bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-106 Growth Hormone Treatment Response in Children
Authors: Rath Mitchell , Pacaud Daniele , Winston Karin , Ho Josephine , Dawrant Jonathan M , Luca Paola D , Perry Rebecca Jane , Huang Carol 
Published: May 2020

Abstract
OBJECTIVES: Growth hormone (GH) therapy is an effective treatment in addressing growth failure in children with GH deficiency (GHD). It has also been increasingly used in non-GH deficient (nGHD) conditions. We sought to report the growth response of GHD and nGHD patients who received GH therapy at a tertiary care center. METHODS: Data was collected from health records of patients followed in the endocrinology clinic at Alberta Children’s Hospital, Calgary, Canada, from 2005 to 2019, and used to analyze clinical responses based on indication for GH treatment. RESULTS: A total of 167 patient records (87 males and 80 females) were used for analysis. The average age at the start of GH therapy was 7.3 years (range 0.25 to 16.98 yrs). 74 patients were in the GHD group while 93 were nGHD. Of the patients in the nGHD group, the most common diagnosis were: idiopathic short stature (ISS)(n=45), Turner syndrome (TS)(n=26), and Prader Willi Syndrome (PWS)(n=8). The mean height velocity (HV) in year 1 was highest in the GHD group at 11.68 cm/year (n= 62, sd = 5.93), followed by ISS at 9.41cm/year (n = 52, sd = 4.34). The mean first year HV of those who had received chemotherapy (n= 5, mean = 5.48, sd = 1.92) or had Turner syndrome (n= 24, mean = 7.20, sd = 2.15) was significantly lower than both the GHD and ISS groups. GH peak during a GH stimulation test at baseline was not correlated to the first year height velocity while on GH treatment. However there was a negative linear correlation between baseline IGF1 level and first year height velocity (Spearman’s rho = 0.312216, p-value= 0.01516). Age at GH initiation was negatively correlated with height velocity during GH treatment. Height velocity over time decreased sharply from year 1 to year 3, and became stable for the remaining years of GH therapy. For the entire group, HV for years 1-5 was 9.81 (sd=4.83), 7.40 (sd=2.89), 6.29 (sd=2.38), 5.92 (sd=2.56), 5.66 (sd=2.51). There is no significant correlation between GH dose and height velocity response after adjusting for diagnosis. CONCLUSION: In our population, the response to GH therapy was consistent with those reported in the literature. Response to GH therapy was not associated with GH peak on stimulation but rather to baseline IGF-1 level and age at initiation. Although peak GH to stimulation is required to obtain public funding for GH therapy, these findings demonstrate that GH stimulation test results may not indicate which patients may benefit the most from GH therapy. Follow-up until final adult height will allow us to have a better understanding of the efficacy of GH therapy in patients with both GHD and nGHD conditions.
MON-114 Patient Perceptions of Obesity: African American vs. Caucasian Adults in an Urban Endocrinology Clinic
Authors: Todkar Supriya , Lahiri Sharon Wu 
Published: May 2020

Abstract
Introduction: The prevalence of obesity in the U.S. is highest in non-Hispanic black adults (38.4%) and Hispanic adults (32.6%) compared to non-Hispanic white adults (28.6%). Despite known racial disparities in obesity, not much is known about why these differences exist.
Objective: This study evaluated awareness of obesity, perceptions of obesity management, and barriers to adequate care in African American and Caucasian patients.
Methods: A 48-question survey was administered in 2018–2019 to an urban Endocrinology clinic’s adult patients with a body-mass index (BMI) ≥ 30 kg/m2. Chi-squared or Fisher’s exact tests were used to compare variables between groups.
Results: Of 137 respondents, 98 were African American and 39 were Caucasian. Most respondents were female (59–63.9%), had some college education (61.2–71.8%), and an annual income ≤ $50,000 (51.3–63.2%). Comorbidities included hypertension (64–66%), diabetes (73–79%), and arthritis (47–51%). Significantly more Caucasians than African Americans were aware of their BMI (65.8% vs 40%, p=0.0071). Both African Americans and Caucasians perceived their weight to be less than their actual BMI (African Americans: 23.2% perceived “obese” vs. 72.5% BMI 30–39.9 kg/m2 [p&lt;0.001] and 6.3% perceived “extremely obese” vs. 27.6% BMI &gt; 40 kg/m2 [p&lt;0.001]; Caucasians: 37.8% perceived “obese” vs. 66.6% BMI 30–39.9 kg/m2 [p=0.02] and 8.1% perceived “extremely obese” vs. 33.3% BMI &gt; 40 kg/m2 [p=0.01]). Over 90% in both groups agreed that obesity is related to hypertension, diabetes, heart disease, and early death, and 100% considered obesity treatable. Most (72.2–73.7%) recalled their health care provider (HCP) discussing obesity in the past year. Weight loss options discussed were similar between groups. Most discussed diet (70–82%) and exercise (59–62.2%) with HCPs, but few discussed formal weight loss programs (16.3–20.5%), anti-obesity medications (10%), or bariatric surgery (7–10.3%). Barriers were similar for both groups. Top barriers to diet were cost and lack of time and knowledge. Barriers to exercise were lack of time and inability to exercise. Top reasons for not discussing anti-obesity medications and bariatric surgery included concern for side effects or complications, lack of knowledge of the medications/procedures, and cost with surgery.
Conclusions: This study found similar perceptions of obesity management among African American and Caucasian patients with obesity. Despite excellent awareness of obesity as a health problem, decreased awareness of BMI and misperception of weight status were present in both groups. Discussion of diet and exercise was frequent, but discussion of formal weight loss programs, anti-obesity medications, and bariatric surgery was poor. These findings suggest a need for greater patient education and discussion of BMI and treatment beyond diet and exercise for patients with obesity.
MON-479 Acute Thyroid Edema: A Rare Complication of Thyroid Fine Needle Aspiration
Authors: Hosein Rachael Bree , Shah Neel L , Cillo Marc 
Published: May 2020

Abstract
Background: Acute thyroid swelling is a rare complication of thyroid fine needle aspiration (FNA). The first documented case was in 1982 and to date there are less than 20 cases currently reported in the literature (1).
Case Presentation: A 66-year-old female with a history of non-ischemic cardiomyopathy and heart failure was admitted to hospital to expedite heart transplant evaluation. A neck ultrasound was performed due to voice hoarseness and concern for vocal cord nodules. The ultrasound showed a 1.3 cm hypoechoic nodule in the right thyroid lobe. Given that the nodule had irregular borders and microcalcifications, a thyroid FNA was recommended.
The patient’s home warfarin had been held for at least three days prior to the biopsy and her INR on the procedure date was 1.4. Her heparin drip was held four hours prior to the thyroid FNA. Immediately following the procedure, a 3.2 cm hematoma formed inferior to the thyroid gland. The heparin drip was restarted 6 hours post-FNA as per radiology’s recommendation. Cytology of the nodule was benign.
The patient recovered well post FNA and improvement in the hematoma was noted on exam. Her hemoglobin was stable and she was restarted on warfarin. On day two post thyroid FNA, she reported significant neck pain, with no corresponding increase in the extra-thyroidal hematoma. No stridor or other concerning features were present on exam. A repeat thyroid ultrasound was performed three days after the FNA. It demonstrated fluid filled ‘cracks’ within the thyroid parenchyma and tripling in the volume of the thyroid gland, concerning for diffuse edema. No heterogeneity or subcapsular thickening was seen to suggest hemorrhage, and the previously demonstrated 3.2 cm extra-thyroidal hematoma was not visualized.
She was treated with ibuprofen 800 mg and prednisone 30 mg, and noted an improvement in her neck pain with these measures. A repeat ultrasound done three weeks after initial thyroid FNA showed marked improvement of the diffuse swelling.
Conclusion: The phenomenon of diffuse thyroid edema after fine need aspiration has been termed acute thyroid swelling (ATS). Given how frequently thyroid fine needle aspirations are performed, ATS appears to be a very rare complication. The etiology of ATS remains unknown, but the use of blood thinners, such as in our patient, does not appear to be a risk factor (1). The radiological appearance of fluid filled ‘cracks’ within the thyroid parenchyma suggests a more diffuse process, rather than a localized reaction. While NSAIDs or steroids may help with symptoms, patients appear to improve irrespective of whether or not medications are given. This suggests that ATS is a self-limiting condition without long term complications.
Reference: (1) Polyzos SA, Anastasilakis AD, Arsos. Acute transient thyroid swelling following needle biopsy: An update. Hormones. 2012;11(2);147-150
SAT-634 The Effect of Continine Verified Smoking on the Development of Diabetes
Authors: Jung Inha , Cho Mi Ae , Rhee Eun-Jung , Kwon Hyemi , Park Cheol-Young , Lee Won-Young , Oh Ki Won , Park Sung-Woo , Park Se Eun 
Published: May 2020

Abstract
Background: Cigarette smoking is a major public health problem and the leading cause of death. We aimed to analyze the effects of cotinine verified smoking on the development of diabetes mellitus.
Methods: Among individuals enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study, a total of 17,626 men (mean age 37.9 years) who underwent a health screening program in 2011 and 2017 were enrolled. Anthropometric and biochemical parameters, including urinary cotinine level were measured. The odds ratios (OR) for the presence of diabetes were analyzed in three groups according to their self-reported smoking status (Never smoker; Quitter and Current smoker) and cumulative amount of smoking. Individuals with urinary cotinine levels&gt;50 ng/mL were defined as cotinine-verified current smokers.
Results: Among the total participants without diabetes at baseline, 605 (3.4%) participants had diabetes after 6 years. The risk for diabetes was lower in nonsmokers than in current smokers and quittters after adjusting for confounding factors (OR 0.71; 95% confidence interval (CI)0.56-0.89) with current smokers as the reference group. The risks of diabetes were gradually increased with amount of smoking in both quitters and current smokers. When the participants were analyzed in subgroups according to the urinary cotinine levels, those with high urinary cotinine levels &gt;500ng/mL showed the higher risk for the development of diabetes (OR 1.57; 95% CI 1.27 – 1.93).
Conclusions: This study showed that cotinine-verified smoking was associated with the development of diabetes. Furthermore, there was a potential association between smoking amounts and the development of diabetes regardless of smoking cessation. We also found that those with high urinary cotinine levels showed an increased risk for diabetes compared with participants with low urinary cotinine levels.
SAT-722 Structure-Based Discovery of Hydraulic Fracturing Chemicals as Novel Androgen Receptor Antagonists
Authors: Tachachartvanich Phum , Singam Ettayapuram Ramaprasad Azhagiya , Durkin Kathleen , Smith Martyn , Merrill Michele La 
Published: May 2020

Abstract
Hydraulic fracturing (HF) technology is increasingly utilized for oil and gas extraction operations. The widespread use of HF has led to concerns of potential negative impacts on both the environment and human health. Indeed, the potential endocrine disrupting impacts of HF chemicals is one such knowledge gap. Herein, we used structure-based molecular docking to assess the binding affinities of 60 HF chemicals used in California to the human androgen receptor (AR). Five HF chemicals had relatively high AR binding affinity, suggesting the potential to disrupt AR effects. We next assessed androgenic and antiandrogenic activities of these chemicals in vitro. Of the five candidate AR ligands, only Genapol® X–100 was found to significantly reduce the AR transactivation by 22%. To better understand the structural effect of Genapol® X–100 on the potency of receptor inhibition, we compared the antiandrogenic activity of Genapol® X–100 with that of its structurally similar chemical, Genapol® X–080. Interestingly, both Genapol® X–100 and Genapol® X–080 elicited a significant antagonistic effect with 20% relative inhibitory concentrations (RIC20) of 0.43 and 0.89 μM, respectively. This indicated that Genapol® X–100 was more potent in inhibiting AR than Genapol® X–080, consistent with longer Genapol® X–100 chain length causing greater potency of AR activity inhibition. Furthermore, we investigated the mechanism of AR inhibition of these two chemicals in vitro. The result revealed that both Genapol® X–100 and Genapol® X–080 inhibited AR through noncompetitive binding mechanism. The effects of these two chemicals on the expression of AR responsive genes such as PSA, KLK2, and AR were also investigated. Genapol® X–100 and Genapol® X–080 notably altered the expression of these genes at relatively low concentrations of 0.5 µM to 1 µM. Using these integrated in vitro and in silico approaches, we identified HF chemicals as novel noncompetitive AR antagonists. Our findings heighten awareness of endocrine disruption by HF chemicals and provide evidence that noncompetitive antiandrogenic Genapol® X–100 could possibly cause adverse endocrine health effects in humans.
OR24-07 Fetal Sex Impacts First Trimester Maternal-Fetal Communication in Humans
Authors: Gonzalez Tania L , Sun Tianyanxin , Deng Nan , DiPentino Rosemarie , Clark Ekaterina L , Lee Bora , Wang Yizhou , Stripp Barry R , Yao Changfu , Tseng Hsian-Rong , Karumanchi S A , Koeppel Alexander F , Turner Stephen D , Farber Charles R , Rich Stephen S , Wang Erica T , Williams John , Pisarska Margareta Danuta 
Published: May 2020

Abstract
The placenta serves as a regulator of fetal growth throughout pregnancy. Signaling at the maternal-fetal interface is critical during placentation and lays the groundwork for placenta function, affecting pregnancy outcomes. Fetal growth is impacted by fetal sex, with males larger than females, and maternal gestational diabetes and obesity independently increase the risk of macrosomia in male fetuses only. We previously demonstrated differentially expressed genes (DEGs) among sexes involves ancient canonical pathways and metabolic functions in placenta tissue. As these are likely impacted by signaling at the maternal-fetal interface, our aim here was to identify sex differences in signaling at the maternal-fetal interface and among individual cell types within the placenta to explain these differences. RNA-sequencing of first trimester placenta and maternal decidua as well as single cell RNA-sequencing in first trimester placenta was performed in ongoing pregnancies. We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. From these, 35 of 115 receptors and/or ligand genes were also found to be upstream regulators of pathways critical in sexually dimorphic placentation which may define regulation. Single cell analysis identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen presenting cells, and endothelial cells), and all had sexually dimorphic genes. Among individual cell types, ligands from the CC-family of cytokines were most highly representative in females, with their corresponding receptors present on the maternal surface. Furthermore, upstream regulator analysis of sexually dimorphic genes demonstrated TGFβ1 and estradiol to significantly affect all cell types. Dihydrotestosterone, which is produced by the male fetus, was an upstream regulator that was most significant for the trophoblast population. In addition, gene ontology enrichment analysis identified distinctive enriched functions between male and female trophoblasts, with cytokine mediated signaling pathways most representative. MUC15 and NOTUM were the most highly expressed sexually dimorphic autosomal genes found in distinct cell types of the trophoblast population, cell types critical for placentation and nutrient exchange. Thus, differences in hormone and immune signaling pathways may account for differential gene expression and differences in trophoblast function during placentation, which may in turn explain developmental differences, including fetal size, well-being, and overall outcomes.
MON-368 A Case of Uremic Tumoral Calcinosis with Secondary Hyperparathyroidism
Authors: Mathew Justin , Kishore Preeti 
Published: May 2020

Abstract
Background: Uremic tumoral calcinosis is an uncommon clinical entity that can be seen in patients with end-stage renal disease, characterized by development of calcific deposits in the soft tissue. This condition can cause significant pain and impairment of mobility for patients. While it appears that elevation in calcium-phosphate product and hyperparathyroidism may each play a role in the development of these deposits, these conditions are neither necessary nor sufficient for this process to occur. As a result, the optimal treatment of this condition is not well-established.
Case: A 50-year-old man with history of ESRD since 2015 secondary to autosomal dominant polycystic kidney disease on peritoneal dialysis, HTN, and secondary hyperparathyroidism presented to the emergency room with progressive right lateral hip pain, reaching the point where the patient could no longer ambulate. Exam demonstrated a thin man whose right hip was tender to palpation with limited range of motion, as well as a palpable, deep right upper leg mass. Laboratory findings were significant for a creatinine of 14.83mg/dL (n &lt;1.5mg/dL), calcium of 9.1 mg/dL (n 8.5-10.5mg/dL), phosphate of 7.9mg/dL (n 2.5-4.5mg/dL), intact PTH of 1129pg/mL (n 15-65pg/mL), and 25-OH Vit D of 20.4ng/mL (n&gt;30ng/mL). X-ray of the right femur demonstrated a 9cm calcified soft tissue lesion, which was not present on imaging 7 months earlier. Subsequent CT of the pelvis showed a cystic, multilobulated calcified mass in the right gluteus, measuring 6.1 x 3.5 x 7.5cm, consistent with tumoral calcinosis. Attempts to normalize his serum phosphorous level using treatment with phosphate binders or changes to his dialysate had failed previously, and the patient declined transitioning to hemodialysis. Nuclear medicine parathyroid scan demonstrated four-gland hyperplasia, and the decision was made to perform 3.5 gland parathyroidectomy. Two days post-operatively calcium had dropped to 7.7 mg/dL, phosphate to 6.8mg/dL, and intact PTH to 29pg/mL.
Conclusions: Uremic tumoral calcinosis is a very rare but potentially debilitating consequence of end-stage renal disease that can be significantly detrimental to quality of life in patients with ESRD. Elevated calcium-phosphate product is frequently implicated in its development, and evidence exists that lowering these levels can lead to complete resolution of these lesions. However, in patients for whom medical therapy is not effective and who have concomitant secondary hyperparathyroidism, subtotal parathyroidectomy is a reasonable treatment option.
SAT-311 Role of SREBP in Regulation of Corticotroph Tumor ACTH Secretion and Cell Proliferation
Authors: Zhang Dongyun , Damoiseaux Robert , Bergsneider Marvin , Wang Marilene B , Yong William H , Kelly Kathleen A , Heaney Anthony P 
Published: May 2020

Abstract
Cushing Disease (CD) is a life-threatening condition with suboptimal medical treatment. To identify drugs that not only inhibit ACTH secretion to attain eucortisolemia but also inhibit tumor growth, we conducted a high throughput screen employing a novel “gain of signal” ACTH AlphaLISA assay. From a kinase inhibitor library containing 430 compounds, we identified the dual PI3K/HDAC inhibitor, CUDC-907, as a potent inhibitor of both in vitro and in vivo corticotroph tumor ACTH secretion and growth. By stepwise comparison of CUDC-907 with mono-functional PI3K and HDAC inhibitors, we demonstrated that CUDC-907 exerts its inhibitory effect on ACTH secretion primarily through its inhibition of HDAC activity at the POMC transcriptional level; while PI3K-mediated inhibition of corticotroph cell viability further contributes to reduced ACTH secretion. We also used RNA-seq to characterize the global transcriptiome changes associated with CUDC-907 treatment. Hierarchical clustering showed that 1432 differentially expressed genes (DEGs, p≤0.05 and fold-change≥1.5) were altered by CUDC-907 treatment in comparison to the vehicle-treated control cells. Gene ontology (GO) analysis of 456 downregulated and 976 upregulated DEGs revealed that the most enriched biological processes were cholesterol biosynthesis (GO:0006695, p=1.977e-17) and the type I interferon signaling pathway (GO: 0060337, p=4.928e-7) respectively. Further analysis demonstrated downregulation of the membrane-bound transcription factor sterol regulatory element binding proteins (SREBPs). Downregulation of SREBP-2 by CUDC-907 as well as the several other target enzymes in the cholesterol biosynthesis and uptake pathway including IDI2, NSDHL, MVD, and HMGCR, was confirmed by real-time PCR. To further characterize a role for SREBP-2 in regulation of corticotroph tumor ACTH secretion and proliferation, we employed siRNA targeting endogenous SREBP-2 (SREBP-2 mRNA, Control vs. siRNA 1±0.03 vs. 0.6±0.08, p&lt;0.05), and demonstrated that knockdown of SREBP-2 not only inhibited POMC mRNA expression (POMC mRNA, 1±0.03 vs. 0.7±0.01, p&lt;0.01), and ACTH secretion (ACTH (ng/mL) 29±0.4 vs. 23±0.3, p&lt;0.005), but also suppressed cell proliferation (Relative Proliferation Rate, 1±0.01 vs. 0.7±0.01, p&lt;0.005). This was further confirmed by overexpression of cleaved mature SREBP-2, which led to increased POMC expression and cell proliferation. We demonstrate for the first time the role of the SREBP-mediated cholesterol biosynthesis pathway in regulation of corticotroph tumor POMC regulation and growth. Our studies identify SREBP and cholesterol biosynthesis as a therapeutic target in CD.