bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-565 The Effect of Leptin Treatment on Blood Pressure and Autonomic Nervous System Function in Patients with Lipodystrophy
Authors: Grover Andrew , Brychta Robert J , Startzell Megan , Chen Kong , Marshall Brandon , Christensen John , Meehan Cristina , Valencia Areli , Gorden Phillip , Brown Rebecca J 
Published: May 2020

Abstract
Leptin is an adipokine that reflects energy storage levels. Patients with obesity have high leptin, hypertension, and increased cardiovascular disease (CVD) risk. In rodents, leptin increases blood pressure (BP), by increasing sympathetic nervous system (SNS) activity, suggesting high leptin may cause hypertension and CVD. Studies of leptin administration in 2 human models of leptin deficiency (weight reduced and congenital leptin deficiency) showed decreased SNS activity in the leptin-deficient state, which increased after leptin replacement. This has clinical relevance as high SNS and low parasympathetic nervous system (PNS) activity correlate with increased risk of hypertension and CVD. In lipodystrophy syndromes adipose tissue is deficient thus leptin is low. We hypothesized that leptin treatment in patients with lipodystrophy would increase SNS activity and BP. SNS and PNS activity in the heart can be assessed using heart rate variability (HRV). The high frequency (HF) component of HRV is directly related to PNS activity whereas the low frequency (LF) component reflects both SNS and PNS. The LF/HF ratio reflects sympathetic-vagal balance. Lower standard deviation of the beat to beat interval (SDNN) inversely correlates with CVD risk. Leptin-naïve patients with lipodystrophy (N=17, 5 generalized, 12 partial) were housed on an inpatient unit for 19 days. Patients were studied without leptin for the first five days. Leptin was administered for the next 14 days. At the end of the OFF-leptin and ON-leptin periods, 24-hr EKG recordings were used to derive HRV parameters and an automated BP monitor measured BP every 30 minutes during the day and every 60 minutes at night. 5 patients had generalized lipodystrophy (median 25th,75th percentile] endogenous leptin [0.5 [0.4, 0.6] ng/mL); 12 had partial lipodystrophy (leptin 7.5 [3.9, 20.3]). In the combined cohort with generalized and partial lipodystrophy, leptin treatment did not alter BP or any measure of autonomic nervous system function after 24 hours, 2 weeks, or 6 months. In exploratory subgroup analyses of generalized vs partial lipodystrophy, those with generalized lipodystrophy had an increase in LF after 2 weeks of leptin and a 4.5 mm Hg increase in systolic BP after 6 months; no changes were observed in those with partial lipodystrophy. Unlike previous human and rodent studies, we did not see increased SNS tone or BP after leptin treatment in patients with lipodystrophy. However, exploratory analyses in patients with generalized lipodystrophy and very low endogenous leptin levels showed small increases in systolic BP and increased LF component of HRV after 2 weeks, which is regulated by both SNS and PNS. This suggests that leptin may alter autonomic function in the transition from very low to normal plasma leptin levels.
SAT-315 CircVPS13c Promotes Tumor Growth and Invasiveness in Pituitary Adenoma by Downregulating IFITM1
Authors: Jiang Xiaobing , zhang weiyu , zhang piaopiao 
Published: May 2020

Abstract
Background and objectives
Invasive nonfunctioning pituitary adenoma (NFPA) remains the major cause of hypopituitarism and infertility. Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression in a wide range of tumors. The present study was designed to explore the role of circRNAs in proliferation and invasion of NFPAs.
Methods
The expression profile of circRNAs was compared with circRNA array between NFPA (n=10) and normal pituitary tissues (n=4), invasive (n=5) and noninvasive (n=5) NFPA samples. A total of 249 circRNAs were shown to be significantly upregulated in human invasive NFPA tissues, comparing to the noninvasive ones. CircVPS13C was identified for further study, whose oncogenic effect were explored with in vitro and in vivo experiments.
Results
CircVPS13C was markedly upregulated in NFPA samples and positively correlated with NFPA invasiveness. Silencing of circVPS13C effectively suppressed NFPA cell proliferation, invasiveness and promoted apoptosis, in vitro, and suppressed tumor growth, in vivo. The oncogenic effects were significantly enhanced when circVPS13C was overexpressed. By whole exome sequencing, interferon induced transmembrane protein 1 (IFITM1) was found significantly increased in cells with circVPS13C knockout. Decreased level of IFITM1 protein was confirmed in NFPAs samples, and negatively correlated with the level of circVPS13C and tumor invasiveness. Upregulation of IFITM1 could partly reverse the effect of IFITM1 on tumor cells, and IFITM1 downregulating enhanced the oncogenic effect of circVPS13C. CHIRP analysis suggested that circVPS13C may inhibit the IFITM1 transcription by competitively binding the RNA-associated proteins.
Conclusions
CircVPS13C promotes NFPA growth and invasiveness by regulating tumor suppressor IFITM1, revealing a therapeutic target in preventing the tumorigenesis of NFPA.
SUN-177 A Silent Bomb: A Case of Severe Primary Adrenal Insufficiency in the Context of Adrenal Metastatic Disease
Authors: Mathew Jilcy Joy , Li Yulong 
Published: May 2020

Abstract
Background: Adrenals glands are the most commonly involved endocrine organ in cancer metastasis due to its abundant lymphatic communication and blood supply. Up to 4% of non-small-cell lung cancers and 71% of lymphomas have bilateral adrenal metastasis. Early detection with hormone replacement can be life-saving.
Clinical Case:
A 58 year old male was admitted for hyperkalemia (potassium 6.4 mmol/L, range: 3.5-5.1) with prolonged PR interval on EKG, hyponatremia (sodium 131 mmol/L, range: 136-145), hypoglycemia (glucose 48mg/dl), and renal function impairment (creatinine level elevation of 1.38 mg/dl from a baseline of 0.94 mg/dl). He had been diagnosed with Stage IVb non-small-cell lung cancer about 20 months prior, and had a known history of chemotherapy, adrenal metastasis and left adrenal gland radiation (20 G in 5 daily fractions) about 10 months ago. For the past 10 months, the patient had reported no weight loss, nausea, vomiting, or other symptoms or signs of adrenal insufficiency, apart from intermittent fatigue, which he had attributed to his lung cancer diagnosis. On review, a previous PET/CT scan showed intense FDG uptake in the bilaterally enlarged adrenal glands, measuring 3.3 x 2.8 cm on the left, and 3.1 x 1.8 cm on the right. His ACTH level was found to be elevated to 1,023 pg/ml (range: 6-63) with borderline low free cortisol level 0.06 mcg/dl (range 0.04-0.35). Aldosterone level was found to be 3.4 ng/dl (range: 4-31), with a renin level of 36.2 ng/ml/hr (range: 0.5-4). Primary adrenal insufficiency was diagnosed, and the patient was started on hormone replacement therapy, which was titrated as outpatient. Now he is continued on a regimen of hydrocortisone 15 mg and 5 mg, at 8 am and 3 pm respectively, and fludrocortisone 0.1 mg daily. In two months, his ATCH level fell from 1,023 to 89 pg/ml with normalization of kidney functions, sodium level (now 137 mmol/L) and potassium level (now 4.8 mmol/L). He gained 4 kg, and has been feeling more energetic and functional on his follow up visits.
Conclusion: Patients with adrenal metastatic cancer may have atypical symptoms and signs despite having severe primary adrenal insufficiency. High risk patients should be monitored, even in the absence of symptoms, for the development of adrenal insufficiency.
Reference:
1. Yamamoto, T. (2018). LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine Practice, 24(8), pp.746-755.
2. Angelousi A, Alexandraki KI, Kyriakopoulos G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2019.
MON-236 Central Diabetes Insipidus in a Patient with Crohn’s Disease
Authors: Johns Caroline Susan , Weare-Regales Natalia , Fernandez Carlos Pla , Tourtelot John Brooke 
Published: May 2020

Abstract
Unusual Presentation of Central Diabetes Insipidus in a Patient with Crohn’s disease
Introduction
Autoimmune hypophysitis is defined as an inflammatory condition of the pituitary gland of autoimmune etiology that leads to pituitary dysfunction. There are three different histopathological categories of inflammatory hypophysitis including lymphocytic, granulomatous, and xanthomatous hypophysitis. Although, an autoimmune link has been suggested for lymphocytic hypophysitis (LH), the pathogenesis of autoimmune hypophysitis is still incompletely defined. The co-existence of LH and Crohn’s is a rare combination with only a few case reports in the literature.
Case presentation
We present a 39-year-old female with history of Crohn’s disease who presented to the ED with abdominal pain, poor oral intake and headaches. Lab work showed hypernatremia. A neck CT incidentally noted a nodular density along the superior aspect of the pituitary gland. A focused MRI of the pituitary showed abnormal thickening of the pituitary stalk with a prominent and heterogeneous gland. Endocrinology was consulted and on interview patient reported chronic headaches, polyuria and polydipsia for the past year, worsening over the past month. She denied any visual disturbances. Labs showed Na 159, K+ 4.0, serum osmolality 307, urine osmolality 178, specific gravity urine 1.006, cortisol 18, FSH 1.26, LH 0.12, prolactin 55, TSH 1.45 and free T4 0.84. Patient diagnosed with Diabetes Insipidus (DI) from LH and was started on PO desmopressin. Unfortunately, patient continued to have hypernatremia and increased urine output despite increases in the dose and frequency of the oral desmopressin. Given no clinical improvement, decision was made to switch from PO to IV desmopressin considering malabsorption of PO medication in the setting of Crohn’s disease. DI labs including plasma sodium, plasma osmolality, urine osmolality, specific gravity of urine and urine output were closely monitored. Patient’s hypernatremia and increased urine output started to improve with the switch to IV and was ultimately discharged home with intranasal desmopressin.
Discussion
Lymphocytic hypophysitis is a rare disorder predominantly affecting females during the antepartum or postpartum period. This case illustrates the importance of considering its presence in the setting of other autoimmune conditions. It also serves to illustrate the complex management and decision making followed in adjusting the desmopressin formulation in the setting of a malabsorptive disease such as Crohn’s.
MON-470 Biotin Masquerading as Subclinical Hyperthyroidism
Authors: Eapen Anita , Oktaei Hooman 
Published: May 2020

Abstract
Introduction: Thyroid conditions are among the most common endocrine disorders. Diagnosis is dependent on interpretation of laboratory tests. The challenge comes when the clinical picture is discordant with laboratory results.
Case Report: Patient is a 53-year-old male with history of cardiac transplantation, type 2 diabetes mellitus, history of amiodarone-induced hyperthyroidism. He was noted to have labs indicative of hyperthyroidism, while taking amiodarone, in 2016-2017, which was treated with methimazole. He was then noted to have abnormal thyroid function tests with low TSH to 0.3 IU/L, normal T3 and normal T4 levels. Thyroid stimulating immunoglobulin had been checked multiple times, and was normal, which is inconsistent with Graves’ disease. Prior radioactive iodine uptake scan, while off amiodarone, was noted to be normal. He was also scheduled for thyroidectomy at another hospital, which was cancelled due to normalization of thyroid function tests. Consultation was received for suppressed TSH to 0.323 IU/L, without symptoms of hyperthyroidism. He had been taking biotin during this time, which he subsequently stopped taking. Repeat TSH following discontinuation of biotin, was within normal range, most recent TSH 2.48 IU/L, free T4 1.03 ng/dL, free T3 2.7 pg/mL.
Discussion: Thyroid function tests are commonly ordered. Interpretation of these tests relies on the provider’s understanding of thyroid physiology in addition to interferences with medications and other conditions. High doses of biotin, which people take as supplements for multiple sclerosis, or metabolic disorders, or for healthy nails and hair, can cause thyroid function test abnormalities. Streptavidin and biotin are used in some immunoassay platforms to capture antigens (TSH, free T4) or antibodies. High levels of serum biotin can inhibit the formation of T4 antibody complex, which results in a falsely high free T4 result.
Conclusion: Thyroid Function tests should be interpreted very cautiously, especially in the setting of discordant clinical findings. Prior to ordering these tests, should attempt to obtain a detailed history of medications including over-the-counter supplements, which are commonly not reported during medication history.
References:Elston, Marianne S., et al. “Factitious Graves’ Disease Due to Biotin Immunoassay Interference—A Case and Review of the Literature.” The Journal of Clinical Endocrinology & Metabolism, vol. 101, no. 9, 30 June 2016, pp. 3251-3255., doi:10.1210/jc.2016-1971. Koehler, Viktoria F., et al. “Fake News? Biotin Interference in Thyroid Immunoassays.” Clinica Chimica Acta, vol. 484, 30 May 2018, pp. 320-322., doi:10.1016/j.cca.2018.05.053. Soh, Shui-Boon, and Tar-Choon Aw. “Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.” Annals of Laboratory Medicine, vol. 39, no. 1, 13 Jan. 2019, pp. 3-14., doi:10.3343/alm.2019.39.1.3.
SAT-500 Response to Tocilizumab Retreatment in Refractory Thyroid Eye Disease
Authors: Kaplan Daniel , Erickson Benjamin , Kossler Andrea , Chen Julie , Dosiou Chrysoula 
Published: May 2020

Abstract
Background: The current standard of care for moderate to severe thyroid eye disease (TED) is intravenous methylprednisolone (IVMP), though alternative immunosuppressive options are emerging. In a recent randomized trial, Tocilizumab (TCZ), an anti-IL-6 receptor antibody, demonstrated improved efficacy for corticosteroid-resistant TED compared to placebo. Clinical response to TCZ retreatment, however, has not been previously reported.
Clinical case: A 64-year old man presented with progressive diplopia, eyelid retraction and edema and retrobulbar pain. Initial labs revealed TSH 0.221 uIU/mL, free thyroxine (FT4) 1.11 ng/dL, total T3 172 ng/dL and a thyroid stimulating immunoglobulin (TSI) index of 329 (normal &lt; 140). The patient was a former cigarette smoker who had recently transitioned to e-cigarettes. He was treated with 12 weeks of IVMP with improvement in ocular redness and swelling. Three months following completion of treatment, he presented with worsening left sided proptosis, restrictive strabismus, and compressive optic neuropathy (CON) evidenced by deteriorating central acuity and color vision. He underwent urgent surgical decompression for CON with full restoration of visual acuity. He then received a second 12-week course of IVMP with concomitant orbital radiation. Of note, his hyperthyroidism was well controlled with methimazole. Two months after his second IVMP course, he had a third flare of ophthalmic symptoms. He was then treated with TCZ 8 mg/kg (800mg) IV monthly for six months. The patient’s Clinical Activity Score (CAS) improved from 4 to 2 and TSI index decreased from 610 to 92 (normal). He had significant improvement in periorbital edema, caruncle/plica swelling, and conjunctival injection. However, ten months following completion of the TCZ course he again complained of worsening diplopia and left proptosis. Of note, relapse of his TED symptoms was preceded by an increase in TSI from 92 to 300 two months prior. Orbital CT demonstrated progression of left orbitopathy and increased orbital apex crowding. Following these CT findings he was restarted on TCZ, of which he has now completed 5 additional infusions. His CAS has improved from 3 to 2 and TSI index has decreased from 284 to 100.
Conclusion: This is the first reported case of response to successive courses of TCZ in relapsing, severe, corticosteroid-resistant TED. TCZ can be an effective option for refractory TED though retreatment may be necessary for recurrent inflammation. Further study of TCZ is required to determine its role in relapsing TED and the optimal duration of therapy needed.
References:
Perez-Moreiras et al., 2018. Efficacy of Tocilizumab in patients with moderate to severe corticosteroid resistant Graves’ orbitopathy: a randomized controlled trial. Am J Ophthalmol 195:181
SUN-137 Clonal Status of Multigland Disease Primary Hyperparathyroidism
Authors: Azimzadeh Pedram , Shi Yuhong , St. John Ace , ferlitch Janice , Olson John A 
Published: May 2020

Abstract
Primary hyperparathyroidism (PHPT) is a common endocrine disorder that arises due to single or multiple parathyroid gland disease (MGD). The molecular mechanism(s) of parathyroid neoplasia are incompletely understood and both monoclonal (mono-X) and polyclonal (poly-X) parathyroid tumors have been described using methylation-sensitive PCR of X-linked Human Androgen Receptor (HUMARA) alleles. Our previous investigations of parathyroid tumor clonal status has shown that poly-X tumors are common and are associated with MGD in patients with non-familial PHPT (Shi et al. 2014 & 2018). This work examined the clonal status of the dominant gland and the clonal relationship of multiple tumors from the same patient has not been examined. The goal of the current study was to determine the clonal relationship of parathyroid tumors from PHPT patients with MGD. Banked parathyroid tissues from twenty-nine PHPT patients with MGD were examined in this study. Clonal status (mono-X vs poly-X) of multiple abnormal parathyroid glands from each patient was determined using a modification of the HUMARA assay used in our prior work. Briefly, methylation-sensitive PCR of HUMARA alleles was performed followed by fragment analysis using Capillary-Electrophoresis performed. Raw fragment sizing data analyzed using Peak Scanner software. Classification of samples as either mon-X or poly-X was made as described in (Shattuck et al.) Of 29 PHPT patients with MGD, 13 (45%) had pure mono-X, 5 (17%) had pure poly-X, and 11 (38%) had a mixture of mono-X and poly-X tumors. Five of 29 patients had three or more abnormal glands evaluated: 3 had mixture of poly-X and mono-X, 2 had pure mono-X tumors, and none were pure polyclonal-X. Eighteen (62%) out of 29 patients had paired upper or lower double adenomas. Of these, 9 (50%) were pure mono-X, 4 were pure poly-X, and 5 were mixed mono-X/poly-X. In 2 patients with multiple mono-X tumors, allele distribution was not the same in different abnormal glands. Our previous work has demonstrated that among patients with non-familial PHPT, poly-X parathyroid tumors are common and are associated with MGD. Our new data extend these findings to show that the clonal relationship between multiple parathyroid tumors from the same patient is complex and may reflect the emergence of single or multiple tumors from a background of parathyroid hyperplasia, or other mechanism(s). Future studies to explore the mechanisms behind these apparent clonal relationships are warranted and ongoing. Reference: (1) Shi et al., PNAS 2014, 201319742. (2) Shi et al., Surgery 2018, 9-14. (3) Shattuck. N Engl J Med 2005, 2406-12.
MON-904 Behind the Mask: The Stories of Insulinoma- a Case Series
Authors: Reddy Danda Vijay Sheker , Thaduri Krishna Reddy , konda chaitanya , Verpula Madhavi , Paidipally Srinivasrao 
Published: May 2020

Abstract
Introduction: Insulinoma is a rare, slow growing pancreatic neuroendocrine tumor, leading to hyperinsulinemic hypoglycemia. It runs a very insidious course often masquerading as neurologic, psychological or cardiac disease. We present a series of four cases with varying clinical presentations, diagnoses and latency to diagnosis.
Case Report: This is a retrospective analysis of four cases of Insulinoma diagnosed between Sep 2016 and Mar 2019. All the patients were males and aged 36, 22, 63 and 15 years respectively. Baseline characteristics, duration to diagnosis of Insulinoma, diagnosis and treatment given before definitive diagnosis and post-surgery outcomes were analyzed. All the four patients had relatively long latency to diagnosis despite frequent, spontaneous hypoglycemic episodes, longest being ten years. The patients had a neurological and/or psychiatric diagnosis prior to definitive diagnosis. The symptoms improved with consumption of food. One of the four patients was on antipsychotics for episodic abnormal behavior before the diagnosis of Insulinoma. Two of them were on anti-epileptic medications for seizures. All the insulinomas were localized with CECT without requirement for additional localization techniques. All our patients responded well to surgical resection of the tumor. All insulinomas were benign grade 1 tumors. Acanthosis nigricans regressed in all the patients post-surgery. In addition, all the patients had significant weight loss post-surgery. Two of the four patients developed diabetes mellitus and were on insulin therapy.
Conclusion: A strong index of suspicion of Insulinoma is warranted while dealing with patients presenting with seizure disorders, behavioral abnormalities and neurological symptoms because the spectrum of symptoms is wide and non-specific. Seeking diagnosis is of utmost importance because of implications on treatment and prognosis.
Reference:
Valente LG, Antwi K, Nicolas GP, Wild D, Christ E. Clinical presentation of 54 patients with endogenous hyperinsulinaemic hypoglycaemia: a neurological chameleon (observational study). Swiss Med Wkly. 2018 Nov 18;148:w14682.
SUN-020 Waist Circumference Is Associated with Insulin Resistance in Young Korean Women with Polycystic Ovary Syndrome
Authors: Song Do Kyeong , Lee Hyejin , Hong Young Sun , Sung Yeon-Ah 
Published: May 2020

Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and associated with metabolic disturbances such as insulin resistance (IR) and obesity which are risk factors for cardiovascular diseases. Many studies have shown that waist circumference (WC) representing abdominal obesity is an important risk factor for IR. However, there were few studies whether WC were associated with IR in young women with PCOS. We aimed to evaluate the role of WC in IR among young Korean women with PCOS. We enrolled age- and body mass index-matched women with PCOS (n = 100) and controls (n = 100). WC was measured and the 75-gram oral glucose tolerance test (OGTT) was performed. Insulin sensitivity was assessed by the Stumvoll index which was calculated from an OGTT. Multiple linear regression analysis was performed to evaluate the association between WC and IR. WC, fasting glucose, post-load 2-hour glucose, fasting insulin, and post-load 2-hour insulin did not differ between women with PCOS and controls. Women with PCOS had lower values of the Stumvoll index than the controls. In correlation analysis, WC was negatively correlated with the Stumvoll index in women with PCOS, however not in controls. In multiple regression analysis, WC was negatively associated with the Stumvoll index even after adjustment for age, total cholesterol, and total testosterone in women with PCOS. In young Korean women with PCOS, WC was negatively associated with insulin sensitivity independent of hyperandrogenemia. Simply measuring of WC could be used to screen the high risk group having IR in young women with PCOS.