bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-683 Was Metformin the Culprit for This Lactic Acidosis?
Authors: Vemparala Pranathi , Krishnamurthy Mahesh
Published: May 2020

Introduction

Metformin is the first-line drug for treatment of Type 2 diabetes. A meta-analysis of 70,490 patient-years of metformin use reported no lactic acidosis. We present a case of a patient who developed lactic acidosis while on Metformin; with other contributing factors.

Case Description

A 72-year old male with dementia, diabetes, hypertension, hypothyroidism and “muscular dystrophy” was admitted with encephalopathy. Medications included levothyroxine, donepezil, insulin glargine and metformin. A Brain CT scan revealed frontal lobe atrophy and lacunar infarcts. Admission blood work revealed lactic acidosis of 5.6. Sepsis workup was negative. Metformin was discontinued, and the patient improved with intravenous hydration. Upon discharge, Metformin was restarted. Follow-up lactic acid was normal. After a subsequent hospitalization with similar presentation and peak lactic acid of 4.7, metformin was stopped altogether. The patient was referred to a neuromuscular specialist and a diagnosis of Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) was made. The “muscular dystrophy” was likely mitochondrial disease. A third hospitalization (while not on Metformin) saw a peak lactic acid of 2.8. We concluded that the lactic acidosis was secondary to MELAS, but Metformin had caused the significant spikes seen during the first two hospitalizations.

Discussion

Mitochondrial disorders must be in the differential diagnosis for patients diagnosed with muscular dystrophy. The hallmark of MELAS syndrome is stroke-like episodes that result in hemiparesis, hemianopia, or cortical blindness. Other features include seizures, recurrent headaches, vomiting, short stature, and muscle weakness. Patients with mitochondrial diseases also have a high incidence of diabetes. Lactic acidosis occurs during stress. DNA testing is the gold standard for diagnosis.

Conclusion

Metformin is contraindicated in patients with mitochondrial disease and diabetes due to the predisposition for lactic acidosis. This is not part of the current package inserts for prescribers and patients- and we strongly recommend inclusion of this language.
SUN-688 Pancreatic Cancer in Longstanding Diabetes
Authors: Suarez Janine
Published: May 2020

Background

Pancreatic Cancer carries one of the highest mortality rates in the US and it is established that there is a relationship between Pancreatic Cancer and Type 2 Diabetes Mellitus. We present a case of a woman with longstanding T2DM who developed Pancreatic Cancer and worsening of her T2DM.

Case Presentation

86 year old female was brought to the ER by her family due to jaundice and scleral icterus. Additionally, her blood glucose levels had been uncontrolled in the previous month despite good control for years. Her AST was 871 and ALT was 827, Alkaline Phosphatase was 591, and Total Bilirubin was 13.9, mainly direct with a value of 11.11. The patient had a CT Abdomen and was found to have a mass in the head of her pancreas. She underwent an Endoscopic Ultrasound and FNA biopsy. Cytology results were consistent with Pancreatic Adenocarcinoma. The mass was unresectable and it was recommended she transition to hospice. Regarding her T2DM, she was diagnosed 15 years ago and prior to the last month, her glucose had been well controlled on Metformin and Glipizide, never requiring Insulin. HbA1C 1 year prior was 6.7 and HbA1C during the admission was 8.5. During the month preceding her pancreatic cancer diagnosis, her family noticed her blood glucose levels were running higher than usual. During her admission, her glucose continued to range from 178-315 even though she was on Lantus 12 units nightly and an Insulin Sliding Scale before meals.

Discussion

Although a relationship between Pancreatic Cancer and T2DM has been found, recent studies have shown that this relationship is bidirectional and complex. Several reports have shown that there is a risk association that the shorter the duration of T2DM the higher the average risk association between Pancreatic Cancer and T2DM. Several cohort and case-control studies of patients diagnosed with Pancreatic Cancer show that 25-50% of patients will have developed T2DM within 1-3 years before their diagnosis of Pancreatic Cancer and 85% of patients diagnosed with Pancreatic cancer have impaired glucose tolerance. The mechanism of action of T2DM causing Pancreatic Cancer includes insulin resistance, hyperinsulinemia, hyperglycemia, and chronic inflammation and it is proposed that this pathogenesis is more of a humoral process rather than local tumor destruction of the gland. A factor supporting this is that insulin and C-Peptide levels are reported to be higher in patients with Pancreatic Cancer and T2DM.

Conclusion

Unexplained elevation in HA1C should prompt clinicians to run a differential diagnosis of factors that can induced hyperglycemia. This case highlights the importance of recognizing pancreatic malignancy as a possible cause of worsening hyperglycemia in T2DM.
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

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 >625 uU/mL (negative if <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

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 <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

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 (<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 >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

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

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

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

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 >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 > 28.8 ng/dl and showed that the sensitivity of diagnosis of PA is 100% in our patients with spontaneous hypokalemia, who had PAC < 30 ng/dl, when PAC was set at > 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 < 10 ng/dl. Collectively, 100 out of 102 (98%) with hypokalemia, who had PAC > 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 >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<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

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 > 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 >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.
SAT-667 Partial Beta-Cell Destruction: An Atypical Case of Immune Checkpoint Inhibitor Diabetes Mellitus
Authors: Quandt Zoe , Tsai Katy K , Hsiao Victoria C
Published: May 2020

Background: Autoimmune diabetes mellitus (CPI-DM) caused by immune checkpoint inhibitors (CPIs) is rare- occurring in approximately one percent of patients exposed to this form of cancer immunotherapy. Typically, this immune related adverse event occurs after treatment with PD-1/PD-L1 inhibitors. It is characterized by abrupt insulinopenia leading to acute hyperglycemia. Beta cell autoantibodies are positive in approximately half the cases. DKA is common at the time of diagnosis. Recovery of beta cell function has been reported in only two case reports. In one case, spontaneous resolution occurred following cessation of CPI therapy and in the other the patient was treated with infliximab for concurrent inflammatory arthritis prior to resolution of CPI-DM.

Clinical Case: A 50-year-old woman was started on adjuvant pembrolizumab for stage IIIC melanoma following surgery. She had no prior history of diabetes mellitus, thyroid disease, or other autoimmune disease. Pre-infusion random blood glucoses (RBG) were 84 - 105 mg/dL. After 36 weeks, she developed hypothyroidism (TSH 17.5 (0.5-4.1 mIU/L), FT4 6 (10-18 ug/dL)) and started levothyroxine. Pembrolizumab was continued. For nine weeks following her diagnosis with CPI- hypothyroidism, her pre-infusion RBG ranged from 102-133. At 45 weeks (15 cycles) after initiating pembrolizumab, her RBG was 260. She was not on glucocorticoids and had no other signs of inflammation or stress. Pembrolizumab was continued. Just prior to her 17th cycle, 48 weeks after initiating adjuvant pembrolizumab, her RBG was 482 with a normal anion gap and HCO3, and her A1c was 8.9%. Her last dose of pembrolizumab was held. She started metformin and liraglutide. In just three weeks, a random c-peptide was inadequate at 1.7 (0.8-3.5 ng/mL) with a recent RBG of 220 and A1c of 10.3%, showing the acuity and extremity of her hyperglycemia. Over the course of the year, she has achieved excellent glucose control (A1c 6.3-7.1) on this regimen with preservation of insulin production (c-peptides 1.4-1.8 with matched RBG 92-129). She never required insulin. Her beta cell autoantibodies are negative.

Clinical Lessons: This is a case of CPI-DM in which the patient did not have complete loss of beta-cell function. The acuity of her hyperglycemia is not consistent with new onset type 2 diabetes. At diagnosis, her c-peptide was inadequate suggesting insufficient insulin production rather than insulin resistance. Therefore, her hyperglycemia is more consistent with CPI-DM than type 2 diabetes. Atypically, she did not progress to fulminant beta cell failure, which could have been due to cessation of pembrolizumab (which is not unique to this case), initiation of liraglutide and metformin, or other unknown immunologic responses that inhibited full beta cell loss. This case raises the possibility of preventing fully insulin dependent CPI-DM if hyperglycemia is caught and treated early.
SAT-231 A Case of Metastatic Pheochromocytoma Associated with Beckwith-Wiedemann Syndrome
Authors: Ravindra Sindhura , Jagdeesh Ullal
Published: May 2020

Introduction:

Beckwith-Wiedemann Syndrome (BWS) is an autosomal dominant disorder of chromosome 11p15 that results in increased IGF-2 and CDK1NC. This leads to excessive cell proliferation and tumor formation. The following highlights a case of metastatic pheochromocytoma in a patient with BWS.

Clinical Case:

A 30-year-old male presented with sudden onset blurry vision without any associated complaints. His past medical history was significant for BWS. His family history was negative for uncontrolled hypertension, sudden death, thyroid cancer or hyperparathyroidism. Physical examination was notable for an elevated systolic blood pressure of 200/160 mm of hg and fundoscopy revealed features of hypertensive emergency. Laboratory investigations revealed an elevated plasma normetanephrine [10445 pg/ml (normal: <148)], metanephrine [93 pg/ml (normal: <57)], total metanephrine [10538 pg/ml (normal: <205)], epinephrine [134 pg/ml (normal:<50)], norepinephrine [23526 pg/ml (normal: 112-658), total catecholamine level [23660 (normal: 123-671pg/ml)] and dopamine [403 pg/ml (normal<30)] levels. His PTH, corrected serum calcium, gastrin, insulin, carcinoembryonic antigen, calcitonin levels and basal metabolic panel were all normal. MRI of the abdomen demonstrated bilateral adrenal nodules with a large mass encasing the celiac axis along with evidence of hepatic lesions. I-123 MIBG scan showed mild radioactive tracer uptake in the adrenal nodules and mass near the celiac axis but not in the hepatic lesions. PET scan confirmed MRI findings and was negative for any evidence of malignancy in the chest, pelvis and skeleton. MRI of the brain was negative for metastasis as well as pituitary abnormalities. Ultrasound-guided liver biopsy was positive for malignant cells that stained positive for chromogranin and synaptophysin confirming the diagnosis of metastatic pheochromocytoma. He was treated with phenoxybenzamine, diltiazem and lisinopril. He underwent cycles of cyclophosphamide, vincristine and dacarbazine. Genetic testing revealed a variant in SDHD gene which was of uncertain significance. Repeat biochemical testing on follow up after a year and a half showed a decreased plasma normetanephrine [487pg/ml] and metanephrine levels [110 pg/ml] in comparison to his levels on presentation. Repeat imaging revealed a decrease in tumor burden including bilateral adrenal nodules, celiac axis mass and hepatic metastases.

Conclusion:

This is an unusual case of malignant pheochromocytoma in the absence of SDHB mutation in a patient with BWS. Genetic causes in these patients are yet to be determined. However, genes H19 and KCNQ1OT1 have been implicated in addition to IGF-2 and CDK1NC
MON-485 Thyroid Abscess in a Healthy 22-Year Old Female
Authors: Sharma Rahul K , McManus Catherine , Kuo Jennifer H
Published: May 2020

Background: Thyroid abscess is a rare pathology, exhibiting an incidence of less than 1% of all thyroid diseases. The thyroid is highly resilient against infections. Those who do experience thyroid abscesses are commonly immunocompromised. We illustrate a case of a thyroid abscess in a young, healthy patient.

Clinical Case: A previously healthy 22-year-old woman presented to the emergency department complaining of a sore throat, fever, nausea, and body aches. On exam, the patient was febrile, but had no obvious cervical lymphadenopathy, masses, or oropharyngeal lesions/growths. Initial labs showed leukocytosis to 13.5 k/ul with left-shift. The patient was diagnosed with acute pharyngitis, and was discharged on oral steroids and antibiotics for an incidental urinary tract infection.

After some improvement, the patient returned to the ED 14 days later with a worsening odynophagia, dysphagia, and hematemesis. The patient was afebrile, but had neck swelling and possible thyromegaly. Lab results showed leukocytosis to 17.3 k/ul, and CT of the neck identified a 3.1cm x 3.3cm x 4.4c heterogeneous cystic/solid mass that nearly completely replaced the normal right thyroid lobe parenchyma and extended to the isthmus. Right-sided lymphadenopathy was also present. Initial evaluation suggested thyroid carcinoma. The patient was re-initiated on steroids due previous improvement, and was referred to a tertiary academic medical center for biopsy and further evaluation. 2 days later, the patient returned to the ED for worsening symptoms. However, she was discharged to home with no further management.

At her endocrine surgery consultation visit, the patient reported worsening pain, inability to move her neck, inability to eat or drink, inability to lie flat, and new-onset sialorrhea and voice changes. A bedside ultrasound was performed with findings suggestive of an abscess. An in-office fine-needle aspiration produced purulent fluid, which relieved some of the patient’s compressive symptoms. Cytology showed inflammatory cells (mostly neutrophils) and numerous bacteria. The patient was emergently taken to the operating room for neck exploration, hemithyroidectomy, and incision/drainage of a suspected thyroid abscess. A drain was placed and removed POD 2 after minimal output.

The patient was discharged on oral antibiotics. 1-week post-operatively, the patient returned to the ED due to reaccumulation of the abscess. This was successfully treated with IR placement of a drain. The drain was removed 2-weeks post-operatively, and the patient is doing well.

Conclusion: Thyroid abscesses are rare but possible in young and immune-competent patients. While the imaging findings can point towards a more common diagnosis, such as thyroid carcinoma, avoiding anchoring bias is important. Imaging data should be considered in the context of the clinical picture to avoid the possibility of misdiagnosis.
MON-208 Age-Dependent Progression of Renal Dysfunction After Adrenalectomy for Aldosterone-Producing Adenomas in Japan
Authors: Yoshioka Masayuki , Nakajima Yasuyo , Igarashi Takamihi , Ishida Emi , Horiguchi Kazuhiko , Yoshino Satoshi , Matsumoto Syunichi , Yamada Eijiro , Saito Tsugumichi , Shirabe Ken , Yamada Masanobu
Published: May 2020

Context: In patients with aldosterone-producing adenomas (APAs), adrenalectomy causes a rapid decrease in blood pressure and increase in blood potassium levels; however, the effects of these intensive metabolic changes on kidney function with age have not yet been examined in Japan.

Objective: To investigate factors related to the progression of kidney dysfunction after adrenalectomy in different age groups.

Participants: Fifty Japanese patients with APAs with 27,572 health check-up subjects as controls were examined.

Main Outcome Measures: We investigated changes in eGFR after adrenalectomy and characterized patients who progressed to chronic kidney disease (CKD).Results: Receiver Operating Characteristic and multivariate analyses revealed the postoperative cut-off age of CKD to be 50 years (sensitivity, 57%; specificity; 82%; AUC, 0.69) and identified age as a unique factor for the progression of CKD after adrenalectomy. Among preoperative patients with APAs, CKD was 6% for those younger than 50 years (<50) and 40% for those 50 years and older (≥50). As a control, in 27,572 health check-up subjects, the prevalence of CKD was 4.2% in men and 2.5% in women aged 41-50 years and 18.9% in men and 13.3% in women older than 61 years, clearly demonstrating the higher prevalence of CKD in patients with APAs than in healthy subjects, particularly those with APAs ≥50 years. In patients with APAs <50 years, median eGFR before and after adrenalectomy were 95 mL/min/1.73m2 and 88 mL/min/1.73m2, respectively, indicating that the percentage of the decrease in eGFR was -7%, which was not significant (paired t-test, p=0.13). In contrast, in patients with APAs ≥50 years, median eGFR after adrenalectomy decreased to 42 mL/min/1.73m2 from 67 mL/min/1.73m2 (adjusted by age, paired t-test, p=0.01) (percent decrease in eGFR, -24%) Patients with APAs ≥50 years who progressed to CKD showed higher preoperative aldosterone/renin ratios, lower potassium and chloride levels, lower BMI, and a higher incidence of a history of cardiovascular events and KCNJ5 mutation rates.Conclusion: Age is the most important predictor of the progression of kidney dysfunction after adrenalectomy in Japanese patients with APAs, particularly those with a history of cardiovascular events and positivity for KCNJ5 mutations.
SAT-115 A Rare Case of Metastatic Insulinoma in a Patient with Huntington’s Disease
Authors: Petrenko Olesya , Clark Brinton
Published: May 2020

A 49-year-old female with past medical history of Huntington’s disease presents to the ED after being found unresponsive at her assisted-living facility. She was noted to be hypoglycemic with a glucose of 21 and responded to dextrose. For the past several months, patient had symptoms of dizziness, tremors. She has no history of diabetes, and only home medication is Zyprexa. Patient required D10 drip to maintain glucose levels. Given patient’s psychiatric history, there was concern for surreptitious use of diabetic medications. Labwork showed an insulin level of 163 and an elevated C-peptide of 7.0 consistent with endogenous insulin secretion. Patient underwent a 72-hour fasting protocol which revealed a glucose of 23, C-peptide of 4.1 and insulin of 101, undetectable beta-hydroxybutyrate levels and pro-insulin level of 782 which is consistent with a diagnosis of insulinoma. She was started on diazoxide, which diminishes insulin secretion, to treat the hypoglycemia. Patient underwent a pancreas CT protocol which showed multiple hypervascular hepatic masses up to 9 cm and one 4 cm mass in pancreatic tail concerning for metastasis. Pathology revealed metastatic well-differentiated neuroendocrine tumor grade 3. She was not a candidate for surgical resection of tumors and she was started on Octreotide 200 mcg TID. Patient underwent two Y90 radioembolization treatments, 2 months apart with improvement of hypoglycemia and discontinuation of diazoxide. Patient remains on Octreotide LAR injection every 4 weeks. Insulinoma, although rare, occurs in 1-4% of the population and is the most common type of functional neuroendocrine tumor of the pancreas. It secretes insulin which results in hyperinsulinemic hypoglycemia. Diagnosis involves persistent hypoglycemia with glucose <50 mg/dL, neuroglycopenic symptoms and prompt relief after glucose administration. Gold standard diagnosis is a 72-hour fast and measurement of plasma insulin, C-peptide and pro-insulin, which detects 99% of insulinomas. After lab confirmation, imaging is necessary with either CT, MRI or EUS. Surgical resection is curative in most patients. Other treatment modalities include injection of octreotide, EUS-aided alcohol ablation, radio-frequency ablation or embolization of insulinoma, as well as targeted therapy with everolimus or sunitinib. Malignant insulinomas are extremely rare and often invade into surrounding soft tissue or have lymph node or liver metastasis. They are usually unresectable and require targeted therapy. We present the case of a 49 YO patient with Huntington’s disease who presented with severe persistent hypoglycemia secondary to metastatic insulinoma. Diagnosis of insulinoma is often delayed or missed as symptoms may be attributed to psychiatric, cardiac or neurological disorders or medication misuse. Clinicians should be aware of insulinoma as a cause of life-threatening hypoglycemia.
SAT-230 Newly Diagnosed Schmidt’s Syndrome and Steroid Induced Psychosis
Authors: Soe Myat Han
Published: May 2020

In 1926, Schmidt reported the combination of hypothyroidism and adrenal insufficiency (AI) with lymphocytic infiltration of both the thyroid and adrenal glands.1 This syndrome is now known as autoimmune polyendocrine syndrome (APS) type 2, characterized by two of the following three endocrinopathies: type 1 diabetes, autoimmune thyroiditis, and Addison’s disease.2 It may seem surprising that transient relative hypercortisolemia in AI patients at the beginning of treatment results in steroid induced psychosis (SIP). Here, we present a patient who developed SIP after starting steroid for AI.

44 year old Caucasian female with bipolar disorder and Hashimoto’s thyroiditis was admitted for generalized weakness, nausea, vomiting and weight loss of about 15 pounds in 3 months. On exam, blood pressure was 93/54 mmHg and pulse rate was 99. Her abdomen and arms looked hyperpigmented. Lab test revealed plasma glucose of 68 mg/dl, serum sodium of 129 mmol/l (133-145), potassium of 4.9 mmol/l (3.6 – 5.2), bicarbonate of 20 mmol/l (22 – 29). TSH was 16.93 mIU/ml (0.4 – 4.00) and FT4 was 0.74 ng/dl (0.7 1.8). CT abdomen and pelvis with contrast was unremarkable. As AI was suspected, cortisol level was checked and low at 0.5ug/dl. Cosyntropin stimulation test (CST) revealed pre-CST cortisol of 0.4 ug/dl, and post CST cortisol of 0.5 ug/dl at 45 min. ACTH was elevated at 514.4 pg/ml (7.2 – 63.3). A diagnosis of Schmidt’s syndrome was made based on elevated 21 hydroxylase of 8.5 U/ml (<1.0) and anti-thyroid peroxidase antibody of 20.5IU/ml (<5.6). Screening for type 1 diabetes and celiac disease was negative. After CST, stress dose hydrocortisone was started and dose was gradually tapered down in a few days. However, five days after steroid therapy, patient was admitted for suicidal ideation and catatonia which resolved quickly with Ativan and steroid taper to physiologic dose.

APS type 2 has a prevalence of 1:1000. Clinicians should raise the suspicion for this syndrome in the appropriate context as seen in this patient presenting with classic features of AI. Although SIP in AI patients is not frequently reported, we should be mindful about this potential event especially in patients with underlying psychiatric illness. It is postulated that prolonged hypocortisolism in undiagnosed AI might lead to upregulation of central glucocorticoid receptors and hence glucocorticoid replacement might elicit a relative supraphysiological response in these patients.3
OR29-02 Natural Language Processing of Radiology Reports Improves Identification of Patients with Fracture
Authors: Kolanu Nithin , Brown A Shane , Beech Amanda , Center Jacqueline , White Christopher Patrick
Published: May 2020

Fracture liaison services (FLS) address the treatment gap for those with osteoporosis (OP) who fracture and are not treated. Given the limited human resources in FLS, screening high volumes of radiology reports for fractures with Natural Language Processing (NLP) could identify patients that have not been recognized or treated. This study is an analytical and clinical validation of X-Ray Artificial Intelligence Tool software (XRAIT) at its development site (a tertiary hospital) and external validation in an adjudicated cohort from the Dubbo Osteoporosis Epidemiology Study (DOES).Methods: XRAIT uses NLP to perform a Boolean search of radiology reports for fracture and related terms. It can be trained for site-specific reporting styles and use rules to refine identification (e.g. age>50y; bone involved; etc). At the development site, XRAIT was used to search the emergency patient presentations of people over 50 years of age and compared to referrals to FLS (usual care) during the same 3-month period. XRAIT analyzed all plain radiographs and CT scans (n = 5089) while n = 224 were referred to FLS for usual care. External validation: XRAIT was used to analyze digitally readable radiology reports in an untrained cohort from DOES (n = 327) to calculate sensitivity and specificity.Results: XRAIT identified a 5-fold higher number of potential significant fractures (349/5089) compared to manual case finding (70/224). 339/349 were confirmed fractures (97.1%). Only 29% of those eligible were started or recommended anti-resorptive therapy, including those seen by the fracture liaison service. XRAIT unadjusted for the local radiology reporting styles in DOES had a sensitivity of 69.6% and specificity of 95%. Conclusion: XRAIT identifies clinically significant fractures efficiently with minimal additional human resources. Its high specificity in an untrained cohort suggests it could be used at other sites. Automated methods of patient identification may assist fracture liaison services to identify fractures that still remain largely untreated.