bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-484 Thyroid Nodules: Not so Simple to Manage
Authors: Cruz Alegyari Figueroa , Torres Yineli Ortiz , Carlo Chévere Victor J , Garcia-Mateo Jose M 
Published: May 2020

Abstract
Thyroid Nodules: Not So Simple to Manage
Thyroid nodules diagnosis and malignancy risk stratification remains a challenge for decision making between conservative vs invasive management. The development of the clinical guidelines provides alternatives for evaluation and management for thyroid nodules, but can be used for all patients?
A 43 y/o female without known past medical history is referred to the endocrine service by her primary care physician for evaluation of a thyroid nodule. She was presenting with 1 month history of mild discomfort on the neck and was evaluated with thyroid US that was relevant for multiple bilateral solid nodules measuring &lt;1.0cm and a one spongiform measuring 1.7 x 1.2 x 1.3cm in the right lobe extending minimally to the capsule laterally and to the carotid artery wall. Patient denies cough, hoarseness, odynophagia, shortness of breath, family history of thyroid cancer or radiation exposure. On examination there were no goiter nor palpable thyroid nodules, as well as no clinical signs and symptoms of thyroid disease. Patient is clinically and biochemically euthyroid with a very low suspicion thyroid nodule (3% estimated malignancy risk). Despite nodule is below the 2.0cm cutoff point for fine needle aspiration biopsy (FNAB) according to American Association of Clinical Endocrinologist (AACE) and American Thyroid Association (ATA) guidelines, it was done based on additional suspicious sonographic features detect by the endocrinologist on evaluation of ultrasound images. FNAB was performed and reveals Atypia of undetermined significance/Follicular Lesion of undetermined significance (AUS/FLUS) Bethesda system category III with a risk of malignancy of 5–15%. Patient was reluctant to surgery given the very low risk nodule and biopsy results of AUS/FLUS. In order to further manage this patient with undetermined significance thyroid nodule, Gene Expression Classifier (GEC) Molecular Analysis (AFIRMA) was performed. AFIRMA test was done with a second FNAB that also reveals AUS/FLUS but was found positive for BRAFv600, Bethesda system category IV: Suspicious of Papillary Thyroid Carcinoma. BRAFv600 is the only mutation that have high specificity (99%) for papillary thyroid carcinoma and is associated with increased disease-specific mortality, aggressive histologic phenotypes, lymph node metastases, extrathyroidal extension and risk of recurrence. Based on this data patient now have 95% risk of malignancy and requires surgical therapy. Patient preferred total thyroidectomy over lobectomy; pathology results shows 2.0cm Papillary Thyroid Carcinoma Stage I (T1N0M0).
Despite very low risk nodule finding, malignancy was diagnosed. As depicted in this case, thyroid nodules aren’t so simple to manage, and their management should involve imaging and pathology findings along with clinical judgement and patient individualization in decision making process.
SAT-421 Novel Role of Chloroquine and Hydroxychloroquine in Graves’ Orbitopathy Therapy by Targeting Orbital Fibroblasts
Authors: Guo Yan , Li Hai , Chen Xueying , Guan Hongyu , He Xiaoying , Chen Yuxin , Xiao Haipeng , Li Yanbing 
Published: May 2020

Abstract
Abstract: Context: Graves’ orbitopathy (GO) presents with infiltrative exophthalmos due to excessive proliferation, adipogenesis and glycosaminoglycans production of orbital fibroblasts (OFs). There are few therapies potent for proptosis. Intervention in autophagy of OFs could be a potential therapy. Objectives: Here, our purpose was to evaluate the effects of chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), as autophagy inhibitors commonly used in clinical practice, on GO-OFs from human orbit in vitro. Design/Setting/Participants: OFs isolated from patients with GO (n = 10) or control persons (non-GO) (n = 8) were allowed to proliferate in the proliferation medium (PM) or differentiate into adipocytes in the differentiation medium (DM), co-treated with CQ of different concentrations, and subsequently examined in vitro. Main Outcome Measures: CCK-8, EdU incorporation and flow cytometry were used to assess cellular viability. Adipogenesis was assessed by Western blot, real time-PCR, and Oil Red O staining. Hyaluronan was determined by real time-PCR and ELISA. Autophagy flux was detected using RFP-GFP-LC3 fluorescent staining and Western blot. Results: CQ (10μM) or HCQ (10μM) treatment for 48h was sufficient to block autophagy flux without exhibiting cell toxicity in OFs from either GO or non-GO participants. Cellular proliferation of GO-OFs was halted by both CQ and HCQ. Also CQ and HCQ exerted an inhibitory action on lipid accumulation of GO-OFs during differentiation as well as expression of adipogenetic markers such as PPARγ and c/EBP-α/β. Moreover, hyaluronan secretion, concurrent with expression of hyaluronan synthase 2 (HAS2), was obviously decreased by CQ and HCQ. Conclusions: We reported the efficacies of CQ and HCQ on proliferation, adipogenesis and hyaluronan generation of GO-OFs via inhibiting autophagy, providing proof of concept that quinoline-based antimalarial (QBA) drugs like CQ and HCQ have potential to be a new treatment for GO as autophagy inhibitors.
SAT-118 Rapid Decompensation from Complications of Severe Hypercortisolism in an Unusual Presentation of an Ectopic ACTH-Secreting Neuroendocrine Tumor
Authors: Sumal Amit Kartar Singh , Liao Charles , Chen Julie 
Published: May 2020

Abstract
Background: Ectopic Cushing’s syndrome from an ACTH-secreting neuroendocrine tumor (NET) is a rare condition whose onset and disease progression is often more aggressive than other forms of Cushing’s syndrome due to complications from severe hypercortisolism.
Clinical Case: A 75-year old woman presented with profound proximal muscle weakness, severe hypokalemia, Cushingoid features, and biopsy-proven Candida esophagitis. Initial testing was consistent with ACTH-dependent Cushing syndrome: elevated 24 hour urinary cortisol excretion (1,310.54 mcg/24h; n &lt;50 mcg/24h), abnormal 1 mg dexamethasone suppression test (68.3 ug/dL), and elevated ACTH level (200 pg/mL; n: 7.2–63.3 pg/mL). MRI was negative for a pituitary lesion but abdominal CT revealed an 8.8 cm liver mass with biopsy consistent with a well-differentiated neuroendocrine tumor, WHO Grade 2. Subsequent 68Ga-DOTATATE-PET/CT noted DOTATATE uptake in the liver lesion, a 0.9 cm right pulmonary nodule, and the pancreatic tail without CT correlate. Initially, the patient was prescribed mifepristone and spironolactone for hypokalemia. Given her NET of unknown primary, metastatic disease, and immunocompromised state due to hypercortisolism, the patient was not a candidate for surgical resection of her NET but was instead referred for bilateral adrenalectomy. However, she rapidly decompensated from complications of her hypercortisolism prior to surgery. Her weakness progressed to immobility, and she developed acute psychosis manifested as agitation and mutism. The patient was immediately admitted to the hospital where she developed new-onset atrial flutter and myelosuppression requiring multiple transfusions. She underwent urgent bilateral adrenalectomy, but despite surgery, her post-operative course was complicated by hypoxemic respiratory failure and shock. The patient shortly thereafter expired from pulseless electrical activity arrest.
Conclusion: This atypical case of an ectopic ACTH-secreting NET highlights the life-threatening complications associated with severe hypercortisolism, including: opportunistic infection, severe metabolic abnormalities, psychosis, myopathy, and critical illness that can incite myelosuppression and unstable arrhythmias. These patients can quickly deteriorate and are at high risk for mortality. Early diagnosis and swift reversal of their hypercortisolism with bilateral adrenalectomy are oftentimes needed to prevent these potentially fatal complications.
SAT-153 PTHrP Mediated Hypercalcemia
Authors: Arguello Mingxue 
Published: May 2020

Abstract
PTHrp mediated hypercalcemia
Introduction:
PTHrp is a normal gene product, which helps tooth eruption and mammary gland development. However, PTHrp production in an adult is mostly related to solid tumor malignancy. The homology of PTHrp to PTH from the 1st to 13th amino acids decided the similar mechanism of acting at PTH-1 receptor on increasing bone resorption and calcium reabsorption at the distal renal tubule. Lung cancer is known to secrete PTHrp and PTHrp secreting hepatic cellular carcinoma (HCC) is exceedingly rare. It’s only been documented in case reports. Two cases of PTHrp secreting atypical HCC are included in this case report.
Case presentation:
67 year old with history of alcohol abuse with 17.8 x 8.8 cm mass in the left hepatic lobe presented with acute encephalopathy and calcium of 14.4 mg/dl. Patient was treated with zolendronic acid 4mg, IV fluid and calcitonin. Patient has a PTH level of 7 pg/ml and PTHrp level of 335 pg/ml. Bone turnover marker Beta crosslaps of 1595 pg/ml. 25-hydroxy vitD of 25 ng/ml and 1,25 dihydroxy vitD of 42 pg/ml. Liver biopsy demonstrated moderately differentiated hepatocellular carcinoma. The undifferentiated portion was positive with CD56, CAM 5.2 suggestive of neuroendocrine differentiation and epithelial lineage. Patient had negative metastatic bone scan and no pathologic fractures. Second case is a 63 year old male with NASH cirrhosis was admitted for hypercalcemia of 13.2 mg/dl. Patient was found to have metastatic atypical hepatocellular carcinoma and L4 vertebral lesion. PTHrp was 30 pg/ml and PTH 14 pg/ml. Bone turnover marker Beta crosslaps of 405 pg/ml. 25-hydroxy vitD of 48 ng/ml and 1,25 dihydroxy vitD of 9 pg/ml. Patient expired prior to biopsy.
Discussion:
4 cases of similar HCC were found in the literature. The treatment approach was resection of tumor, chemo or ablation. Hypercalcemia is controlled with reduction of the tumor burden and rarely by zolendronic acid alone. Both of presented cases were too advanced for surgery or chemo treatment. When tumor was not amendable for treatment, the hypercalcemia was not controllable long term. A small size study in japan administering 10mg alendronate via hepatic artery rather than IV route for patients with HCC showed enhancement of the apoptosis of HCC in addition to controlling hypercalcemia. An animal study on anti-PTHrp monoclonal murine antibody showed improved mortality of PTHrp producing pancreatic carcinoma (FA-6) in transplanted nude mice.
Conclusion:
Most of the patients with PTHrp mediated hypercalcemia have advance cancer that is not amendable for surgery or chemotherapy. A non-invasive treatment approach other than alendronate should be investigated to control PTHrp mediated hypercalcemia.
MON-611 Using Machine Learning on Electronic Health Records to Predict Inpatient Glucose Levels and Physicians’ Insulin Dosing
Authors: Jankovic Ivana , Liu Xiran , Chen Jonathan H 
Published: May 2020

Abstract
The current optimal inpatient diabetes management schema involves administration of basal, prandial, and correctional insulin to maintain blood glucose (BG) within a target range. Nonetheless, practical management often fails to reach the ideal in both insulin dosing regimens and patients’ BG outcomes. Given the challenges of achieving adequate BG control for hospitalized patients using guidelines and expert knowledge alone, we attempted to use machine learning methods to predict (1) individual BGs, (2) average daily BGs, and (3) physician-ordered insulin doses based on data in an electronic health record-based repository between January 2014 and December 2018. We considered inpatients on subcutaneous insulin having a BG ≥ 200 mg/dL or ≤ 70 mg/dL or with an A1c percentage ≥ 6.5%. We excluded those missing critical data (such as weight), with fewer than five BG checks in 72 hours, or those on hemodialysis, resulting in a cohort of 3,461 patients with 175,934 BG checks among them. In this cohort, the average age was 61.4 years, the average A1c was 7.1%, and the average BG was 171.6 mg/dL, with approximately 25% of BGs ≥ 200 mg/dL and 1.7% of BGs &lt; 70 mg/dL. Using linear regression, we identified features that contributed most to prediction of each of the outcomes. For all three outcomes, the average glucose in the past 24 hours was the most important feature. For prediction of glucose levels, previous BG, BG at the same time the previous day, A1c, BG variance, recent long-acting insulin dose, and glucocorticoid dose were all in the top 10 features. Similar features were important for predicting physician-ordered insulin doses. Surprisingly, neither weight nor creatinine were identified as top features for any outcome. Using these features in our predictive model, we found that individual BGs were highly erratic and could not be predicted precisely (R2 0.24). Similarly, and perhaps unsurprisingly, how physicians would order insulin for patients was also difficult to predict (R2 0.25). However, average daily glucose levels were predicted more reliably (R2 0.36), as was prediction of frank hyperglycemia (BG ≥ 200 mg/dL) in the next day (sensitivity 0.73, specificity 0.79). Given the typical practice pattern of a clinician evaluating the previous day’s insulin regimen performance and adjusting it by anticipating BGs for the next day, prediction of hyperglycemia in the next 24 hours can support decision-making for inpatient BG management.
SAT-313 Synaptojanin 2 Binding Protein Is Required for Efficient Somatostatin Receptor 2A Phosphorylation by G Protein Coupled Receptor Kinases and Signaling to the ERK/MAPK Pathway
Authors: Carr Heather S , Frost Jeffrey A 
Published: May 2020

Abstract
Somatostatin receptor 2A (Sst2A) agonists are the primary pharmacological treatment for growth hormone (GH) secreting pituitary tumors to inhibit GH secretion and limit the destructive effects of these tumors. Sst2A agonists are also widely used as imaging agents for neuroendocrine tumors, and are under investigation for treatment of these cancers. However, despite the clinical importance of Sst2A agonists, regulatory mechanisms controlling Sst2A internalization and signaling are not fully understood. Sst2A contains a C-terminal PDZ binding site that serves as a docking platform for PDZ domain containing proteins. In an unbiased screen for PDZ domain proteins that can interact with Sst2A, we identified Synaptojanin 2 binding protein (SYNJ2BP) / Outer mitochondrial protein 25 (OMP25). SYNJ2BP is an outer mitochondrial protein that has been shown previously to promote the internalization of the Activin Type II receptor. We find that SYNJ2BP interacts with Sst2A in a ligand-dependent manner. Importantly, we show that SYNJ2BP promotes interaction of Sst2A with the G protein couple receptor kinase 2 (GRK2), and that siRNA-mediated knockdown of SYNJ2BP dramatically inhibits Sst2A phosphorylation by endogenous GRKs. Moreover, overexpression of SYNJ2BP strongly potentiates Sst2A phosphorylation on the GRK phosphorylation sites. Modulation of SYNJ2BP expression also regulates somatostatin-stimulated β-arrestin recruitment to the plasma membrane. Interestingly, in contrast to the large effects on Sst2A phosphorylation and β-arrestin recruitment, modulation of SYNJ2BP expression only caused a small change in ligand-stimulated receptor internalization. When we assessed downstream signaling, we found that SYNJ2BP overexpression potently stimulated receptor-dependent activation of ERK1/2, but had little effect on the ability of Sst2A to repress forskolin-stimulated cAMP production. Taken together, these data demonstrate for the first time that interaction of Sst2A with a PDZ domain protein affects receptor regulation and signaling. Because multiple PDZ domain containing proteins have been shown to interact with Sst2A, these data also suggest that interaction of Sst2A with this class of proteins may be an important regulatory mechanism to bias its function within the cell.
SAT-180 Adrenocortical Carcinoma - A Tertiary Center’s Recent 5-Year Experience
Authors: Ehrenwald Michal , Tordjman Karen Michele , Stern Naftali , Klausner Joseph , Nachmany Ido , Lahat Guy , Lubezky Nir , Goykhman Yaakov , Wolf Ido , Geva Ravit , Aizic Asaf , Barnes Sophie , Greenman Yona , Osher Esther 
Published: May 2020

Abstract
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with poor prognosis. The aim of this study was to characterize patients diagnosed with ACC at a single center between 2014-2019.
METHODS: We retrospectively reviewed data regarding demographics, tumor characteristics and functionality, treatment and survival.
RESULTS: The study cohort included 27 subjects (56% females), followed for 27±10.6 months. The mean age at diagnosis was 49.4±9 years. Co-morbidities at presentation included hypertension (63%), diabetes mellitus (22%) and dyslipidemia (26%). 74.1% of tumors were functioning – of which 85% were cortisol-secreting and 15% androgen-secreting. Aldosterone was secreted additionally in 15%. ENSAT stage at diagnosis was stage 1 in 15%, stage 2 in 35%, stage 3 in 12% and stage 4 in 38%. Eighty-nine % of patients underwent surgery. Treatment with mitotane was initiated in 82% of patients, reaching a mean maximal dose of 3.3 ±0.4 grams/day. Chemotherapy and/or radiation were given in 37% and 22%, respectively. Several patients (14.8%) had a second primary cancer, diagnosed before ACC in 75%. Progression was observed in 48% of patients, with a progression-free survival of 8.3±6.6 months. Thirty-five % of patients died during follow up, time to death was 12.8±0.4 months. Twenty two % of patients survived over 30 months after diagnosis. KI67 above 20% or stage above 2 negatively affected survival.
CONCLUSIONS: ACC remains a rare disease with a poor prognosis. However, it is a heterogeneous disease, with some patients achieving survival of over 30 months after diagnosis. Further characterization of this population may improve our understanding of the biology and treatment of this rare disease.
OR23-03 Post-Operative Day One Morning Cortisol Value as a Biomarker to Predict the Recurrence of Cushing Disease
Authors: Wang Fang , Catalino Michael , Bi W Linda , Dunn Ian , Smith Timothy , Guo Yunlei , Kaiser Ursula B , Laws Edward Raymond , Min Le 
Published: May 2020

Abstract
Tumor removal by transsphenoidal surgery (TSS) is the first line treatment for Cushing disease (CD). However, recurrence is relatively common. A one week post-operative (post-op) nadir cortisol has been used as a biomarker to predict recurrence1. We identified 299 CD patients from our longitudinal multidisciplinary clinic or our institutional RPDR search tool who met biochemical diagnostic criteria1 and had undergone TSS between May 2008 and May 2018, to evaluate post-op cortisol levels as biomarkers to predict long-term remission and to characterize clinical features of Cushing syndrome. Predictors of recurrence were identified with logistic regression, using recurrence as the dependent variable, and a Kaplan-Meier survival curve analysis was performed to compare long-term remission after TSS among the 202 patients who reached initial remission and had at least 1 year of follow-up. The post-op day 1 morning (AM) cortisol had significant association with CD recurrence (OR=1.025, 95%CI:1.002-1.048, p=0.032). The time to recurrence was significantly longer in patients with post-op day 1 AM cortisol &lt;5 μg/dL. In contrast, one week post-op nadir cortisol (OR=1.081, 95%CI: 0.989-1.181, p=0.086), urinary free cortisol (OR=1.032,95%CI: 0.994-1.07, p=0.098), or late night salivary cortisol (OR=1.383, 95%CI:0.841-2.274, p=0.201) had no significant correlation with recurrence. There were no significant differences in time to recurrence for post-op day 2 AM cortisol &lt;5 μg/dL. Among patients who developed post-op adrenal insufficiency, recurrence was significantly lower if glucocorticoid replacement continued for more than one year. In addition, tumor proliferative index (MIB-1) had a significant correlation with recurrence (OR=1.287, 95%CI:1.106-1.498, p=0.001). The most common symptoms and signs of initial presentation of CD were weight gain (91.6%), central obesity (79.6%), menstrual disorders (77.9%), round face (65.9%), hypertension (63.2%), mood disorders (60.2%), dorsocervical fat deposition (59.9%), supraclavicular fat deposition (59.9%), osteoporosis (58.9%), fatigue (58.2%), bruising (55.9%) and facial hirsutism (54.2%). Most of the best discriminating CD features did not have high sensitivity, such as purple striae (31.4%), facial plethora (33.4%) and proximal muscle weakness (30.8%). Our data show that post-op day one morning cortisol level above 5 μg/dL had significant association with recurrence. In contrast, the one week post-op nadir cortisol level had no significant value to predict recurrence. Our data also suggest that nonspecific symptoms and signs of CD are more common than stereotypical signs. Reference: Nieman LK, et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:2807-2831
SUN-201 Adrenal Insufficiency After Treatment for Vaping Associated Pulmonary Injury
Authors: Pierce Melinda , Griffiths Anne 
Published: May 2020

Abstract
Background: In 2019 a record number of patients were admitted to our children’s hospital with e-cigarette or vaping-associated lung injury (EVALI). The majority of patients were treated with high-dose prednisone therapy including 3 days of 1000 mg daily followed by a 4 week wean. Because of the concern for iatrogenic adrenal insufficiency, all patients were then placed on a 3-4 weak hydrocortisone taper followed by ACTH stimulation testing. The purpose of this study is to document the incidence of iatrogenic adrenal insufficiency following a 2 months glucocorticoid wean. Methods: All patients seen by the Pulmonary team for EVALI who also received high dose prednisone therapy were referred to Pediatric Endocrinology for ACTH testing. A low dose (1 mcg) ACTH stimulation test was performed with cortisol measurements at baseline, 30 minutes, and 60 minutes. A passing result was any cortisol over 18 ug/dl. Results: An anticipated 20-25 patients will have had ACTH stimulation testing by the time of abstract presentation. Of those that have already completed testing, three of four patients failed the first time. Discussion: High-dose prednisone therapy for EVALI is associated with significant rates of iatrogenic adrenal insufficiency, even after slow hydrocortisone wean. Structures need to be implemented to teach patients about adrenal insufficiency prior to hospital discharge and organize adequate post-discharge follow-up until HPA function returns.