bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-097 Gonadotropins Levels Measurement in First Morning Voided Urine as a Diagnostic Tool for Central Precocious Puberty
Authors: Sakdinun Wasawee , Komkhum Oranut , Phatarakijnirund Voraluck , Chaiyakul Phairuch , Numbenjapon Nawaporn
Published: May 2020

Background: GnRH stimulation test is the gold standard for the diagnosis of central precocious puberty (CPP). However, it is invasive and costly. Previous studies showed that increased urinary gonadotropins (Gn) level in first morning voided (FMV) urine reflected the integration of elevated nocturnal Gn secretions. Therefore, it could be used to diagnose CPP. Nevertheless, its cutoff value for diagnosis of CPP is limited. Objective: To determine the association of Gn levels in FMV urine and serum during pubertal development and establish cutoff value of FMV urinary Gn as an alternative noninvasive method for diagnosis of CPP in girls. Methods: Sixty-one girls who had breast development before 8 years of age with sign of rapid pubertal progression (advanced bone age and/or increased height velocity) underwent subcutaneous GnRH agonist test. FMV urinary Gn were also collected on the same day. Both serum and urinary Gn levels were measured using electrochemiluminescence immunoassay (ECLIA) technique. The definite diagnosis of CPP is based on stimulated serum LH > 5 IU/L. FMV urinary Gn were compared between CPP and premature thelarche (PT) groups. The correlation between serum and urinary Gn were assessed and the cutoff value of urinary Gn to diagnose CPP was established. FMV urinary Gn of 480 Thai school girls (control) were also collected to determine the reference values according to their breast Tanner (BT) stages. Results: FMV ULH level in girls with CPP was significantly higher than that of PT (2.46 VS 0.8 IU/L; median, P <0.001). However, the level of ULH in PT group was not different from control group with BT1. FMV ULH and ULH: UFSH were well correlated with basal serum LH (r=0.63 and 0.73, respectively, Ps<0.001) and peak serum LH (r=0.44 and 0.54, respectively, Ps<0.001). Base on receiver operating characteristics analysis, basal serum LH was the best parameter to differentiate CPP from PT (area under the curve 0.797–0.926). ULH levels at ≥ 1.13 IU/L and ≥ 1.52 provide optimal sensitivity (72.3 and 68.1 %, respectively) and specificity (85.7 and 100 %, respectively). Combined ULH level ≥ 1.13 IU/L with ULH: UFSH ≥ 0.17 increased specificity from 85.7 to 92.9 % for predicting a positive GnRH agonist test. (peak LH ≥ 5 IU/L) Conclusions: First morning voided urinary Gn levels measurement is a highly potential method for the diagnosis of CPP in girls due to its good correlation with GnRH agonist test. Further study in a larger number of patients with close monitoring of clinical outcome is required before recommending as a standard investigation in CPP.
SAT-LB42 Bilateral Large Calcified Adrenal Leiomyoma Mimicking Adrenal Malignancy: A Rare Case Report With Literature Review
Authors: Jajah Mohammad Bilal M , Hassan Asim , Haiba Moutaz , Elkhouly Tohamy , Haj Elamin Mohammed M , Almalki Abdulkareem
Published: May 2020

Background: Adrenal leiomyoma is a very rare benign soft tissue tumor, it is even more unusual if presenting bilaterally; 21 cases have been reported in the literature and only six had bilateral involvement; 5 in the pediatric population and only one in an adult patient. Radiological appearance may frequently be confused with malignancy especially if large, calcified and with central necrosis. We report a rare case of bilateral, large, calcified, non-functioning adrenal leiomyoma in a 20-year-old female, who was suspected for a malignancy preoperatively.

Clinical Case: A 20 year-old-female presented with chronic abdominal discomfort, fatigue, and inability to gain weight. On examination, she was normotensive, underweight with BMI of 15.6 kg/m2, and there were no stigmata of Cushing’s syndrome, Addison’s disease or pheochromocytoma. A contrast CT scan of the abdomen revealed the presence of bilateral well-defined suprarenal lesions measuring 8.5 x 8.5 x 7.2 cm and 4.7 x 4.2 x 3.5 cm on the right and left side, respectively. The lesions showed large central areas of necrosis with multiple punctate calcifications and heterogenous peripheral enhancement. The radiological differential diagnosis included adrenal cortical carcinoma, adrenal metastasis, infectious etiology, and bilateral pheochromocytoma. Her hormonal assays showed normal free cortisol and catecholamine metabolites in the urine and normal serum androgens. Thus, the tumors were concluded to be non-functioning. Adrenal insufficiency was ruled out after a short Synacthen test. The patient underwent a successful right adrenalectomy. Resected specimen measured 10 x 9.5 x 7.5 cm. Histology revealed a well-circumscribed and pseudo-encapsulated smooth muscle tumor comprised of bland, spindle-shaped cells. The panel of immunohistochemical stains supported the diagnosis of leiomyoma. Postoperatively, the symptoms improved, she gained 4 kg weight over the following 4 months, and short Synacthen test confirmed an intact adrenal function. To avoid lifelong adrenal insufficiency and after discussion with the patient, we agreed to leave the left adrenal mass and follow it by serial imaging. There was only a minimal increase in the size over the following 4 years (5.5 x 4.5 x 3.8 cm).

Conclusion: Adrenal leiomyoma is an extremely rare adrenal tumor and can be confused with adrenal malignancy. Therefore, it should be considered in the differential diagnosis of adrenal incidentalomas. In the case of bilateral etiology, permanent adrenal insufficiency and longterm replacement therapy can be avoided in certain population by removing the larger tumor and continuous follow-up for the other side.
MON-457 Reactive Thyroid C-Cell Hyperplasia or Medullary Thyroid Cancer in a Patient with Nodular Thyroidopathy. May the Calcitonin Measurement in Fine-Needle Aspirate Washout Fluid of the Healthy Lobe Help to Define These Conditions?
Authors: Chevais Anastassia , Beltsevich Dmitry , Vanushko Vladimir , Mikheenkov Alexander , Ladygina Daria , Pokrovskaya Elena , Roslyakova Anna
Published: May 2020

Background: Serum basal calcitonin (bCT) is used as a biomarker of medullary thyroid carcinoma (MTC) but bCT can also be elevated in patients with hypercalcemias, hypergastrinemias, thyroiditis, neuroendocrine tumors, renal end-stage kidney disease, obesity and cigarette smoking. The application of bCT and calcitonin measured in the FNA washout fluid sample (FNA-CT) for screening certain patients with nodular thyroidopathy can be controversial. Case: A 44 yo patient presented with elevated bCT level - 24pg/ml (N for male <18). He had a morbid obesity (BMI-45kg/m2) and thereby received GLP-1 receptor agonists Liraglutide 18 mg in total throughout one month. The ultrasound thyroid examination showed 2 nodules in the right lobe: 11mm and 9 mm (EU-TIRADS 2 and 4). Thyroid nodules were evaluated by fine needle aspiration biopsy (FNAB) which revealed benign colloid nodules (Bethesda II). Following the most updated ATA guidelines, to accurately diagnose MTC we performed FNA-CT measurement. The concentration from both nodules exceeded the upper reporting range of 2000 pg/ml. The patient stopped his therapy with Liraglutide and after one month of following, his bCT dropped at 18 pg/ml. He underwent a second workup with same results. We examined FNA-CT of contralateral healthy lobe and obtained 913 pg/ml. After this case, 17 patients with high-normal rate of bCT: 14 of them had a nodule (Bethesda II) and elevated FNA-CT of healthy tissue of the contralateral lobe (>2000 pg/ml) were determined in follow-up group. The remaining 3 patients with nodules (Bethesda IV-VI) and FNA-CT of healthy lobe which did not exceed bCT rate, were operated. MTC was confirmed. Discussion: Our patient had not only many factors which can occur his bCT level (obesity, smoking), but also unfavourable FNA washout results. Additionally, since in clinical studies GLP-1 receptor activation has been associated with C-cell hyperplasia (CCH), we cannot completely exclude the possible effect of this treatment on patient’s bCT level. We confronted a situation when, on the one hand, FNA-CT data indicate the MTC nature of hypercalcitoninemia, but on the other hand, decreasing bCT-level in dynamic observation is not common for MTC. FNAB of the healthy lobe and obtaining high rates of CT in the washout fluid sample allowed us to confirm the diffuse CCH process, thus to follow up these patients. CT stimulation test cannot distinguish between minimal MTC and CCH and has no reference range. The weak point of the proposed study is the lack of morphological data in the follow-up group of patients. Conclusion: It is possible to use rate of FNA-CT of the healthy lobe to differentiate between various C-cell diseases, but requires new data.
MON-LB81 Ultrasound-Guided Radiofrequency Ablation RFA of Benign Symptomatic Thyroid Nodules - Initial Colombian Experience
Authors: Hernandez-Triana Eric , Forero-Cuellar Oscar Mauricio , Herrrera-Rendon Dimas F , Hernandez-Santamaria Valentina
Published: May 2020

Introduction: Radiofrequency ablation (RF) is a minimally invasive technique probed as effective and safe treatment alternative for the manage, We describe the results of efficacy and safety up to 12 months following the first thyroid nodules with ablative radiofrequency in Colombia.Objective: Evaluate the efficacy and safety of RF thyroid radiofrequency ablation for benign thyroid nodules in a protocol in our center in Bogotá Colombia, case series. Methodology: Prospective, observational and descriptive Trial Patients and procedure: From May/2017 to Nov/2019 we Treated 38 patients with 59 mainly solid nodules were treated with a Radiofrequency Ablation system with cooling 2 standard techniques (Trans-isthmic approach and moving Shut technique). Starmed system with cool type antenna of 16 G. and 10 mm active tip (3 cases) and Cosman RF cooled with 15 cm long active tips 5 to 15 mm 18 G electro Teflon. (35 cases). Here the first 59 nodules who completed a clinical and ultrasound follow-up to 12 months. Outcomes: initial volume was 15.4 +/-28 cc (0.03 a 203 cc) After radiofrequency ablation, the volume decreased significantly, in VRR%**. 40%, 55%, 62% y 68% at 1,3,6 & 12 months. final volume was 4.46 cc P= 0.000*. Compressive Symptoms drop from 5.84 to 1.19, 0.17, 1.76 at 1,3 & 6 moths p <0.001, Cosmetic Symptoms from 2.02/4 to 0.73, 0.58, 0.41 at 1,3 & 6 moths p <0.01. and Quality of Life symptoms from 0 to 10 drop from 5.6 to 2.4, 1.27 & 1.53 at 1,3 & 6 moths p<0.001. Not even one serious adverse event happened. Non-serious adverse events that did happened include minimal skin ecchymosis and transitory pain during less than 3 days, average 4/10 VAS (Visual Analog Scale). None developed hypothyroidism or required hospitalization. one patient presents transitory Horner syndrome and other nodule rupture. Two patients present a transitory dysphonia. Conclusions Radiofrequency ablation performed in our institution is effective and safe for the treatment of thyroid nodules. With patient satisfaction, improve the compressive, cosmetic symptoms and quality of life and without severe complications. It is necessary to continue to enrich this experience, because reducing volume and solving compressive and cosmetic problems, is ambulatory procedure.
SAT-334 A Genetic Cause of Primary Hyperparathyroidism
Authors: Weaver Travis , Hoang Thanh
Published: May 2020

Background: Primary hyperparathyroidism is a relatively common endocrine condition, affecting up to 7 out of every 1000 adults. Median age of onset is during the sixth decade of life. When present in younger patients primary hyperparathyroidism may indicate an underlying genetic cause. Case: A 23-year-old woman is referred for evaluation of hypercalcemia that was found on labs drawn after surgery for bilateral ovarian cyst removal. At the time of presentation she felt well and was without complaint. Her medical history is otherwise unremarkable. Her family history includes multiple family members with nephrolithiasis. Physical exam revealed a well appearing Caucasian woman without a palpable neck mass. Laboratory results showed: serum calcium 11.7 mg/dL (ref 8.4–10.2), ionized calcium 1.44 mmol/L (ref 1.12–1.32) and serum PTH 192 pg/mL (ref 11–65). Technetium-99 sestamibi scan revealed a low attenuating mass with focal and persistent uptake just inferior to the left thyroid lobe. She subsequently underwent left inferior parathyroidectomy, which confirmed parathyroid adenoma, with resultant normalization of serum calcium and PTH. Due to her young age of diagnosis genetic testing was performed which revealed a mutation if CDC 73. Discussion: CDC 73 mutation is known cause of inheritable neoplasia’s with a high prevalence of parathyroid dysfunction. Although penetrance and expression is variable, the mutation is associated primarily with Hyperparathyroidism Jaw Tumor Syndrome (HPT-JT), Familial Isolated Hyperparathyroidism and sporadic parathyroid carcinoma. Our patient had an allele mutation associated with HPT-JT. This syndrome classically presents with parathyroid adenoma, ossifying tumors of the mandible and renal or uterine neoplasms. The mutation is inherited in an autosomal dominant pattern and family history plays a key role in diagnosis of this rare condition. This patient had an early age of onset for hyperparathyroidism and a family history suggestive of an inherited calcium metabolism disorder. A single parathyroid adenoma is the most common presentation and surgical resection is often curative of hyperparathyroidism. In Hyperparathyroidism Jaw Tumor Syndrome patients classically develop ossifying tumors of the mandible and renal or uterine neoplasms in addition to parathyroid lesions. Rarely patients with CDC 73 mutation can develop parathyroid carcinoma. For this reason it is recommended that all first degree relatives undergo testing for CDC 73 mutation. This patient currently has no evidence of jaw, uterine or renal tumors on screening imaging. Ovarian tumors have been described separately to be associated with CDC 73 mutation, this patient may actually have an unrecognized phenotype of CDC 73 mutation. Given the potential impact of inheritable neoplasia, all young patients with unexplained hyperparathyroidism should be considered for genetic screening.
MON-LB310 Relationship Between Obesity-Induced Metabolic Abnormalities and Nutrient Intake: Sex Differences in Japanese University Students
Authors: Yamamoto Mayumi , Mehta Mausam , Nishio Akihiro , Horita Ryo , Izurieta Ricardo
Published: May 2020

Background: Preventive measures and interventions for obesity in young adults are urgently needed. However, evidence-based guidelines for interventional programs in this generation have not been established worldwide because of limited access to data on this group. To establish effective methods of obesity prevention in young adults, we analyzed the relationship between nutrient intake and obesity-related metabolic factors in each body mass index (BMI) group among Japanese university students. Methods: A cross-sectional analysis was performed using annual health checkup data, which is conducted mandatory for all students according to the School Health and Safety Act in Japan, from Gifu University’s incoming class of 2017. Nutrient intake information was obtained from the brief-type self-administered diet history questionnaire (BDHQ), which has been adjusted and validated for the Japanese population. Inclusion criteria were aged 18-30 years and completed the all examination items including BDHQ. From a total of 1277 students’ data, 1202 satisfied and were included in the analyses (participation rate: 94.1%). Nutrition and metabolic data were compared among BMI groups (lean, <18.5 kg/m2; normal, 18.5-24.9 kg/m2; obese, ≥25.0 kg/m2, according to criteria of the Japan Society for the Study of Obesity [2002]) using one-way analysis of variance with post-hoc Tukey honestly significant difference analysis in SPSS software version24 (IBM Corporation, Armonk, New York). Results: The percentage of obesity was 8.1% in men and 1.4% in women, showing a significant difference. Among men, BMI groups were significantly (p<0.05) different in the intake of 11 nutrients which were protein, fat, saturated fat, cholesterol, omega 3 and 6 fatty acids and micronutrients K, Mg, P, Fe, and Zn, significantly high in nine metabolic parameters, which were blood glucose, hemoglobin A1c, uric acid (UA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), systolic and diastolic blood pressure (BP), low-density lipoprotein (LDL) cholesterol, triglycerides (TG) and significant low in high-density lipoprotein (HDL) cholesterol among obese group. Among women, BMI groups were not significantly different in nutrient intake, significantly high in five metabolic parameters, which were UA, ALT, systolic BP, LDL, and TG, and significant low in HDL among obese group. Conclusion: This study suggested that the effect of obesity on metabolic abnormalities in Japanese university students may be more remarkable in men than in women. This sex difference might be partially explained by the significant increase in protein and fat intake in obese men. For women, other factors may contribute to obesity and metabolic abnormalities. Education for appropriate volumes of nutrient intake could be effective in male university students.
SAT-LB37 Frailty in Patients With Mild Autonomous Cortisol Secretion Is Higher Than Patients With Nonfunctioning Adrenal Tumors
Authors: singh sumitabh , Atkinson Elizabeth , Achenbach Sara , Bancos Irina
Published: May 2020

Background: Mild autonomous cortisol secretion (MACS) affects up to 50% of patients with adrenal adenomas. Frailty is a syndrome characterized by diminished strength and endurance and serves as a marker of declining health and dependency. We hypothesized that patients with MACS are more frail when compared to patients with nonfunctioning adrenal tumors (NFAT).

Methods: This is a retrospective study of adult patients with adrenal adenoma evaluated at a tertiary center from 2004 to 2018. MACS and NFAT were defined as cortisol after 1 mg overnight dexamethasone suppression (DST) between 1.8-5 mcg/dl and <1.8 mcg/dl, respectively. Frailty index (FI, range 0-1) was calculated using a 47 variables -deficit model (20 comorbidities, 14 activities of daily living, and 13 symptoms). Patients were excluded if treated with exogenous glucocorticoids, if diagnosed with overt adrenal hormone excess, another adrenal disorder, or if missing variables of interest.

Results: MACS was diagnosed in 168 patients (67% women) at a median age 65 (30-91) years and NFAT in 275 patients (61% women) at a median age of 59 (21-84) years. Patients with MACS demonstrated higher prevalence of hypertension (73% vs 62%), cardiac arrhythmias (50% vs 40%), and chronic kidney disease (25% vs 17%), but lower prevalence of asthma (5% vs 14%), when compared to patients with NFAT, p<0.05 for all. Patients with MACS reported more symptoms of weakness (21% vs 11%), falls (7% vs 2%), and sleep difficulty (26% vs 15%) as compared to patients with NFAT, p<0.05 for all. Age, sex and BMI-adjusted FI was higher in patients with MACS vs patients with NFAT (0.17 vs 0.15, p=0.009). Using cut-off FI of 0.2, 42% of patients with MACS were frail, versus 30% of patients with NFAT (p=0.01).

Conclusion: Higher frailty in patients with MACS supports a more aggressive management, such as adrenalectomy over conservative follow up. Future prospective studies are needed to characterize frailty in greater detail in patients with MACS, as well as to examine frailty reversal by adrenalectomy.
SUN-LB131 Association of Receptor for Advanced Glycation End Product (RAGE) Gene Polymorphisms & Serum Levels of Soluble RAGE (sRAGE) With Metabolic Syndrome (MS) in Mexican Population
Authors: Gonzalez-Guerrero Diana Elizabeth , Rojas-Rubio Armando , Lazo-de-la-Vega-Monroy Maria-Luisa , Gomez-Ojeda Armando , Luevano-Contreras Claudia , Macias-Cervantes Maciste , Fajardo-Araujo Martha Eugenia , Garay-Sevilla Ma Eugenia
Published: May 2020

Background. RAGE, a multi-ligand type 1 transmembrane glycoprotein belonging to the immunoglobulin superfamily, transduces biological signals associated with chronic cellular stress related with inflammatory responses, tissue damage, chronic and degenerative diseases (1). sRAGE is a variant of RAGE derived from cell surface cleavage mechanisms that could potentially act as endogenous inhibitors of RAGE activity (2). RAGE gene is highly polymorphic, with polymorphisms that could be responsible for disease development, like -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms. These are located in the promoter region and have marked effect on transcriptional activity. However, there have been conflicting findings between the potential association of RAGE polymorphisms and the development of diseases. In this work, we evaluated -374T/A (rs1800624) and -429T/C (rs1800625) polymorphisms and measured serum sRAGE levels in Mexican population with MS.

Methods. A group of healthy men without any component of the MS (n=80), and a group of men with the MS (n=80) according to the harmonized criteria for the MS were included in this study. Blood genomic DNA was isolated and genotyped by RT-PCR for the -374T/A and -429T/C polymorphisms of RAGE gene. sRAGE in serum was measured with an ELISA kit. Results. The studied population complied with the Hardy-Weinberg equilibrium (p=0.58 for -374T/A, and p=0.79 for -429T/C). Differences were observed in all the components of the MS between the two groups (MS vs. healthy subjects, p<0.000). However, there were no differences in the population according to their genotype for the -374T/A (p=0.57) and -429T/C (p=0.59) polymorphisms. There was no difference in glucose (p=0.22), triglycerides (p=0.99), and cHDL (p=0.88) levels, or waist circumference (p=0.84) according to the genotype for the -374T/A polymorphism. The same was observed for the -429T/C polymorphism (glucose p=0.57, triglycerides p=0.69, cHDL p=0.77, waist circumference p=0.99). No association of MS with the -374T/A nor 429T/C polymorphism was found. There were no differences between groups in circulating sRAGE levels (p=0.132). Conclusion. According to our results, the -374T/A and -429T/C polymorphisms of RAGE gene are not associated with the MS in Mexican population, and have no influence on serum sRAGE levels. Some other factors could be playing a role for the high prevalence of the MS, such as eating habits. Gender should be taken into consideration, for our study was performed in men exclusively. References. (1) Serveaux-Dancer M et al., Dis Markers. 2019 Feb 4;2019:2067353. (2) Schmidt AM. Vascul Pharmacol. 2015 Sep;72:1-8.
SUN-LB40 Chronic Cortisol Works Through the Transcription Factor KLF9 to Deregulate Immune Response and Metabolism
Authors: Gans Ian M , Hartig Ellen I , Tilden Andrea R , Graber Joel H , Coffman James
Published: May 2020

Chronically elevated levels of glucocorticoids (GC) are associated with a number of disease states and negative side effects, including metabolic syndrome. Epidemiological studies show that elevated GC during a brief but vulnerable developmental window can have life-long and potentially multi-generational impacts on health. To elucidate underlying pathogenic mechanisms, our lab has used chronic treatment with a physiological dosage of cortisol (CORT) in developing zebrafish, Danio rerio, a model organism that has emerged as a useful tool for investigating GC signaling. In this paradigm, we have found evidence that high CORT during development alters a set point for the HPA axis and leads to continuous induction of aberrant GC production and transport, accompanied by altered immune gene regulation and decreased ability to maintain blood glucose homeostasis. To identify molecular and genetic pathways perturbed by chronic CORT treatment, we used CRISPR to generate mutant lines lacking the glucocorticoid receptor (GR) or the transcription factor Klf9, which we have found to be an important target/regulator of GC signaling. We performed RNA sequencing in these mutant lines and compared the transcriptomes of wild type (WT) and mutant animals treated with either chronic CORT or vehicle control (VEH). A broad overview of the data shows similarities between CORT treated wild-type fish and VEH treated GR mutants suggestive of GC resistance in the CORT treated WT animals. In Klf9 mutants, a number of genes involved in immune processes that were upregulated by chronic CORT in WT animals were not similarly upregulated, suggesting that Klf9 is an important feed-forward mediator of immune gene regulation by GC. Additionally, CORT increased expression of a number of metabolic genes in Klf9 mutants that were not similarly upregulated in WT, suggesting that Klf9 plays a regulatory role in the response of cellular metabolism to GC. To further investigate Klf9’s role in governing cellular metabolism, metabolic rate assays were performed on live animals. The results show that Klf9 mutants have lower total respiration, and that chronic CORT increases non-mitochondrial respiration in both WT and Klf9 mutants. Mitochondrial respiratory capacity was unaffected across conditions. This, coupled with gene expression data, suggests that measured metabolic differences are due to shifts in substrate usage and differential reliance on non-mitochondrial metabolic pathways such as glycolsis and peroxisomal beta-oxidation. Additional studies are required, but the regulation of glycolysis by Klf9 could contribute to this gene’s known tumor-suppresive role, and regulation of peroxisomal metabolism—key in immune cells—could partially explain the role of Klf9 in mediating these cells’ responsiveness to CORT.
SAT-015 Incidence and Predictors of Hypertension in a Cohort of Australian Women with and Without Polycystic Ovary Syndrome
Authors: Kakoly Nadira Sultana , Earnest Arul , Loxton Deborah , Teede Helena Jane , Joham Anju Elizabeth
Published: May 2020

Background: There is a lack of longitudinal studies exploring the relationships between polycystic ovary syndrome (PCOS) and hypertension, in population-based settings.

Objectives: To identify predictors of hypertension in women with and without PCOS and the relationship to body mass of index (BMI).

Methods: We undertook a community-based cohort analysis of the Australian Longitudinal Study (ALSWH) data conducted on 9,688 young adult women, aged 21–42 years from 2000–2015. We conducted survival analysis using the Cox Proportional Hazards Model to identify predictors and person-time analysis to calculate incidence rates of hypertension.

Results: Overall, 9,508 women were followed for 145,159 PY (person-years) and 1,556 (16.37%) women developed hypertension during the follow-up. The incidence of hypertension was significantly higher (p = 0.001) among women with PCOS (17/1000 PY) compared to women without (11/1000 PY). There were significant differences in time to hypertension development between women +/- PCOS. Hypertension was observed among women with PCOS from early adulthood and across BMI categories. The difference in the actual number of incident hypertension cases (incidence rate difference (IRD)) between women with and without PCOS, was fourfold higher (15.8 vs. 4.3 respectively) among women who were obese at baseline, compared to age-matched lean women. PCOS was independently associated with hypertension with a 36% greater risk, adjusting for BMI and other confounders.

Conclusion: Our results suggest women with PCOS as more likely to develop hypertension from early adulthood, independent of BMI and with risk exacerbated by obesity.
SAT-LB124 Phosphatidylcholine Transfer Protein Interacts With PPARδ to Modulate Activity
Authors: Druzak Samuel Adam , Mays Suzanne , Ortlund Eric
Published: May 2020

Obesity is one of the largest public health crises in the USA. Obesity can be lethal due to the development of cardiovascular complications such as, hypertension, heart attack, and stroke. Recently, peroxisome proliferator-activated receptor δ (PPARδ), the least-characterized member of the PPAR family of nuclear receptors (NRs), has shown great promise in treating obesity and associated cardiovascular complications. Recent reports have shown that PPARδ activation is tuned, in part, through an interaction with fatty acid binding protein 5 (FABP5) in a polyunsaturated Fatty acids (PUFAs) dependent manner. This enhancement is thought to occur due to ligand transfer, however, FABP5 only binds a subset of reported PPARδ ligands. To find other candidate lipid transport proteins (LTPs), we performed a protein complementation assay (PCA) between LTPs and NRs. We uncovered a novel interaction between PPARδ and phosphatidylcholine transfer protein (PC-TP), sensitive to cellular nutrient levels. Preliminary data show that this interaction opposes canonical PPARδ signaling, leading to a decrease in PPARδ transactivation in cells and isolated mice livers. This led me to hypothesize that PC-TP senses nutrient status through membrane composition. Specific PC molecular species drive PC-TP translocation to inhibit PPARδ transactivation of genes. Utilizing our novel PCA assay I have shown that the interaction is modulated in part by cellular levels of methionine and choline, as cells cultured in media depleted of methionine and choline (MCD) show a decreased in the interaction. Using the same assay, I have shown a requirement of full length PPARδ for the interaction with PC-TP. This analysis will be complimented by mutagenesis and chemical perturbations aimed to alter PC-TP and PPARδ function. Additionally, I have assayed the in vivo relevance of PC-TP interaction with PPARδ using livers harvested from PCTP-/- and littermate control mice fed a variety of diets. Preliminary RNA-seq characterization, show interesting alterations in gene expression that suggest more complex regulation between PC-TP and PPARδ in vivo. MCD, which was shown to reduce the inhibitory interaction between PC-TP and PPARδ in vitro, seems to lead to an increased effect on PPARδ transactivation when PC-TP is depleted. Analysis comparing the effect of diet within each genotype shows a loss of differential PPARδ regulation for both CHEA and KEGG analysis when comparing WT to PCTP -/- mice supporting a role for PC-TP in differential PPARδ regulation caused by MCD diet. These studies will further the understanding of how lipid homeostasis is sensed and maintained through PPARδ by interactions with two separate LTPs.
SAT-LB4 Novel Hormonal and Metabolic Markers of Recovery From Overtraining Syndrome Unveiled by the Longitudinal ARM of the Eros Study - the Eros-Longitudinal Study
Authors: Cadegiani Flavio , da Silva Pedro Luiz H , Abrao Tatiana P C , Kater Claudio E
Published: May 2020

Background: Overtraining Syndrome (OTS) is an unexplained underperformance syndrome triggered by excessive training, insufficient caloric intake, inadequate sleep, and excessive cognitive and social demands. Investigations of markers of the challenging recovery from OTS have not been reported to date. The objective of the present study is to describe novel markers, and biochemical and clinical behaviors during the restoration process of OTS.Design: A 12-week interventional protocol in 12 athletes affected by OTS was conducted, including increased food intake, transitory interruption of the trainings, improvement of sleep quality, and management of stress.Methods: We assessed 50 parameters, including hormonal responses to an insulin tolerance test (ITT), basal hormonal and non-hormonal biochemical markers, body metabolism and composition. Results: In response to an ITT, early cortisol (p = 0.026), early GH (p = 0.004), and late GH (p = 0.037) improved significantly. Basal estradiol (p = 0.0002) and nocturnal urinary catecholamines, (p = 0.043) reduced, while testosterone (p = 0.014), testosterone:estradiol (T:E) ratio (p = 0.0005), freeT3 (p = 0.043), IGF-1 (p = 0.003), and cortisol awakening response (CAR) (p = 0.001) increased significantly. All basal parameters and early responses to ITT normalized, when compared to healthy athletes. Basal metabolic rate, fat oxidation, body fat, muscle mass, and hydration status had partial but non-significant improvements. Conclusion: After 12 weeks, athletes affected by actual OTS demonstrated substantial improvements, remarkably IGF-1, freeT3, CAR, testosterone, estradiol testosterone:estradiol ratio, CK and catecholamines, and early cortisol, early prolactin, and overall GH responses to stimulations.
MON-266 The Association Between Prolactinomas and Weight Gain
Authors: Tariq Zunera , Sabie Farah Al , Donegan Diane
Published: May 2020

Introduction: The prevalence of obesity is increasing worldwide and treatment remains challenging. Certain endocrine disorders may contribute to weight gain. These are important to recognize as treatment may have beneficial impact on weight. Studies have reported an increased prevalence of obesity in patients with prolactinomas. While several studies have examined the association between weight gain and prolactinomas, the results are conflicting. Therefore, the aim of this study was to determine if BMI is higher among those with a prolactinoma compared to those without.

Methods: We identified all patients ≥18 years of age referred to endocrinology between 2008–2018 with a newly diagnosed prolactinoma (defined as a prolactin levels ≥40 ng/ml on 2 separate occasions and a pituitary adenoma evident on MRI without secondary causes for hyperprolactinemia). We extracted the following variables from the medical record: patient demographics, presenting symptoms, prolactin level and tumor size at diagnosis. Comparative data was obtained from the National Health and Nutrition Examination Survey (NHANES) 2015–2016, from which we included only those ≥18 years of age who had BMI data.

Results: In total 34 patients with a newly diagnosed prolactinoma (female: 27 /34, 79%, mean age at diagnosis: 35.4 ± 10.7 years) met inclusion criteria. The majority of patients (23/34, 68 %) had microadenomas defined as <1cm. The median prolactin level at diagnosis was 103.3 (IQR 51.3- 249.25). Although the most common presenting symptoms were those consistent with hypogonadism (27/34, 79%) and galactorrhea (16/34, 47%), 1/3 patients also described weight gain. In comparison, 5662 individuals from NHANES (48 ± 18 years, female: 2955/5662, 52%) reported their BMIs. BMI was significantly increased among those with a prolactinoma compared to survey population [median BMI 30.9 kg/m2 (IQR, 24.9- 39) vs 28.3 kg/m2 (24.3- 33), P= 0.02]. This difference persisted even when adjusted for age and sex (P= 0.0002). In addition the prevalence of class II obesity (BMI ≥35 kg/m2) was higher in those with a prolactinoma compared to survey population (38% vs 18%, P=0.005). Among prolactinoma patients, there was a correlation between BMI and log-transformed prolactin levels (R2= 0.24, P=0.003).

Conclusion: Weight gain is a presenting symptom for many patients with a newly diagnosed prolactinoma. When compared to a large cohort of adults in the US, those with a prolactinoma have higher BMI and an increased prevalence of class II obesity. Based on the correlation between BMI and log-transformed prolactin levels, we hypothesize that this weight difference may be related to hyperprolactinemia. These findings suggest that, in the appropriate context, hyperprolactinemia should be considered when a patient presents with weight gain.
MON-639 Melanocortin 4 Receptor Contributes to Glucose Homeostasis by Regulating Kidney Glucose Reabsorption via the Glucose Transporter GLUT2
Authors: de Souza Cordeiro Leticia M , Devisetty Nagavardhini , Chhabra Kavaljit H
Published: May 2020

Melanocortin 4 receptor (MC4R) is essential for normal body weight and food intake. Deficiency of MC4R causes obesity in humans and mice. While the function of MC4R is well established in appetite regulation, its direct role in glucose homeostasis is unclear. Humans and mice with MC4R deficiency exhibit hyperinsulinemia and insulin resistance; however, they remain protected from fasting hyperglycemia/diabetes. To determine the role of MC4R in glucose homeostasis, we performed oral glucose and intra-peritoneal insulin tolerance tests (OGTT / ITT) in male and female Mc4r knockout (KO) and wild type (WT) mice. Remarkably, Mc4r KO mice exhibited improved glucose tolerance compared to WT mice (Area under the curve for OGTT, male: 29,125±2,028 vs. 38,493±1,161 mg/dL.min; female: 36,322±1,100 vs. 49,539±1,911 mg/dL.min, p<0.0001). The improvement in glucose tolerance was despite insulin resistance in Mc4r KO mice (Plasma insulin, male: 9.9±1.7 vs. 0.7±0.1 ng/mL, female: 6.2±2.0 vs. 1.1±0.3 ng/mL, p<0.05; Area under the curve for ITT, male: 13,174±1,073 vs. 8,132±255 mg/dL.min; female: 13,927±1,253 vs. 7,506±267 mg/dL.min, p<0.01). Based on our previous findings from POMC deficient mice, we hypothesized that the improved glucose tolerance in the Mc4r KO mice is due to their elevated glycosuria (excretion of glucose in urine). To test this hypothesis, we challenged Mc4r KO and WT mice with oral glucose (250 mg) and collected their 24h urine to evaluate glycosuria. Indeed, the KO mice demonstrated elevated glycosuria compared to their WT littermates (Urine glucose, male: 284±48 vs. 0.4±0.03 mg/24h, female: 63.4±14 vs. 1±0.6 mg/24h, p<0.002). To assess molecular mechanisms underlying elevated glycosuria in Mc4r KO mice, we measured the gene expression and levels of the kidney glucose transporters GLUT1, GLUT2, SGLT1 and SGLT2. Glut2 mRNA was reduced by ̴ 40% and the protein level was decreased by ̴ 20% in Mc4r KO mice compared to their WT littermates. The other glucose transporters remained unchanged. Altogether, our study demonstrates that MC4R contributes to glucose homeostasis by regulating kidney glucose reabsorption via GLUT2. These findings may explain why MC4R deficient mice or humans remain protected from diabetes despite their longstanding obesity and insulin resistance.
SUN-564 ATG7 Overexpression Results in Reduction of Hepatocellular Lipid Content in Vitro
Authors: Tavaglione Federica , Baselli Guido , Ciociola Ester , Gentilucci Umberto Vespasiani , Valenti Luca , Romeo Stefano
Published: May 2020

Abstract: Non-alcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, paralleling the epidemic of obesity and type 2 diabetes. Despite the high prevalence of NAFLD, only a minority of patients progress to NASH and advanced fibrosis. The reasons for this inter-individual variability are not completely understood but can be partially accounted for by genetic risk factors (1). Although several common genetic variants associated with liver disease have been identified, there is still a proportion of NAFLD heritability that remains unknown. The rare rs143545741 C>T variant in the autophagy related 7 (ATG7) gene (P426L) has been associated with a higher risk of progressive NAFLD (2). Interestingly, ATG7 encodes a E1-like ubiquitin activating enzyme which is involved in hepatic lipophagy (3). We hypothesized that the unknown heritability of NAFLD might be partially explained by rare genetic variants, therefore not identified in the GWAS studies. Moreover, we assumed that loss-of-function variants in ATG7 might confer an increased susceptibility to NAFLD by reducing autophagic catabolism of lipid droplets in the liver. To examine the underlying mechanism of the low-frequency V471A variant and the rare T86I, L127I, Q170E, and P426L variants in ATG7, we performed in vitro experiments of HepaRG cells overexpressing the human V5-tagged ATG7. We observed a reduction in intracellular lipid content in HepaRG cells overexpressing the ATG7 wild type and the 86I mutant protein (p=0.029, n=4) but not the 127I, 170E, 426L, and 471A mutant proteins. Cells with the ATG7 127I, 170E, 426L, and 471A mutants had higher intracellular lipid content compared to cells overexpressing the wild type protein (p=0.029, n=4). Our data suggested that the low-frequency V471A variant and the rare L127I, Q170E, and P426L variants in ATG7 are loss-of-function, resulting in defective lipophagy, reduced hepatocellular lipid droplets turnover, and excessive lipid accumulation. More experiments are needed to clarify the underlying mechanism of the T86I variant. In conclusion, we highlighted a role for ATG7 in reducing hepatocellular lipid content. Furthermore, we provided evidence showing non-synonymous variants in ATG7 increase the risk of NAFLD and that these variants are loss-of-function. We speculate that ATG7 might be a new susceptibility risk genetic locus for liver disease development and progression. References: (1) Eslam et al. J Hepatol. 2018;68(2):268–279. (2) Baselli et al. The Liver Meeting 2018 - AASLD. Hepatology. October 2018. Volume 68, Issue S1. (3) Martinez-Lopez and Singh. Annu Rev Nutr. 2015;35:215–37.
MON-447 Schwannoma Masquerading as Metastatic Papillary Thyroid Carcinoma in a Cervical Lymph Node
Authors: Kim Stephanie , Goldstein Ruth , Liu Lisa , Duh Quan-Yang , Liu Chienying
Published: May 2020

Background: Schwannomas originate from peripheral nerve sheath Schwann cells and develop in various locations, commonly seen in the head and neck in up to 45% of cases. On ultrasound, they appear hypoechoic, lack a hilum, and can resemble a metastatic lymph node in patients with thyroid cancer. We describe a case of a schwannoma masquerading as metastatic papillary thyroid carcinoma. Clinical Case: A 59-year-old woman presented to our clinic with a history of Graves’ disease and papillary thyroid cancer (PTC) for which she underwent surgery over fifteen years ago at an outside institution. Pathology revealed two microfoci of PTC (0.5 and 0.4 cm) and 0 of 3 positive lymph nodes, with no other concerning features. She underwent radioactive iodine therapy (RAI) with 100 mCi postoperatively. There was no evidence of metastasis on her post-treatment scan. She had surveillance including neck ultrasounds with no evidence of recurrence. Five years later, neck ultrasound revealed a 5 mm nodule in the right neck posterior to the jugular vein. This nodule remained stable a year later and was not mentioned on subsequent ultrasounds. Two years ago upon presentation to our institution, she was found to have a suspicious hypoechoic solid mass on neck ultrasound. It was located in the lateral neck deep to the internal jugular vein and immediately adjacent and lateral to the common carotid and measured 8 x 7 x 7 mm enlarging to 13 x 9 x 10 mm in the next year. On one of the ultrasounds, the mass was noted to be inseparable from the surrounding nerve fibers and the possibility of nerve sheath tumor was suggested although a metastatic lymph node could not be excluded. This nodule enlarged to 13 x 9 x 10 mm in the next year. Due to the location, biopsy was deemed difficult and she underwent surgical resection of the mass. Intraoperatively, the lesion was noted to be very firm and intimately involved with the vagus nerve, which had to be sacrificed as it could not be dissected off. Pathology revealed a schwannoma, which was confirmed by immunohistochemical staining. Conclusion: This case highlights the importance of recognizing subtle but important ultrasonographic features of a schwannoma in the neck as it can resemble a metastatic lymph node, especially in a patient with history of thyroid cancer. Clinicians should consider this in the differential diagnosis when there are appropriate imaging findings that may be consistent with a schwannoma, including homogeneous hypoechogeneity and nerve continuity.
SAT-423 Anti-thyroid Drug Response in Graves’ Disease: Predictors of Biochemically Persistent Disease
Authors: El Kawkgi Omar M , Li Dingfeng , Vallejo Sebastian , Lincango Eddy , Mohan Sneha , Kohlenberg Jacob , Giblon Rachel , Stan Marius , Brito Juan P
Published: May 2020

Introduction: Anti-thyroid Drugs (ATD) have become the most frequently used treatment for Graves’ disease (GD) in the United States. However, the response to this therapy is variable. Factors that predict biochemically responsive vs. biochemically persistent disease remain unknown. Identifying predictors of disease poorly responsive to ATD can help guide treatment decision making, follow up planning and prognosis.

Methods: From a database of patients with GD treated with ATD and receiving care at an academic medical center between 2009–2019, we selected adults with incident GD treated with ≥14 days of ATD.

Results: 172 patients (from a database of 730 patients with GD on ATD) were sampled for the purpose of this pilot and 97 of these met inclusion criteria. Patients had a median age of 50 (18–90); female, 70.1%; never smokers, 64.9%; median goiter size of 40 g (15–100); and median TRAb on presentation of 8.1 mIU/L (1.0- 60). Graves’ orbitopathy (GO) was present in 13.4% at baseline. Patients (100%) were started on methimazole at a median dose of 20 mg (2.5–60). The median time from presentation until biochemical improvement (defined as the first instance of FT4 ≤1.7 ng/dL) was 120.9 days (18–1525), and to biochemical euthyroidism (normal TSH & FT4) was 251 days (41–1259) including a median of 3 (0–17) dose adjustments. In a univariate analysis, response to ATD was divided into two groups; biochemically responsive and biochemically persistent disease (based on reaching biochemical improvement in ≤6 months, or >6 months respectively). Biochemically persistent disease was more common in those with GO at presentation (38.5% vs.11.1%) (p .024). There was a trend towards greater prevalence of biochemically persistent disease in those with TRAb ≥ 8.0 mIU/L (46.2% vs. 27.8%) (p .204), and goiter estimated 30 grams or above by physical examination (30.8% vs. 19.4%) (p .460). Biochemically responsive disease was associated with higher frequency of hypothyroidism during treatment (p .047).

Conclusion: Our preliminary results illustrate the spectrum of response to ATD and predictors of biochemically persistent disease. We aim to expand this analysis utilizing a large database. As use of ATD increases, clinicians and patients can apply this data to estimate response to therapy, and identify patients that may require more aggressive therapy, thereby tailoring management plans.