bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-LB116 FGF-21 Is A Reliable Marker Of Insulin Resistance Before The Occurrence Of Glucose Intolerance
Authors: sawah ahmed , Seyoum Berhane , Msallaty Zaher
Published: May 2020

Background and aims: Fibroblast growth factor (FGF)-21 is a polypeptide that results in metabolic rearrangement mostly related to glucose and lipid metabolism. Serum FGF-21 level is elevated in obesity and in type 2 diabetes. The goal of this study is to evaluate the relationship between FGF-21 and peripheral insulin resistance in a wide range of baseline BMI and glucose metabolism status. Materials and methods: seventy one participants reported to the clinical research center in a fasting state twice. BMI and fat mass were calculated. Glucose metabolism was determined by fasting glucose, hemoglobin A1c and OGTT. Serum lipids panel was measured. Peripheral insulin resistance was determined using the hyperinsulinemic euglycemic clamp study. FGF-21 level was measured using enzyme-linked immunosorbent assay before and after clamp study. Study was approved by university institutional review board. Results: Of 71 participants, 48 were obese and 23 were lean. Normal glucose metabolism was documented in 43 individuals. Serum FGF-21 was significantly elevated in insulin resistant compared to insulin sensitive subgroups (0.28 ng/ml ± 0.136 vs. 0.14 ng/ml ± 0.112. p < 0.001). Despite the fact that FGF-21 is elevated in all obese population, the level was significantly higher in the insulin resistant obese subgroup compared to the insulin sensitive obese one (0.30 ng/ml ± 0.167 vs. 0.17 ng/ml ± 0.126. P =0.003). Furthermore, significantly higher FGF-21 level was also found in lean insulin resistant compared to lean insulin sensitive subgroups (0.18 ng/ml ± 0.106 vs. 0.09 ng/ml ± 0.061, p = 0.04]. Adjustment to preexisting impaired glucose tolerance did not affect the correlation between FGF-21 level and insulin resistance which remained statically significant in the seemingly healthy obese and lean subgroups. Conclusion: Serum FGF-21 level strongly correlates to peripheral insulin resistance in both obese and lean population. Nonetheless, FGF-21 level rises way before glucose metabolism abnormality can be detected. Our study suggests a cutoff level for each subgroup which may enable clinicians to risk-stratify patients and allow for early intervention.
SAT-LB63 A Case of PTHrP-Negative Hypercalcemia of Malignancy
Authors: Murati Jonila , Cannavo Ariana , Lee Sun , Pearce Elizabeth N
Published: May 2020

Case Presentation:

A 55-year-old male who had recently arrived from Haiti presented to the Emergency Department with chief complaint of a progressively enlarging neck mass. He first noticed the mass in 2000. From 2000-2017, he underwent resection of the mass three times in Haiti, with recurrence after each surgery. On presentation, he reported unintentional 10 kg weight loss over several months and night sweats. Endocrine was consulted for evaluation of hypercalcemia. On examination and imaging, 8.7 x 14.0 x 14.0 cm fungating tumor on the nape of his neck extending to the occipital area and cervical lymphadenopathy were noted. Labs were notable for WBC of 21.7 K/uL, hemoglobin of 6.0 g/dL, calcium of 12.0 mg/dL, albumin of 3.1 g/dL, free calcium of 6.4 mg/dL, corrected calcium of 12.6 mg/dL, phosphorus of 2.6 mg/dL, and intact PTH of < 4 pg/mL. The PTH-related peptide (PTHrP) level was found to be normal at 19 pg/mL (reference range 14–27 pg/mL). SPEP was normal. Neck mass and cervical lymph nodes were biopsied. Histopathological examination of neck mass showed an ulcerated, moderately-differentiated squamous cell carcinoma with multifocal areas of necrosis. There was no evidence of malignancy in the cervical lymph nodes. CT scan showed 3 mm lung nodules, thought to be granulomas, and no clear evidence of metastatic disease. Hypercalcemia was treated with IV hydration and one dose of bisphosphonate and patient underwent resection of neck mass. Immediately after surgery, his calcium level precipitously decreased and has remained normal in the months since surgery.

Discussion: Hypercalcemia of malignancy is a common finding affecting up to 44.1% of patients with malignancy (1,2). The major mechanism, accounting for approximately 80% of malignancy-related hypercalcemia, is mediated via PTHrP, which can cause hypercalcemia by increasing bone resorption and renal tubule calcium reabsorption (2). Squamous cell carcinoma (SCC), especially of the lungs, breast, or GI tract, is more frequently associated with hypercalcemia. There are also several case reports of primary cutaneous SCC associated with hypercalcemia. In these cases, tumors were large and hypercalcemia was thought to be due to elevated PTHrP (3,4,5). The skin has been shown to express PTHrP and PTHrP receptors (10). PTHrP has also been detected in 100% of cutaneous SCCs even in the absence of hypercalcemia. (6,7). Furthermore, PTHrP mRNA has been localized in 100% of squamous tumors with hypercalcemia and PTHrP peptide were detected in 91% of cases in a study of 11 patients (9). The patient presented in this case did not have an elevated level of PTHrP. However, resolution of hypercalcemia with resection of the mass supports a diagnosis of hypercalcemia of malignancy. This case illustrates that hypercalcemia due to primary cutaneous SCC typically, but not always, results in an elevated serum PTHrP level.
OR28-03 Drug Repurposing Identifies Inhibitors of the Proteostasis Network to Augment Radioiodine Uptake in Combinatorial Approaches Targeting Thyroid Cancer
Authors: Read Martin L , Brookes Katie , Fletcher Alice , Thornton Caitlin E M , Alshahrani Mohammed , Khan Rashida , Nieto Hannah R , Adcock Holly V , Webster Jamie R M , Cox Liam , Alderwick Luke J , Boelaert Kristien , Smith Vicki E , McCabe Christopher J
Published: May 2020

New combinatorial drug strategies are urgently needed to improve radioiodine (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. Drug repurposing offers the promise of identifying already approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. However, a lack of thyroid cell-based assays amenable to high-throughput screening has limited progress. We utilised the mutated yellow fluorescent protein (YFP) as a surrogate biosensor of intracellular iodide and screened the Prestwick Chemical Library (1200 drugs; 95% approved) for quenching of YFP fluorescence. This allowed us to identify putative candidate drugs which increased iodide uptake >2 SD above mean. Categorisation of these revealed a high proportion of drugs that modulate the proteostasis network (19/48; ~40%), including key processes in protein homeostasis such as endoplasmic reticulum-associated protein degradation (ERAD) and autophagy. Secondary screening validated the activity of proteostasis modulators in enhancing iodide uptake after ranking 73 leading compounds based on their pharmacologic (AUC, EMAX and EC50) and specificity of response (NIS+ve vs NIS-ve YFP-thyroid cells) at ten different drug doses (0.1 to 50 μM). Of importance, several repurposed drugs (e.g. ebastine, Prestwick N, Prestwick C and clotrimazole) in combination with the HDAC inhibitor vorinostat induced a robust enhancement in RAI uptake in thyroid cancer cells (TPC-1 and 8505C NIS+ve cells, up to 11-fold vs DMSO, P<0.001), which was significantly greater than using vorinostat alone (up to 3-fold, P<0.01). For clotrimazole, we designed 7 new chemical derivatives, 3 of which showed enhanced aqueous solubility and retained the ability to significantly enhance RAI uptake. TaqMan RT-PCR revealed that, in contrast to vorinostat, our repurposed drugs failed to alter NIS mRNA expression, highlighting post-transcriptional mechanisms. Critically, 11 repurposed drugs induced significant gains in RAI uptake in human primary thyroid cells (up to 4.1-fold; P<0.05), the most physiological setting for NIS function. In conclusion, we performed high-throughput screening and identified proteostasis modulators, as well as other repurposed drugs, that markedly enhance radioiodine uptake. Further clinical investigation of these drugs might offer new combinatorial approaches, especially with existing therapies, to improve the treatment of thyroid cancer.
SUN-LB112 Efficacy & Safety After Switchover to Remogliflozin in Indian T2DM Patients - a Real World Study
Authors: Bhattacharyya Supratik , Katare Sagar
Published: May 2020

INTRODUCTON: Remogliflozin is new SGLT2i recently approved in India, but more economical than the previously available SGLT2i. It is prudent to evaluate its effectiveness & tolerability in comparison to other SGLT2i in real world setting. METHODS: In this observational retrospective study, medical data from EMR of tertiary care hospital in Kolkata was retrieved. The records of adult Type 2 diabetes mellitus (T2DM) patients who were on a dual therapy of Metformin plus SGLT2i (Canagliflozin, Dapagliflozin or Empagliflozin) for at least 6 months with adequate glycaemic control (HbA1c to target based on age & duration of diabetes) & subsequently switched over to Remogliflozin 100 mg twice daily because of economic reasons were screened. The day of switchover was considered as index day (Day 1) The patient records whose data was unavailable, metformin dose was altered during period of next 6 months, who had evidence of active UTI on index day, were receiving injectable anti-diabetic drugs or had recorded eGFR <45 mL/min were excluded. The effectiveness was assessed in terms of maintenance of HbA1c, FBS, PPBS, body weight after 3 & 6 months of treatment. The safety was assessed by adverse events recorded in medical records in terms of abnormal symptoms, signs or laboratory reported values during the observation period of 6 months & compared to equivalent period of 6 months before index day. The data was collected & analysed using appropriate statistical techniques. RESULTS: After screening, medical records of 50 adult T2DM patients (54% male) were found to be eligible. The mean baseline characteristics on Index day in terms of Age, HbA1c levels, FBS, PPBS, weight & BMI was 51.3±12.5 years, 6.8±0.4%, 108.7±8.1 mg/dL, 144.5±21.3 mg/dL, 65.5±5.7 kg & 25.8±2.8 kg/m2 respectively. After treatment period of 6-months with Remogliflozin-based regimen, the mean HbA1c, FBS, PPBS, -Body weight & BMI was 6.7±0.8%, 110.3±10.5 mg/dL, 138.5±12.7 mg/dL, 66.3±6.5 kg & 25.9±3.2 kg/m2 Mean change from baseline in HbA1c levels, FBS, PPBS, weight & BMI were-0.1±0.19%, -1.6±7.2 mg, -6.0±8.3 mg, +0.8±0.2kg, & +0.1±0.0.7 kg/m2 respectively. These change from baseline of all above parameters were not found to be statistically significant (P>0.05) No events of hypoglycaemia, disturbance in electrolytes or any unusual adverse events were reported. Combined incidence of UTI & genital Mycotic infection was similar during 6 month observation period as compared to 6 months prior to index day. (8% vs 6%) CONCLUSION: In real world clinical practice, replacement of ongoing SGLT2i with Remogliflozin was observed to provide consistent glycaemic control without any tolerability issues. Hence, novel SGLT2i Remogliflozin can be considered as equivalent alternative for SGLT2i based regimen in management of Indian T2DM patients
SUN-LB66 Oral Risedronate Treatment in Children With Osteogenesis Imperfecta
Authors: Nguyen Antoine T , Pitukcheewanont Pisit , Ryabets-Lienhard Anna
Published: May 2020

Introduction: To date, there are no approved pharmaceutical therapies for children with OI. Intravenous bisphosphonates have been used for years to treat children with OI with variable efficacy and tolerability. However, a few studies have evaluated the effects and tolerability of oral risedronate in children with OI (1)(2). In this study, we aimed to present our experience with oral risedronate treatment in children with OI. Methods: A retrospective chart review of patients with OI and history of multiple fragility fractures, who were treated with oral risedronate and followed in our bone clinic between the years of 2013 and 2019. Primary outcomes included changes in fracture rate, urinary N-terminal telopeptide (uNTX), height z-scores, and lumbar and femur BMD z-scores. Safety and tolerability of risedronate were reviewed. Wilcoxon matched-pairs sign-ranks test was used to assess the medians (IQR) between pre- and post-treatment with p value of < 0.05 set as statistically significant.Results: A total of 17 patients ages 5—19 ys were reviewed (11 males, 65% type I OI, 12% type III, 18% type XI, and 5% unknown). At the time of the review, 69% were on weekly, 19% on daily, and 12% on monthly risedronate treatment. Mean duration of therapy was 2.7 y ± 2.3 y, ranging 0.5 to 8 ys. The bone resorption marker, uNTX, decreased > 30% from baseline in 93% of subjects within the first year of treatment, and was statistically lower by the end of treatment period [245 (159, 393) to 170 (39, 261), p=0.02]. Height z-score did not change with treatment, -0.80 (-1.20, 0.10) pre- and -0.85 (-1.60, -0.40) post-treatment, p = 0.2 in patients with Type I OI. There was a clinically significant reduction in the rate of fractures from baseline 0.6 per y (0.4, 0.8) to 0.24 (0, 0.5) by the end of the treatment period, though it did not reach statistical significance. Within a year of treatment, 80% of children were fracture free with improvement in bone pain and mobility. BMD pre- and on treatment for lumbar and femur were -2.5 (-3.43, -1.94) and -2.36 (-3.25, -1.35), and -2.05 (-2.95, 0.3) and -1.18 (-1.73, 2.13), respectively. However, there was no statistical significance. There was one case of reflux without erosive esophagitis, which resolved with reflux treatment. Overall, risedronate was well tolerated with no cases of clinically significant acute phase reaction, hypocalcemia, erosive esophagitis, or osteonecrosis of the jaw.Conclusion: Based on our experience, oral risedronate effectively decreased bone resorption, showed a trend towards decrease in fracture rate with improvement in symptoms, and was well tolerated in children with OI. More data are needed to systematically evaluate its long-term effects on growth, bone mineral density, fracture frequency, and quality of life in children with different types of OI. Reference: (1) Rauch et al., J Bone Miner Res. 2009; 24: 1282-1289 (2) Bishop et al., Lancet. 2013;382(9902):1424-32.
SUN-LB129 Thyroglobulin Stimulates the Secretion of Thyroxine From Thyroid Epithelial Cells in Suspension Culture via Nuclear Factor-κB Signaling Pathway
Authors: Tanaka Mei , Yamada Yukiko , Hayashi Moyuru , Emoto Naoya , Shimonaka Motoyuki
Published: May 2020

The nuclear factor (NF)-κB signaling pathway controls a variety of biological functions such as cell growth and differentiation as well as immune and inflammatory responses. Two distinct pathways of NF-κB activation are known. NF-κB signaling via non-canonical pathway plays an important role in maintaining normal thyroid function, namely, thyroid cells survival and expression of thyroid-specific proteins, such as NIS, TPO and thyroglobulin (Tg). The primary function of thyroid cells is the production of thyroid hormones, which are cleaved out by various processing enzymes from the modified tyrosine residues of the Tg molecule. Although Tg is currently recognized as no more than a scaffold protein for thyroid hormone synthesis, our group has shown that Tg stimulates the proliferation of rat thyroid follicular FRTL-5 cells via PI3K pathway. The signaling pathways underlying various functions of thyroid cells have been extensively investigated but some discrepancies still exist, depending on the experimental model systems and the types of cells used. Recently, our group discovered that Tg may directly regulate the synthesis of thyroid hormones in thyroid cells. In this study, we performed suspension culture of porcine thyroid cells and aimed to elucidate the mechanism of the effect of Tg on thyroid cells. Porcine thyroid epithelial cells were prepared from thyroid gland by enzymatic digestion and cultured in monolayer or in suspension culture. Various concentrations of Tg were added to the medium and cultured for several days. Then, the conditioned medium was collected and the amount of thyroid hormone was measured by reversed phase chromatography; the cells were harvested and mRNA levels of hormone-processing enzymes, cathepsin B, K, L and dipeptidyl peptidase I, II (DPP I, II), were measured by quantitative PCR. The amount and activation of cell signaling molecules were also evaluated by western blotting. Tg stimulated the secretion of thyroid hormone, thyroxine, from porcine thyroid cells in suspension culture, however, no stimulation by Tg was observed in monolayer culture. The expression of mRNAs of cathepsin B, K and L were reduced and that of DPP II was increased by the treatment of Tg in suspension culture. Tg increased the amount of NF-κB p52 and Rel B dose dependently. On the other hand, TSH had little effects on the amount of these proteins. Tg and TSH both activated PDK1 and MAPK p44/42 but not Akt. These results suggest that Tg regulates thyroid hormone synthesis in totally different way from TSH by altering the expression levels of hormone-processing enzymes in thyroid cells. This stimulatory effect might be mediated by NF-κB signaling pathway, whereas the proliferative effect of Tg under these conditions might be exerted via MAPK signaling pathway. The detailed mechanisms of these effects of Tg on thyroid cells are under investigation.
MON-LB47 An International Simulated Use Study (PRESTO) to Evaluate Nurse Preferences Between the Lanreotide Autogel New Syringe and Octreotide Long-Acting Release Syringe
Authors: Adelman Daphne T , Truong-Thanh Xuan-Mai , Feuilly Marion , Houchard Aude , Cella David
Published: May 2020

Background: A new lanreotide autogel/depot (LAN) syringe was developed based on feedback from a human factors study to improve user experience.

Methods: PRESTO was a multinational, simulated-use study in nurses with ≥2 years’ experience injecting LAN or octreotide long-acting release (OCT LAR) in patients with acromegaly and/or neuroendocrine tumors, which aimed to assess injector preference between the LAN new syringe and the current OCT LAR syringe. Participating nurses were invited to test both the LAN new syringe (120 mg) and the current OCT LAR syringe (20 mg or 30 mg), using injection pads. The sponsor was not involved in these sessions. In an anonymous web-based questionnaire, nurses reported overall preference (‘strong’ or ‘slight’; primary endpoint), and rated and ranked the importance of nine attributes for each syringe (1 [not at all] to 5 [very much]).

Results: In total, 90 nurses attended injection sessions and completed valid questionnaires. Overall, 97.8% of nurses expressed a preference (85.6% ‘strong’, 12.2% ‘slight’) for LAN new syringe (p<0.0001 vs current OCT LAR). Attribute performance ratings were consistently higher for LAN new syringe vs current OCT LAR, with the greatest differences in ‘fast administration’ and ‘confidence the syringe will not be clogged’ (mean [standard deviation]: 2.6 [1.2] and 2.3 [1.5], respectively; p<0.0001). The attribute ranked most important was ‘confidence the syringe will not be clogged’ (24.4%) and least important was ‘convenience of syringe format, including packaging, from preparation to injection’ (34.4%).

Conclusions: The PRESTO study showed that nurses preferred the user experience of the LAN new syringe over the current OCT LAR syringe across all attributes tested.
MON-LB016 Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An Institutional Review
Authors: Arora Shruthi , Chuang Janet
Published: May 2020

Tyrosine Kinase Inhibitor Induced Hypothyroidism in Pediatric and Young Adult Population: An institutional reviewBackground:Tyrosine kinase inhibitors (TKIs) are a class of molecular targeted therapies approved for the treatment of several hematological and solid tumors in pediatric population. Thyroid dysfunction, most commonly primary hypothyroidism, is a well described adverse effect in adults. There is no available data in the pediatric population regarding the risk of thyroid dysfunction with the use of TKIs.Objective:To document the incidence of hypothyroidism in the pediatric and young adult patients on TKI therapy.Methods:A retrospective chart review including patients’ ≤ 21 years of age who had been treated with at least 1 of 10 predetermined TKIs for malignancy was performed. Demographics, TKI use and duration, thyroid hormone labs, and history of head/neck radiation were collected. We excluded patients with pre-existing thyroid disease prior to start of TKI therapy. Thyroid dysfunction was defined as TSH >5mcIU/mL during TKI therapy. Results:A total of 152 patients who were treated with TKIs for malignancy were identified. The mean age was 12.4 years (SD 6.5). About 20% of patients had therapy with multiple TKI drugs. A total of 24 patients were noted to have TSH elevation >5mcIU/ml of which 19 had a TSH >10 mcIU/mL or low free T4. Fourteen patients were started on levothyroxine. Average duration of TKI therapy prior to development of thyroid dysfunction was 6.7 months but over half developed hypothyroidism within 3 months of initiation of TKI therapy. Cabozantinib and pazopanib were responsible for 70% of TKI associated cases of thyroid dysfunction.Conclusion:This is the first report of incidence of primary hypothyroidism in pediatric and young adult patients treated with TKIs. Thyroid dysfunction can develop in the first few months of therapy and often is clinically significant. Early recognition and treatment of this complication will be important for patient care especially as use of these class of drugs increase.
SAT-LB119 Diabetic Ketoacidosis With PUMP Failure: Analysis of the 2006-2016 U.S. Kid Inpatient Database
Authors: Everett Estelle , Copeland Timothy , Moin Tannaz , Wisk Lauren
Published: May 2020

Background: Insulin pumps are valuable tools in diabetes management and their use has increased dramatically over the past decade. Unfortunately, insulin pump use has also been associated with diabetic ketoacidosis (DKA), relating to pump malfunctions that result in the disruption in insulin administration. Our objective was to examine the prevalence and characteristics of DKA admissions associated with pump failure among pediatric patients. Methods: We used the national Kids’ Inpatient Database to identify pediatric admissions with a primary diagnosis of DKA in years 2006, 2009, 2012, and 2016. We defined a DKA-pump failure admission as an admission with either a primary diagnosis of DKA plus a secondary diagnosis of pump failure/complication or conversely, a primary diagnosis of pump failure/complication with a secondary diagnosis of DKA. We used descriptive statistics and logistic regression to describe the annual trends and characteristics of children admitted for DKA with or without pump failure. Lastly, logistic regression was used to assess the impact of pump failure on length of stay and severity of illness during DKA admissions. Results: Our dataset included 166,583 DKA admissions, of which 2,291 (1.4%) were associated with a primary or secondary diagnosis of insulin pump failure. Between 2006 and 2016, the number of total DKA admissions increased by 58%. Admissions for DKA with pump failure increased from 387 to 665 admissions during this time. Among all children admitted with DKA, those with pump failure were primarily older (60% above age 12), mostly white (63%), female (57%), from urban areas (78%), and almost 2/3rds had private insurance (60%). Adjusted analyses revealed that compared to DKA admissions without pump failure, pump failure was associated with older age, white race, residing in a rural area, private insurance, and higher income. Pump failure admissions were more likely in western and southern hospitals, otherwise there were no significant differences with respect to hospital characteristics. Compared to DKA admissions without pump failure, DKA admissions associated with pump failure had a longer mean length of stay (2.6 vs 1.5 days) and were more likely to have a higher severity of illness category. Conclusion: In this national sample, DKA with pump failure was more often observed among white, privately insured and high income children; these patient characteristics likely reflect the population of youth with diabetes who are more likely prescribed pumps in the US. Admissions for DKA concurrent with insulin pump failure accounted for a minority of pediatric DKA admissions but these admissions were associated with longer lengths of stay and severity of illness. Pump failure has important implications for care and management of children with diabetes.
MON-LB88 Positive Predictive Value of TP53 Variants in Bethesda III/IV Thyroid Fine-Needle Aspirates
Authors: Livhits Masha J , Hu Mimi I , Waguespack Steven G , Wirth Lori J , Ladenson Paul W , Stack Brendan C , Hao Yangyang , Babiarz Joshua E , Kennedy Giulia C , Kloos Richard T
Published: May 2020

Introduction: Somatic DNA variants in the tumor suppressor gene TP53 have been reported in papillary thyroid carcinoma (PTC), Hürthle cell carcinoma (HCC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid carcinoma. However, TP53 variants are uncommon among cytologically indeterminate thyroid nodules, so their positive predictive value (PPV) for malignancy, when identified, is unknown. The original Afirma Xpression Atlas reported genomic variants from the mRNA of 511 genes, including TP53. Here we report the PPV of TP53 alterations among Afirma Genomic Sequencing Classifier (GSC) Suspicious Bethesda III/IV nodules in real-world clinical practice.

Methods: A consecutive cohort of Afirma GSC Suspicious Bethesda III/IV nodules submitted to Veracyte for molecular analysis and positive for only TP53 alterations by the Xpression Atlas was identified. Local surgical pathology diagnoses were sought with IRB approval. One nodule per patient was included.

Results: Thirty-eight TP53 variants were present among >13,000 Bethesda III/IV Afirma GSC Suspicious samples. Among the 22 with only a TP53 alteration, the first 16 consecutive nodules were included (7 nodules were Bethesda III and 9 nodules were Bethesda IV). Local surgical pathology diagnoses were available for 11 of these nodules. Seven nodules (64%) were malignant on surgical pathology: 3 cases of HCC, 1 PDTC, 1 follicular thyroid carcinoma (FTC), 1 follicular variant PTC, and 1 classical PTC. The mean size of malignant nodules was 3.6 cm (range 1-7.7 cm). The remaining four nodules (36%) were benign on surgical pathology, with a mean size of 2.6 cm (range 1.5-4.2 cm). Benign cases included 2 follicular adenomas (FA), 1 Hürthle cell adenoma (HCA), and 1 adenomatoid nodule (AN). Seven different TP53 variants were identified, and only one was observed at least 3 times (TP53: p.R248Q in 2 cases of HCC and 1 adenomatoid nodule). Given the small numbers, meaningful estimates of the variants’ individual PPVs could not be calculated.

Conclusions: TP53 variants among Afirma GSC Suspicious Bethesda III/IV nodules are very rare and associated with malignancy in 64% of nodules based on local pathology review. A broad range of both benign and malignant neoplasms, including HCC, PDTC, FTC, PTC, FA, HCA, and AN, were reported among nodules with TP53 alterations. The prognostic value of finding an isolated TP53 variant in Afirma Suspicious nodules remains unknown.
MON-LB115 Ready-To-Use Glucagon for the Prevention of Exercise-Induced Hypoglycemia in a Clinical Research Setting
Authors: Aronson Ronnie , Riddell Michael , Close Nicole C , Junaidi Khaled
Published: May 2020

OBJECTIVE: A mini-dose of a novel ready-to-use liquid stable glucagon (RTUG; Xeris Pharmaceuticals) was evaluated for the prevention of exercise-induced hypoglycemia (EIH) during and after moderate-to-high intensity aerobic exercise, in both a clinical research center (CRC) and outpatient setting. The observations from the CRC setting are reported here.

METHOD: A Phase 2 randomized, placebo-controlled, double-blind, two-treatment, crossover study enrolled 48 adults with Type 1 diabetes (T1D) treated with continuous subcutaneous insulin infusion, to evaluate the efficacy of pre-exercise RTUG in addition to standard of care basal insulin rate reduction. The CRC setting included 2 separate daytime exercise sessions 2 to 28 days apart. At 5 minutes prior to each exercise session, subjects reduced their basal rate of insulin infusion by 50% and self-administered placebo or RTUG 150 micrograms (μg) before performing 45 minutes of moderate-to-high intensity, aerobic exercise with a target of 80% maximum heart rate. Blood glucose was measured before, during, and after exercise to evaluate the incidence and severity of hypoglycemia.

RESULT: Of the 45 subjects (93.8%) that completed both exercise sessions in the CRC, EIH occurred more in placebo (n=8) compared to RTUG (n=1). More subjects used glucose tablets to treat EIH in placebo (n=4) compared to RTUG (n=1). Placebo-treated participants consumed 7-fold greater glucose tablets during and after exercise, and experienced more episodes of post-exercise hyperglycemia (blood glucose >250 mg/dL), compared to RTUG. Treatment emergent adverse events with RTUG were comparable to placebo. RTUG 150 μg caused no edema, erythema, nor injection site reactions. RTUG was safe and well tolerated and no serious adverse events occurred.

CONCLUSION:RTUG 150 μg adequately maintained euglycemia during and following prolonged, continuous, moderate-to-high intense aerobic exercise in the controlled CRC setting. When used prior to moderate-to-high intensity aerobic exercise, RTUG may reduce exercise-induced hypoglycemia in adults with T1D. These findings support the continued evaluation in the outpatient setting.
SAT-LB2 Elevated Testosterone Secondary to Leydig Cell Hyperplasia in Bilateral Ovaries
Authors: Ali Sarah , Jaffee Ian , Kirkeby Kjersti Meyer
Published: May 2020

Background: Postmenopausal hyperandrogenism can be caused by androgen use, ovarian hyperthecosis, ovarian neoplasms, and adrenal neoplasms. Clinical case: A 64 year old post-menopausal woman presented for evaluation of hirsutism. She had developed generalized hair loss, terminal hairs on face and chest, and new onset acne after discontinuing hormone replacement therapy. During workup for hirsutism, she was found to have elevated testosterone at 119 ng/dL (reference range: 2-45 ng/dL). Other hormonal evaluation came back within normal limits, with DHEA sulfate <15 mcg/dL (reference range <186 mcg/dL), estradiol 25 pg/ml (reference range <12-32 pg/ml), FSH 34.9 mIU/ml (reference range 23-116.3 mIU/ml), and LH 30.1 mIU/ml (reference range 15.9-54 mIU/ml). Transvaginal ultrasound did not reveal any abnormal adnexal masses. CT abdomen showed a 1.0 cm nodule in the left adrenal gland consistent with a lipid rich adenoma. Further work up showed a normal 24 hour urine free cortisol at 25 ug/24h (reference range: 4-50 ug/24h), normal 24 hour urine metanephrines at 709 ug/24h (reference range: 224-832 uh/24h), normal aldosterone at 13 ng/dL (reference range <21 ng/dl) and renin at 0.37 ng/mL/h (reference range 0.25-5.82 ng/mL/h). MRI of the adrenal glands showed a slightly lobular left adrenal gland and no discrete adrenal mass. MRI of the pelvis showed mildly prominent ovaries bilaterally, but no adnexal or ovarian masses. After repeat laboratory testing showed consistently elevated testosterone levels up to 170 ng/dl and symptoms of hyperandrogenism persisted, the patient underwent bilateral salpingo-oophorectomy. Testosterone level post-operatively dropped to 18 ng/dl and remained within normal limits on repeated measurements. Her symptoms of hyperandrogenism resolved over the next several months. Surgical pathology showed endosalpingiosis, benign paratubal cysts, and confluent aggregates of Leydig cell hyperplasia in bilateral ovaries. Conclusion: Leydig cell hyperplasia is a rare cause of hypertestosteronemia that may be considered in patients with negative work up for alternative etiologies for post-menopausal hirsutism.
SUN-LB121 Nifedipine Worsens Glucose Tolerance in C57BL/6J Mice Exposed to Intermittent Hypoxia
Authors: Cardenas Stanley M Chen , Shimoda Larissa A , Punjabi Naresh M
Published: May 2020

Background: Intermittent hypoxemia (IH), a pathognomonic component of obstructive sleep apnea (OSA), has been independently associated with development of glucose intolerance, insulin resistance, and type 2 diabetes. L-type calcium channel blockers (CCB) influence glucose homeostasis including insulin sensitivity and secretion. To date, the potential impact of the combined effects of L-type CCB and IH on fasting glycemia and glucose tolerance have not been examined. The objective of this study was to determine whether CCB alters glucose metabolism in a murine model of IH. Methods: Adult male C57BL6/J mice (age 19-week-old) were exposed to IH using an automated system with specially-modified cages that oscillated FiO2from 21% to 5.5% at a target rate of 60 events/h during a 12 h (7am – 7pm) light cycle to simulate severe OSA for 5 days. The L-type CCB, nifedipine, or vehicle (polyethleneglycol-400) were administered at a dose of 20mg/kg/day via subcutaneous osmotic pumps (Alzet model 2001). Mice were exposed to IH or intermittent air (IA) with four resulting groups: IA-vehicle (n=12), IH-vehicle (n=16), IA–nifedipine (n=10), and IH–nifedipine (n=13). Fasting glucose, intraperitoneal glucose tolerance test, and insulin levels were obtained after exposures. Results: In the absence of a L-type CCB, IH increased fasting (105.1 vs. 71.2 mg/dL; p<0.001) and 2-hour glucose levels (104.8 vs. 82.0 mg/dL; p=0.003). The area under the glucose tolerance curve (AUC) was also higher with IH than IA in mice treated with vehicle (17896.3 vs.13965.8 mg-min/dL; p<0.001). Although the effects of IH on fasting glucose levels were comparable with and without L-type CCB treatment, the 2-hour glucose levels and the AUCs were substantially different. A statistically significant interaction was noted for the 2-hr glucose levels between IH and treatment with a L-type CCB (IH-CCB: 193.7; IH-V: 122.6; IA-CCB: 103.5; and IA-V: 82.0 mg/dL; p<0.05 for interaction between IH and CCB). Finally, the AUC for IH-CCB treated mice was significantly higher than the AUC for IH-V treated mice (IH-CCB: 30223.1; IH-V: 17896.3. mg-min/dL; p=0.0001) Conclusions: In a murine model of IH, treatment with an L-type CCB exacerbates the deleterious effects of IH on glucose tolerance. Thus, use of CCB in patients with OSA should take into consideration these unfavorable effects particularly in those who are metabolically compromised.
SUN-LB110 The Nutrition Education Using a Health Care Application With Artificial Intelligence in Patients With Diabetes Mellitus
Authors: Higashitani Takuya , Kometani Mitsuhiro , Oka Rie , Gondo Yuko , Nomura Akihiro , Yasugi Ayaka , Aono Daisuke , Karashima Shigehiro , Yoneda Takashi
Published: May 2020

Background: Diet control is the basis of the treatment of type 2 diabetes. However, the education and practice of diet control for the patients with type 2 diabetes mellitus (T2DM) need a lot of manpower and time. In 2009, we have developed a telemedicine model that nutritionists analyze photos of T2DM patients’ meal and supervise them remotely. Our system resulted in the improvement of glycemic control of T2DM patients. Recently, the image analysis technology using the artificial intelligence (AI) progresses rapidly. The smart device application “Asken” has an AI-powered photo analysis system which analyzes the photo of the entire meal and identifies the frame of each item as well as its menu and serving amount. In addition, this application delivers individualized dietary messages and feedbacks. Case reports: We report two T2DM cases who conducted nutrient intervention by this application. One case was a 72-year-old man whose HbA1c decreased from 7.2% to 6.6% and weighed from 58.7kg to 57.5kg in 4 months. However, his total cholesterol increased from 119mg/dl to 200mg/dl, and low-density lipoprotein cholesterol (LDL) also increased from 47mg/dl to 106mg/dl. Another case is a 60-year-old man whose HbA1c improved from 7.0% to 6.6% and his weight decreased from 78.0kg to 76.0kg in 3 months. Total cholesterol was 140mg/dl to 128mg/dl, and LDL-cholesterol was from 65mg/dl to 54mg/dl. Conclusion: Using this application might be useful for diet control of T2DM patients. The effects of AI-supported nutrient intervention using application like this should be further clarified in the large number of patients.
SAT-LB306 A Case of Synchronous Non-Functioning Paraganglioma of the Urinary Bladder and Prostate Cancer
Authors: Choi Moon Kyung , Mahmood Ejaz , Ginzburg Serge , Minimo Corrado , Blocher Nissa
Published: May 2020

Introduction

The bladder is an uncommon site for a paraganglioma, with only <1% of all paragangliomas occurring in the bladder. Management of non-functioning bladder paraganglioma is uncharted due to its rarity, and there is even less data for cases with synchronous malignancy. We found two case reports of synchronous paraganglioma and prostate cancer, only one in the bladder. Here we report a second case and discuss management.

Clinical Case

A 72-year-old man with high risk prostate cancer, Grade group 5 on biopsy, was found to have a 1.2 x 1.6 cm bladder wall mass on staging CT scan. The transmural mass was only partially resectable via transurethral approach. Pathology unexpectedly revealed paraganglioma, confirmed by immunohistochemical stains for Synaptophysin, Chromogranin, and CD56.

The patient had longstanding hypertension controlled on losartan and denied any symptoms of catecholamine excess. He had no family history of paraganglioma, pheochromocytoma, or related neoplastic syndrome. Plasma free metanephrine and normetanephrine levels were 57pg/mL (normal 57pg/mL) and 157pg/mL (normal 148pg/mL), respectively. Urinary studies were not performed due to stage 4 chronic kidney disease.

Staging CT scan and bone scan did not show any other lesions. Even in cases of known distant metastases of paraganglioma, surgical resection of all tissue is recommended if possible. Thus, he underwent radical prostatectomy, bilateral pelvic lymphadenectomy and partial cystectomy. Prostate cancer was downgraded to Grade group 2, pT3aN0Mo and complete excision of the paraganglioma was confirmed.

Evaluating for metastases and follow up are challenging in all paraganglioma cases, but especially non-functioning paragangliomas. Bladder paragangliomas carry a 10-15% risk of malignancy, but no separate data is reported for non-functioning ones. Histology scoring systems that are somewhat predictive in pheochromocytoma are less helpful in paragangliomas. Imaging is also challenging. CT, MRI, and a variety of functional imaging modalities have sensitivities for paraganglioma metastases in the range of 50 – 94% depending on location, functionality, and presence of germline mutation. For now, we recommend non-contrast CT with 18F-fluoro-2-deoxy-2-D-gluocse (FDG) PET. Though guidelines recommend annual biochemical surveillance, the usefulness in non-functioning paraganglioma is questionable.

Genetic testing is recommended for all patients with paraganglioma. Succinate dehydrogenase B (SDHB) is most important given the propensity for metastases. Thus, we recommended the SDHx germline mutation package.

Clinical Lesson

This case is the second reported synchronous bladder paraganglioma and prostate cancer. It highlights the challenge, lack of data, and need for advancement in our knowledge for the best management of incidental, non-functioning, extra-adrenal paragangliomas.
SAT-LB89 Choriocarcinoma Induced Hyperthyroidism: Molecular Mimicry Between HCG and TSH
Authors: Ankireddypalli Anvitha Reddy , Chandran Chandriya , Lamichhane Rabindra , Chirag Boradia , Nambi Sridhar Srinivasan
Published: May 2020

Introduction: Human chorionic gonadotropin(HCG) induced hyperthyroidism is a rare cause of hyperthyroidism. It is usually seen in conditions with extremely high beta HCG levels like hyperemesis gravidarum, hydatiform moles and germ cell tumors. We present a young male patient who had primary mediastinal choriocarcinoma with widespread lung metastasis and hyperthyroidism. Case: 18-year-old male presented to the emergency department for a fever of 105 F, cough, shortness of breath and night sweats for 9 days. He also reported unintentional weight loss for the past few weeks. Upon presentation, he was tachycardic at 104 beats/min, tachypneic and febrile. Physical examination revealed bibasilar crackles. Thyroid and scrotal examination were unremarkable. Laboratory work was significant for leukocytosis of 18.7 k/cmm, AST: 69 Unit/L, ALT: 60 Unit/L, ALP: 123 unit/L and LDH: 438Unit/L. Chest radiology showed bilateral multiple cannonball lesions with mediastinal and periaortic lymphadenopathy. CT chest, abdomen, and pelvis revealed innumerable diffuse bilateral lung masses, large anterior mediastinal mass, enlarged periaortic and paratracheal lymph nodes. Infectious workup was unremarkable. MRI brain revealed leptomeningeal involvement and vasogenic edema. Ultrasound of testicles revealed bilateral severe microlithiasis. CT guided biopsy of lung mass showed poorly differentiated choriocarcinoma. Treatment was initiated with systemic steroids, bleomycin, and cisplatin. Additional blood work revealed, B-HCG:736,598 mIU/mL, TSH:0.009UIU/ml, free T4:2.95ng/dL and total T3: 292.3ng/Dl. Thyroid radioiodine uptake scan was normal and planar imaging was also normal. Treatment with methimazole was deferred due to the up-trending transaminases and the resolution of tachycardia. Repeat labs after chemotherapy were TSH: 0.005UIU/mL, free T4: 2.04ng/dL, free T3:1.70pg/mL and BHCG: 202,471UIU/mL. Unfortunately, the patient had chemotherapy-resistant choriocarcinoma and succumbed to death after 4 cycles. Discussion: Beta HCG has an intrinsic thyroid-stimulating activity. The HCG -alpha subunit is common to all glycoprotein hormones like follicle-stimulating hormone, luteinizing hormone or thyroid-stimulating hormone. Frankly elevated levels should be treated symptomatically with beta-blockers and/or anti-thyroid drugs. Subclinical hyperthyroidism should be monitored closely. Some patients do not develop hyperthyroidism or a toxic goiter, as it is dependent on the timing of onset of cancer or due to the secondary modifications of HCG that can affect the bioactivity of HCG on the TSH receptor. This case draws our attention to the importance of focusing on the molecular mimicry of the HCG and TSH and management of HCG mediated hyperthyroidism.
MON-LB011 Retrospective Comparison of Cystic Fibrosis Related Diabetes Pediatric Screening Rates
Authors: Alkhatib Einas H , Kasim Nader
Published: May 2020

Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in those with CF, affecting 20% of adolescents and 40-50% of adults with CF. If uncontrolled, it can cause worsened pulmonary outcomes, increased hospital length of stay, and increased mortality. It is typically clinically silent, and hemoglobin A1C and fasting plasma glucose are not sensitive enough to diagnose it. Per national guidelines, the proper outpatient screening method is oral glucose tolerance test (OGTT), annually beginning age 10. Inpatient diagnosis involves fasting glucose >126 mg/dl or 2 hour postprandial glucose >200 persisting for more than 48 hours. It is believed that national screening guidelines are unfortunately not being met, particularly while inpatient. At our institution, there are 137 pediatric patients with CF; of those, 8 have a diagnosis of CFRD, and 4 have impaired glucose tolerance.

We aim to study the adherence of our institution to the best practice guidelines for CFRD screening in pediatric patients with Cystic Fibrosis.

Retrospective chart review is occurring through our institution’s EMR for inpatient data, and through a CF database (PortCF) for outpatient data. Inclusion criteria includes pediatric patients (below 1 day or above 17 years and 364 days) with CF. Exclusion criteria is those outside this age range, and those with CFRD. Consent is waived, as this is a retrospective data collection. Several variables including demographics, glycemic status, CFTR modulator and class, corticosteroid and vitamin use, and feeding regimen are also being reviewed. REDCap is being used for secure data entry and analysis. Descriptive statistical analysis will be used. Categorical data will be expressed as frequency (percent). Numeric data will be expressed as mean ± standard deviation or median [25th, 75th percentile], depending on normality of the data. Univariate analysis, like Chi square or Fisher’s exact test, will be used between successful and unsuccessful inpatient screens for CFRD.

Thus far, retrospective chart review of all outpatient data is complete. Preliminary analysis of those who should have received OGTT screening shows 11% have never been screened, and 32% were screened more than one year ago. Completion of inpatient data collection and all statistical analysis is anticipated within the next month. Future direction includes increasing inpatient CFRD screening with use of continuous glucose monitoring sensors during CF exacerbation admissions.
SAT-LB59 Functional MRI Study: Weight Loss Induced Changes in Taste Receipt-Induced Activation in the Striatum and Hypothalamus
Authors: Dunn Julia Passyn , Lamicchane Bidhan , Braver Todd , Hershey Tamara , Klein Samuel
Published: May 2020

Background: Reward behaviors including those related to eating are influenced by output from the ventral striatum (VS), dorsal striatal [caudate(Cau) and putamen(Put)]and hypothalamus (HTH). We hypothesized that weight loss would induce modifications in activation in these regions of interest (ROI) during a consummatory reward task. Methods: We recruited metabolic abnormal obese (MAO) from the VA St.Louis Health Care System and Washington University in St.Louis (WUSTL). MAO was screened for by fasting insulin and plasma glucose, 2 hour 75 gram OGTT, and hemoglobin A1c. MAO was defined as prediabetes by ADA criteria and/ or elevated HOMA-IR. Functional magnetic resonance imaging (fMRI) scanning sessions were completed at the WUSTL Center for Clinical Imaging Research. A rapid event-related design was used to randomly deliver taste of chocolate milk (choc) or tasteless water (wat). Each taste receipt was proceeded by a cue of corresponding image of chocolate milk or a glass of water. A total of 5 runs, each with 24 trials were completed. Imaging analyses included preprocessing with fMRIprep including censoring excessive motion ≥ 0.5mm. Single subject GLM analyses were completed in AFNI. ROIs were designated bilaterally (lt and rt) except for HTH. A canonical HRF was applied to the food cue event and the AFNI tent function over 9 TRs was applied to the taste receipt event. To evaluate for an effect of weight loss (WL) on food cue and taste receipt-induced activation, repeated measures ANOVA for each region was completed with condition (choc or wat) as a covariate. Also in the model for taste receipt, repetition time (TR) was included as a covariate. Results reported as F(sign.). Results: Ten participants achieved at least 7% WL, (range 7-15%), 44±8 years, BMI 38±4kg/m2, f/m 4/6, fasting pg 105±11, 2 hour OGTT pg 132 ±49 mg/dL, HOMA-IR 3.9±1.8. One participant fulfilled criteria for T2D. For taste receipt several significant effects were found for WL: Cau_lt WL 5.9(0.02) and WL*TR 4.9(0.03), Cau_rt WL 8.6(0.004) and WL*TR 8(0.005), Put_lt WL 8.5(0.004), HTH WL*condition 5.4(0.02) and a trend for WL 3.3(0.07). All other comparisons were non-significant including all in the VS and all for food cue. Conclusions: Moderate weight loss in MAO modified taste receipt-induced activation in the Cau, Put, and HTH but not in the VS.