palpitations. She reported experiencing baseline levels of palpitations and sweating with new onset of pre-syncope and hypotension during her pregnancy. Labs revealed normal serum levels of fractionated free metanephrines. Alpha adrenergic blockade, beta adrenergic blockade, and surgery were considered but deemed unnecessary as the patient was asymptomatic, imaging indicated the left adrenal mass was stable in size, and the patient wished to avoid lifelong adrenal replacement therapy. The patient’s blood pressure and heart rate were monitored closely throughout pregnancy and the use of alpha blockade or beta blockade was not needed. The patient had an uncomplicated induced delivery at 39 weeks. MRI with contrast of abdomen performed 10 months postpartum confirmed the presence of an enhancing 8 mm lesion on the inferior pole of the left adrenal gland with imaging characteristics again consistent with pheochromocytoma.
Conclusion: This case demonstrates that a conservative approach of monitoring blood pressure and heart rate can be sufficient and appropriate for management of some patients with pheochromocytoma and VHL during pregnancy.
Citation:
1.
ENDOCRINOLOGY IN PREGNANCY: Pheochromocytoma in pregnancy: case series and review of literature in: European Journal of Endocrinology Volume 177 Issue 2 (2017).
SUN-615 Does Patient Location (Urban or Rural) Influence Risk Factors and Incidence Rate for 30-Day Readmission for Diabetic Ketoacidosis?
Authors: Varghese Ron Thomas , Jacob Diana G , Khasawneh Khaled , Kamoga Roy , Mehta Neal 
Published: May 2020

Abstract
Introduction Nearly 1 in 10 individuals in the US have Diabetes Mellitus [1]. One potential preventable complication is Diabetic Ketoacidosis (DKA). Urban and rural patients may have different mortality [2]. Better understanding of the risk factors for readmissions of DKA will allow the development and implementation of specific patient-centered interventions to decrease future readmissions. We determined the 30-day all-cause readmission rate for adults (age &gt;= 18) admitted with a principal diagnosis of DKA and compare the risk factors for urban and rural patients. Methods We utilized Agency of Healthcare Research and Quality’s (AHRQ) 2014 Nationwide Readmission Database to identify admissions with a principal diagnosis of DKA related ICD-9 diagnosis (250.10, 250.11, 250.12, and 250.13) associated with both Type 1 and Type 2 Diabetes Mellitus. Applicable admissions were all adults (age &gt;= 18) with an index hospitalization between January 1 to November 30, 2014. Patients who died during index admission and those with missing covariates were excluded. The 2013 NCHS Urban-Rural Classification System was used to classify if originating from an urban or rural location. All-cause readmission within 30-days of DKA were analyzed. Predictors for readmission were determined using logistic regression model. Results A total of 65,249 patients met criteria for inclusion. Of which, there was 12,561 readmissions (19.25 %) within 30-days of the index admission. Patients originating from urban locations had a readmission rate of 19.36% compared to 18.56 % for patients from rural locations (p=0.07). Multivariate analysis showed patients from either rural or urban location each had a higher likelihood of readmission if their disposition was home health or AMA, younger age (&lt;65), female, Medicare as payer, LOS 7-14 days, absence of obesity, and presence of renal failure. In addition, disposition to short term hospital increased the odds for readmission from rural patients. Conclusion Almost 1 in 5 patients discharged with a principal diagnosis of DKA will be readmitted within 30 days. No difference was noted in rates of readmissions for patients originating from urban or rural locations. Risk factors are similar with further research needed to better understand the drivers of readmission. References: [1] CDC: National Diabetes Statistics Report (2017) [2] Ferdinand AO, et al. (2017). Diabetes-Related Hospital Mortality in Rural America: A Significant Cause for Concern. Policy Brief #3. Southwest Rural Health Research Center
MON-155 Retrospective Cross-Sectional Study to Assess the Utility of 30 vs 60 Minutes Serum Cortisol Value Attained During a Short Synacthen Test (SST)
Authors: Butt Muhammad Imran , Amer Lama Ghassan , Aljamei Hadeel Salah , Riazuddin Muhammad , AlZuhairy Nouf , Abufarhaneh Mohammad , Alahmed Reem , AlRajhi Eman , AlNassar Anhar , Khan Muhammad Sohaib Ejaz , Aljayar Dina Mahmoud , Abothenain Fayha Farraj , Devol Edward Bentz 
Published: May 2020

Abstract
Background
SST is done to assess adrenal gland function by measuring basal serum cortisol followed by injecting 250 μg of Synacthen (ACTH) & measuring cortisol at 30 & 60 minutes.
Design
All patients over 14 years (adulthood age in the region) who had undergone a SST from January 2010 to December 2017 were included. Patients who underwent pituitary surgery in preceding 2 months, on exogenous steroids, opioids & oral contraceptives were excluded. Stimulated cortisol of 550 nmol/L or more achieved at 30, 60 minutes or both was classified as a normal response.
Results
965 patients were identified from pharmacy, medical & laboratory records. 116 patients were excluded and 849 were included in the analysis.
Mean age was 50.5 ± 20.45 years. Mean weight was 67 ± 21 Kg. 54% patients were female. Mean basal, 30 and 60 minutes cortisol values after ACTH injection were 394 ± 286.58 nmol/L, 722 ± 327.11 nmol/L, 827 ± 369.30 nmol/L respectively. 715 patients (84 %) had a normal response and 134 patients (16 %) had suboptimal response. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35% respectively. No ACTH value was available in 55% of the patients.
Suboptimal response was observed at 30 minutes in 9.49% (n=72) of the patients: all crossed 550 nmol/L threshold at 60 minutes. Mean change of cortisol level from baseline to 30 minutes was 240 nmol/L in this particular sub group which was higher than the mean change of 152 nmol/L observed in patients who failed the test overall up to 60 minutes. No patient with optimal response at 30 minutes had suboptimal response at 60 min.
Morning basal cortisol threshold of 226 nmol/L or over had 80% sensitivity, 71 % specificity & 93% positive predictive value to detect a normal SST (P-value &lt;.0001).
Conclusion
60 minute cortisol correctly identified all normal and abnormal results. Relying only on 30 min value resulted in significant false positive results.
Morning basal cortisol over 226 nmol/L should be considered reliable threshold for adequate adrenal function particularly when clinicians have low pretest probability for hypoadrenalism.