bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-486 A Case of Severe Thyroid Ophthalmopathy Requiring Emergency Orbital Decompression and Total Thyroidectomy
Authors: Leonard Talayna , Subramanian Preethi , Mahmood Ruyam , Shahlapour Mahmood , Vazquez Bianca , Horani Mohamad Hosam 
Published: May 2020

Abstract
Introduction: Graves is the most common cause of hyperthyroidism (5). In graves orbitopathy (GO) the activation of T-cells causes fibroblast proliferation and accumulation of hydrophilic glycosaminoglycans, causing osmotic muscle swelling and inflammation resulting in increased orbital pressure (5). Mild GO is managed with selenium, moderate GO with high dose steroids (methylprednisolone) (2). Rituximab is an alternative treatment (4). Severe GO is treated with orbital decompression surgery (2).
Case presentation:A 43-year-old incarcerated male with a history of Graves disease of 4 years,on methimazole, dry eye syndrome, and proptosis, presented to the ED with 5 days of increasing right eye pain, decreased vision and inability to close his right eye. In the ED he had increased intraocular pressure. Glaucoma was considered and the patient was treated with acetazolamide. His ocular pressures improved slightly but vision did not correct. Labs revealed: TSH &lt;.005, FT3 5.48, FT4 1.75, Alkphos 318, TPO Ab 153, TS immunoglobulin &gt;500. Steroids were given but ineffective. Treatment with potassium iodide lowered FT3 to 2.18 and FT4 to 1.27. With continuing eye pain rituximab was started, but was not tolerated. Selenium was not considered due to the severity of GO. The patient was cleared for acute surgical decompression that successfully improved ocular symptoms. The patient’s GO was so severe that a total thyroidectomy was completed for long-term treatment, without complications.
Discussion:In the setting of GO it has been shown that thyroglobulin passes to the orbit where autoantibodies cause inflammation, preventing correction even when hormone levels have been managed (3). Smoking is a known risk factor for GO, cessation is one of the first keys to management (2). A complete thyroidectomy is favored compared to radioiodine (worsens orbitopathy) or antithyroid drug therapy. Surgery has been shown to have a positive impact on the regression of GO Rituximab is a relatively safe and viable treatment that is superior to glucocorticoids or saline for patients with moderate to severe GO.
(1).References:1 Regression of Ophthalmopathic Exophthalmos in Graves’ Disease After Total Thyroidectomy Indian Journal of Surgery. 2017;79(6):521–526
2.The 2016 European Thyroid Association/European Group on Graves’ Orbitopathy Guidelines for the Management of Graves’ Orbitopathy. European Thyroid Journal. 2016 Mar 2; 5(1): 9–26
3.Does autoimmunity against thyroglobulin play a role in the pathogenesis of Graves’ ophthalmopathy: a review. Clinical Ophthalmology (Auckland, NZ). 2015;9:2271–2276.
4. Rituximab in the Treatment of Thyroid Eye Disease: A Review. Neuro-Ophthalmology (Aeolus Press). 2015;39(3):109–115.
5. Thyrotropin receptor autoantibodies are independent risk factors for Graves’ ophthalmopathy J Clin Endocrinol Metab. 2006;91(9):3464.
MON-187 Prevalence and Assessment of Overnight Dexamethasone Suppression Tests for Screening Endogenous Hypercortisolism When Serum Dexamethasone Is Below Threshold
Authors: Farinelli Denise Genaro , Kater Claudio E 
Published: May 2020

Abstract
Background: The 1mg-dexamethasone (DXA) suppression test (DST) is used to verify cortisol (F) autonomy in Cushing’s syndrome (CS) and subclinical hypercortisolism (SCH) of adrenal incidentalomas (AI), based on the ability of DXA to suppress F by inhibiting the HPA axis. A post-DST serum F &gt;1.8 μg/dL usually defines autonomy. Aim: 1) determine the prevalence of invalid tests in a large series of DST used to investigate hypercortisolism during a 12y period in a single institution; 2) assess the percentage of negative tests (normal F suppression) among the subpopulation of invalid DST; 3) examine for interfering substances and clinical conditions that may justify and low DXA levels. Methods: DXA-controlled 1mg-DST was carried out in 162 control subjects (Cont; 107F/55M; 20-75y [median 50y]), to determine a valid threshold for serum DXA, and in 768 patients (80% female; 11-91y [median 53y]), investigated from 2007-19, for F autonomy (a total of 1,300 tests, with 41% repetitions). F and DXA were determined by specific RIA. We search our laboratory data bank for “invalid” DST, tests in which post-DST serum DXA values were below the cutoff established from the control subjects. Results: we set a cutoff for post-DST serum DXA at 140 ng/dL, the lowest value obtained from controls in whom post-DST serum F levels were &lt; 2.5 µg/dL. From the 1,300 DST examined, 146 (11.2%) were considered invalid (DXA &lt;140 ng/dL), and in 36 of them (25%), DXA was undetectable. Also, 35 DST (25%) gave F results below 1.8 µg/dL. Of all 146 invalid DST, 8 (6%) did not take DXA the night before as directed and 14 (10%) admitted being on glucocorticoids (GC), most of them from the undetectable DXA subgroup. Also, 21 patients (14%) were on anticonvulsants, another 21 (14%) were using other moderate or potent CPY3A4 inducers (phenytoin, rifampicin, efavirenz), and 15 (10%) subjects had gastrointestinal abnormalities (colectomy, colostomy, erosive gastritis and disabsorptive syndromes). Conclusions: Test accuracy depends on the serum levels reached by DXA, after adequate ingestion and absorption. Inappropriately low values may result in false-positive test results. One-fourth of “invalid” tests, presented DXA levels below the assay limit of sensitivity, suggesting patient noncompliance. Adherence to verbal and written recommendations and use of medication are essential to interpret the test. Conditions that alter gastric pH, as well as surgical procedures in the GI tract may reduce absorption or accelerate GI transit affecting DXA absorption. DXA metabolism by cytochrome p450 enzymes, mainly CYP3A4, can be enhanced by inducing drugs, making mandatory DXA dosage to validate the test. The wide individual variability in DXA metabolism may be associated not only with environmental and health factors, but also with CYP gene polymorphisms, which can modify drug clearance.
SAT-549 Identification of Somatic Mutations in CLCN2 as a Cause of Aldosterone-Producing Adenomas
Authors: Rege Juilee , Nanba Kazutaka , Blinder Amy R , Else Tobias , Tomlins Scott , Vats Pankaj , Kumar-Sinha Chandan , Giordano Thomas J , Rainey William E 
Published: May 2020

Abstract
Background: Primary aldosteronism (PA) results from both unilateral and bilateral adrenal disease. Unilateral disease is most often caused by aldosterone-producing adenomas (APAs). We recently identified aldosterone-driver somatic mutations in approximately 90% of APAs using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided DNA sequencing approach. In the present study, we analyzed DNA from APA samples found to be mutation negative. Methods: Formalin-fixed paraffin-embedded tissue samples from PA patients who underwent adrenalectomy were studied. Genomic DNA was isolated from 118 APAs (identified by CYP11B2 IHC). Next generation sequencing (NGS) was performed to identify known aldosterone-driver mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D. APA DNA that was mutation negative and the adjacent normal adrenal tissue DNA were subjected to Whole Exome Sequencing (WES). Results: Targeted NGS and WES detected two variants in the voltage-gated chloride channel ClC-2 (encoded by CLCN2), which were confirmed by Sanger sequencing. One of the CLCN2 mutations (p.Gly24Asp) was identical to that previously found to cause germline early-onset PA. The second CLCN2 mutation, which would affect the same region of the protein, was an unreported PA mutation (p.Met22fs). The presence of these variants in two tumors suggests that CLCN2 mutations as a cause of APAs are rare with an approximate prevalence of 1.7% (2/118 APAs). Conclusion: In this study, we identified somatic mutations in CLCN2, in two of 118 APAs. Germline variants in this gene have previously been shown to cause of familial hyperaldosteronism type II and the current findings indicate that similar mutations cause a small proportion of APAs. These findings also indicate that WES of CYP11B2-guided mutation negative APAs can help determine rarer genetic causes of sporadic PA.
OR15-06 Integrative and Analytical Review of the 5 Alpha Reductase Type 2 Deficiency Worldwide
Authors: Batista Rafael Loch , Mendonca Berenice Bilharinho 
Published: May 2020

Abstract
Introduction: The conversion of testosterone into dyhidrotestosterone is catalyzed by the 5 α reductase type 2 enzyme which plays a crucial role in the external genitalia virilization. It is encoded by the SRD5A2 gene. Allelic variants (AV) in this gene cause a 46,XY DSD with no genotype-phenotype relationship. It was firstly reported at early 70’s from isolated clusters. Since then, several cases have been reported. Putting together, it will expand the knowledge about the molecular bases of androgen regulation. Methods: We searched for SRD5A2 AV in the literature (Pubmed, EMBASE, Medline) and websites (ensemble, HGMD, ClinVar). Only cases with AV in both alleles, either in homozygous (HM) or compound heterozygous state (CH) and 5ARD2 phenotype were included. The AV were analyzed according to ethnicity, exon, domain, aminoacid (aa) conservation, age at diagnosis, sex assignment, gender change, external genitalia virilization and functional studies. External genitalia virilization was scored using Sinnecker scale. Conservation analysis was carried out using CONSURF platform. For categorical variables we used X2 test and Cramer’s V. Continuous variables were analyzed by t test or ANOVA. Concordance was estimated by Kappa. Results: We identified 434 cases of 5ARD2 deficiencies from 40 countries. Most came from Turkey (23%), China (17%), Italy (9%), and Brazil (7%). 69% were assigned as female. There were 70% of AV in HM and 30% in CH state. Most were missense variants (76%). However, small indels (11%), splicing (5%) and large deletions (4%) were all reported. They were distributed along all exons with exon 1 (33%) and exon 4 (25%) predominance. AV in the exon 4 (NADPH-binding domain) resulted in lower virilization (F=10.5; p&lt;.0001). The positions 55, 65, 196, 235 and 246 are hotspots making up, 25% of all AV. Most AV (76%) were located at conserved aa. However, AV at non-conserved aa were more frequently indels (28% vs 6%; p&lt;.01). The overall rate of gender change from female to male ranged from 16% to 70%. The lowest rate of gender change occurred in Turkey and the highest in Brazil. Virilization was similar between those who changed and kept their gender. The gender change rate was significantly different across the countries (V=0.44; p&lt;.001) even with similar virilization scores. There was no concordance between genotype and phenotype in all recurrent AV (196, 235 and 246; k 0.6, 0.12 and 0.19). Conclusion: 5ARD2 deficiency has a worldwide distribution. AV at NADPH-ligand region cause lower virilization. Genitalia virilization influenced sex assignment but not gender change which was influenced by cultural aspects across the countries.
SUN-624 Low Risk of Major Adverse Cardiovascular Events After Pancreas Transplantation Alone
Authors: Kaur Ravinder Jeet , Smith Byron H , Rizvi Shafaq R , Batthula Sreedhar , Kukla Aleksandra , Dean Patrick G , Kremers Walter K , Stegall Mark D , Kudva Yogish C 
Published: May 2020

Abstract
INTRODUCTION: Type 1 Diabetes (T1D) patients have an increased risk for major adverse cardiovascular events (MACE). Pancreas Transplantation Alone (PTA) in patients with T1D achieves near normal glucose control for a prolonged period but limited data are available to date regarding MACE during a 10 year follow up period after the procedure.
OBJECTIVE: We studied incidence of MACE after PTA in T1D patients over a 10 year follow-up period.
METHODS: Retrospectively, we studied 113 T1D recipients of PTA at Mayo Clinic, Rochester with the procedure performed between January 1998 and August 2018 and follow up of at least 1 year. Data were collected before transplantation and up to 10 year follow up after the first PTA. MACE data were gathered until primary non function, re-transplantation, or complete loss of c-peptide (&lt;0.01ng/ml). We report vascular risk factors including hypertension, hyperlipidemia, smoking and BMI along with MACE (defined as cardiac events as unstable angina, Myocardial Infarction (MI), need for re-vascularization, cardiac death, cerebral events as Transient ischemic attack (TIA), stroke, need for re-vascularization and peripheral arterial disease as need for re-vascularization, gangrene and amputation).
RESULTS: Eighteen subjects had pre-transplant MACE. A total of 14 subjects had graft failure within 24 to 36 hours due to thrombosis, with 3 in pre-transplant MACE cohort and 11 in no MACE cohort. Thus, we followed 99 subjects for the development of post-transplant MACE for a period of 6.3 ± 3.6 years. T1D subjects with MACE (n=15) had baseline characteristics: Age 48± 7.8 years, gender F/M 9/6,, duration of diabetes 33 ± 12 years, BMI 26± 3.1(Kg/m2), HbA1c 9.3 ± 1.5% and C-peptide 0.09 ng/ml. 84 T1D patients without MACE were age 42 ± 10.6 years, gender F/M 55/29, duration of diabetes 26.5 ± 10.7 years, BMI 26 ± 5.2(Kg/m2), HbA1c 6.7 ± 2.5 and C-peptide 0.09 ng/ml. There are a total of 584 person-years of follow up to first MACE event and 632 person-years of graft failure, death or last follow-up. Nine patients developed 11 MACE events post-PTA. Therefore, the event rate is 1.5 MACE events per 100 person-years for first MACE event and the total event rate is 1.7 MACE events per 100 person-years of follow-up. Age, smoking (yes), gender, duration of diabetes, HTN and Hyperlipidemia presence did not show any significant impact on post-transplant MACE outcome based on univariate Cox regression but the pre-transplant BMI (HR = 1.14; CI = (1.04, 1.26); p = 0.008) and pre-transplant HbA1c (HR = 1.26; CI = (1.06, 1.51); p = 0.01) showed statistically significant impact.
CONCLUSIONS: At our center, MACE is low in PTA recipients. There is no impact of presence of pre-transplant MACE on development of post-transplant MACE but pre-transplant BMI and HbA1c account for risk of MACE.
SAT-672 An Unusual and Enigmatic Etiology for Diabetic Ketoacidosis: Safety Needles
Authors: Modi Ankur , Cryar Keith 
Published: May 2020

Abstract
Diabetic ketoacidosis is associated with a mortality rate of upto 6.1% and accounts for an estimated 115000 hospital discharges per year in the United States. In order to reduce mortality related to DKA, precipitating causes must be identified and addressed. The most common precipitant for DKA is infection with other precipitating factors including acute illness, medications and inadequate insulin therapy (1).
A 76 year-old woman with type 2 diabetes was transferred from her assisted living facility for hyperglycemia. This was her fifth admission in the last month and a half attributed to either hyperglycemia or DKA. Her medications included insulin glargine and insulin aspart. She mentioned compliance with her insulin as well as her diabetic diet. In the ER, her vitals were stable with physical examination showing an obese woman in no acute distress. Her labs showed a blood glucose of 780, an anion gap of 17 and positive serum ketones. Further investigation did not reveal a source of infection or ischemia. The patient was treated in the ICU with intravenous insulin and fluids with resolution of her ketoacidosis. The patient was discharged with a 67% increase in her prandial insulin. On further review, her facility had recently required safety needles to be used for insulin pens. Patient was asked to demonstrate her technique with observation that patient was not pushing down enough to allow for the needle to enter her skin with subsequent trapping of her insulin within the needle. Prior to discharge, she was educated on proper administration of her insulin and since her discharge, she has had no subsequent readmissions for hyperglycemia.
Hospitals and long-term facilities are the primary utilizers of needles with a retractable safety shield. Reduction of accidental puncture, elimination of reuse of needles and helping patients overcome anxiety about needles are some of the key advantages of these needles. Upon application of pressure onto the skin, the automatic shield or plastic cannula retracts and thus hides the needle before, during and after the injection. The major disadvantage is insulin being deployed while the needle is outside the body if incorrectly applied. Therefore, appropriate administration must be taught to the patient, including perpendicular insertion of the needle into the subcutaneous tissue and ensuring a more firm surface by injecting into a lifted skin fold. Legislation in the US has been passed requiring safety-engineered devices when feasible.In situations where the safety-engineered devices can impair effectiveness or cause harm, alternative approaches can be utilized, including insulin syringes or self-administration of insulin along with safe work procedures (1).
1. Yu Catherine H.Y.. “Safety” technology: a hidden cause of diabetic ketoacidosis. Canadian Medical Journal Journal. 2012 Mar 20;184(5):557–558.
SUN-253 PROKR2 Neurons of the Amygdalohippocampal Area in Reproductive Function
Authors: Larios Brenda Cisneros , Elias Carol F 
Published: May 2020

Abstract
Kallmann Syndrome (KS) is characterized by infertility and anosmia due to deficiency in gonadotropin releasing hormone (GnRH) neuronal migration and olfactory bulb dysgenesis. Genetic studies have revealed that KS is caused by loss-of-function mutations in several genes including the prokineticin receptor 2 (PROKR2) gene (Abreu et al., 2008, Hardelin & Dode 2008). Mice with global deletion of Prokr2 replicate the phenotype of KS patients (Ng et al., 2005, Matsumoto et al., 2006). Whereas the role of PROKR2 during development is defined, little is known about PROKR2 neurons in adult reproduction. PROKR2 mRNA are highly expressed in reproductive control sites of the adult mouse brain (Cheng et al., 2006). Previous studies in our lab found PROKR2 mRNA and Prokr2-Cre GFP+ cells highly expressed in the amygdalohippocampal area (AHi, also called posterior nucleus of the amygdala) in a sexually-dimorphic pattern. Male mice have higher PROKR2 expression in the AHi compared to female mice (Mohsen et al., 2017). The amygdala is an important site of socio-sexual inputs and reproductive neuroendocrine responses in rodents and primates, including humans. We hypothesize Prokr2-Cre neurons in the AHi have a role in both male and female reproductive function. Using genetic tracing techniques, we mapped AHi Prokr2-Cre neuronal projections in both male and female mice and found dense innervation to reproductive control sites such as the medial preoptic area and the ventral premammillary nucleus in a sexually dimorphic pattern. A soiled bedding exposure test in sexually experienced male mice showed that an estimated 45% of cFos + cells in the AHi express Prokr2-Cre GFP. Dense sex steroid receptors expression was observed in AHi Prokr2-Cre GFP neurons of both male and female mice. Our preliminary data suggests AHi Prokr2-Cre neurons have a reproductive function in male and potentially also in female mice. Future studies will focus on selective activation and inhibition of these neurons using chemogenetic technology to determine putative inputs to brain sites that control the hypothalamo-pituitary-gonadal axis. We expect our studies will contribute to the understanding of the role of PROKR2 neurons in adult reproduction and reproductive deficits associated with PROKR2 mutations.
SAT-651 Ethnic Differences in the Relationship Between Uric Acid Clearance and Insulin Sensitivity
Authors: Armiyaw Abdul-Latif , Fosam Andin , Sarcone Camila , Aradhya Ahimsa , Walter Mary , Rabel Antoinette , Muniyappa Ranganath 
Published: May 2020

Abstract
Background: Hyperuricemia is associated with gout, type-2 diabetes, hypertriglyceridemia, and other insulin resistant (IR) states. Impaired clearance of uric acid (UA) has been proposed to play a role in hyperuricemia in IR. In a small study, urinary UA clearance was negatively associated with IR. African-Americans (AA) are more insulin resistant than Caucasians (CA). However, plasma UA levels are lower in AA. Ethnic differences underlying the relationship between UA clearance and insulin sensitivity (Si) remain unknown.
Objective: To compare the relationships between UA production, clearance, and Si in AA and CA.
Design: In a cross-sectional study, AA (n = 40; age 43 ± 10 years; BMI 41.3 ± 9.7 kg/m2) and CA (n = 88; age 44 ± 13 years; BMI 32.9 ± 8.2 kg/m2) subjects underwent an intravenous glucose tolerance test (IVGTT) to derive Si using the Minimal Model. Plasma UA and creatinine (Cr), were measured in the NIH Department of Laboratory Medicine. Urinary UA and Cr levels in spot urine samples were measured using a colorimetric assay. Fractional Excretion (FE) of UA and urine urate-to-creatinine ratio (UUCR), a measure of uric acid production, were calculated.
Results: AA had a significantly higher BMI (p &lt; 0.0001), percent body fat (45.8 ± 8.9 vs. 39.7 ± 11.5 %, p = 0.0007), A1C (5.8 ± 0.4 vs. 5.5 ± 0.3 %, p = 0.0006), diastolic BP (74 ± 9 vs. 71 ± 8 mm of Hg, p = 0.02), and lower Si (2.36 ± 2.7 vs. 4.43 ± 3.4 min−1·μU·ml−1, p = 0.0004) compared to CA. Stepwise multiple regression analysis was performed with independent variables A1c, fasting glucose, fasting insulin, triglycerides, and Si. Among these, Si was a significant predictor of FE of UA in CA (r = 0.33, p=0.001), but not AA (r = - 0.02, p=0.92).There was also a negative association between Si and plasma UA in CA (r = 0.48, p &lt; 0.0001), but not in AA (r = 0.06, p = 0.70). There was no association between Si and UA production in both groups (AA: p = 0.33, CA: p = 0.69).
Conclusion: These findings suggest that reduced insulin sensitivity may not play a major role in the pathogenesis of hyperuricemia in AA in insulin-resistant states.