bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-249 Polyarticular Osteoarthritis: A Disabling Manifestation of Acromegaly
Authors: Khan Azkia , Ejaz Hashim , Sekar Vijaykumar , Syed Sofia 
Published: May 2020

Abstract
Background
Acromegaly is a slow-onset rare endocrinopathy that is characterized by chronic overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Excess GH and IGF-1 levels lead to insulin resistance, which is implicated in most of the complications associated with acromegaly. We present a case of acromegaly, wherein the patient presented with worsening polyarthralgia and decreasing mobility. As the patient was undergoing workup for rapidly progressing osteoarthritis, the internist became suspicious of patient’s changing physical appearance.
Case
A 53-year-old man with medical history of diabetes mellitus and hypertension was referred to endocrine clinic on account of high IGF-1 levels, 909 ng/ml (normal: 37-245 ng/ml). He was seeking medical attention because of rapidly progressing polyarthralgia and stiffness for the last two years. His symptoms were intensifying despite use of non-steroidal anti-inflammatory drugs and intra-articular steroid injections. Imaging revealed severe degenerative changes and narrowing of joint space in bilateral hip, knee and glenohumeral joints. Internist observed that the patient was exhibiting stigmata of acromegaly such as enlargement of hands and feet, prognathism and dental space widening. Patient reported headaches, blurry vision, sleep apnea, dysphagia and right ear exostosis. Colonoscopy revealed hyperplastic polyps.
Repeat IGF- 1 levels were 910 ng/ml (Normal: 37-245 ng/ml). Oral glucose tolerance test showed failure of suppression of GH. Serial GH levels were 4.50, 5.08, 6.74, 5.81 and 5.21 ng/ml (Normal: 0.01- 0.97 ng/ml).
Tests for other endocrinopathies revealed the following results: serum prolactin 4 ng/ml (Normal &lt;18 ng/ml), serum cortisol 7.9 ug/dl (Normal: 6-27 ug/dl), 24 hour urine cortisol 23mcg/24 hours (Normal: 3.5-45 mcg/24 hours), serum TSH 2.25 uIU/ml (Normal: 0.34- 3 uIU/ml), serum T4 level 0.7 ng/dl (Normal: 0.6-1.6 ng/dl) and serum T3 level 144.9ng/dl (Normal: 87-178 ng/dl). Serum total and free testosterone levels were 111 ng/dl (Normal: 240-950 ng/dl) and 3.89 ng/dl (Normal: 4.06-15.6 ng/dl) respectively and were suggestive of hypogonadism.
MRI Brain showed 12x10x8mm pituitary adenoma. He was referred for transsphenoidal surgery for resection of pituitary adenoma.
Conclusion
Polyarticular osteoarthritis is an early manifestation of acromegaly. Systemic diseases associated with acromegaly are the primary reason for which most patients seek medical attention. It is important to look for coexisting endocrinopathies whenever the diagnosis of acromegaly is established, since mass effect of pituitary adenoma can wreak havoc on the endocrine system of the body. High index of suspicion, early diagnosis and prompt treatment are the key to reverse some but not all comorbid conditions associated with acromegaly.
MON-699 Artifactual Hypoglycemia in a Patient with Prolonged Hospital Stay for Neuroleptic Malignant Syndrome
Authors: Swami Janya 
Published: May 2020

Abstract
Background: Hypoglycemia is rare in patients without diabetes. A low capillary glucose concentration is not sufficient to make a diagnosis of a hypoglycemic disorder. In fact, this has multiple sources of error. Fulfillment of Whipple’s triad is an essential step for establishing the diagnosis of a hypoglycemic disorder. Clinical case: A 47-year old Caucasian male with past medical history of paranoid schizophrenia was admitted to the ICU from an outside facility with catatonia and apneic spells following an acute change in mental status. He was diagnosed with neuroleptic malignant syndrome and Endocrinology was consulted after 137 days in the hospital for concerns of severe and recurrent hypoglycemia. The patient was non-verbal on evaluation and despite multiple capillary blood glucose readings of &lt;70 mg/dL, including measurements as low as 29 mg/dL, he remained asymptomatic with absence of any clinical signs of an adrenergic response to hypoglycemic episodes. He was on continuous tube feeding through a PEG tube. The low capillary blood glucose measurements prompted rapid management with intravenous or oral dextrose based on the hypoglycemia protocol designed by the hospital. As a last resort, the patient was placed on a continuous dextrose infusion in addition to tube feeding to prevent hypoglycemia.Diagnostic evaluation: Following consultation, we ordered for a corresponding plasma glucose measurement to be done with any capillary blood glucose measurement of &lt; 55 mg/dL prior to correction for hypoglycemia. For a capillary blood glucose measured at 48 mg/dL, corresponding plasma glucose was 95 mg/dL. Whipple’s triad was not fulfilled and no additional work up was pursued. We recommended calibration of the glucose monitors for the hospital unit where the patient was admitted with recommendations to stop monitoring capillary blood glucose in this patient in the absence of diabetes, signs/symptoms of hypoglycemia, medications implicated to cause hypoglycemia and ongoing nutrition with tube feeding. Follow-up: The patient remains in the hospital and is waiting placement at an extended care facility. Plasma blood glucose measurements remain within normal range.Clinical lesson: Artifactual hypoglycemia, though uncommon, is an important consideration when evaluating and managing hypoglycemia. Whipple’s triad is essential to make a diagnosis of true hypoglycemia. Several factors; patient, operator and machine-related, can impact measurements of capillary blood glucose measurements and often result in unnecessary treatment measures often causing inefficient and often preventable wastage of hospital resources and sometimes even harm the patient.
MON-435 Hashimoto Thyroiditis and Goiter: Never Cease Follow-Up
Authors: Sekar Vijaykumar , Ejaz Hashim , Khan Azkia , Syed Sofia Junaid 
Published: May 2020

Abstract
Background
Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Its incidence is estimated to be 3.5 per 1000 per year in women and 0.8 per 1000 per year in men (3). Primary thyroid lymphoma (PTL) is a rare complication of HT, but often forgotten. Regular follow-up and high clinical suspicion is needed to diagnose this complication early. We present a patient who developed PTL as a complication of HT after 10 years of diagnosis of HT and goiter.
Clinical case
A 70-year-old male with history of hypertension and obstructive sleep apnea followed up in the endocrine clinic for the last 10 years for Hashimoto thyroiditis and stable goiter presented with a sudden enlargement of right neck mass. In 2008 he was incidentally diagnosed with HT. In 2010 the patient returned with a neck swelling and further investigation revealed a cold nodule in the right lobe. The patient underwent aspiration biopsy with repeat finding of HT, and was followed up yearly with thyroid ultrasound and TSH. In 2014 due to concern in the echotexture of thyroid on ultrasound, he had a biopsy of the right thyroid nodule with findings again consistent with HT. No significant changes were noted on yearly follow-up ultrasound until March 2019. He presented 5 months later with a large mass on the right side of his neck. Ultrasound showed enlarged and confluent lymph nodes anterior to the enlarged right thyroid gland. Further CT evaluation showed a large right neck mass measuring 5.2 x 7.5 x 12 cm extending from the right thyroid lobe to the level of C1. The mass crossed the midline posteriorly. Fine needle aspiration was positive for malignant cells. A core biopsy confirmed diffuse large B-cell lymphoma. The patient had tests for staging, including bone marrow biopsy, and was found to be stage II E diffuse large B-cell lymphoma involving the thyroid. Subsequently, the patient was started on chemotherapy with RCHOP(Rituximab, Cyclophosphamide,Doxorubicin,Vincristine,Prednisolone).
Conclusion
Although Primary thyroid lymphoma (PTL) is a rare condition, it should always be considered in the differential diagnosis of a rapidly growing goiter or thyroid nodule. Its incidence is 2 per million, with nearly all cases the non-Hodgkin’s type. PTL accounts for only 0.5–5% of all thyroid malignancies and 1% to 7% of all extranodal lymphomas. The prevalence of Hashimoto thyroiditis in patients with PTL is highly variable, but patients with HT have a 40- to 80-fold increased risk of developing PTL. A rapidly enlarging neck mass with or without compressive symptoms is the common presentation of PTL. Most common histotype is diffuse large B cell lymphoma which accounts for 50% to 70% of cases. High clinical suspicion and awareness among physicians is needed to diagnose PTL early. The main treatment is chemotherapy. Surgical interventions are needed to relieve pressure symptoms. The prognosis of PTL is generally excellent.
SAT-456 Reduced Cholesterol Absorption and Synthesis Markers in Patients with Hyperthyroidism Due to Graves’ Disease
Authors: Nagamine Tomoko , Inagaki Kyoko , Kobayashi Shunsuke , Shuto Yuki , Nagao Mototsugu , Tamura Hideki , Oikawa Shinichi , Sugihara Hitoshi 
Published: May 2020

Abstract
Background:Thyroid hormones have been reported to promote cell-surface expression of low-density lipoprotein receptor (LDL-R), and also increase mRNA expression of HMG-CoA reductase at the same time. Since LDL cholesterol (LDL-C) uptake via LDL-R is relatively superior to cholesterol synthesis in hyperthyroidism, plasma LDL-C levels can be lower as compared to euthyroid state. Conversely, hypothyroidism can increase plasma LDL-C levels because cholesterol absorption via Niemann-Pick C1-like 1 has been suggested to increase in hypothyroidism. However, there have been no reports about changes of cholesterol absorption and synthesis markers by the treatment of hyperthyroidism in patients with Graves’ disease. Patients and method: We collected plasma samples from patients with hyperthyroidism, who were diagnosed as Graves’ disease (n=17, M/F: 4/13, age: 24-70 years old). Thyroid hormones, general lipid profiles (Total cholesterol: TC, LDL-C, high-density lipoprotein cholesterol: HDL-C and triglyceride: TG), apolipoproteins, markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, cholestanol), lipoprotein lipase (LPL), and proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed before treatment, and at euthyroid state (eu), 3 and 6 months after attaining euthyroid state (eu-3M and eu-6M). Result: It took 159.2±108.6 days to attain euthyroid state by the thiamazole treatment. TC, LDL-C and HDL-C levels were increased at eu (TC, 144.5±26.7 to 225.0±61.6; LDL-C, 77.8±20.9 to 138.9±43.9; HDL-C, 49.7±12.6 to 67.9±20.0 mg/dL: P&lt;0.0001 vs before treatment, respectively). Such changes remained at eu-3M and eu-6M. TG was not changed at eu, but significantly increased at eu-6M (85.0±49.1 to 113.7±60.8 mg/dL, P=0.02). Cholesterol absorption markers were increased at eu, eu-3M and eu-6M (e.g. campesterol, 2.6±1.2 to 4.9±2.3; sitosterol, 1.5±0.6 to 2.9±1.4; cholestanol, 1.9±0.6 to 3.2±1.1 μg/mL: P&lt;0.0001, eu vs before treatment, respectively). Cholesterol synthesis marker was increased at eu, eu-3M and eu-6M (e.g. lathosterol, 1.8±0.7 to 2.3±0.9 μg/mL: P=0.005, eu vs before treatment). Both LPL and PCSK9 were also increased at eu, eu-3M and eu-6M. Conclusion: These data suggest that both cholesterol absorption and synthesis are downregulated in patients with hyperthyroidism due to Graves’ disease and can be restored by attaining euthyroid state. In turn, LDL-C and TG levels should be carefully monitored during the treatment of Graves’ disease because hyperlipidemia could emerge in euthyroid state.
MON-640 Endogenous Insulin and C-Peptide Suppression Test Using a Rapid-Acting Insulin Analog in the Diagnosis of Insulinoma
Authors: Laotaveerungrueng Nattapong , Lertwattanarak Raweewan , Sriussadaporn Sutin 
Published: May 2020

Abstract
C-peptide suppression test (CPS) was shown to diagnose the cause of hyperinsulinemic hypoglycemia, i.e. insulinoma, as effectively as supervised 72-hour fast test with less time consuming and cost. In the conventional CPS, regular insulin (RI) is used to induce hypoglycemia that subsequently suppresses endogenous insulin secretion. As RI is measurable in plasma insulin (PI) assay, plasma C-peptide (PCP) but not PI response is therefore used for assessment of endogenous insulin secretion in CPS using RI. As rapid acting insulin analogs (RA) are not measurable in a selected PI assay, both PCP and PI levels can be used to assess endogenous insulin secretion if an RA is used instead of RI in CPS. There is no study on PI and PCP responses to RA in insulinoma. This study aimed to examine efficacy of modified CPS, so-called insulin and C-peptide suppression test (ICPS) by using an RA (insulin aspart) in the diagnosis of insulinoma. Ten patients, 7 with histopathological proven insulinoma (IN) and 3 with non-insulinoma (non-IN), underwent ICPS. Blood samples were collected for measurement of plasma glucose (PG), PCP, and PI using a Roche Cobas 8000 module e602 which does not measure insulin aspart at before and every 10-20 minutes during intravenous infusion of insulin aspart at the rate of 0.05-0.075 unit/kg/hr. The test was terminated if the patients had a PG level of &lt;40 mg/dL. There was no difference in baseline biochemical data between two groups. At the end of the test, IN had significantly higher PCP level (range: 0.60-10.20 vs. 0.31-0.48 ng/mL and median: 4.67 vs. 0.47 ng/mL; p = 0.017), lower percentage of PCP suppression (range: 2.10-53.10% vs. 63.08-91.24% and mean: 24.78 ± 19.4% vs. 73.17 ± 15.7%; p = 0.005), higher PI level (range: 1.13-113.70 vs. 0.22-0.73 µIU/mL and median: 21.29 vs. 0.49 µIU/mL; p = 0.017) and lower percentage of PI suppression (range: -14.63-81.32% vs. 88.14-96.10% and mean: 28.45 ± 36.2% vs. 93.31 ± 4.5%; p = 0.003) than did the non-IN. No overlapping of these parameters was observed between IN and non-IN. Using the same cut-off levels as the supervised 72-hour fast test, the insulin criterion (≥3 µIU/mL) in ICPS had a sensitivity of 86% and a specificity of 100% and the C-peptide criterion (≥0.6 ng/mL) in ICPS had a sensitivity of 100% and a specificity of 100%. There was a high correlation of 89% between using PCP and PI responses. In conclusion, ICPS using an RA is effective in the diagnosis of insulinoma.
SAT-010 Non-Classic POR Deficiency as a Cause of Menstrual Disorders & Infertility
Authors: Papadakis Georgios E , Dumont Agathe , Bouligand Jerome , Chasseloup Fanny , Raggi Anna , Catteau-Jonard Sophie , Boute-Benejean Odile , Pitteloud Nelly , Young Jacques , Dewailly Didier R 
Published: May 2020

Abstract
P450 oxidoreductase deficiency (PORD) is an autosomal recessive disease caused by bi-allelic mutations of the POR gene. It is responsible for decreased activity of several P450 enzymes including CYP21A2, CYP17A1 and CYP19A1 that are involved in adrenal and/or gonadal steroidogenesis. PORD is typically diagnosed in neonates and children with ambiguous genitalia and/or skeletal abnormalities. Adult-onset PORD has been very seldom reported and little is known about the optimal way to investigate and treat such patients. In this series, we report five women aged 19-38 years, who were referred for unexplained oligo-/amenorrhea and/or infertility. Genetic testing excluded 21-hydroxylase deficiency (21OH-D), initially suspected due to increased 17-hydroxyprogesterone (17-OHP) levels. Extensive phenotyping, steroid profile by mass spectrometry, pelvic imaging and next-generation sequencing of 84 genes involved in gonadal and adrenal disorders were performed in all patients. In Vitro Fertilization (IVF) followed by frozen embryo transfer under glucocorticoid suppression therapy was performed in two patients. All patients had oligomenorrhea or amenorrhea. None had hyperandrogenism. Low-normal serum estradiol (E2) and testosterone levels contrasted with chronically increased serum progesterone (P) and 17-OHP levels, which further increased after ACTH administration. Despite excessive P, 17OH-P and 21-deoxycortisol rises after ACTH stimulation suggesting non-classic 21-hydroxylase deficiency, CYP21A2 sequencing did not support this hypothesis. Basal serum cortisol levels were low to normal, with inadequate response to ACTH in some women, suggesting partial adrenal insufficiency. Pelvic imaging revealed bilateral ovarian macrocysts in all women. All patients were found to harbor rare bi-allelic POR mutations classified as pathogenic according to American College of Medical Genetics standards. IVF was performed in two women after retrieval of a normal oocyte number despite very low E2 levels during controlled ovarian hyperstimulation. Frozen embryo transfer under glucorticoid suppression therapy led to successful pregnancies. These observations suggest that diagnosis of PORD must be considered in infertile women with chronically elevated P and 17OH-P levels and ovarian macrocysts. Differentiation of this entity from non-classic 21-hydroxylase deficiency is important, as the multiple enzyme deficiency requires a specific management. Successful fertility induction is possible by IVF, providing that P levels be sufficiently suppressed by glucocorticoid therapy prior to implantation.
SAT-554 Genetic Profile of Early-Onset Aldosterone-Producing Adenomas
Authors: Baker Jessica E , Nanba Kazutaka , Blinder Amy R , Bick Nolan , Wachtel Heather , Cohen Debbie L , Williams Tracy Ann , Reincke Martin , Else Tobias , Tomlins Scott A , Giordano Thomas J , Rainey William E 
Published: May 2020

Abstract
Background: Aldosterone-producing adenoma (APA) is a major subtype of primary aldosteronism (PA) which is the most common cause of endocrine-related hypertension. The Endocrine Society clinical practice guideline suggests that young patients (&lt; 35 years old) with a CT-detected adrenocortical adenoma and typical phenotype of PA may not need adrenal venous sampling prior to adrenalectomy. In recent years, aldosterone-driver somatic mutations have been identified in APA, and prevalence studies suggest potential effects of patient age and sex. However, the rare nature of early-onset PA has prevented a detailed study of the histologic characteristics and aldosterone-driver somatic mutations in adrenal tumors from these patients.
Objective: To determine histologic and somatic mutation profile in early-onset APA.
Methods: Fifty-five formalin-fixed paraffin-embedded (FFPE) adrenals from patients at the age of 35 years old or younger who underwent adrenalectomy at the participating centers were studied (45 women, 9 men, and 1 unknown sex). CYP11B2 immunohistochemistry (IHC)-guided tumor capturing was used to selectively obtain DNA from APA. Mutation status was determined either by Sanger sequencing or targeted next-generation sequencing.
Results: CYP11B2 IHC identified APAs in all adrenal specimens. Solitary APAs were found in 53 adrenals. One adrenal had multiple APAs and one had a dominant CYP11B2-negative tumor and a smaller APA. In total, DNA from 57 APAs were sequenced. Two APAs were excluded from the analysis due to low sample quality. In 52 of the 55 APAs, somatic mutations were identified in one of the aldosterone-driver genes or CTNNB1 gene, encoding β-catenin. The most common genetic alteration was seen in KCNJ5 (37/55, 67%), followed by CACNA1D (7/55, 13%), ATP1A1 (3/55, 5%), CTNNB1 (3/55, 5%), and ATP2B3 (2/55, 4%). No sex difference in the prevalence of KCNJ5 mutation was observed in this age group.
Conclusion: The majority of adrenals from early-onset PA patients had a solitary APA. Regardless of sex, the most common genetic cause of early-onset APA was somatic mutations in KCNJ5.
SAT-738 Sources of Error in Estimation of Cortisol Half-Life Using Conventional, Single-Compartment Model: Bias Due to Variation in CBG Concentration
Authors: Fuh Jennifer , Urban Frank , Qualls Clifford , Dorin Richard I 
Published: May 2020

Abstract
Most reports of cortisol half-life in the literature report a range of 90-130 min, which results are based on descriptive model that assumes mono-exponential decay of a single, total cortisol compartment. Free cortisol half-life has been similarly assessed using a descriptive single compartment model (1). However, the descriptive model is not physiologic in view of the rapid exchange between protein-bound and free cortisol compartments and evidence that metabolic elimination is restricted to the free cortisol compartment. In the present study, we sought to explore potential limitations of the descriptive, single-compartment model for cortisol elimination by assessing the influence of CBG concentration ([CBG]) on cortisol half-life estimates obtained using the descriptive model. We studied the influence of [CBG] and other variables on descriptive cortisol half-life using a Monte Carlo simulation of cortisol concentration decay curves developed using data from healthy controls (1). Total cortisol concentration ([TF]) curves were generated on the basis of 4 predictor variables: (i) [CBG], (ii) albumin concentration, (iii) [TF] at time zero following iv bolus (total cortisol at time 0, y-intercept), and (iv) free cortisol half-life central to a mechanistic (dynamic, 3-compartment) model (2). Simulations used a multivariable normal distribution and selected means, SDs, and correlation structure among these 4 variables in healthy controls. After generation of a series of cortisol decay curves (n=1000), half-lives for total and free cortisol were solved using the conventional (descriptive, single-compartment) model. The influence of predictor variables on conventional half-life estimates were assessed using standardized beta (STB) coefficients, which represent change in the SD of the outcome (numerator, i.e. total or free cortisol half-life obtained by descriptive model) for each SD change in a predictor (denominator) in a multivariable context (3). For total cortisol half-life (descriptive model) STBs were 0.91 ([CBG]), 0.73 (free cortisol half-life), -0.37 (y-intercept), and 0.04 ([albumin]) (all P&lt;0.001). For free cortisol half-life (descriptive model), STBs were 0.98 ([CBG]), 0.73 (free cortisol half-life), -0.78 (y-intercept), and 0.11 [albumin]) (all P&lt;0.001). We conclude that the conventional descriptive model for estimation of cortisol has significant limitations, including inaccuracy and systematic bias related to the influence of CBG concentration on half-life estimates. By inference, a similar bias confounds interpretation of the half-life obtained using conventional single-compartment model of other hormones associated with high-affinity serum binding proteins. References: (1) Perogamvros et al. Clin Endo 2011;74:30-36, (2) Keenan et al. Am J Physiol Endocrinol Metab 2004;287:E652-E661 (3) Dorin et al., J Endocrinol Soc 2017 July;1(7):945-56.