bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB22 PLK1 as a New Treatment Target for Adrenocortical Carcinoma
Authors: Smith Gabrielle , Liang Raimunde , Chortis Vasileios , Khan Sana , Lippert Juliane , Hantel Constanze , Altieri Barbara , Fassnacht Martin , Foster Paul Alexander , Ronchi Cristina Lucia 
Published: May 2020

Abstract
Background: Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited medical treatment options. We previously identified polo-like kinase 1 (PLK1) as one of most overexpressed genes in ACC; thus PLK1 represents a potential treatment target for this cancer type. Some PLK1 inhibitors are under evaluation in clinical trials for other solid organ malignancies, and seem to be more effective in TP53 mutated tumours. The aim of this study was to evaluate PLK1 protein levels in a large series of ACC and assess the in vitroefficacy of PLK1 inhibitors in two different ACC cell lines. Methods: 104 formalin-fixed paraffin-embedded ACC tissue samples with available genetic data were investigated. Nuclear PLK1 protein expression was evaluated by immunohistochemistry and a semi-quantitative H-score was calculated. PLK1 expression levels were correlated to clinical and histological parameters. Efficacy of PLK1-specific inhibitor Volasertib (0-200 nM) was tested in the standard NCI-H295R ACCcell line, which presents PLK-1 overexpression and a large TP53 deletion, and in the newly established MUC1 cell line, which bears a frameshift mutation in TP53. Cell proliferation was analysed using DNA fluorescence and cell apoptosis by Caspase Glo 3/7 assay. Results: Nuclear PLK1 expression was classified as high in 59% of ACC samples, with a significant difference noted between TP53-mutated (n=24) and wild-type (n=80) cases (87.5 vs 51%, p&lt;0.01). PLK1 levels did not correlate with either progression-free or overall survival. H295R cells showed a significant time- and dose-dependent reduction of cell proliferation compared to vehicle control after 72h of Volasertib treatment (p&lt;0.005 per trend, p=0.01 by 200nM by non-parametric two-way ANOVA). A less pronounced and non-significant trend towards inhibited proliferation was observed in MUC1 cells. Cell apoptosis was significantly higher in the H295R cells treated with 175nM and 200nM Volasertib when compared to control (p&lt;0.05), while there was no significant difference in MUC1 cells. Conclusion:In this pilot study, we propose PLK1 inhibitors as promising candidates for treatment of a subset of ACC patients that may be pre-selected according to the tumour molecular pattern. We plan to extend functional experiments to further PLK1 inhibitors, including additional ACC cell lines with a different molecular profile.
MON-LB83 The Initial Dose of 131I as a Potential Independent Predictor for Residual/Relapsed Disease in Pediatric Differentiated Thyroid Cancer
Authors: Bustamante Escobar Carmen L , Bao Yong 
Published: May 2020

Abstract
Introduction: In the guidelines for management of pediatric Differentiated Thyroid Cancer (DTC) 131I therapy is recommended for treatment of iodine-avid persistent locoregional disease that cannot be resected as well as iodine-avid distant metastases. To date, no consensus has been reached regarding the 131I dose for treatment of DTC in children. We report our institutional experience and highlight the initial dose of 131I as a potential independent predictor of residual/relapsed disease.
Methods: We performed a retrospective analysis of all pediatric patients diagnosed with DTC between 2010 and 2018. The cohort included all patients up to 21 years of age, with minimal length of follow-up of 24 months. The risk stratiﬁcation was done following the American Thyroid Association guidelines for pediatric DTC. We defined residual/relapsed disease as detectable thyroglobulin and positive anatomical lesions in imaging studies during the follow-up period. The log-rank test was used to evaluate disease-free survival. The P value was set at &lt; 0.05.
Results: Among 59 eligible patients, females were 69.5% (n=41) and males were 30.5% (n=18). The mean age at diagnosis was 16 years (9-21 years). All patients were alive at follow-up (median, 42 months; range 24 to 144 months). Fifty-eight patients had classic papillary thyroid cancer (PTC) and only 1 patient had follicular thyroid cancer. Among the patient with PTC, 39.6% (23/58) had follicular-variant PTC, 8.6% (5/52) had diffuse-sclerosing PTC and 17.2% (10/58) had other variants. Nineteen (32%), 30 (51%), and 10 (17%) had low-risk, intermediate-risk, and high-risk disease, respectively.
Within the Low-risk group, 68% (13/19) received 131I. The mean initial dose was 60.9 mCi [26-150 mCi]. Eighty four percent (11/13) received ≤100 mCi and 27% (3/11) had residual/relapsed disease. Fifteen percent (2/13) received &gt;100 mCi and none had residual/relapsed disease. Sixteen percent (1/6) of patients without 131I therapy had residual/relapsed disease. (P=0.48)
Within the Intermediate-risk group, all 30 patients received 131I. The mean initial dose was 97.5 mCi [27.3-215 mCi]. Sixty percent (18/30) received ≤100 mCi and 38.8% (7/18) had residual/relapsed disease. Forty percent (12/30) received &gt;100 mCi and 16.6 % (2/12) had residual/relapsed disease. (P=0.15)
Within the High-risk group all 10 patients received 131I. The mean initial dose was 159.9 mCi [129.3-384 mCi]. Fifty percent (5/10) received ≤150 mCi and 60% (3/5) had residual/relapsed disease. Fifty percent (5/5) received &gt;150 mCi and 20% (1/5) had residual/relapsed disease. (P=0.2)
Conclusion: There are no statistical differences of disease-free rate between the initial dose of 131I among all risk categories. However, the use of more than 100 mCi in the intermediate-risk category and more than 150 mCi in the high-risk category may be recommended.
SAT-LB121 Development of a Machine-Learning Method for Predicting New Onset of Diabetes Mellitus: A Retrospective Analysis of 509,153 Annual Specific Health Checkup Records
Authors: Nomura Akihiro , Yamamoto Sho , Hayakawa Yuta , Taniguchi Kouki , Higashitani Takuya , Aono Daisuke , Kometani Mitsuhiro , Yoneda Takashi 
Published: May 2020

Abstract
Diabetes mellitus (DM) is a chronic disorder, characterized by impaired glucose metabolism. It is linked to increased risks of several diseases such as atrial fibrillation, cancer, and cardiovascular diseases. Therefore, DM prevention is essential. However, the traditional regression-based DM-onset prediction methods are incapable of investigating future DM for generally healthy individuals without DM. Employing gradient-boosting decision trees, we developed a machine learning-based prediction model to identify the DM signatures, prior to the onset of DM. We employed the nationwide annual specific health checkup records, collected during the years 2008 to 2018, from Kanazawa city, Ishikawa, Japan. The data included the physical examinations, blood and urine tests, and participant questionnaires. Individuals without DM (at baseline), who underwent more than two annual health checkups during the said period, were included. The new cases of DM onset were recorded when the participants were diagnosed with DM in the annual check-ups. The dataset was divided into three subsets in a 6:2:2 ratio to constitute the training, tuning (internal validation), and testing datasets. Employing the testing dataset, the ability of our trained prediction model to calculate the area under the curve (AUC), precision, recall, F1 score, and overall accuracy was evaluated. Using a 1,000-iteration bootstrap method, every performance test resulted in a two-sided 95% confidence interval (CI). We included 509,153 annual health checkup records of 139,225 participants. Among them, 65,505 participants without DM were included, which constituted36,303 participants in the training dataset and 13,101 participants in each of the tuning and testing datasets. We identified a total of 4,696 new DM-onset patients (7.2%) in the study period. Our trained model predicted the future incidence of DM with the AUC, precision, recall, F1 score, and overall accuracy of 0.71 (0.69-0.72 with 95% CI), 75.3% (71.6-78.8), 42.2% (39.3-45.2), 54.1% (51.2-56.7), and 94.9% (94.5-95.2), respectively. In conclusion, the machine learning-based prediction model satisfactorily identified the DM onset prior to the actual incidence.
SAT-474 Amiodarone-Induced Thyrotoxicosis After Weight Loss Following Sleeve Gastrectomy
Authors: Osafehinti Deborah , Rakhlin Luba , Park Patricia , Resta Christine A 
Published: May 2020

Abstract
AMIODARONE-INDUCED THYROTOXICOSIS AFTER WEIGHT LOSS FOLLOWING SLEEVE GASTRECTOMY
INTRODUCTION:
Bariatric surgeries have shown major health benefits improvement in co-morbidities such as HTN and DM. We are less familiar with how these surgeries affect the pharmacokinetics of drugs.1,2
CLINICAL CASE:
Our patient is a 65-year-old man with a fib/v tach and no prior thyroid history. He was on amiodarone 200 mg daily since September 2016. He had sleeve gastrectomy in March 2019 at weight 380 lbs. By June 2019, weight was 278 lbs.
In June 2019, he had palpitations, diarrhea, and heat intolerance for one month. Labs showed: TSH &lt;0.01 (0.4 – 4.5 MCIU/L), FT4 6.5 (0.8 – 1.8 NG/DL), and TT3 309 (76 – 181 NG/DL). Other labs: TPO antibodies &lt;1 IU/mL (&lt;9 IU/mL) TSI &lt;89 (&lt;140% baseline). Thyroid sonogram was heterogeneous without nodule
He started Methimazole (MMI) 20mg BID and Prednisone 40mg daily. In the next seven weeks, symptoms and TFTs improved. FT4 was 3.1 NG/DL, TT3 was 85 NG/DL, but TSH remained &lt;0.01 MCIU/L. Because of the rapid improvement, he was felt to have type 2 AIT (destructive thyroiditis). MMI was quickly tapered. Prednisone was tapered to 30mg daily.
At week 8, he was hospitalized for septic shock from diverticulitis and perianal abscess. He also had leukopenia attributed to MMI and sepsis. MMI was stopped. Amiodarone was stopped by cardiology. TFTs during hospitalization improved on only steroids: TSH was 0.01 MCIU/ML, FT4 was 2.34 NG/DL, and TT3 was 0.56 NG/ML. He was discharged on Prednisone 30mg daily with plans to taper off steroids.
CONCLUSION:
Our patient is the second reported case of AIT after bariatric surgery-induced weight loss. Amiodarone is a highly lipophilic drug that accumulates in adipose tissue. Rapid weight loss may result in the release of large amounts of amiodarone into the circulation with resultant thyrotoxicosis. As clinicians, we should be aware that patients who undergo bariatric surgery are at risk for complications that are not only directly related to the operation but also related to rapid weight loss that affects how the body handles drugs.
REFERENCES
1.
Bourron O, Ciangura C, Bouillot J-L, Massias L, Poitou C, Oppert J-M. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass. Obes Surg. 2007;17(11):1525–1528. http://www.ncbi.nlm.nih.gov/pubmed/18219784. Accessed September 21, 2019.
2.
Geraldo M de SP, Fonseca FLA, Gouveia MR de FV, Feder D. The use of drugs in patients who have undergone bariatric surgery. Int J Gen Med. 2014;7:219–224. doi:10.2147/IJGM.S55332
SUN-LB87 De-Novo Graves Ophthalmopathy After Total Thyroidectomy With Exacerbation Following Rifampicin Therapy for Latent Tuberculosis: A Call for Attention to Disease Modifying Interventions
Authors: Shaklai Sigal , Marcus-Perlman Yonit , Klein Ainat , Stern Naftali , Greenman Yona 
Published: May 2020

Abstract
Introduction Factors influencing development and course of ophthalmopathy, the most common extrathyroidal manifestation of Graves’ disease, remain poorly defined. Clinical Case A 46 year old healthy, non-smoking, medical secretary, presented with Graves’ disease. Laboratory investigation showed thyrotoxicosis with high thyroid stimulation immunoglobulin (TSI) levels (1608 %, normal &lt;140%). At presentation there was no evidence of thyroid eye disease on clinical exam and orbital MRI. Treatment with Methimazol and PTU induced severe pruritus and she underwent total thyroidectomy. One month after surgery she presented with retroorbital pain, eyelid edema and chemosis, as well as bilateral limitation in abduction; a clinical activity score (CAS) of 3/7. She received IV pulse methylprednisolone 4.5 gr with minor improvement. MRI showed bilateral thickening of all rectus muscles with orbital fat infiltration. TSI increased concomitantly to 3600%. Three months later, she underwent standard retrobulbar radiotherapy (20 Gy), again with only minor improvement. She continued treatment with oral prednisone 20mg with small fluctuations in disease activity in the following months during which TSI remained high (3145%) and latent tuberculosis was detected (elevated interferon-gamma release assay). Therefore, rifampicin 600mg/d was started. A month later the ophthalmopathy worsened (a CAS score of 5/7 without optic neuropathy). Laboratory tests showed new perturbation in thyroid function tests (TSH increased from 5 to 15 mIU/l, normal: 0.5-5; FT4 decreased from 16 to 11 pmol/l, normal: 10-20) and TSI increased to 3879%. Euthyrox dose was increased by 50% from 800 to 1200 microgram/week. It was postulated that prednisone was also being rapidly metabolized by rifampicin mediated induction of the CYP450, and therefore the dose was increased from 20 to 40 mg/d. Six weeks later, normalization of thyroid function tests was followed by improvement in the ophthalmopathy (CAS-3). Conclusion (Clinical lesson) A) De-novo severe Graves’ ophthalmopathy after thyroidectomy requiring multiple forms of treatment is rare but close surveillance is advisable, perhaps particularly in the presence of high TSI. A plausible mechanism may be transient increase in antigenic exposure/dissemination during surgery. B) Rifampicin, through induction of cytochrome P450-mediated metabolism of levothyroxine, steroids and mycophenolate (the latter not used in our patient) can lead to disease flare-up. Tight clinical and laboratory monitoring of thyroid function tests with individualized dose escalation might be needed. In the future, pharmacogenomics may serve to personalize treatment protocols.
SUN-LB114 Remission of Type 2 Diabetes (DMT2) in Hypogonadal Men Under Long-Term Testosterone Therapy
Authors: Mskhalaya George , Tishova Yuliya , Skiba Olga , Mskhalaia Maria , Kalinchenko Svetlana 
Published: May 2020

Abstract
Objective: The increasing prevalence of DMT2 and obesity represents a growing clinical and health-care cost problem. These two pathologies simultaneously increase the risk of hypertension, myocardial infarction, stroke or venous thromboembolism. An existing but undetected testosterone deficiency will substantially hamper weight loss or render it impossible. In such cases, returning the testosterone level to normal range is therefore the necessary pre-condition to fight obesity and thus the related comorbidities. Materials and methods: 35 obese (waist circumference (WC) &gt; 94 cm) men aged 48 [33;57] with diagnosed DMT2 (IDF 2019 criteria), hypogonadism (ISSAM 2015 criteria) and vitamin D deficiency (Endocrine Society Guidelines 2014 criteria) were treated with testosterone undecanoate (1000 mg 4 mL injected i.m. every three months following an initial 6-week interval), cholecalciferol 5. 000-10.000 IU per day. 29 patients received 1000-2000 mg per day, 1 patient received liraglutide 1,8 mg a day + metformin 1500 mg a day, 1 patient received Sitagliptin 100 mg and metformin 1000 mg a day. 4 patients did not use anti-diabetic treatment ever. The duration of follow up was 36 months. Waist circumference (WC, cm), glucose (mmol/L), HbA1c (%), total testosterone (nmol/L) and vitamin D (25(OH)D3, ng/mL) were assessed at baseline and after 36 months of follow up. Statistical research was made using a software package statistics (StatSoft Inc. U.S., version 6.0). Quantitative data are presented as medians and quartile range. When comparing the quantitative data of two groups Wilcoxon test was used. Values were considered statistically significant if p &lt;0.05. Results: All patients had no DMT2 diagnostic criteria after 24 months of treatment. WC changed from 107 [102;116] to 94 [88.5;97.5], HbA1c from 7,2 [6.9;7,7] to 5,7 [5.25;5.8], TT from 7.37 [6.2;9.18] to 24.65 [22.3;25.9], 25(OH)D3 from 20.2 [11.7;26.2] to 72 [65;88] at baseline and after 24 months of follow up, respectively. All changes were statistically significant. Anti-diabetic therapy was cancelled in all patients after 20,5 [15;24] months of follow up. All patients remained under further follow up for the period up to 36 months, no cases of DMT2 recurrence were registered.Conclusion: We conclude that correction of testosterone and vitamin D deficiency may work as a necessary stimulus for consequential facilitation of weight reduction and associated recovery, particularly in terms of a complete remission of diabetes. Long term data is needed.
SAT-LB111 Improving Classification of Diabetes Etiology in Electronic Resources Using Phenotype Algorithms and Polygenic Risk Scores
Authors: Sulieman Lina , He Jing , Carroll Robert , Bastarache Lisa , Ramirez Andrea 
Published: May 2020

Abstract
Electronic Health Records (EHR) contain rich data to identify and study diabetes. Many phenotype algorithms have been developed to identify research subjects with type 2 diabetes (T2D), but very few accurately identify type 1 diabetes (T1D) cases or more rare forms of monogenic and atypical metabolic presentations. Polygenetic risk scores (PRS) quantify risk of a disease using common genomic variants well for both T1D and T2D. In this study, we apply validated phenotyping algorithms to EHRs linked to a genomic biobank to understand the independent contribution of PRS to classification of diabetes etiology and generate additional novel markers to distinguish subtypes of diabetes in EHR data. Using a de-identified mirror of medical center’s electronic health record, we applied published algorithms for T1D and T2D to identify cases, and used natural language processing and chart review strategies to identify cases of maturity onset diabetes of the young (MODY) and other more rare presentations. This novel approach included additional data types such as medication sequencing, ratio and temporality of insulin and non-insulin agents, clinical genetic testing, and ratios of diagnostic codes. Chart review was performed to validate etiology. To calculate PRS, we used genome wide genotyping from our BioBank, the de-identified biobank linking EHR to genomic data using coefficients of 65 published T1D SNPS and 76,996 T2D SNPS using PLINK in Caucasian subjects. In the dataset, we identified 82,238 cases of T2D but only 130 cases of T1D using the most cited published algorithms. Adding novel structured elements and natural language processing identified an additional 138 cases of T1D and distinguished 354 cases as MODY. Among over 90,000 subjects with genotyping data available, we included 72,624 Caucasian subjects since PRS coefficients were generated in Caucasian cohorts. Among those subjects, 248, 6,488, and 21 subjects were identified as T1D, T2D, and MODY subjects respectively in our final PRS cohort. The T1D PRS did significantly discriminate well between cases and controls (Mann-Whitney p-value is 3.4 e-17). The PRS for T2D did not significantly discriminate between cases and controls using published algorithms. The atypical case count was too low to calculate PRS discrimination. Calculation of the PRS score was limited by quality inclusion of variants available, and discrimination may improve in larger data sets. Additionally, blinded physician case review is ongoing to validate the novel classification scheme and provide a gold standard for machine learning approaches that can be applied in validation sets.
SAT-LB83 Amiodarone Induced Myxedema Coma
Authors: Kim Keun Young , Syed Sabah 
Published: May 2020

Abstract
Introduction Amiodarone is widely used as a rhythm-conversion agent in atrial fibrillation. It’s low negative inotropic activity and low risk of ventricular arrhythmia makes it an advantageous agent for atrial arrhythmia. One of the major limiting factors in the use of amiodarone can be its thyroid toxicity leading to thyroid-dysfunction; ranging from thyrotoxicosis to myxedema coma. Myxedema coma, although rare, is a deadly complication of hypothyroidism with a mortality rate as high as 60%. It is considered an endocrinologic emergency that requires prompt attention and treatment. We present a case of myxedema coma in the setting of chronic amiodarone intake.
Case Presentation A 75-year-old female with a past medical history significant for atrial fibrillation, hypothyroidism, end stage renal disease from diabetic nephropathy on hemodialysis, Hepatitis C, hypertension, and hyperlipidemia was admitted to the hospital for evaluation of generalized weakness. Her medications included amiodarone 200mg/day among others. The next day, the rapid response team was called when the patient became hypotensive, bradycardic and unresponsive. She was transferred to the ICU and intubated immediately. On exam, her skin was dry and cold. Her laboratory findings revealed a markedly elevated TSH level of 185uIU/mL. Her most recent TSH level was 9.044uIU/mL from a year back. Other laboratory tests revealed WBC count of 9.0k/mm cu, hemoglobin 13.7 g/dL, platelet count 48 k/mm cu. A diagnosis of myxedema coma was made based on her presentation and lab findings. The patient was started on intravenous levothyroxine 100mg daily with intravenous hydrocortisone 100mg every 8 hours. T4 levels were 0.38ng/dL, T3 levels were 1.83pg/mL and TPO antibodies were negative. A decision was made not to administer intravenous T3 because of the patient’s advanced age and underlying atrial fibrillation. Over the course of the hospitalization, the patient was showing signs of clinical improvement and attempts were being made to wean her off the ventilator. However, later she died due to hemorrhagic shock.
Conclusion Myxedema coma may manifest nonspecifically as lethargy and altered mental status and can present without the more specific symptoms of skin changes or myxedematous soft tissue changes. It is therefore, very important for physicians to consider myxedema coma as one of the differential diagnoses in patients on amiodarone with underlying thyroid disease. Administering amiodarone for elderly patients with underlying thyroid problems warrants attention to polypharmacy. The treatment guidelines for myxedema coma are yet to be established. While intravenous levothyroxine with intravenous hydrocortisone remains the mainstay of therapy, there are no consensus on T3 administration.