bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-LB118 Euglycemic Diabetic Ketoacidosis in Type 2 Diabetes Mellitus
Authors: Arao Kevin A , Bhatt Harikrashna , Capistrano Christina M , Zhang Hui , Cosgrove Christopher 
Published: May 2020

Abstract
Introduction
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes. It is characterized by the triad of hyperglycemia (&gt;250mg/dL), high anion gap metabolic acidosis (HAGMA), and ketonemia. Rarely, it would present with normal or mildly increased glucose levels (&lt;200mg/dL) making it a diagnostic challenge. We present a case of euglycemic DKA in type 2 diabetes mellitus (T2DM).
Case Presentation
A 77-year-old woman living in a nursing home with a history of T2DM treated with insulin glargine, but for the past three days refused medications with decreased caloric intake. There were no new medications or ingestion of alcohol or toxic substances. She then developed worsening altered mental status hence admission to the hospital. Her vital signs were within normal limits. Physical examination revealed no abdominal tenderness. Initial laboratory studies showed glucose 83 mg/dL, bicarbonate 10 mmol/L, and anion gap 23 meq/L. Urinalysis significant with trace ketones. The following day, further work-up was done remarkable with beta-hydroxybutyrate 8.3 mmol/L, lactic acid 0.8 mmol/L, and toxicology panel negative. Arterial blood gas showed pH 7.137, pCO2 14 mmHg, and bicarbonate 4.8 mmol/L. DKA protocol was initiated and she was treated with insulin drip, bicarbonate drip, and intravenous fluid administration with D5W. After two days, DKA resolved and was subsequently transitioned to subcutaneous insulin.
Discussion
Similar to the findings of Burge et al, our case showed that decreased caloric intake predisposes patients with diabetes mellitus to euglycemic DKA during periods of insulin deficiency. A proposed mechanism for the accelerated ketosis is due to the effects of elevated levels of glucagon or catecholamines on lipolysis. Other causes of euglycemic DKA include pregnancy, heavy alcohol use, SGLT2 inhibitors, cocaine abuse, pancreatitis, sepsis, and chronic liver disease. It is also important to rule out other causes of HAGMA. In our case, although she has decreased caloric intake, starvation ketoacidosis usually leads to serum bicarbonate levels &gt;18mmol/L. Management is similar to DKA but important difference is the dextrose administration to prevent hypoglycemia.
Conclusion
Euglycemic DKA is a medical emergency that may be overlooked as patients present without marked hyperglycemia. Physicians should have a high suspicion as this may result in delayed management and potential adverse metabolic consequences.
SUN-LB103 The Relationship Between Alcohol Consumption Patterns and Insulin Sensitivity in Obesity
Authors: Han Katrina , Reeds Dominic Nicholas , Dunn Julia Passyn 
Published: May 2020

Abstract
BACKGROUNDThe effects of alcohol intake on insulin sensitivity have produced conflicting results with both beneficial and adverse effects observed. This study aimed to compare the relationship between patterns of alcohol consumption and insulin sensitivity in obese Veterans. METHODSWe performed a cross-sectional study of obese (BMI 30.0-45.0 kg/m2), nondiabetic U.S. Military Veterans without active mental health diagnoses, including no report of dependent alcohol use within the last 12 months. Alcohol exposure over the previous 12 months (mos) was assessed using a study-developed questionnaire and Michigan Alcoholism Screening Test (MAST). Fasting insulin, glucose, and a 75gm OGTT were completed to determine Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and prediabetes (preDM) score of 0, 1, or 2 based on fulfilling 0, 1, or at least 2 of the ADA criteria for preDM, respectively. Linear regression was used to assess for associations between measures of insulin resistance and alcohol consumption; unstandardized β and p-value are reported for variable of interest. RESULTS104 Veterans participated (66% males; 44±8years (range: 25-60); BMI 36±4kg/m2 (range: 29-45); 53% White, 46% African American, 2% Alaskan/Native American, 1% Other). 83 participants reported any alcohol intake in the previous 12 mos and neither preDM score (p=0.57) nor HOMA-IR (p=0.14) were predicted by this question. PreDM score groups were similar in gender, BMI, and weight, but age predicted both preDM score (r2=0.09, β=0.025, p=0.006) and HOMA-IR (r2=0.05, β=-0.09, p=0.034); therefore, all regressions were adjusted for age. There was a negative association between the number of days of alcohol intake with HOMA-IR (β=-0.271, p=0.037) but no association occurred with preDM score (p=0.15). Fewer days of binge drinking was associated with higher HOMA-IR (β= -0.342, p=0.058) and preDM score (β=-0.075, p=0.05). There was no significant association between total quantity of alcohol intake and HOMA-IR (p=0.13) nor preDM score (p=0.15). There was no association between MAST score and HOMA-IR (p=0.7) or preDM score (p=0.3). CONCLUSIONIn our cohort of obese, non-alcohol dependent Veterans, the reported number of days of alcohol intake and days of binge drinking in the previous 12 mos were lower in those with markers of insulin resistance. These results suggest that drinking patterns among obese patients may have unique effects on insulin sensitivity that warrant further investigation.
SAT-511 Alpha Gal Allergy in a Hypothyroid Patient
Authors: Slayden Tanner A , Bauer Elizabeth M , Shakir Mohamed K M , Hoang Thanh Duc 
Published: May 2020

Abstract
Background: The IgE-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate expressed on nonprimate mammalian proteins, has gained more clinical significance as it can present with serious, potentially fatal anaphylaxis or angioedema. In general, recognizing a specific allergy is the first step in prescribing avoidance; but with delayed symptoms, uncertain prevalence, and unclear diagnostic approach, alpha-gal allergies are difficult to recognize and prevent. To further complicate the clinical picture, some patients can tolerate small portions of nonprimate mammalian meat or tolerate one kind of meat over another. We hereby present a case that highlights the lack of guidance and resources currently available to treat a patient with alpha-gal allergy and hypothyroidism. Case Presentation: A 45-year-old woman with a history of an alpha-gal allergy and follicular thyroid neoplasm status post right hemithyroidectomy presented with postoperative hypothyroidism. After the surgery, she had undetectable serum thyroglobulin levels; her thyroid stimulating hormone (TSH) levels were ranging 5–6 µIU/mL (not on thyroid replacement). The goal was to prescribe thyroid replacement to initiate cancer suppressive strategy. The American Thyroid Association (ATA) recommends a TSH of 0.5-to-2 mcIU/mL in low risk patients postoperatively. The standard treatment of choice for correcting hypothyroidism is synthetic thyroxine (T4, levothyroxine). Commercially available levothyroxine, liothyronine, combo, and desiccated thyroid formulations - whether brand name, generic, tablet, soft gel capsule, or liquid - all contain meat byproducts and can be a concern for anaphylaxis or angioedema if one has an alpha gal allergy. Because of the possible reactions with all common formulations of thyroid hormone replacement in this patient, choosing a safe option was complicated and involved a multidisciplinary team, including allergy and immunology consultation. Daily parenteral synthetic thyroid hormone therapy was considered; however, it is not practical and was not feasible for the patient. She was eventually prescribed pure Levothyroxine, with a plant-based filler and vegetarian capsule. She tolerated this pure levothyroxine well without any adverse reactions, and the TSH goal was achieved. Conclusion: This case emphasizes the importance of recognizing various risk factors and common drugs associated with the alpha-gal allergy. Further research and pharmaceutical attention to this allergy is needed.
SAT-LB1 Detection of Serum Macro-Luteinizing Hormone
Authors: Ogura-Ochi Kanako , Itoshima Koichi , Kamada Yasuhiko , Otsuka Fumio 
Published: May 2020

Abstract
Macromolecules of prolactin (PRL) and thyrotropin (TSH), so called macro-PRL and macro-TSH, respectively, are rarely detected in the patients’ serum containing high concentrations of these hormones. The macromolecules are involved in increasing the serum concentrations due to aggregation with the autoantibodies in serum. Here we show a case having macromolecules of luteinizing hormone (LH), possibly due to the complex to immunoglobulin-G (IgG). A 35-year-old Japanese female who has complained menstrual irregularity and had a past surgical history of thyroid cancer was referred to our hospital. Laboratory examination showed an extremely high concentration of serum LH (&gt;200 mIU/ml), while serum levels of follicle-stimulating hormone, estradiol, thyroid hormones, human chorionic gonadotropin, testosterone, and prolactin were all within the normal ranges. MRI study showed a normal pituitary shape without any tumorous lesion. Responses of gonadotropins to LH-releasing hormone (LHRH) stimulation were marginally blunted but showed an LH-dominant pattern such as polycystic ovary syndrome. We suspected the presence of macro-LH because of the divergence between the clinical features and the LH level. Of note, the recovery rate of LH levels after precipitation with polyethylene glycol (PEG) was less than 5%, and the gel-filtration analysis further demonstrated an LH peak slightly earlier fraction than IgG. One case report documented the presence of macro-LH in the serum from a young female patient complicated with autoimmune thyroiditis, suggesting the formation of macro-LH related to some latent autoimmune diseases. To assume macro-LH and to re-examine LH levels after serum precipitation by PEG or protein A/G and fractionation are important to avoid unnecessary treatment to increased LH conditions. In clinical practice, we should suspect the presence of macro-LH, if serum LH levels are unexpectedly high compared to the clinical signs.
MON-LB037 Adrenocortical Carcinoma: A Case Report
Authors: Ebadi Farha Naz , Karim Marcus , Chen Kenneth , Abraham Reshma 
Published: May 2020

Abstract
Introduction:
Unilateral adrenal tumors are relatively common; adrenal incidentaloma has a prevalence of 4% on CT imaging. These masses are classified by their functional and malignant potential. We present here a case of adrenocortical carcinoma (ACC), a rare and often aggressive tumor that accounts for 2% of all adrenal incidentalomas. ACC has a worldwide incidence of disease of 0.5-2 cases per million population per year. While some instances of ACC are associated with hereditary conditions, most cases are sporadic mutations.
Case:
A 44-year-old male with a past medical history of hypertension, polysubstance use, and anasarca presented with a one-year onset of abdominal swelling. This was associated with a 16 pound weight loss over the prior 4 months and bilateral lower extremity swelling for the previous 3 weeks. Of note the patient had been detained in an adult corrections institution for over 5 years. Review of systems was negative for night sweats, nausea, vomiting, headaches, confusion, or palpitations. CT of the abdomen demonstrated a large mass involving the left adrenal gland measuring 28 x 27 x 31 cm, with punctate and delayed calcifications. Also noted were numerous bilateral lung nodules, and multiple liver lesions. Bilateral lower extremity ultrasound revealed a DVT involving the left gastrocnemius vein. A heparin drip was initiated and the patient was transitioned to Xarelto. CT scan of the chest demonstrated gastroesophageal junction lymphadenopathy, right hilar lymphadenopathy, numerous lung metastases and a prominent lesion in the left lower lung. Laboratory studies included both a low and high dexamethasone suppression test demonstrating a cortisol level 24 mcg/dL, metanephrines &lt; 0.2 nmol/L, low testosterone 2.1 ng/dL (free) and 54 ng/dL (total), and DHEA 7.1 ng/mlL. Aldosterone &lt;4.0 ng/dL and ACTH &lt; 5 pg/mL. Biopsy for the adrenal mas was consistent with cortical neoplasm. Surgery recommend against debulking due to wide-spread metastases. Oncology recommended chemotherapy; a regimen of mitotane, etoposide, doxorubicin, and cisplatin, with glucocorticoid replacement in 28-day cycles x 6 through venous port.
Conclusion:
Adrenocortical carcinoma is a rare, aggressive tumor that often secretes excess cortisol and/or androgens. In the case presented a large advanced stage ACC was nonfunctional. First-line therapy for ACC includes resection with debulking surgery, radiation therapy, and/or chemotherapy. 5-year survival rates range 62-82% for those with disease confined to the adrenal gland and 13% for tumors associated with distant metastases. Repeat CT scans for our patient demonstrated stable appearance after four cycles of chemotherapy, thus indicating this treatment regimen may be beneficial for such an aggressive disease.
SAT-LB98 Early Atherosclerosis in Polycystic Ovary Syndrome. a Systematic Review, Meta-Analysis and Meta-Regression
Authors: Parolin Matteo , Beghetto Marco , Fallo Francesco , Vincenzo Angelo Di , Vettor Roberto , Mioni Roberto , Aguiari Paola , Milanesi Anna , Rossato Marco , Pagano Claudio 
Published: May 2020

Abstract
Backgroung. Polycystic ovary syndrome (PCOS) is a common disorder affecting reproductive age women and is a cluster of endocrine and metabolic alterations ranging from impaired ovulation and androgen excess to abdominal obesity and metabolic syndrome leading to increased cardiovascular risk profile. Aim. To perform a meta-analysis on the effect of PCOS on surrogate markers of atherosclerosis, namely intima media thickness (IMT), flow-mediated dilation (FMD) and pulse wave velocity (PWV) and to run a meta-regression on the potential determinants of preclinical atherosclerosis. Methods. A search through Pubmed/Medline and ISI-web of knowledge retrieved 90 studies that were used for meta-analysis. Selected outcomes were IMT (n=6199), FMD (n=3090), and PWV (n=2477) while age, BMI, waist circumference, total testosterone, free androgen index (FAI), total-, HDL- and LDL-cholesterol, HOMA-index, systolic and diastolic blood pressure were used for meta-regression analysis. Results. Random effect meta-analysis showed that IMT was significantly increased (ES 0.47, 95% C.I. 0.64 to 0.30, p&lt;0.0001), FMD was significantly impaired (ES -0.92, 95% C.I. -0.69 to -1.15, p&lt;0.0001) and PWV was significantly increased (ES 0.28, 95% C.I. 0.48 to 0.08, p=0.006) in PCOS compared to controls. Meta-regression analysis showed that FMD was positively correlated with FAI (p=0.018) while negative correlations were found between Effect Size (IMT) and BMI (p=0.02), waist circumference (p=0.05) and total cholesterol (p=0.02). Conclusions. This meta-analysis shows a clear effect of PCOS on all markers of preclinical atherosclerosis (IMT, FMD and PWV). Heterogeneity of results is explained in part by the androgen status that was positively linked to impairment of FMD while increasing of anthropometric and metabolic variables (waist, BMI and total cholesterol) seem to overcome PCOS on preclinical atherosclerosis.
MON-LB85 Aberrant Glycan Expression Changes With the Phenotype of Follicular Thyroid Tumours
Authors: Lee Kai Yin , Sreenivasan Dinesh Kumar , Feng Pan , Yang Peiling , Parameswaran Rajeev 
Published: May 2020

Abstract
Glycosylation is the most common post-translational modification of proteins and plays an important role in cell communication, interaction and adhesion. Aberration of glycosylation is a hallmark of cancer cells and plays an important role in oncogenesis and cancer progression including metastasis1. One of the markers of aberrant glycosylation (O-linked) is the binding of the lectin Helix pomatia agglutinin (HPA), and this has been shown in a wide range of human cancers2, especially in tumours with a more aggressive phenotype. To study the alteration in cellular glycosylation, detected by lectin Helix pomatia agglutinin (HPA) binding in various phenotypes of follicular thyroid tumours, ranging from adenoma to carcinoma and metastatic follicular thyroid cancers. Lectin histochemistry was performed on archival paraffin wax-embedded specimens of 6 follicular adenomas, 10 minimally invasive follicular carcinomas, 13 widely invasive follicular cancers and 4 metastatic follicular thyroid cancers. For positive controls, sections of rat kidney were used, which shows strong and characteristic HPA labelling were included in each labelling experiment. For negative controls, the lectin was omitted and the specificity of binding was confirmed by incubating the sections with HPA in the presence of 0·1-mol/l GalNAc. Sections were scored as positive when 5% or more of the cancer cells labelled positive and scored as negative when less than 5% labelled positive for HPA binding. Assessments of HPA binding were performed by two observers who were blinded to the identity of the sample, and their results were compared. Positive labelling was seen in 20% of adenomas, 60% of minimally invasive carcinomas, 77% of widely invasive carcinomas and 100% of metastatic carcinomas (p&lt;0.05). In the minimally invasive carcinoma group, all tumours that showed vascular invasion showed positive HPA labelling, whereas only 20% of patients with capsular invasion showed positivity. We speculate that as the phenotype of the thyroid tumours changes from benign to the malignant phenotype, the glycan expressions change. However, the underlying molecular mechanisms leading to this change needs to be further investigated.
References:1. Magalhães, A., Duarte, H.O. & Reis, C.A. 2017, “Aberrant Glycosylation in Cancer: A Novel Molecular Mechanism Controlling Metastasis”, Cancer Cell, vol. 31, no. 6, pp. 733-735.2. Parameswaran, R., Sadler, G. & Brooks, S. 2011, “Helix pomatia Agglutinin Binding Glycoproteins in Thyroid Tumors”, World Journal of Surgery, vol. 35, no. 10, pp. 2219-2227.3.
Parameswaran, R., Tan, W.B., Nga, M.E., Soon, G.S.T., Ngiam, K.Y., Brooks, S.A., Sadler, G.P. & Mihai, R. 2018, “Binding of aberrant glycoproteins recognizable by Helix pomatia agglutinin in adrenal cancers”, BJS open, vol. 2, no. 5, pp. 353-359.
SUN-LB107 Functional Characterisation of Human Heterozygous Non-Synonymous MC3R Variants
Authors: Melvin Audrey , Cowan Ceili , Lam Brian , Buller Sophie , Rainbow Kara , Yeo Giles S , O’Rahilly Stephen 
Published: May 2020

Abstract
Background: Melanocortin 3 receptor (MC3R) is a member of the melanocortin family of G-protein coupled receptors predominantly expressed in hypothalamic tissue. Rodent models have implicated MC3R in the pathogenesis of obesity, however in humans the relationship between obesity phenotypes and impaired MC3R function is less well established than that observed for loss of function mutations in the homologous MC4R.
Aim: Recently three heterozygous MC3R variants identified from candidate gene sequencing of an obese human cohort were reported to be pathogenic. We sought to functionally characterise the these MC3R non-synonymous variants (p.Q11X, p.I50T and p.A149V) in vitro and examine their associations to body mass index in an unselected population-based cohort.
Methodology: Functional characterisation of each variant was undertaken in HEK293 cells transiently overexpressing either wild-type MC3R or the respective MC3R mutant where cAMP-dependant luciferase activity in response to alpha-melanocyte stimulating hormone (α-MSH) was measured. Body mass index (BMI) was compared between heterozygous carriers of the MC3R variants of interest and control participants (matched for age and sex and ethnicity) identified within the UK Biobank whole exome sequencing dataset.
Results: Impairment of the canonical MC3R cAMP signalling response to α-MSH was observed for both p.Q11X and p.A149V MC3R variants when compared to wild-type MC3R receptor function in vitro. In contrast the cAMP signalling response of MC3R p.I50T to α-MSH was non-inferior to wild-type. Thirty-nine (male=18) heterozygous carriers of MC3R p.I50T were identified in the UK Biobank whole exome cohort. There was no statistical difference in median (IQR) BMI for female carriers 27.1(7.8) kg/m2 vs. matched female control participants 26.2(5.5) kg/m2 or male carriers 27.7(5.4) kg/m2 vs. matched male control participants 27.4(4.9) kg/m2. A single participant heterozygous for the MC3R p.Q11X variant (BMI= 28.3 kg/m2) and two participants heterozygous for MC3R p.A149V (BMI= 24.7 and 25.1 kg/m2 respectively) variant were identified in the UK Biobank whole exome cohort. BMI did not significantly differ from the match control population median for either of these variants.
Conclusion: In vitro assessment and phenotype correlates suggest that MC3R p.I50T is not an obesity causing mutation. Despite evidence of impaired receptor function in vitro, MC3R p.Q11X and p.A149V did not associate with obesity in this unselected population and further study are required to elucidate their pathogenicity in humans.
SAT-LB6 First Human Trial of an Oral Native Testosterone Shows Physiological Levels of Testosterone and Dht in Both Fasted and Fed State in Hypogonadal Men
Authors: Newell-Price John D C , Porter John , Quirke Jo , Daniel Eleni , Mumdzic Enis , Ross Richard John M 
Published: May 2020

Abstract
Introduction: The prevalence of male hypogonadism is estimated to be 6% in the USA (1). Current therapies have limited acceptability: gels can be messy and risk inadvertent dosing of others; injections are painful; and oral testosterone undecanoate (TU) delivers variable testosterone levels, requires concurrent ingestion of a fatty meal and may produce supraphysiological dihydrotestosterone (DHT) levels. We present the first human trial of an oral native testosterone preparation formulated to deliver physiological levels of testosterone irrespective of food intake. Aim: To compare the pharmacokinetics of DITEST (Diurnal Ltd Cardiff, UK) to an oil based oral TU formulation (Andriol Testocaps MSD, UK) and explore the effect of food on DITEST bioavailability. Methods: Single centre, phase 1b study of DITEST in 25 adult males with hypogonadism, one subject withdrawn after single period and only included in safety analysis (Clinicaltrials.gov: NCT02966652). Part 1 compared the pharmacokinetics of 80mg TU with 120mg DITEST after a high fat meal. Part 2 the pharmacokinetics of 200mg of DITEST administered in either fed or fasted states. Results are baseline adjusted. Results: DITEST showed a testosterone dose response between 120mg and 200mg with Cmax 550 (19.1) and 877 (30.4) ng/dl (nmol/l) and AUC0-10h 59.5 and 88.6 h*nmol/L. DITEST 200mg gave an equivalent Cmax and AUC0-10h to TU 80mg: Cmax 877 (30.4) vs 906 (31.4) ng/dl (nmol/l) and AUC0-10h 88.6 vs 102 h*nmol/L. Fed and fasted DITEST had similar pharmacokinetics: Cmax 764 (26.5) vs 877 (30.4) ng/dl (nmol/L), AUC0-10h 87.0 vs 88.6. DITEST resulted in lower levels of DHT than TU: Cmax 84 (2.9), 131 (4.5) & 194 (6.7) ng/dl (nmol/l); AUC0-10h 11.0, 16.7 & 36.3 h*nmol/L for DITEST 120mg, 200mg & 80mg TU, respectively. There was one serious adverse event (urinary retention) in the study during TU dosing. There were no emerging safety concerns, and adverse event frequency and severity was similar between the two treatments. Discussion: These results demonstrate that 200mg DITEST provides similar testosterone exposure with more physiological DHT exposure than 80mg TU given with a high fat meal. Administration of DITEST in fed and fasted states provides similar testosterone and DHT exposure. Compared to published literature on a self-emulsifying formulation of TU at 200mg, DITEST at 200mg provides a similar testosterone Cmax and no requirement for a fatty meal (2). Conclusion: DITEST is an oral native testosterone formulation with anticipated advantages over current oral therapy of dosing without food and a lower risk of supraphysiological DHT levels. References: 1. Basaria S. Male hypogonadism. Lancet 2014; 383:1250-1263. 2. Yin AY, et al., J Androl 2012; 33:190-201.