bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-679 What’s in a Bottle? the Importance of Careful Medication Review to Prevent Life Threatening Hypoglycemia
Authors: Banerjee Ela , Doshi Sejal B , Lebastchi Jasmin , Fernandes Amanda 
Published: May 2020

Abstract
Background: Over 1 in 9 emergency department (ED) visits are due to drug-related adverse events (1) and careful medication review is essential for patient safety.
Clinical Case: A 73-year-old male presented to the ED after his family found him to be tremulous with a blood glucometer reading of 30 mg/dL. He was given glucagon and oral glucose however this did not help his blood glucose and he was brought in for further evaluation. He had a history of chronic kidney disease, hepatocellular carcinoma (HCC) and diabetes mellitus type 2 for which he was on no medication at the time of presentation. He reported being on Glipizide nine months ago. In the ED, he had a temperature of 98.3°F; pulse of 76 beats/min; respiratory rate of 18 breaths/min and blood pressure of 166/71. On physical examination, he was in no acute distress with normal neurologic, cardiac and respiratory exam. Laboratory workup was notable for glucose 40 mg/dL, HbA1c 5.0%, Cr 2.55 mg/dL, eGFR 24, ALT 7 IU/L and AST 23 U/L. CT abdomen and pelvis was consistent with known diagnosis of HCC. The patient was given 4 boluses of D50W and started on a continuous dextrose infusion along with octreotide infusion due to persistent hypoglycemia. Patient’s blood glucose improved one day later and he remained stable off the dextrose and octreotide infusions. Further laboratory evaluation revealed ACTH 9 pg/mL (ref 6-50), Random Cortisol 16.1 at 1:36pm, TSH 1.40uIU/ml, Free T4 1.09 ng/dL, Cosyntropin stimulation test at baseline 15.4 ug/dL; at 30 min 22 ug/dL; at 60 min 28.3 ug/dL and Beta-Hydroxybutyrate 0.11 mmol/L. With a blood sugar level of 32 mg/dL, he was found to have Insulin level 35.9 (ref 3.0-25.0mU/L), Pro-insulin 55.6 (ref &lt 18.8pmol/L) and C-peptide 9.21 (ref 0.8-3.85ng/mL). The patient’s family brought his medications for review with no clear discrepancies noted. Closer inspection of the tablets inside each pill bottle revealed that the pills inside the Docusate-Senna container did not match the description for the same but instead matched the description for Glipizide. The patient disclosed that he had emptied the Glipizide tablets into the bowel regimen container for “safe keeping” when it was discontinued. He was inadvertently taking two Glipizide tablets twice a day as the VNA had mistakenly used these pills to fill his pill box. This serious error in confirming the patient’s medications resulted in his severe hypoglycemia. His Sulfonylurea screen returned positive for Glipizide.
Conclusion: Sulfonylureas, an essential component of diabetes management, have a dangerous side effect of hypoglycemia and errors in its administration can be fatal. Therefore, thorough medication reconciliation and review of the actual pills is essential to prevent such errors.
Reference: Zed PJ, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. Can Med Assoc J. 2008;178(12):1563-1569.
MON-635 FDXR Regulates Iron Metabolism and Glucose Metabolism in Liver
Authors: Sakuma Ikki , Yokoyama Masataka , Yamagata Kazuyuki , Hashimoto Naoko , Nakayama Akitoshi , Shulman Gerald I , Tanaka Tomoaki 
Published: May 2020

Abstract
Iron is an essential cofactor for many proteins that function in electron transport or oxygen transport as heme or iron-sulfur cluster. On the contrary, iron also has the potential to cause oxidative damage if not carefully regulated and when in labial iron excess. Clinical studies show that elevated serum ferritin levels are observed in most patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In this context, p53 is shown to induces some mitochondrial iron regulatory genes. The role of crosstalk between p53 and iron metabolism has not been sufficiently examined in the pathogenesis of diabetes and NAFLD.
Here, we examined the role of ferredoxin reductase (FDXR), a key mitochondrial regulator for iron metabolism, as p53-inducible gene with focusing on the hepatocyte and liver. We confirmed that p53 induced FDXR expression in HepG2 cells and SKEHP1 cells. Biochemical analysis demonstrated that FDXR regulated ROS levels via iron metabolism. In vivo analysis, high-fat diet activated the p53-FDXR pathway in mice liver. We generated transgene expression in mice liver using adenovirus infection carrying shRNA or CRISPR Cas9 system. Treatment with the FDXR knockdown increased hepatic iron content and aggravated glucose intolerance. Besides, forkhead box protein O1 (FOXO1), a key transcriptional factor that induces phosphoenolpyruvate carboxylase and glucose-6-phosphatase increased ratio of nuclear localization, indicating hepatic gluconeogenesis activation. Consistently, biochemical analysis in HepG2 cells demonstrated that FDXR regulated insulin-dependent FOXO1 nuclear exclusion through oxidative stress.
In conclusion, p53-inducible FDXR regulates iron metabolism and oxidative stress. FDXR inhibits iron accumulation and oxidative stress in liver and links to suppression of hepatic gluconeogenesis via insulin-dependent FOXO1 nuclear exclusion. The results of this study provide important new insights into relationship between iron metabolism and glucose metabolism as well as potentially identify novel therapeutic targets for the treatment of diabetes and NAFLD.
SAT-481 Pembrolizumab-Induced Thyroiditis with Negative Thyroid Peroxidase Antibody
Authors: Ragunanthan Branavan , Zmeili Omar Suheil 
Published: May 2020

Abstract
Introduction: Immune checkpoint inhibitors (ICI) have reformed oncology treatment through its immunomodulatory effect on T-lymphocytes to target metastatic and locally advanced cancers but have been known to produce immune-related adverse events (irAEs). Thyroiditis is a well-documented endocrinopathy occurring in patients receiving ICI; however, a Thyroid Peroxidase Antibody (TPO Ab) negative case of ICI induced thyroiditis suggests that its pathogenesis is independent of antibody mediated thyroid destruction and more associated with an alternative immunoregulatory mechanism. Case Description: A 60-year-old Caucasian, male with a 37-year smoking history and lung adenocarcinoma with metastasis to the brain was referred to Endocrinology clinic for evaluation of suppressed thyroid stimulating hormone (TSH) level. Patient was treated with a four-month course of IV Pembrolizumab every three weeks. TSH was &lt;0.015 (NL 0.465-4.680 IU/mL) four weeks before being seen at the office. TSH level was normal 2.359 before starting immunotherapy. Patient reported occasional anxiety and heat intolerance, but did not experience other hyperthyroid symptoms. Physical examination in office demonstrated no significant thyromegaly, nodules, or tenderness. Vital signs were normal. Thyroid function tests obtained during the office visit were consistent with subclinical hypothyroidism. TSH was mildly elevated 7.545 with normal Free T4 of 0.94 (NL 0.78 - 2.19 ng/dL) and normal Free T3 level of 3.61 (NL 2.77 - 5.27 pg/mL). TPO antibodies were negative. Four weeks later, patient developed overt hypothyroidism; TSH level was higher 12.437 with low Free T4 of 0.71. Patient was then complaining of fatigue and cold intolerance. A diagnosis of drug-induced thyroiditis from Pembrolizumab was made. The patient was prescribed levothyroxine 75 mcg daily and followed closely. Discussion: While literature exists documenting the rare side effect profile of ICI endocrinopathies, few studies illustrate the implications and correlations of TPO Ab negative findings in ICI induced thyroiditis. The role of thyroid autoantibodies in the presumed antibody mediated pathogenesis of thyroid abnormalities is unclear and warrants further longitudinal studies to determine its function in these patients. This case report hopes to both identify the deficit of pathophysiological knowledge contextualizing irAEs while encouraging current healthcare practitioners to continue close monitoring of patients receiving ICI.
MON-088 Impact of Vertebral Fracture on Auxological Profile and Insulin-Like Growth Factors of Children After Acute Lymphoblastic Leukemia Treatment
Authors: Ahn Moon Bae , Lee Yoon Ji , Lee Nayeong , Kim Seul Ki , Kim Shin Hee , Cho Won Kyoung , Cho Kyoung Soon , Jung Min Ho , Suh Byung Kyu 
Published: May 2020

Abstract
Purpose: To investigate the overall prevalence of vertebral fractures (VF) following childhood acute lymphoblastic leukemia (ALL) treatment and examine the association of VF with growth trajectory and insulin-like growth factors. Methods: Children (n=172; 59.3 % male) diagnosed with ALL at age between 2 and 18 years were assessed for VF by screening the lateral thoracolumbar spine radiographs (Genant’s semi-quantitative method) when treatment was completed (baseline). Anthropometric measurements between pre- to post-treatment period were obtained and the association of VF with insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were examined. Results: Thirty-five children (20.3 %) had vertebral fractures at baseline. Among children with vertebral fractures, 97.1 % had either mild or moderate deformity, and the 5th lumbar vertebrae was the most frequently injured site (20.0 %). Median lumbar spine bone mineral density Z-score was -1.0 (IQR of -1.6 and -0.8) in children with VF. Baseline Z-scores for height and weight were lower in children with VF than without VF (-0.5±1.3 and 0.0±0.9, P=0.01; -0.2±1.6 and 0.3±1.1, P=0.04, respectively). Height Z-score in children with VF had greater height decline than without VF (0.5±0.6 and 0.2±0.8; P=0.02). Children with VF had lower IGF-1 and IGFBP-3 Z-score than without VF at baseline (-1.2±1.0 and 0.0±0.8, P&lt;0.01; -2.3±1.1 and -1.3±1.0, P&lt;0.01). Decrease in IGF-1 level was associated with the presence of VF (OR=0.3(95 % CI of 0.2-0.5), P&lt;0.01). Conclusion: Substantial number of children encounter VF after ALL treatment is completed and the presence of VF might be associated with compromised auxological state, prominent height decline and IGF-1 deficiency.
MON-451 An Unusual Case of Follicular Thyroid Cancer with Pulmonary Metastasis and Concurrent Hyperthyroidism
Authors: Monsour Elio , Zuazaga Dewid Zayas , Chacko Jay , Abdelmasih Randa , Ramharrack Frank 
Published: May 2020

Abstract
Introduction: Follicular Thyroid Cancer (FTC) accounts for approximately 12 % of all thyroid cancers and is the second most common cause of differentiated thyroid cancer. However, coexisting hyperthyroidism and thyroid malignancy is considered a rare event and is thought to have a prevalence of 0.21–9.0 %. We describe a compelling case of metastatic FTC initially presenting with subclinical hyperthyroidism progressing to overt hyperthyroidism.
Clinical Case: An 88-year-old man with a history of prostate cancer, previous tobacco dependence, and hypertension initially presented with complaints of a chronic non-productive cough associated with unintentional weight loss and fatigue. Initial imaging included a chest CT that showed several bilateral pulmonary nodules suspicious for metastatic disease, as well as an enlarged left-sided thyroid mass, which extended from the inferior pole into the mediastinum. FDG PET/CT showed avid disease identified in the lung. CT-guided lung biopsy was performed, and histopathology revealed FTC. Thyroid function tests (TFTs) revealed a Tg level of 1427 (0.00–33.70), TgAb &lt;1.0 (&lt; 13.6), TSH 0.05 (0.40–4.50), FT4 1.1 (0.8–1.8) and FT3 3.4 (2.3–4.2). Biochemical testing was consistent with subclinical hyperthyroidism. Neck ultrasound showed bilateral thyroid nodules, the largest located on the left mid-pole measuring 3.4 x 3.2 x 3.7 cm. He underwent a whole-body I-131 diagnostic scan, which showed intense uptake of the radionuclide within the thyroid gland, more evident on the left, but additional metastatic lesions elsewhere in the visualized body were not possible. TFTs were repeated, which showed a TSH of 0.01, FT4 of 2.0, and FT3 of 6.4. He was subsequently started on methimazole daily and eventually became euthyroid. Due to advanced age, significant mediastinal extension, and lung metastasis, the patient was not a candidate for surgical resection and treatment with a targeted tyrosine kinase inhibitor. He ultimately opted for an observational approach.
Conclusion: Although metastatic FTC carries a poor prognosis, concurrent hyperthyroidism is thought to be associated with a more aggressive disease course and higher mortality compared to differentiated thyroid cancers in euthyroid patients.
Sources: 1. Pazaitou-Panayiotou, K., Perros, P., Boudina, M., Siardos, G., Drimonitis, A., Patakiouta, F., & Vainas, I. (2008). Mortality from thyroid cancer in patients with hyperthyroidism: the Theagenion Cancer Hospital experience, European Journal of Endocrinology, 159(6), 799–803.
2. Benjamin Momo Kadia, Christian Akem Dimala, Ndemazie Nkafu Bechem, Desmond Aroke. BMC Res Notes. 2016; 9: 369.
3. Parameswaran R, Shulin Hu J, Min En N, Tan WB, Yuan NK. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. Ann R Coll Surg Engl. 2017;99(2):151–154.
MON-499 Nivolumab-Induced Hypothyroidism Is Irreversible in Most Patients
Authors: Yoon Jee Hee , Park Ji Yong , Hong A Ram , Kim Hee Kyung , Kang Ho-Cheol 
Published: May 2020

Abstract
Background Thyroid dysfunction caused by the immune checkpoint inhibitor (ICPI) is common, however mild dysthyroidism could occur easily in cancer patients due to other causes. The aim of this study was to investigate the incidence and clinical course of ICPI-induced hypothyroidism requiring thyroid hormone replacement. Patients and methods We analyzed baseline and follow up thyroid function tests of cancer patients treated with nivolumab between March 2016 and March 2019 at Chonnam University Hwasun Hospital retrospectively. Results Among 265 cancer patients treated with nivolumab therapy, six patients were excluded from the study because they were on thyroid hormone replacement therapy before starting nivolumab therapy. Twenty-one patients (8.1%) newly developed thyroid dysfunction during nivolumab therapy and sixteen patients (6.2%) required thyroid hormone replacement therapy due to drug-induced hypothyroidism. Cancer diagnoses included lung cancer (n=7), renal cell carcinoma (n=4), malignant melanoma (n=2), hepatocellular carcinoma (n=2), and esophageal cancer (n=1). Six patients (37.5%) showed thyrotoxic phase prior to overt hypothyroidism and the others (n=10, 62.5%) revealed hypothyroidism without thyrotoxic phase. Most ICPI-induced hypothyroidism was irreversible, only one patient was able to discontinue thyroid hormone replacement after quitting nivolumab therapy. Conclusion A significant number of patients treated with nivolumab developed ICPI-induced hypothyroidism requiring thyroid hormone replacement and its clinical course was irreversible in most patients.
OR26-07 Mild Physiologic Hyperglycemia Does Not Affect Glucose Mediated but Impairs Insulin-Mediated Suppression of Plasma Glucagon in Healthy Normal Glucose Tolerant Subjects
Authors: Tripathy Devjit , chen Xi , merovci aurora , Trejo Jonathan , DeFronzo Ralph 
Published: May 2020

Abstract
Plasma glucagon levels are regulated by plasma glucose concentrations as well as intra-islet and circulating insulin concentrations. Hyperglycemia adversely affects skeletal muscle and hepatic insulin sensitivity (glucotoxicity). However, the effect of physiologic hyperglycemia on glucose-mediated and insulin-mediated suppression of glucagon is not known. The aim of the present study was to evaluate effect of chronic (48 or 72 hours) physiologic increase (+45 mg/dl) in plasma glucose concentration on the suppression of plasma glucagon concentration in healthy NGT individuals: 12 without family history of T2DM (FH-) (9M/3F, age = 50± 4 yrs, BMI = 27 ± 1 kg/m2) and 8 with FH of T2DM (FH+) (4M/4F, age = 48±2, BMI = 26±1 kg/m2). Subjects received an OGTT and 2-step hyperglycemic (+125 and +300 mg/dl) clamp (duration of each step = 80 minutes) before and after 72 hour glucose infusion. On another occasion subjects participated in a 3-step hyperinsulinemic (10, 20, 40 mU/m2·min) euglycemic clamp before and after a 48 hour glucose infusion. Plasma insulin and C-peptide concentrations were obtained every 2-5 minutes during each hyperglycemic clamp step and plasma glucagon concentrations were measured every 10 minutes. The ratio of insulin/glucagon was measured and used as an index of insulin-medicated suppression of plasma glucagon. FPG concentration increased from 97±4 to 140±4 mg/dl during the 72 hour glucose infusion. Following chronic glucose infusion, plasma insulin levels were significantly higher during the basal state and during each hyperglycemic clamp step (by 59% and 78%). There was no difference in plasma glucagon levels following chronic glucose infusion and the degree of suppression of glucagon during 2-step hyperglycemic (+125 and +300 mg/dl) were similar. However, the plasma insulin/glucagon ratio was significantly higher during the fasting state (by 76%) and during the first (by 128%) and second (by 178%) hyperglycemic clamp steps. Similarly during the three step euglycemic clamp (10, 20, 40 mU/m2·min) studies following 48 hr glucose infusion, despite similar plasma glucose concentrations during each clamp step, plasma insulin and glucagon concentrations were higher following chronic glucose infusion. These results demonstrate that sustained physiologic hyperglycemia for 48 hrs or 72 hours (i.e. glucotoxicity) does not affect the glucose mediated suppression of glucagon, but impairs insulin-mediated suppression of glucagon, and could contribute to fasting and post-prandial hyperglycemia in T2DM patients.
SUN-298 Spectrum of Imaging in Immune Checkpoint Inhibitor Induced Hypophysitis
Authors: Quandt Zoe , Kim Stephanie , Villanueva-Meyer Javier , Coupe Catherine , Tyrrell J Blake , Bluestone Jeffery A , Anderson Mark Stuart , Masharani Umesh 
Published: May 2020

Abstract
Background: Hypophysitis (HP) is a known immune related adverse event of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and rarely with PD-1/PD-L1 inhibitors. Prior studies of MRIs at HP diagnosis noted pituitary enlargement with resolution within a few weeks. In this study, we examine MRI changes in patients with CPI-induced HP.
Methods: Subjects with biochemical evidence of central hypothyroidism or central adrenal insufficiency and MRIs were reviewed by endocrinology and neuroradiology. MRIs were classified relative to HP diagnosis: baseline (at least 21 days prior), diagnosis (within 21 days), and follow up (over 21 days). Patient characteristics included age at CPI initiation, sex, race/ethnicity, personal and family history of autoimmunity, type of cancer and CPI.
Results: Twenty-six subjects met the inclusion criteria. The mean age was 59 years; 62% were male and 86% were non-Hispanic white. Nineteen percent had a personal history and 31% a family history of autoimmunity. Fifty percent had melanoma. At HP diagnosis, 46% were on PD-1/PD-L1 inhibitors, 42% were on combination PD-1/CTLA-4 inhibitors and 12% were on CTLA-4 inhibitors.
Median time from CPI initiation to HP diagnosis was 95 days. Time to HP was shorter on a CTLA-4 inhibitor combination or monotherapy (median 82 days) compared to a PD-1/PD-L1 inhibitor monotherapy (median 220 days; Wilcoxon rank sum, p &lt;0.01). Central adrenal insufficiency was present in all patients not yet on steroids. Central hypothyroidism was common (10/19) in those without primary thyroid disease and was not associated with type of CPI (Fisher’s exact, p=0.18).
Thirteen subjects had baseline MRIs, 18 had MRIs at HP diagnosis and 13 had MRIs in the follow up period. Baseline MRIs were normal in 12/13; one subject had an enlarged pituitary. At diagnosis, 10 had an enlarged pituitary, 7 a normal pituitary and 1 a partially empty sella. CTLA-4 inhibitor exposure was associated with pituitary enlargement at diagnosis: 9/11 compared to 1/7 on PD-1/PD-L1 inhibitor (Fisher’s exact, p &lt;0.04). Of the subjects who had follow-up MRIs, 3 had an enlarged pituitary, 7 a normal pituitary and 3 a partially empty sella. Follow up imaging did not differ between treatment types (Fisher’s exact, p &gt;0.05). Timing of MRI was significantly associated with pituitary appearance (Fisher’s exact, p &lt;0.01).
Conclusion: The MRI appearance of HP presents as a spectrum, from a partially empty sella, normal pituitary to an enlarged pituitary. HP diagnosed in the setting of CTLA-4 inhibitor treatment occurs earlier and is more likely to induce an enlarged pituitary gland compared to PD-1/PD-L1 monotherapy, which occurs later and is associated with a normal appearing MRI at diagnosis. This suggests that the pathogenesis of HP following CPI exposure may vary depending on the type of CPI.
SAT-039 The Short-Term Effect of Multiple Kinase Inhibitor (Lenvatinib) on Spermatogenesis in Mice
Authors: Lue Yanhe , Gianoukakis Andrew G , Fueger Patrick T , Teramoto Darren , Irimia-Domingues Jose , Bloom-Saldana Elizabeth , Wang Christina C L , Swerdloff Ronald S 
Published: May 2020

Abstract
Lenvatinib, a multi-kinase inhibitor, is used in the treatment of solid malignancies. Lenvatinib belongs to a family of tyrosine kinase inhibitors and targets VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor alpha, RET and KIT. However, it is not known whether Lenvatinib like other chemotherapeutic drugs affects spermatogenesis. The objective of this study was to examine whether Lenvatinib induces damage to spermatogenesis in mice. Twenty adult mice (C57BL/6) were randomly divided into 2 groups to receive daily gavage of either water (as control) or Lenvatinib (10 mg/kg) for 6 weeks. All mice were euthanized at the end of the study. We identified that Lenvatinib significantly (p&lt;0.05) decreased testis weight (TW: 91.75±1.49mg) compared to control mice (TW: 111.9±3.07mg). This difference in testis weight however, became non-significant after correcting for body weight. The cauda epididymal sperm count was significantly (p&lt;0.01) decreased in the Lenvatinib treated (0.82±0.04 million/mg cauda) as compared to control (1.26±0.07 million/mg cauda) mice. There were no differences in plasma testosterone concentrations between Lenvatinib treated (29.76±7.67ng/dl) and control (31.72±6.89ng/dl) mice. Lenvatinib did not induce notable morphological changes in testicular histology. We conclude that 6 weeks of Lenvatinib treatment had minimal effect if any on mouse spermatogenesis. The long-term treatment effect of Lenvatinib on spermatogenesis remains to be determined.