bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-475 New Breast Cancer Therapy Atezolizumab, Leads to Thyroiditis
Authors: Parimi Joseph Theressa Nehu , Patel Richa 
Published: May 2020

Abstract
Background: A NSABP B 59 trial is currently underway to check the efficacy of an experimental drug, Atezolizumab (Anti-PDL 1 monoclonal antibody) in the treatment of triple negative breast cancer. In the trail, the drug is added to the usual neoadjuvant chemotherapy given before surgery and prolonged treatment with it is continued after surgery to reduce the recurrence. Listed adverse effects are immune medicated hyperthyroidism in 2% of population.
Clinical Case:
32 y old Asian woman was diagnosed with triple negative left breast cancer in May 2018. She was started on paclitaxel, carboplatin and study medication Atezolizumab/Placebo in June 2018 and she received 4 cycles of the same and then it was stopped in August 2018. She was started back on the same in September 2018 which ended in November 2018. Patient tested positive for BRCA1 gene mutation and underwent bilateral mastectomy in December 2018. The study medication was restarted in January 2019.
Patient is received a total of 11 doses of study medication and was due to receive 16 doses if she had finished the trial in June 2019. Patient received radiation therapy starting in January 2019 till February 2019.
On her oncology visit in April 2019 patient was found to have a suppressed TSH of 0.009 with a high free thyroxine of 1.72 and an elevated free T3 of 5.4. She was referred to endocrinology for evaluation of thyroid abnormalities, as the study medication can cause thyroid problems. She denied symptoms of hyperthyroidism. TPO, TSI and anti-thyroglobulin antibodies were negative. Thyroid uptake scan showed uniformly decreased tracer distribution in both thyroid lobes consistent with thyroiditis.
As per the protocol for the study medication as well as recommendations by the American Society of oncology, we waited for normalization of the thyroid function test before resuming the study medication. In July 2019, TSH normalized to 2.99 and free T4 0.97.
She was noted to have low random cortisol level of 3.27 at 1000AM. ACTH stimulation test was performed and she responded appropriately.
Hence could not take the remainder of the study medication that were scheduled until June 2019. She is on observation phase since June 2019 and currently doing well.
SUN-590 27-Hydroxycholesterol Triggers the Whitening of Brown Adipose Tissue
Authors: Asghari Arvand , Bui Linh , Stephen Robert , Umetani Michihisa 
Published: May 2020

Abstract
27-Hydroxycholesterol (27HC) is the most abundant oxysterol in circulation and metabolized by a P450 enzyme CYP7B1. Its levels closely correspond to those of cholesterol in the body. In addition, previously it was found that 27HC is an endogenous selective estrogen receptor modulator (SERM), which links cholesterol metabolism to estrogen receptor actions (1). Brown adipose tissue (BAT) is the primary source of energy expenditure and energy homeostasis, as well as body temperature maintenance. While previously it was believed that BAT activity is limited to neonates and young children, it is now recognized that BAT is also active in adult humans and its function is impaired by metabolic diseases such as obesity. BAT is also a secretory organ and produces brown adipokines, although the exact function of BAT and adipokines from this tissue in obesity has not been completely understood. Recently, it was reported that 27HC plays an important role in obesity and augments body weight gain in response to a high fat, high cholesterol (HFHC) diet by increasing pre-adipocyte population in the white adipose tissue. 27HC mimics the effects by HFHC diet-feeding on white adipose tissue, such as promoting the inflammation and macrophage infiltration (2). In this study, we explored the effect of 27HC on BAT morphology and function. First, we compared the morphology of BAT from wild-type mice and Cyp7b1-/- mice that have elevated levels of 27HC using H&E staining. Interestingly, brown adipocytes from Cyp7b1-/- mice were larger in cell size than those from wild-type mice, and the cells were mostly unilocular compared to the multilocular cells from wild-type mice, indicating the transition toward a “whitening” phenotype. Next, We treated mice fed a normal chow or a HFHC diet with 27HC or vehicle control for 8 weeks to examine the direct effect by 27HC on BAT. Similar to the phenotype in Cyp7b1-/-mice, 27HC increased the “whitening” of BAT regardless of the diet. We also determined the gene expression of brown adipocyte markers such as UCP1, PGC1a, and DIO2, and found that 27HC significantly decreased the expression of the BAT markers regardless of the diet, confirming the “whitening” observed in the morphology. Moreover, the energy expenditure in mice treated with 27HC was decreased compared to the vehicle control on a HFHC diet, suggesting that 27HC also alters BAT function. These results show that 27HC causes the whitening of BAT, and shed light on the important role of 27HC in brown adipose tissue function. Future experiments will be warranted toward further understanding of the role of 27HC in BAT function. Reference:(1) Umetani, Michihisa, et al. Nature medicine 13.10 (2007): 1185. (2) Asghari, Arvand, et al. Endocrinology 160.10 (2019): 2485-2494.
SUN-746 Thyroid Hormone Receptor Alpha Sumoylation Is Important for the Development of Adipose Tissue
Authors: Abe Kiyomi , Gastelum Gilberto , Li Chengju , Rubinos Harmie , Yamada Alexandr , Liu Yan-Yun , Brent Gregory A 
Published: May 2020

Abstract
Thyroid hormone (TH) plays an essential role in normal development. TH action requires binding to its receptor. There are two types of thyroid hormone receptor, alpha (THRA) and beta (THRB). THRB is important for regulation of the Hypothalamic-Pituitary-Thyroid axis and regulating cholesterol metabolism. THRA is involved in the development and the function of brain, adipose tissue, small intestine, bone and heart. Both THRA and THRB are post-translationally modified by small ubiquitin-like modifier (SUMO). Previously, we showed in an in vitro model that mutation of a THRA sumoylation motif impairs proliferation and differentiation of human primary white adipocytes. This is due to interference of the desumolyated THRA in the cell cycle at G1/S phase and disruption of PPAR signaling. To determine the in vivo effects of a desumoylated THRA, we generated a mouse model carrying a mutation of the THRA gene, which eliminates SUMO conjugation at lysine (K) 283. At 12 weeks of age, there was no difference in body composition (body weight, fat mass, and lean mass) in THRA mutant mice compared to wild-type (WT). From 12 weeks onward mutant mice and WT did not have significant change body weight compared to Wt mice. However, THRA sumoylation mutant mice had much lower percent body fat. Dissected WAT fat pads from mutant mice were significantly smaller compared to WT mice. Histological analysis showed that the cell size of white adipose tissue in mutant mice was significantly smaller than that in Wt mice as well. Serum leptin levels in the mutant mice were significantly lower than that in mice, consistent with reduced fat mass. We isolated fat stem cells from stromal vesicular fraction of 6 week old mice and found that the number of fat stem cells was significant less in mutant mice compared to those in WT mice. This data suggest that de-sumoylated THRA is associated with reduced fat stem cells at a young age, resulting in reduced adipose tissue mass in adult. THRA sumoylation is important for thyroid hormone modulation of fat mass.
Reference: (1) Yan-Yun Liu et al, JBC 2012 (2) Yan-Yun Liu et al., JBC 2015
SAT-617 Potential Utility of the Mixed Meal Test for Differential Diagnosis of Partial Lipodystrophy from Common Type 2 Diabetes and Truncal Obesity
Authors: Guraya Armaan , de Freitas Maria Cristina Foss , Akinci Baris , Eldin Abdelwahab Jalal , Oral Elif A 
Published: May 2020

Abstract
Background: Better clinical tools are needed to improve the differential diagnosis of partial lipodystrophy (PL) from type 2 diabetes (DM) with truncal obesity. Here, we investigated differences in metabolic parameters during a mixed meal test in PL and DM patients to determine if this test may have a role in this regard. Methods: We retrospectively evaluated data collected from 17 PL patients (4M/13F, ages 12-64) and 20 DM patients (13F/7M, ages 24-72) with truncal obesity, who also had nonalcoholic fatty liver disease. All patients underwent a Mixed Meal Test (MMT) with 474 ml of Optifast (320 kcal, 50% carbs, 15% fat, and 35% protein). Blood was collected before and at 30, 60, 90, 120, and 180 minutes post-meal to measure glucose, insulin, free fatty acids (FFA), triglycerides, inflammatory markers, GIP, GLP-1, PYY, and Ghrelin. All samples of the same cohort were run at the same time in duplicates and results were averaged. Mixed linear models were constructed to compare PL and DM cohorts taking into account within-subject effects. Data were controlled for BMI, sex and age, and glucose when necessary. Results: Patients with PL had higher glucose and triglyceride levels throughout the MMT at all-time points (p &lt; 0.05). While the glucose levels showed an increase and subsequent decrease, the triglyceride levels remained flat throughout the test in both groups. Free fatty acid levels were suppressed compared to baseline during the test, but PL patients had significantly higher FFA from time 30 to time 180 (p &lt; 0.05) and tended to suppress less. While controlling for the differences in glucose levels, GIP levels displayed a large peak at time 30 min in both groups but were significantly higher over the course of the test in the PL group (AUC: 32542, pg/mL x min (20528-57728) vs. 3343 pg/mL x min (1728-4498), p &lt; 0.05). In contrast, GLP-1 levels (also peaking at time 30 min in both groups), were significantly lower in PL throughout the test (AUC: 3017 pg/mL x min (2309-6051) vs. 28387 pg/mL x min (20422-36045), p &lt; 0.05). Ghrelin and PPY levels did not differ significantly between the two groups. Interpretation/Conclusion: PL patients displayed more profound hyperglycemia and impaired suppression of FFAs. Interestingly, PL patients did not show substantial increases in triglyceride levels during MMT. There was a striking difference in the incretin responses between the two populations despite controlling for glucose, suggesting that MMT may have a role in differential diagnosis PL. Also, altered incretin response should be investigated as a contributor to metabolic perturbations and pathophysiology of PL.
SAT-587 Molecular Markers of Beige Adipose Following ESR1 Knockdown in the Mediobasal Hypothalamus of Adult Female Rhesus Monkeys
Authors: Bandaru Sindhura , Flowers Matthew T , Perlin Sona , Willging Molly M , Greinwald Emily P , Levine Jon E , Abbott David Howard 
Published: May 2020

Abstract
Our studies in female marmoset monkeys show that the ablation of ovarian estradiol (E2) production fails to alter energy homeostasis or body fat accumulation. Peripheral E2 may therefore not play a crucial role in metabolic regulation in female primates. shRNA-mediated knockdown of ESR1 expression in the hypothalamic ventromedial nucleus (VMN) in adult female rodents, however, induces obesity and suggests ESR1 is a hypothalamic target for E2 regulation of energy homeostasis, and likely mediates thermogenesis in brown/beige adipose depots. In female primates, including humans, the hypothalamic estrogen receptor mediating metabolic regulation is unknown. To test the hypothesis that ESR1 mediates female primate regulation of energy homeostasis, 11 ovary intact, adult female rhesus macaques, pair housed with female peers, received five 12µl MRI-guided MBH infusions into the rostral-to-caudal extent of both right and left VMN. Each infusion comprised a gadolinium contrast agent and ~3–4 x 1010 adeno-associated virus 8 (AAV8) particles containing either an shRNA specific for ESR1 (n=6, ERaKD) or scrambled shRNA (n=5, control). Mid-surgery MRI scans identified targeting accuracy. ~ 1.5 yrs following AAV8 infusion, pronounced gain in BMI enabled conversion of 83% of ERaKD females to overweight/obese compared to 20% of controls (p=0.08). Percent increase in BMI remained intermittently greater (p&lt;0.05) than controls thereafter. Adipose depots were harvested at necropsy ~2.5–3 yrs following treatment. Total RNA was isolated using the Qiagen AllPrep DNA/RNA/miRNA Universal kit. RNA was reverse transcribed with High-Capacity cDNA Reverse Transcription kit (Applied Biosystems). All quantitative real-time PCR (qRT-PCR) were performed on a StepOnePlus System using Power SYBR Green master mix (Applied Biosystems). Primer sequences were designed using NCBI Primer-Blast. Expression of TATA-box binding protein (TBP) was used as the internal control housekeeping gene. The relative expression of target genes was measured using the comparative cycle threshold (Ct) method with results expressed as target mRNA expression relative to TBP using the formula 2^-delta Ct. Upper body beige adipose represents an organ system in primates, including humans, involved in thermogenesis. Axillary beige adipose depots in ERaKD females, however, did not exhibit significantly diminished gene expression for selected markers of beige adipocytes, including PAT2, CD137 and C/EBPβ, compared to control females. More crucially, thermogenically relevant UCP1 expression also did not differ between ERaKD females and controls. Taken together, these results suggest that knockdown of VMN ESR1 in adult female monkeys, while inducing modest weight gain after 1.5 years, may not markedly alter beige adipose gene expression of initially selected thermogenically relevant genes.
MON-293 The Prevalence of Impulse Control Disorders in Patients with Acromegaly and Prolactinomas Treated with Dopamine Agonists
Authors: Ozkaya Hande Mefkure , Sahin Serdar , Korkmaz Ozge Polat , Durcan Emre , Sahin Humeyra Rekali , Poyraz Burc Cagri , Kadioglu Pinar 
Published: May 2020

Abstract
Objective: There is emerging evidence linking dopamine agonist (DA) use with the development of impulse control disorders (ICD) in patients with prolactinomas. On the other hand, no data exist whether DA use in acromegaly is associated with ICD. We aimed to evaluate the prevalence of ICD, psychiatric symptoms in patients with prolactinoma and acromegaly receiving DA in comparison to those with nonfunctioning pituitary adenomas (NFA) and healthy controls (HC).
Material and Method: Forty patients with prolactinoma, 40 patients with acromegaly, 38 patients with NFA and 32 HC were included in this study. All patients and controls included in the study were evaluated with revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Symptom Check List (SCL-90-R) questionnaire, Barratt Impulsiveness Scale (BIS-11), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). All of the patients with prolactinoma and acromegaly had been receiving cabergoline therapy but patients with NFA had not been receiving cabergoline therapy at the time of the study.
Results: We detected DA associated with ICD in 3 patients (7.5%) with prolactinoma, and 2 patients with acromegaly (5%). All patients’ symptoms resolved after either discontinuation of the drug or surgical intervention. There was no significant difference between patients with acromegaly and prolactinoma in terms of ICD prevalence. On the other hand, ICD was not detected in non functional adenoma and HC. There was no correlation between BIS-11 scores and total dose, mean monthly dose and duration of DA.
According to SCL-90-R, obsession and interpersonal sensitivity positivity was significantly higher in patients with prolactinoma than acromegaly (p: 0.040, p:0.010, respectively). There was no significant difference between the groups in terms of BAI, BDI and BIS-11’s subscales and total scores (p&gt; 0.005). Scl-90 somatization and depression positivity was significantly higher in patients with NFA than acromegaly (p: 0.043, p: 0.024 respectively). Likewise, scl-90 depression, interpersonal sensitivity and additional items subscale positivity was significantly higher in patients with NFA than HC (p: 0.005, p: 0.045, p: 0.045 respectively).
Conclusion: Although DA dose was significantly higher in patients with acromegaly compared to patients with prolactinoma, there was no significant difference in the prevalence of DA -related ICD. We have showed that there was no association between BIS-11 scores and total DA dose, mean monthly DA dose and duration of DA treatment. The higher prevalence of depression, interpersonal sensitivity in patients with NFA in comparison to HC supports the hypothesis the presence of a pituitary adenoma per se might cause a large psychiatric symptom burden.
SUN-041 Hispanic Medical Student’s Knowledge and Attitudes Towards Transgender Patient’s Care
Authors: Muns Sofía , Ortiz-Ramos Kevin J , González-Rodríguez Loida , Romaguera Josefina 
Published: May 2020

Abstract
Transgenders are characterized by having a gender identity and/or expression that is different from their sex at birth. There are guidelines about the proper management of this population. However, health disparities are still present. The lack of education and training about transgender care in the medical curriculum is one of the most significant contributors to these disparities. The aim of this study is to explore the knowledge and attitudes towards transgender care among Hispanic medical students at the University of Puerto Rico (UPR). Medical students (MS) from the UPR were invited to participate in an online anonymous questionnaire to assess their attitudes and knowledge about the healthcare of transgender patients. Data was analyzed as percentages and as means using Likert scale. Responses from pre-clinical and clinical MS were compared. A total of 141 participants were recruited. The majority of MS (80%) claimed to be exposed to transgender patients at least once. A total of 74% of MS reported feeling comfortable taking care of transgender patients. The overall Likert scale score for perceived knowledge about transgender topics among pre-clinical and clinical MS were 2.91 and 2.68, respectively. The scores for how comfortable students felt about working with transgender patients were 3.99 and 4.13 for both pre-clinical and clinical MS, respectively. Sixty percent of MS reported not being familiar with hormonal regimens used for gender reassignment therapy. Significantly more pre-clinical MS thought that discussing sexual behavior with transgender patients was more challenging than discussing it with heterosexual patients when compared to clinical MS (2.90 and 2.36 respectively; p=0.02). The majority of medical students (87%) believed that physicians are responsible for the treatment of transgender patients. Our study reveals that even though there is willingness to treat transgender patients among UPR medical students, there are limitations in their knowledge and training regarding specific healthcare topics. Strategies to improve MS knowledge and training about this topic must be considered.
SAT-492 Impending Thyroid Storm Induced by Checkpoint Inhibitors
Authors: Zhou Ya , Jobbins Kathryn , Panta Raju 
Published: May 2020

Abstract
Introduction:
Thyroid storm is a rare but life threatening condition due to thyroid hormone excess and is usually caused by Graves disease, toxic nodular goiter or rarely due to thyroiditis. Immune checkpoint inhibitors (ICI) are a novel choice for treating cancers, and carry a risk for development of endocrinopathies. We report a case of impending thyroid storm 5 weeks after initiation of ICI.
Case Presentation:
81-year-old Caucasian male with metastatic renal cell carcinoma presented with generalized weakness and fatigue 5 weeks after ipilimumab and nivolumab were started. He had no prior history of thyroid disease and had normal thyroid functions before the treatment. He complained of palpitations, heat intolerance and loose stools on admission. On examination he was disoriented, tachycardic (128bpm) with new onset atrial fibrillation, had moist skin and brisk reflexes. He had non-tender thyroid, no thyromegaly, and no nodules palpated. Burch-Wartofsky score was 35, suggesting impending thyroid storm. Laboratory investigation showed elevated free T4 (&gt;7.77), elevated free T3 (8.6) with a suppressed TSH (&lt; 0.02). He had positive anti-TPO but Thyrotropin receptor antibody was negative. He was treated with propranolol 40 mg three times daily, prednisone 40 daily, methimazole 30mg three times a day with significant improvement in free T4 (5.67) within first 48 hours.
Discussion:
Imipimumab and nivolumab are monoclonal antibodies against cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death receptor-1 (PD-1) respectively. The reported incidence of thyroid dysfunction after combined imipimumab and nivolumab therapy can be as high as 22%1. Thyroiditis could present as early as 2-6 weeks 2 after treatment, and hypothyroidism tends to present between 5 months and 3 years3. According to a current consensus4, baseline TSH and FT4 should be drawn prior to initiating ICI. Thyroid storm is a clinical diagnosis and Burch-Wartofsky score can help in diagnosis. A high degree of suspicion and prompt diagnosis of thyroid storm and treatment is of utmost importance especially in this patient population. Rapid improvements in thyroid hormone levels suggest thyroiditis as a potential cause for thyrotoxicosis.
Conclusion:
ICI induced thyroid disease is not an uncommon condition. It could present as either thyrotoxicosis or hypothyroidism. Both patient and clinician should be aware of potential signs and symptoms of thyroid storm for early recognition and timely treatment of this life-threatening condition.
[1] Byun DJ et al.Nat Rev Endocrinol. 2017 Apr;13(4):195-207 [2] Iyer PC et al. Thyroid. 2018 Oct;28(10):1243-1251 [3] Endocr Relat Cancer. 2014 Mar 7;21(2):371-81 [4] Puzanov et al. Journal for ImmunoTherapy of Cancer (2017) 5:95