bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-514 Nivolumab Related Primary Hypothyroidism: 3 Years of Follow-Up
Authors: Baby Ann Pia , Goldberg Michael 
Published: May 2020

Abstract
BACKGROUND: Primary hypothyroidism is one of the most common endocrinopathies related to the use of nivolumab, a monoclonal antibody against the immune checkpoint molecule programmed death-1 (PD-1). The long-term course of this condition, especially after the completion of nivolumab treatment, has not been widely reported.
CLINICAL CASE: A 70-year-old man presented with weight gain despite poor appetite, cold intolerance, and constipation. He noticed these symptoms after receiving the first three months of treatment with nivolumab for renal cell carcinoma. His heart rate was 66, blood pressure was 130/79 mm Hg, and body mass index was 28.3. The thyroid gland was normal-sized without palpable nodules, deep tendon reflexes were normal, and cardiac and pulmonary exams were unremarkable. Laboratory test results were consistent with primary hypothyroidism: thyroid-stimulating hormone (TSH) was elevated at 97.11 mIU/L (normal, 0.35-4.70 mIU/L), and total thyroxine was less than 1 mcg/dL (normal, 4.5-12.0 mcg/dL). Both anti-TPO antibody (222.6 IU/ml, normal&lt;5.6 IU/ml) and anti-thyroglobulin antibody (10.6 IU/ml, normal &lt;4.1 IU/ml) levels were elevated. There was no prior history of thyroid disease; two of the patient’s sisters had chronic hypothyroidism. Treatment with levothyroxine resulted in rapid resolution of symptoms. With dose titration of levothyroxine over the course of a few months, the patient achieved biochemical euthyroidism. Nivolumab therapy was continued for more than two years, during which a stable levothyroxine dose was maintained, and the patient remained clinically and biochemically euthyroid. Ultimately the renal cell carcinoma was determined to be in remission, and nivolumab therapy was stopped. Subsequently, the anti-TPO antibody titer was observed to have returned to the normal range (2.3 IU/ml). However, as of five months following discontinuation of nivolumab, and 32 months since the onset of thyroid dysfunction, the patient’s hypothyroidism persists as reflected by non-suppressed TSH values on levothyroxine treatment.
CONCLUSION: We have observed the course of nivolumab-induced primary hypothyroidism over almost three years in an individual patient. The hypothyroidism has persisted, requiring ongoing levothyroxine replacement at a dose of approximately 1.4 mcg/kg daily. An interesting feature of this case is the disappearance of anti-TPO antibody positivity after discontinuation of nivolumab. We speculate that the ongoing hypothyroidism despite the absence of detectable autoantibodies may be related to progressive thyroid cell apoptosis. Further long-term observations will determine whether permanence of nivolumab-induced hypothyroidism is the rule.
MON-913 Testosterone Secreting Ovarian Tumor: A Rare Cause of Erythrocytosis and Pulmonary Embolus
Authors: Friedman Naomi , Friedman Seth Gerald , Klein Victor , Sternchos Jason A 
Published: May 2020

Abstract
Background: Ovarian testosterone producing tumors are an uncommon cause of hirsutism, pulmonary embolus and polycythemia.
Clinical Case: A 67-year-old Caucasian postmenopausal woman was referred for Endocrine evaluation of a one-year history of hirsutism, weight gain and elevated total testosterone level of 672 ng/dL (n &lt;75 ng/dL). She reported increased hair growth on her chin for the past year. She denied any male pattern hair loss or any increased hair growth on her legs or chest. She also reported unintentional weight gain of thirteen pounds and low energy levels. Past medical history is remarkable for gastroesophageal reflux disease. Her last menstrual period was at age forty and periods occurred at regular intervals without heavy bleeding. She never became pregnant by choice. At this time physical exam was notable for shaved terminal hair on her chin, vellus hair on abdomen, there was no hirsutism or voice change noted. There were no abdominal striae, moon facies, buffalo hump.
Labs from the initial visit included a total testosterone of 672 ng/dL (n&lt;75 ng/dL), 2pm cortisol 5.6 ug/dL (2.7-10.5 ug/dL in PM), TSH 2.28 uiU/mL (0.27 – 4.20), Androstenedione 133 ng/dL (n&lt;10-93 ng/dL), 11 deoxycortisol 29.3ng/dL (n &lt;32), ACTH 12 pg/mL (n&lt;46), DHEAS 87 ug/dL (13-130 ug/dL) free testosterone index 24.2 (n&lt;2.1), 17-hydroxyprogesterone 207ng/dL (n&lt;272), FSH 26.1 miU/mL (25.8-134.8), LH 17.9 IU/L (7.7-58.5), Hemoglobin 18. g/dL (11.7-15g/dL), hematocrit 50.4% (35-45%), HbA1c 5.4%.
Four months after this initial presentation, the patient developed acute onset of chest pain and shortness of breath and was diagnosed with a right pulmonary embolus on CT Chest Angiogram. Evaluation with imaging for an ovarian mass revealed a negative workup. CT Abdomen Pelvis did not reveal any adrenal masses. Transvaginal Ultrasound did not demonstrate any ovarian masses. MRI of pelvis did not show any adnexal masses.
Despite the negative imaging, because of the markedly elevated testosterone levels, this presentation was thought to correspond to a testosterone secreting ovarian tumor. Furthermore, the normal adrenal hormone levels and significantly elevated testosterone level is consistent with neoplasm range. High levels of testosterone are known to cause a hypercoagulable state leading to a PE. Furthermore, testosterone causes an increase in RBC mass leading to marked elevations in hemoglobin. The patient was referred for bilateral oophorectomy. Pathology of the right ovary revealed a 2 cm steroid cell tumor, not otherwise specified.
Conclusion: This is the first known case of a steroid cell ovarian tumor, not otherwise specified, that secretes testosterone leading to pulmonary embolism and erythrocytosis. Furthermore, testosterone secreting tumors should be considered in the diagnosis of PE as a rare cause of hypercoagulable state.
SUN-606 Identification of NASH Using Data from NHANES III
Authors: Friedman Theodore C , Shaheen Magda , Kermah Dulcie , Pan Deyu , Schrode Katrina , Najjar Sonia Michael 
Published: May 2020

Abstract
Nonalcoholic steatohepatitis (NASH) is a serious liver condition marked by hepatic steatosis (HS), cell damage and inflammation. Patients with NASH are at risk for developing cirrhosis and hepatic cancer. Currently, the definitive method of diagnosing NASH is by liver biopsy. To avoid the costs and risks associated with biopsy procedures, there has been considerable effort to develop a non-invasive method of identifying patients with NASH. However, none of these methods has become accepted as a “gold standard.” Our objective was to compare three non-invasive methods of identifying NASH by using data from NHANES III (1988-1994) to determine variables associated with published formulas to identify NASH. We used ultrasound data to identify subjects with moderate - severe HS. Among those with HS, we identified the NASH population using either the HAIR score, the NASH liver fat score, or the Gholam score. The HAIR score was developed in a sample of obese patients, is based on hypertension, insulin resistance and alanine transaminase (ALT) levels, and had an AUROC of 0.9, a sensitivity of 0.8, and a specificity of 0.89. The NASH liver fat score was developed in a Finnish population undergoing gastric bypass, and validated in an Italian population of liver biopsy patients. This score incorporates metabolic syndrome, type 2 diabetes, serum insulin, AST, and ALT. In the Finnish and Italian populations, respectively, it had AUROCs of 0.73 and 0.74, sensitivities of 59.5 and 92.9, and specificities of 79.7 and 32.7. The Gholam score was developed in a sample of obese patients and uses aspartate aminotransferase (AST) and type 2 diabetes diagnosis. It had an AUROC of 0.82, a sensitivity of 0.76, and a specificity of 0.66. We performed multinomial logistic regression to compare each NASH population to the normal population (those with no or only mild HS). We identified 1236 subjects as having NASH by at least one method. 18% of these were identified by all 3 methods, while 20% were identified by 2 methods. All three methods identified significant risk factors for NASH (p&lt;0.05) as being overweight or obese, having elevated AST or ALT levels, and having elevated C-peptide, serum glucose, or serum triglyceride levels. However, the HAIR and Gholam methods also identified being Mexican-American as a significant risk factor, with the NASH liver fat score did not. Being a former alcohol drinker and not meeting guidelines for physical activity were significant risk factors when using the NASH liver fat score. Further refinement of a noninvasive method for identifying NASH is required. Considerable care must be taken in interpreting risk factors, because the results differ depending which method is used. This could have implications in clinical practice as well, where patients and their risk factors may be mis-identified if formulas are used and not liver biopsy.
SAT-681 Transient Neonatal Diabetes Mellitus Triggered by EIF2AK3 and PTF1A Mutation
Authors: Ahn Moon Bae , Lee Yoon Ji , Lee Na Yeong , Kim Seul Ki , Kim Shin Hee , Cho Won Kyoung , Cho Kyoung Soon , Jung Min Ho , Suh Byung Kyu 
Published: May 2020

Abstract
Background: Neonatal diabetes mellitus (NDM) occurs within the first 6 months of life. Advances in molecular genetics have identified various causatives genes. Mutations in EIF2AK3 causes Wolcott-Rallison syndrome characterized by NDM, multiple epiphyseal dysphasia and growth retardation. PTF1A is associated with the development of pancreas and cerebellum. Both EIF2AK3 and PTF1A mutations are causative genes for permanent NDM with spontaneous and autosomal recessive inheritance. We report a neonate with transient NDM with both EIF2AK3 and PTF1A variants confirmed by Sanger sequencing where each parent found to be a heterozygous carrier of each mutation. Case presentation: A two-day old boy was transferred from a local hospital due to hyperglycemia (blood glucose of 385 mg/dL) and glycosuria. Serum c-peptide (0.06 ng/mL) and insulin (0.64 μU/mL) were low. The patient did not present sings of ketoacidosis and was screened negative for pancreatic autoantibodies. The patient did not have any family history of diabetes. Molecular genetic analysis was performed and continuous infusion of intravenous insulin with pre-prandial bolus was started. Oral sulfonylurea therapy was attempted to prevent adverse neurocognitive outcome however, it showed no response and unable to stabilize blood glucose level. Targeted panel sequencing identified two different novel variants: a heterozygous missense mutation (c.3272G&gt;T) in exon 17 of EIF2AK3 gene and heterozygous missense mutation (c.53C &gt; T) in exon 1 of PTF1A gene; both of which have not been previously reported and were no likely pathogenic variants. The patient’s father confirmed to be heterozygous carriers of the EIF2AK3 mutation while mother being heterozygous carriers of the PTF1A mutation. Blood glucose level gradually began to stabilize with insulin therapy, and upon discharge the patient switched to continuous subcutaneous insulin infusion (pump) with continuous glucose monitoring. Conclusions: NDM caused by in combination of EIF2AK3 and PTF1A gene mutation is a rare condition and could resemble the disease progress of transient form of NDM. Although hyperglycemia might not be an issue of lifelong period, early genetic screening and prompt insulin initiation with consistent glucose monitoring are able to prevent further diabetic complications. In addition, the result of genetic testing in our patient raises the possibility of NDM as polygenic form of diabetes.
MON-192 Comparison of the Seated and Recumbent Saline Infusion Test for the Diagnosis of Primary Aldosteronism in Chinese Population
Authors: Zhang Dan , Chen Tao , Tian Haoming , Li Yuanmei , Mo Dan , Zhang Tingting , Wang Wen , Zhang Guofu , Liu Yuping , Tang Lizhi , Zhu Yuchun , Yang Ling , Yang Ling , Ren Yan 
Published: May 2020

Abstract
Background:
None of the diagnostic tests for primary aldosteronism (PA) are ideal according to the current literature. In a preliminary study, the seated saline infusion test (SSIT) was more sensitive than the recumbent saline infusion test (RSIT) for the diagnosis and subtype classification of PA. However, it is unclear whether the SSIT is suitable for Chinese PA patients.
Objective:
We prospectively investigated the accuracy of the seated saline infusion test (SSIT) in 113 patients with hypertension (including 93 PA and 20 essential hypertension (EH) patients) in the Department of Endocrinology and Metabolism.
Approach and Results:
Each patient underwent an recumbent saline infusion test (RSIT) and seated saline infusion test (SSIT). The accuracy of the SSIT for a confirmative primary aldosteronism (PA) diagnosis and subtype classification was evaluated and compared with the RSIT. The area under the receiver operating characteristic (ROC) curve (AUC) of aldosterone for the SSIT was significantly greater than that for the RSIT (0.945±0.0199 vs 0.828±0.0404; P&lt;0.05). The ROC analysis showed that the optimal plasma aldosterone cutoff values were 12.94 ng/dl for the SSIT (sensitivity 86.02%, specificity 95%; Youden index (YI)=0.810) and 12.04 ng/dl for the RSIT (sensitivity 83.15%, specificity 57%; Youden index (YI)=0.401). The optimal aldosterone concentration cutoff value for classifying aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) was 18.12 ng/dl for the SSIT (sensitivity 73.5%, specificity 79.5%). No patients experienced adverse events during the SSIT.
Conclusions:
The SSIT was safe and convenient for PA diagnosis. The accuracy of the SSIT for a confirmatory diagnosis of PA was better than that of the RSIT. The SSIT is a reliable alternative for PA confirmation in Chinese individuals.
OR01-03 Thyroid Receptor Alpha Interacts with COUP-TFII in the Regulation of Postnatal Skeletal Muscle Regeneration
Authors: Aguiari Paola , Petrosyan Astgik , Liu Yan-Yun , Cheng Sheue-Yann , Perin Laura , Brent Gregory A , Milanesi Anna 
Published: May 2020

Abstract
Myopathic changes, including muscular dystrophy and weakness, are commonly described in hypothyroid and hyperthyroid patients. Thyroid hormone signaling, via activation of thyroid nuclear receptors (TRs), plays an essential role in the maintenance of muscle mass, function, and regeneration. TRs are ligand-inducible transcription factors expressed in almost all tissues, including skeletal muscle. In a mouse model of Resistance to Thyroid Hormone carrying a frame-shift mutation in the TRα gene (TRα1PV)1,2 we observed skeletal muscle loss with aging and impaired skeletal muscle regeneration after injury. We recently described that TRα interacts with the nuclear orphan receptor Chicken Ovalbumin Upstream Promoter-factor II (COUP-TFII, or NR2F2), which is known to regulate myogenesis negatively and has a role in Duchenne-like Muscular Dystrophies3. We showed that COUP-TFII expression declines with age in WT mice, while the skeletal muscle of TRα1PV mice shows a sustained significantly higher expression of COUP-TFII. Our findings suggest that the TRα/COUP-TFII interaction might mediate the impaired skeletal muscle phenotype observed in TRα1PV mice. To better characterize this interaction, we isolated SC from 10 months old WT and TRα1PV mice and cultured them in vitro using novel methods established within our lab. Using siRNA probes, we next silenced COUP-TFII and characterized the cells via RNA-seq analysis. In vitro, we assessed myoblast differentiation and proliferation using differentiation assays and EdU incorporation. We observed that satellite cells from TRα1PV mice display impaired myoblast proliferation and in vitro myogenic differentiation compared to WT SCs. However, when COUP-TFII was silenced, the myogenic potential of TRα1PV satellite cells was restored, with a higher proliferation of myoblasts and a higher number of fully differentiated myotubes after 4 days of myogenic induction. RNAseq analysis on satellite cells from TRα1PV mice after COUP-TFII knockdown showed upregulation of genes involved in the myogenic pathway, such as Myod1 and Pax7, and of genes in the thyroid hormone signaling, such as Dio2. Ingenuity Pathway Analysis further showed activation of pathways regarding cell growth, differentiation, matrix remodeling along with muscle function, muscle contractility, and muscle contraction. These in vitro results suggest that by silencing COUP-TFII we promote the myogenic pathway and may further rescue the impaired phenotype of TRα1PV mice. These studies can help increase our knowledge of the mechanisms involved in thyroid hormone signaling in skeletal muscle regeneration, which will ultimately increase the possibility of designing more specific treatments for patients with thyroid hormone-induced myopathies. References: 1Milanesi, A., et al, Endocrinology 2016; 2Kaneshige, M. et al, Proc Natl Acad Sci U S 2001; 3Lee HJ, et al, Sci Rep. 2017.
MON-396 A Critical Review of the Assessment of Vitamin D Status
Authors: Chausmer Arthur B 
Published: May 2020

Abstract
In the United State the evaluation of osteoporosis frequently includes an assessment of vitamin D status. Most often this is done by evaluation of the serum 25 hydroxycalciferol (25 OHD) level. The reasons for this are not entirely clear since D deficiency is characterized by osteomalacia, pathologically very different from osteoporosis. Presumably the reason is to assess the adequacy of calcium absorption across the gastrointestinal mucosa so as to provide sufficient substrate to the osteoid for bone mineralization. If this is the case, the best assessment of D status should be the active metabolite, 1,25 dihydroxycalciferol, (1,25 OH2 D), not an inactive intermediate, such as 25 OHD. The use of an inexact test results in increased cost for less reliable data and supports factitious deficiency with unnecessary and potentially dangerous treatment. The most often quoted reason for not using the 1,25 OH2 D is the short half life. This neglects the fact that half life is not relevant to substances in equilibrium and that the circulating half life does not necessarily reflect the physiologic half life. Equally important, the 25 OHD as a marker of D status is variable due to, among others, drug metabolites affecting hepatic 25 hydroxylases, hepatic function in general, and differences in the activation of of 25 D related to renal function. Additionally, there is virtually no data about the whole body load for any metabolite in the D pathway, so there is no way of actually assessing whether stores are replete or not. While there are several studies suggesting 25 OHD is only a marginal indicator of D status, primarily in the extreme deficiency states which generally rare in the United States. Well controlled studies of the efficacy of 1,25 OH2 D in the assessment of D status are few for many reasons, most prominently cost and lack of sponsor interest. In the absence of such data, one must rely on basic physiologic principals which strongly suggest abandoning the use of the 25 OH D level as an indicator of vitamin D status and, perhaps, using the 1,25 OH2 D to assess D status.
MON-344 Uncommon Etiology of Hypophosphatemia and Secondary Hyperparathyroidism: Ferric Carboxymaltose Infusion
Authors: Sever Sakine 
Published: May 2020

Abstract
Background: Hypophosphatemia has been recognized as one of the side effect of intravenous ferric carboxymaltose infusion. This effect is thought to be secondary to fibroblast growth factor 23 (FGF 23) mediated renal phosphate wasting and associated with calcitriol deficiency and secondary hyperparathyroidism.
Clinical Case: A 76 years old male patient with medical problems including hypertension, type 2 diabetes mellitus, hyperlipidemia, paroxysmal atrial fibrillation, nephrolithiasis, spinal stenosis and chronic anemia was referred to endocrinology clinic for osteoporosis management. Bone density scan showed left femur neck T-score of -2.5 and L1-L4 lumbar spine T-score of 1.4. He reported pain on back and bilateral posterior thighs, difficulty with ambulation which were partly attributed to severe spinal stenosis that he was planned to have surgery for. Muscle strength was normal on examination. Laboratory studies were obtained for osteoporosis work up and showed: Calcium: 8.9 mg/dL (8.8-10.2 mg/dL), Creatinine: 0.77 mg/dL (0.74-1.35 mg/dL), GFR: 88 mL/min/BSA, Albumin 4.5 g/dL (3.5-5.0 g/dL), 25-Hydroxy vitamin D: 26 ng/mL, Magnesium 1.8 mg/dL (1.7-2.3 mg/mL), 1,25 Dihydroxy Vitamin D 24 pg/mL (18-64 pg/mL), Phosphorus: 1 mg/dL (2.5-4.5 mg/dL), PTH 163 pg/mL (15-65 pg/mL), Hemoglobin 12.9 mg/dL (13.2-16.6 mg/dL). Due to hypophosphatemia tumor induced osteomalacia diagnosis was entertained and further work up was considered in this regard however later noted that patient received ferric carboxymaltose 750 mg infusion two times within last 3 weeks for iron deficiency anemia. Hemoglobin level was 8.6 mg/dL before the infusions. After oral phosphate replacement the phosphate level improved to 2.4 mg/dL. Serum FGF 23 level was measured and it was normal at 108 RU/mL (&lt;180 RU/mL). He was then started on bisphosphonate treatment for osteoporosis.
Conclusion: Hypophosphatemia and secondary hyperparathyroidism can be seen after ferric carboxymaltose infusion due to FGF-23 mediated mechanism. In literature various presentations were reported from transient- asymptomatic hypophosphatemia to severe acute symptomatic hypophosphatemia along with persistent hypophosphatemia with osteomalacia and fragility fractures due to recurrent ferric carboxymaltose infusions. Thus, one should keep this possible side effect in mind during evaluation of hypophosphatemia and osteoporosis.
References: 1. Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W. Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. Dec 6 2018;3(23):e124486 2. Fang W, McMahon LP, Bloom S, Garg M. Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose. JGH Open. October 2019, volume 3, issue 5, P 438-440