bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-685 Approach to a Potential Liver Transplant Candidate with Insulin Antibody-Mediated Severe Insulin Resistance
Authors: Brooks Danielle C , Japp Emily , Shah Nirali 
Published: May 2020

Abstract
Introduction: Insulin antibody (IA)-mediated insulin resistance is a rare autoimmune condition resulting in uncontrolled hyperglycemia. High titers of IA are associated with increased mortality secondary to severe insulin resistance and labile blood sugars. There is a paucity of standardized treatment for these patients. Although there have been reported cases of success with immunosuppressants, none of these cases involved patients with liver cirrhosis. We present a case of IA-mediated severe insulin resistance which resulted in uncontrolled hyperglycemia and ultimately delayed liver transplantation.
Clinical Case: A 61-year-old male with IA-positive type 2 diabetes, decompensated hepatitis B and NASH cirrhosis presented with several episodes of diabetic ketoacidosis (DKA) and worsening insulin resistance. His liver transplant listing had been placed on hold until glycemic control is achieved. The patient was diagnosed with type 2 diabetes mellitus in 1998. He has no prior autoimmune history. His disease was controlled on Levemir 100 units daily until March 2019 when he presented with his first episode of DKA. He subsequently required 200 units of insulin degludec daily and U-500 insulin 200 units with meals. The patient was readmitted to our hospital in August 2019 for a variceal bleed. His hospital course was complicated by a second occurrence of DKA requiring 100-150 units/hour on an insulin drip for resolution. Labs were significant for HbA1c 8.7% and IA &gt;625 uU/mL (negative if &lt;5.0 uU/mL). He required increasing amounts of basal and prandial insulin after discharge. The patient was again admitted within two months for abdominal pain concerning for spontaneous bacterial peritonitis, which was complicated by his third episode of DKA. Glucoses remained uncontrolled in the range of 170 to 300 mg/dL despite high insulin doses upon discharge. Metformin was contraindicated due to episode of lactic acidosis in the setting of his cirrhosis and concern for repeated episodes of DKA prevented use of SGLT-2 inhibitors. Extensive multidisciplinary discussions led to the decision for an upcoming trial of mycophenolate mofetil followed by plasmapheresis. The goal is to improve glycemic control while also minimizing infection risk to ultimately list him for a liver transplant.
Conclusion: This patient highlights a major therapeutic challenge related to uncontrolled hyperglycemia and insulin resistance from anti-insulin antibodies in a cirrhotic patient. This can place patients at high risk for infection, poor wound healing and most importantly prohibit liver transplantation. Immunosuppressant therapy and plasmapheresis may drastically lower insulin antibodies and improve glycemic control, however, it will increase the risk of infection.
SUN-199 A Case of Ectopic Cushing’s Syndrome with Major Complications Leading to Treatment Dilemmas
Authors: McCloskey Karen , Suda Nisha 
Published: May 2020

Abstract
Background: Ectopic ACTH syndrome is an uncommon cause of Cushing’s syndrome and patients are at high risk for serious complications including infections, thromboses, cardiovascular and neuropsychiatric complications; therefore, swift diagnosis and treatment is needed.
Clinical Case: A 63-year old woman presented with lower extremity edema and severe lower back pain. She also reported a 2 month history of polyuria, polydipsia, and headaches. Initial labs showed hypernatremia, hypokalemia, alkalemia and hyperglycemia and an 8AM cortisol of 61.9 mcg/dL (N 5-25 mcg/dL) with an ACTH of 367 pg/mL (N 6-50pg/mL). Imaging showed a right middle lobe lung mass and 3 vertebral body compression fractures. A failed attempt at biopsy of the lung mass resulted in pneumothorax, air embolism, stroke, and cardiac arrest with shock liver. She was then transferred to our tertiary care center.
On arrival at our center, her examination was notable for hypertension, upper and lower extremity edema and 4/5 strength in her right shoulder and hip flexor. She had left hemiparesis and a depressed mood. No facial plethora, acanthosis, buffalo hump or striae were observed. Her 24-hour Urinary Free cortisol (UFC) was 1,176 mcg/dL (n 3.5-45 mcg/24H) and her 8AM cortisol after 8 mg of dexamethasone was 58.3 mcg/dL (N &lt;1.8mcg/dL).
A pituitary MRI did not identify a lesion, and petrosal sinus sampling was considered too high-risk due to recent infarct and cerebral edema. A PET/CT-scan showed increased uptake in the right lung nodule, enlarged hyperactive adrenals, and a retroperitoneal lymph node.
The patient’s course was further complicated by diffuse deep vein thromboses of her left leg and a subsequent retroperitoneal bleed while on anticoagulation, as well as an E.coli urinary tract infection.
Interdisciplinary discussions regarding options for surgical management were ongoing, however given the patient’s fragile medical state, the endocrine team initiated medical therapy to treat her hypercortisolism while awaiting surgical decision. Initially, a continuous etomidate infusion was used that resulted in a 50% reduction in 24Hr UFC. When her liver function improved, she was transitioned to ketoconazole. She ultimately underwent a right middle lobectomy, revealing a 2.3cm typical carcinoid tumor with strongly diffusely positive ACTH staining on pathology. A day after surgery her ACTH level was 12 pg/mL, though cortisol was still elevated at 55.5 mcg/dL. Cortisol declined to 3.3 mcg/dL within one week. Her neuropsychiatric symptoms reversed almost entirely and she was discharged on a steroid taper.
Conclusion: Ectopic ACTH syndrome is a rare paraneoplastic syndrome with significant comorbidity. In many cases, surgical excision can induce profound and rapid reversal of many of the symptoms of cortisol excess; however, if surgery is delayed, prompt medical treatment is vital to prevent compounding complications.
SAT-507 Myxedema Coma: A Fatal Diagnosis in a Patient with No Known History of Hypothyroidism
Authors: Chaker Bayan , Alim Hussam , Chaker Mahmoud , El-Zein Louna S 
Published: May 2020

Abstract
Myxedema coma is a rare yet commonly missed diagnosis. Early detection is key to management as this diagnosis carries a high mortality rate.
We report a case of a 108-year-old female with a past medical history of CKD stage 3, hypertension, CHF, and atrial fibrillation who was brought to the emergency department (ED) by her grandson for seizures. The patient has no history of seizures, hypothyroidism (previous TSH 6 years back was 2.29 micro IU/mL), diabetes, or previous radiation exposure. The family noticed the first seizure 8 hours prior to admission with eyes rolling backward, shaking for 1 minute and slurred speech upon awakening. She had 2 other seizure episodes prior to arrival to the ED. Vitals in the ED showed a temperature of 31.7°C, BP of 85/50, HR of 35, RR of 8, and SpO2 was 83% on room air. Given the patient’s age, code status was changed to DNR/DNI. Blood work in the ED revealed a sodium of 146 mMol/L (136-145), anion gap of 25, Creatinine of 2.67 mg/dL (last creatinine prior to this admission was 1.65 mg/dL), and a troponin of 0.04 ng/mL (&lt;0.04). Thyroid function testing was not done in the ED. Home medications included Lasix, digoxin, isosorbide mononitrate, and atenolol. The patient was admitted to the medical floor for workup of bradycardia and was being worked up for beta-blocker/digoxin toxicity but continued to be bradycardic despite atropine. She became hypoglycemic to 37 mg/dL. The patient was admitted to the CCU at night on day 1 of admission and was started on dopamine and glucagon drips. Sulfonylurea screen was negative, and the patient did not have further hypoglycemic episodes. While in the CCU, blood work showed a lactic acid of 10 mMol/L (0.4-2.0), TSH of 21.03 micro IU/mL (0.45-5.33), free T4 of 0.61 ng/dL (0.70-1.70), and total T3 71 ng/dL (87-178). Myxedema score was &gt;130. Digoxin level came back elevated at 4.5 ng/ml (0.9-2.0). Cosyntropin stimulation testing was negative for adrenal insufficiency and thus the patient was not started on steroids. Urinalysis revealed pyuria with blood, but no urine cultures were done. Blood cultures were negative. The patient was given levothyroxine 200 mcg IV in the AM on Day 2 of admission and was started on antibiotics with azithromycin, cefepime, vancomycin, and metronidazole given concern for sepsis. Hypoglycemia resolved and glucagon was discontinued. In the evening of Day 2 of admission, despite being on a dopamine drip, the patient became increasingly bradycardic, hypotensive, and short of breath. She was initially stabilized after a dose of bicarb, atropine, and epinephrine. However, her BP and respiratory status continued to decline, and the patient passed away.
In conclusion, myxedema coma should be suspected in patients presenting with typical symptoms and should be tested for on presentation even when no prior history of hypothyroidism exists.
OR14-04 A Novel ERRα-Dependent Insulin Signaling Pathway
Authors: Xia Hui , Giguere Vincent 
Published: May 2020

Abstract
Insulin resistance, a condition in which a cell, tissue, or organism fails to respond appropriately to insulin, is a hallmark for the development of type 2 diabetes and a major contributor to the pathogenesis of non-alcoholic fatty liver disease. In addition to altered insulin signaling transduction, more and more research highlights dysregulated gene expression as nuclear mechanisms underlying insulin resistance. ERRα is an orphan nuclear receptor that plays a central role in the regulation of energy homeostasis. Here, we present evidence to support ERRα as a novel and potent transcriptional regulator of insulin action. By using a high-throughput insulin-based phospho-proteomic database of the mouse liver and bioinformatics analysis based on conserved kinase substrate motif, we first identified ERRα as a direct substrate of glycogen synthase kinase 3β (GSK3β). Our data demonstrate that under basal conditions, GSK3β phosphorylates ERRα at residues S19, S22, and S26. Phosphorylated ERRα is then recognized and ubiquitynated by the SCF-FBXW7 E3 ligase complex, resulting in its degradation by the proteasome. Indeed, pharmacological inhibition of GSK3β in vivo as well as liver-specific knockout of Fbxw7 both lead to the accumulation of ERRα in the liver. Insulin, by inhibiting GSK3β, leads to the stabilization of ERRα in the nucleus, resulting in the altered expression of insulin-responsive genes involved in gluconeogenesis and insulin signal transduction. Genome-wide analysis reveals that more than 40% of the insulin-regulated genes in the liver are direct ERRα targets, indicating a prominent role of ERRα in the regulation of insulin signaling. Together, our findings underscore a novel ERRα-dependent mechanism for insulin’s effects in physiology and disease, implicating the therapeutic value of targeting the GSK3β/FBXW7/ERRα axis in vivo.
SAT-424 Assessing Content Validity of the Graves’ Ophthalmopathy Quality of Life Questionnaire (GO-QOL) in the United States
Authors: Stan Marius N , Holt Robert , Padnick-Silver Lissa , Sile Saba 
Published: May 2020

Abstract
Introduction: Thyroid eye disease (TED) is an autoimmune condition that negatively impacts patient’s quality of life (QOL). The GO-QOL questionnaire was originally developed in the Netherlands to quantify how TED and treatments affect patient QOL. This questionnaire includes eight questions each on visual functioning and appearance related QOL; the items are answered on a 3-point Likert scale and transformed to a 0 (worst) to 100 (best) scale. Though widely used and validated outside the US, the questionnaire has not been validated in the United States (US). Here we examine the content validity.
Methods: Patients with moderate or severe TED were identified using an existing market research patient database, clinician referrals, patient groups, and social media. Interested participants were screened for eligibility prior to completing the GO-QOL. Subjects were also questioned about TED-related signs, symptoms, and treatments and underwent a cognitive interview following GO-QOL completion.
Results: Thirteen TED patients completed the assessments (mean age = 44.8 ± 11.5 years, range: 26-67); all were female. Mean TED duration was 4.6 ± 5.5 years (range: 0.4-20.7). Twelve patients (92.3%) had Graves’ disease and one had Hashimoto’s thyroiditis. Descriptions of how TED signs and symptoms impacted quality of life were consistent with GO-QOL items, and qualitative interviews indicated that patients found the GO-QOL content relevant and complete. Responses indicated that minor wording changes may be needed to account for US cultural and language conventions and prevent confusion (specifically related to a bicycling question [12/13 reported not regularly riding a bike before TED symptom onset]). Visual functioning impacts most commonly-reported during the interview were difficulty driving a motor vehicle (92% of participants), difficulty with electronic screens (e.g., televisions, smart phones, and computers; 77%), difficulty moving around outdoors (including issues with light sensitivity, uneven surfaces, and depth perception; 69%), and difficulty doing hobbies or pastimes (69%). Emotional/psychological impacts frequently reported by participants were change in appearance (92%), depression and anxiety (including fear and worry; 77%), and frustration and anger (including moodiness; 69%). Negative reactions from others (staring, asking questions), social impacts and isolation, and lack of self-confidence and embarrassment were also reported (each 62%).
Conclusion: This analysis of US patient interviews offered strong support for GO-QOL content validity. Therefore, the GO-QOL is appropriate to quantify TED-related QOL impact in a US population. However, a few slight wording modifications may be needed for future optimal use in the US.Reference: Terwee CB. Br J Ophthalmol 1998;82:773-779
MON-701 Uncontrolled Diabetes Presenting as Isolated Sixth Nerve Palsy
Authors: Garay Paola Andrea Sanchez , Zerpa Rommel , Zuniga Gabriela , Navarrete Deyger , Lichtenberg Robert 
Published: May 2020

Abstract
BACKGROUND Our case report demonstrates acute onset of diplopia due to Isolated Sixth Nerve Palsy (ISNP) secondary to uncontrolled T2DM, presenting as an ophthalmoplegia. The most frequent one, is ISNP with an incidence of 11.3/100.000 1. Vasculopathic ISNP is associated with atherosclerosis in patients older than 50 years 1.
CASE PRESENTATION A 63 year-old male with history of T2DM, HTN, HL, came for evaluation of acute onset double vision 3 days prior. He noted diplopia while attempting to park his car; he saw that tracking to the left with his eyes would elicit double vision. Denied recent travel, trauma, headache or dizziness. He was awake and alert, BP 200/110mmHg, BMI 33. No pathologic murmur. He had PERRLA bilaterally but impaired lateral rectus muscle movement on the left side. Otherwise, EOMI on the right side. No facial asymmetry or ptosis. Overall, findings positive for ISNP. BMP only remarkable for a glucose of 297, HA1c was 10.0. Head CT was negative for any acute intracranial abnormality. Orbital MRI did not show acute infarction or masses. Patient was admitted for acute diplopia due to ISNP. Differential diagnoses were neoplasm, migraine, MS and diabetic neuropathy. Based on the aforementioned data, we suggested that T2DM was the probable cause. Counseling on improving glycemic control was given. Unfortunately, patient was lost to follow up. DISCUSSION ISNP remains an elusive entity; atherosclerotic risk factors such as DM, HTN, HL, hyperhomocysteinemia 2 or viral infections 3 have been reported in association. This type of palsy seems to be more frequent in children and can be recurrent in nature.
In adults, the most likely cause of ISNP seems to be ischemic mononeuropathy or more aggressive etiologies such as temporal arteritis 4. Inconclusive images prove even a higher diagnostic challenge 3. Of note, we found a case demonstrating evidence for Eicosapentaenoic Acid in the improvement of ISNP with recovery in as shortly as 8 weeks. The basis of this treatment lies in the recovery of endothelial function focusing on the anti-platelet and anti-inflammatory effects of the drug2,4. REFERENCES (1). Elder, Christopher, et al. “Isolated abducens nerve palsy: update on evaluation and diagnosis.” Current neurology and neuroscience reports 16.8 (2016): 69. (2). Takenouchi, Yasuhiro, et al. “Eicosapentaenoic acid ethyl ester improves endothelial dysfunction in type 2 diabetic mice.” Lipids in health and disease 17.1 (2018): 118. (3). Azarmina, Mohsen, and Hossein Azarmina. “The six syndromes of the sixth cranial nerve.” Journal of ophthalmic & vision research 8.2 (2013): 160. (4). Yanai, Hidekatsu, and Mariko Hakoshima. “Eicosapentaenoic Acid for Diabetic Abducens Nerve Palsy.” Journal of Endocrinology and Metabolism 7.4 (2017): 131–132.
SAT-551 Sparing Confirmatory Tests in Primary Aldosteronism
Authors: Umakoshi Hironobu , Sakamoto Ryuichi , Matsuda Yayoi , Yokomoto-Umakoshi Maki , Nagata Hiromi , Fukumoto Tazuru , Ogata Masatoshi , Ogawa Yoshihiro 
Published: May 2020

Abstract
Context: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low priority evidence and is under debate in use of serum potassium. Objective: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. Design and Setting: A retrospective cross-sectional study in a single referral center. Participants: This study included 327 patients who had hypertension under plasma renin suppression and underwent captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. Main outcome measure: Diagnostic value of PAC and serum potassium in confirmation of PA. Results: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC &gt;30 ng/dl were diagnosed with PA. In patients with PAC between 20 and 30 ng/dl, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dl who had spontaneous hypokalemia were diagnosed with PA. Areceiver operator curve analysis showed that the sensitivity of diagnosis of PA is 100% in our patients, when PAC set at &gt; 28.8 ng/dl and showed that the sensitivity of diagnosis of PA is 100% in our patients with spontaneous hypokalemia, who had PAC &lt; 30 ng/dl, when PAC was set at &gt; 19.2 ng/dl. While, the prevalence of PA was higher in patients with hypokalemia, who had PAC between 10 and 20 ng/dl than in those with PAC &lt; 10 ng/dl. Collectively, 100 out of 102 (98%) with hypokalemia, who had PAC &gt; 10 ng/dl were diagnosed as PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC &gt;30 ng/dl or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dl than those who did not meet the criteria (76% vs. 17%, P&lt;0.001). Conclusion: Confirmatory tests in PA could be spared in patients who have typical features of PA and these patients had a high probability of unilateral PA on AVS.
MON-481 Remarkable Euthyroid Hyperthyroxinemia Mistaken for Thyrotoxicosis
Authors: Baghel Annavi , Maier Joshua D 
Published: May 2020

Abstract
CLINICAL CASE
A 46 year old caucasian female with past medical history of menorrhagia was referred from primary care for evaluation of thyrotoxicosis. Thyroid function was assessed in the context of menometrorrhagia. She did not have any history of thyroid disorder or abnormal thyroid function tests. Per outside records, recent labs demonstrated TSH 0.88 uIU/mL (0.36-3.74), Free T4 &gt; 8.00 ng/dL (0.76-1.46), Free T3 2.9 pg/mL (2.18-3.98). All other labs were within normal limits. Thyroid ultrasound revealed normal parenchyma and volume. She did not take any medications or supplements including biotin. She denied heat intolerance, anxiety, palpitations, dyspnea, tremors, hyperdefecation, or change in hair, skin, or mood. No epiphora, diplopia, or eye irritation was reported. Her father had been diagnosed with hyperthyroidism, mother with hypothyroidism.
Repeat labs at our visit revealed normal TSH of 1.05 uIU/mL (0.358- 3.74), normal Free T3 2.58 pg/mL (2.18- 3.98), normal Total T3 136 ng/dL (80-200), elevated Free T4 &gt;8.00 ng/dL (0.76-1.46) and elevated Total T4 11.6 ug/dL (4.5-10.5). These lab values were not consistent with patient’s euthyroid clinical status, prompting assessment of Free T4 by dialysis, normal at 1.5 ng/dL (0.9-2.2) and T3 uptake, high at 40% (24-39%). This picture was consistent with Familial Dysalbuminemic Hyperthyroxenemia (FDH). The decision was made not to treat the patient with anti-thyroid medications and to perform a confirmatory genetic testing to test for mutations in the ALB (albumin) gene.
DISCUSSION
The free T4 assay used by our institution is performed on the Siemens Dimension Vista platform using a two-step chemiluminescent immunoassay. While in theory two-step assays should not yield abnormal results in FDH, several two-step assays are known to yield falsely high results in patients with FDH (1, 2, 3).
Other potential etiologies for discordant Free T4 levels include thyroid hormone autoantibodies, heterophile antibodies, biotin use, and anti-streptavidin antibodies (3).
CONCLUSION
Recognition of laboratory error in the workup of thyroid disease is essential. Clinicians must ensure thyroid function labs are consistent with each other and with the patient’s presentation. In such cases misdiagnosis of hyperthyroidism or thyroid hormone resistance may lead to unnecessary testing and inappropriate treatment (3).
References
1.
Cartwright D et al. Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge. Clin Chem. 2009 May;55(5):1044-6
2.
Ross HA et al. Spuriously high free thyroxine values in familial dysalbuminemic hyperthyroxinemia. Clin Chem. 2011 Mar;57(3):524-5
3.
Favresse J et al. Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocr Rev. 2018 Oct 1;39(5):830-850.