bluuebunny/crossref_metadata_2025 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

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

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<0.001] and 6.3% perceived “extremely obese” vs. 27.6% BMI > 40 kg/m2 [p<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 > 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

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

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>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 >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

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

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

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 <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>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

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<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<0.01), and ACTH secretion (ACTH (ng/mL) 29±0.4 vs. 23±0.3, p<0.005), but also suppressed cell proliferation (Relative Proliferation Rate, 1±0.01 vs. 0.7±0.01, p<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.
SUN-062 Psychiatric Co-Morbidities, Sexual Orientation, and Impact of Therapeutic Interventions in a Gender Non-Conforming Pediatric Practice
Authors: Figueredo Veronica M , Diaz Alejandro
Published: May 2020

Background: There is limited scientific literature regarding gender non-conforming (GNC) youth in pediatric practice. GNC patients of all ages have an increased risk for psychiatric co-morbidities and suicidal risk. An increasing number of GNC youth are seeking therapeutic options to develop physical characteristics to match their gender identity. The study aim is to describe the prevalence of psychiatric co-morbidities and sexual orientation among GNC pediatric patients in a clinic-based setting in Miami, Florida. A secondary aim is to compare the grade of dysphoria before and after therapeutic interventions among GNC youth. Methods: This is a retrospective chart review on records from 2014–2019 among transgender adolescents attending a pediatric endocrinology clinic in Miami. Data on demographics and clinical characteristics were obtained from electronic medical records. We performed descriptive statistical analysis using SPSS version and reported frequencies and percentages. Results: A total of 158 patients were included in this analysis. There were 107 (67.7%) affirmed males (female to male), 47 (29.7%) affirmed females (male to female), and 4 (2.5%) considered themselves non-binary. Median age at onset of gender dysphoria symptoms and beginning of social affirmation was earlier in affirmed females (7.21 and 12.36 years vs. 9.65 and 13.50 years). Among affirmed males, sexual orientation was self-reported as 38% straight, 47% bisexual, 12% homosexual and 1% asexual vs. among affirmed females, whose sexual orientation was reported as 54.3% straight, 37.1% bisexual and 8.6% homosexual. Prevalence of psychiatric co-morbidities in our study population was 78.5%. Depression was the most frequent diagnosis (66.5%), followed by anxiety (33.5%), attention deficit hyperactivity disorder (10.1%), bipolar disorder (1.9%), bulimia (1.3%), anorexia nervosa (0.6%) and post traumatic stress disorder (0.6%). Psychiatric co-morbidities were more common among affirmed males (84.1% vs. 66%). History of suicidal ideation was more common among affirmed males (70.1%) than affirmed females (49%). Self-injuring (cutting) was more common among affirmed males (56.1%) than in affirmed females (25.5%). Mean age at hormonal treatment onset was similar in both groups (15.75 years in affirmed males vs. 15.58 years in affirmed females). The degree of gender dysphoria before and after starting hormonal treatment, reported on a scale of 0 (no dysphoria) to 10 (highest possible dysphoria), declined for both genders (8.08/10 and 3.99/10) and affirmed females (7.87/10 and 2.96/10). Conclusion: The prevalence of psychiatric co-morbidities, suicidal ideation, and self-injuring behavior is high among GNC youth, but in this population, significantly worse among affirmed males. Both groups had significant improvement in the degree of dysphoria after beginning hormonal treatment.
SAT-682 Unusual Presentation of Diabetic Ketoacidosis Associated with Hypernatremia in Adult Patient
Authors: Aljaberi Asma Khaled , Hazin Fatemeh
Published: May 2020

Diabetic ketoacidosis (DKA) is an acute, life threatening complication of diabetes characterized by hyperglycemia, ketonemia and acidosis. It is known to commonly present with hyponatremia and rarely with hypernatremia. DKA can present with hypernatremia in pediatric population which carries poor prognosis when present.

We present a 27 year- old Ethiopian lady, previously healthy who was brought to emergency department (ED) with decreased level of consciousness. She had polyuria and polydipsia associated with weight loss for 1 month and flu like symptoms for 3 days prior to admission. On day of presentation, she was found to be confused, sleepy and not able to recognize people around her. In ED, patient was confused, GCS 8 severely dehydrated with poor skin turgor and marked delay in capillary refill >3s. Patient was afebrile, with HR 115 bpm, BP 95/60mmHg, and BMI 20kg/m2. Initial labs revealed; severe acidosis pH 6.8, blood glucose (BG) >38 mmol/l and corrected Na 155 mmol/l. Calculated serum osmolality 357mOsm/kg, lactic acid 5 mmol/l and HCO3 3 mmol/l. Further labs revealed K 4.4 mmol/l, Urea 10 mmol/l, Cr 150 micromole/l, WBC 26 and Ketones 3+ in urine. DKA was diagnosed and treated in ED with 4L IVF (2L bolus NaCl and other 2L of 0.23% NaCl given at 15 ml/hr) and NaHCO3 150 mmol. Continuous insulin regular infusion at rate of 0.1U/Kg/hr as per protocol was initiated. Patient was admitted to ICU for close monitoring of BG, GCS and electrolytes. After 9 hours of management, patient GCS improved to 13-14. Repeated labs revealed; improvement in PH 7.17, BG 22mmol/l, HCO3 5 mmol/l and lactic acid 1 mmol/l. There was worsening of Na 159 mmol/l and K dropped to 2.6 mmol/l. IV KCL bolus 20mmol followed by 40mmol IV continuous in IVF was initiated. IVF was changed from NaCl to D5W at 125ml/hr. Electrolytes were repeated after 7 hours and showed improvement in and Na and k levels. During her stay in ICU, patient recovered to baseline GCS 15 with no residual symptoms. IV insulin infusion was stopped on 3rd day and commenced on Insulin glargine and insulin Aspart boluses. Further investigations confirmed DM type 1; HbA1c 15%, C-peptide 0.08 nmol/l, IA2Ab of >400 and GAD Ab >250. Patient had an uneventful hospital course, she stayed in ICU for 3 days and then shifted to medical floor. She was discharged on basal bolus insulin regimen. In patients with uncontrolled DM/DKA, serum Na level is variable, reflecting the balance between the hyperglycaemia induced water movement out of the cells that lowers serum Na level, and the glycosuria induced osmotic diuresis, which tends to raise serum Na. When there is marked osmotic diuresis, DKA may present with a normal or even elevated serum Na concentration, despite a markedly elevated serum BG.

To best of our knowledge, this is the second case to report an unusual DKA presenting with hypernatremia in adult patient.
MON-925 A Wolf in Sheep’s Clothing: Intermittent Hypercalcemia from an Intrathyroidal Parathyroid Carcinoma
Authors: Trejo Jonathan , Hernandez Lyan Gondin , Wortham Joy , Sandoval Brenda , Armaiz-Pena Gustavo R , Bruder Jan M , Koops Maureen , Solis-Herrera Carolina , Granda-Rodriguez Ramona
Published: May 2020

Parathyroid carcinomas have an estimated prevalence of <0.1% of all cancers and is found in <1% of patients with primary hyperparathyroidism (PHPT). While they frequently present with PTH- mediated hypercalcemia, they are often distinguished by severe hypercalcemia and markedly elevated PTH levels compared to their benign counterparts. Parathyroid cancers most often arise from existing parathyroid glands, making them identifiable with standard imaging modalities such as parathyroid sestamibi scan, thyroid ultrasound, and 4-D CT scan. There are reports of non-functioning parathyroid carcinomas, including those that are intrathyroidal. Most of the reported cases are found de novo. We present a case of an intrathyroidal parathyroid carcinoma with intermittent hypercalcemia. A 72-year-old man with a history of Graves’ disease and RAI ablation in the 1970’s was found to have hypercalcemia up to 14.1 mg/dL (8.5 - 10.1) with a PTH level of 223 pg/mL (14 - 64). He denied any constipation, bone pain, fractures, renal stones, or changes in mental status. Thyroid ultrasound demonstrated a 3.9 cm R lobe complex nodule reported as TI-RADS 4, and a hypoechoic 1.0 cm nodule in the L lobe. No definitive parathyroid adenoma was reported. A parathyroid sestamibi scan showed persistent uptake in area of the L 1.0 cm nodule favoring a PTH adenoma while the R nodule had initial radiotracer uptake with delayed washout but no technetium uptake. Laboratory evaluation demonstrated a 24-hour urinary calcium of 338 mg/24hr, low 25-OH vitamin D, and normal vitamin D 1,25 levels. Osteoporosis was diagnosed by BMD with T-score of -3.2 at the femoral neck. Repeat serum corrected calcium level was 9.7 mg/dL and PTH was 93 pg/mL. FNA cytology of the R thyroid mass was reported as benign thyroid tissue. Due to size of the R thyroid nodule, the patient underwent a R hemithyroidectomy with L parathyroidectomy. Intraoperative PTH levels decreased from 154 to 120 pg/mL after removal of L parathyroid adenoma; PTH level decreased further to 12.9 pg/mL after R hemithyroidectomy. Surgical pathology revealed 4.5 cm R parathyroid carcinoma without thyroid tissue with positive margins, and a hypercellular L parathyroid gland. PHPT resolved. After review of all aspects of the case and discussion with patient, the decision was made to monitor his calcium and PTH levels and repeat BMD 1 year from resection. This is an uncommon presentation of a rare endocrine malignancy. To our knowledge, there are few case reports of non-functional parathyroid carcinomas that were initially reported as thyroid cancer or benign thyroid tissue after biopsy. This report underscores the importance in keeping this rare diagnosis in the evaluation of PTH-mediated hypercalcemia.
SUN-686 Diabetic Retinopathy in Latinos with Type 2 Diabetes: Temperance Is Protective
Authors: Fukunaga Alex , Genter Pauline , Ipp Eli
Published: May 2020

Diabetic retinopathy (DR) is a duration-dependent complication of diabetes (DM). Yet some people with DM do not develop DR despite long disease duration. We evaluated such a group in search of novel factors that might signal protection from DR, using a large cohort of Latinos with type 2 DM and readable retinal images in the GOLDR study (n=614). Participants were phenotyped and 7-field retinal images were evaluated using Airlie House criteria. We identified 90 participants with DM>10y without evidence for DR (NoDR). We compared this group of patients with another group more susceptible to DR with evidence for earlier onset DR, in DM <10y duration (EoDR, n=103). Duration of diabetes in NoDR was [x+SEM] 14.2+ 0.6y, and in EoDR, 4.3+ 2.9 y (p<0.001), a 10-y spread. We found that most of the typical DR-associated risk factors could not explain DR protection in NoDR, including age, sex, age at DM onset, systolic blood pressure (SBP), percent insulin users, duration of hypertension, fasting plasma glucose, A1C, urine albumin/creatinine ratio and estimate glomerular filtration rate; these parameters were not significantly different in the two groups. Protective factors that did emerge were female sex (p=0.02), lower diastolic BP 69.1+0.9 vs. 72.5+0.9 (p<0.01) and lower alcohol intake 3.1+0.8 vs. 7.8+2 de/w (14g drink equivalents/week; p=0.025). In a sensitivity analysis to determine whether sex accounted for the apparent effect of alcohol on DR, we evaluated the men in the study, who were more likely to be drinkers. Alcohol consumption was compared in men with DR who reported drinking alcohol (n=93) compared to men without DR who also reported drinking (n=53). Men without DR reported significantly less alcohol intake, 14.8+2.4 vs. 25.9 +3.3 de/w in those with DR (P<0.01), suggesting that a possible protective benefit of lower alcohol consumption observed in NoDR was not likely to be mediated by the presence of fewer men in that cohort. In summary, type 2 diabetic patients with no evidence of DR after 10y were more likely to be women, have a lower diastolic BP, and who imbibed less alcohol when compared with a more accelerated DR subgroup with <10yrs duration of DM. We conclude that in type 2 DM Latino patients, a focus on alcohol intake may be a useful management strategy in addition to traditional medication-based BP control and renal protection, as well as a pathophysiological pathway for DR worthy of investigation.
MON-513 Suppressing the Growth of Human Medullary Thyroid Cancer Cells Using FDA-Approved Drug
Authors: Ramachandran Ilangovan , Ramadoss Sivakumar , Nathan Lauren , Kumaran R Ileng , Chaudhuri Gautam
Published: May 2020

Medullary thyroid carcinoma (MTC) is a solid tumor of the parafollicular cells in the thyroid gland. MTC has worse prognosis, when compared with other differentiated thyroid cancers, and MTC patients with distant metastases have a low survival rate unless thyroidectomy is performed at an early stage. Furthermore, conventional treatments have only marginal benefits. Therefore, there is a need to develop novel therapeutics for MTC. Several drugs that are developed and tested in preclinical trials fail in clinical trials. Therefore, repurposing the already US Food and Drug Administration (FDA)-approved drugs towards the treatment of cancers may have potential benefits, like saving the lives of cancer patients and lowering the investment cost of drug development. Here, we explored a novel precision treatment for thyroid cancers by repurposing the FDA-approved small molecule anti-parasitic drug Nitazoxanide (NTZ). In our study, we examined the anticancer effects of NTZ on human MTC cells using the TT cell line. We treated the TT cells with different concentrations of NTZ and assessed the cell proliferation by water-soluble tetrazolium salt (WST-1) assay and oxygen consumption rate (OCR) by Seahorse extracellular flux analysis (Seahorse XFe24 Analyzer). Additionally, we determined the effects of NTZ on the protein expression of key signaling molecules that regulate MTC cell growth by western blot analysis. Our results indicated that NTZ significantly suppressed the growth of TT cells at 24 h treatment. Very importantly, NTZ reduced the basal OCR demonstrating the inhibition of mitochondrial respiration. Moreover, protein expression studies revealed that NTZ markedly reduced the key Hippo signaling pathway effector molecule TAZ and the oncogene c-myc. Interestingly, NTZ decreased the expression of epidermal growth factor receptor (EGFR) that plays an important role for RET activation in MTC. Importantly, NTZ increased the expression of p53 upregulated modulator of apoptosis (Puma). Taken together, our findings demonstrate for the first time that NTZ inhibits the growth of MTC cells and decreases the cancer cell metabolism. The mechanisms by which NTZ targets the MTC cells involve the suppression of key oncogenic proteins and upregulation of tumor suppressor molecule. Thus, our study highlights that repurposing this FDA-approved currently used drug may have a greater advantage of being tested in preclinical models of MTC, and therefore, for the rapid consideration of NTZ as a potential therapeutic drug to treat MTC patients in the near future.
MON-511 Are Thyroid Nodule Fine Needle Aspiration Washings an Acceptable Alternative to Dedicated Fine Needle Aspirates When Obtaining Tissue Samples for Genetic Expression Classifier Analysis?
Authors: Carrillo Maritza Elide , Rodriguez Renil
Published: May 2020

The Bethesda System for Reporting Thyroid Cytopathology stratifies thyroid nodules by risk associations. Approximately 15-30% of fine needle aspirations (FNA) fall into an indeterminate criteria, and two thirds are found to be surgically benign leading to unnecessary surgeries (1). Veracyte Inc. developed the Afirma gene expression classifier (GEC) to identify whether an indeterminate nodule had benign expression, with a NPV of 95% for AUS/FLUS (Atypia of undetermined significance/ follicular lesion of undetermined significance) nodules making it an excellent way to rule out malignancy (2). The goal of testing for thyroid cytology includes avoiding unnecessary surgery in benign nodules and identifying high risk from low risk lesions. The Afirma validation landmark study aided in the commercial approval for use in clinical practice after showing a 95.1% sample sufficiency when 2 dedicated samples were obtained in addition to the 3-5 FNA samples for cytology, but our institutional practice habits may suggest other techniques may be valid as well (2). We aimed to assess the rate of sufficient sample for GEC based on FNA washings at our institution, without using dedicated FNA for GEC. Data was gathered from all indeterminate nodule FNA washings referred for Afirma GEC from January 2015 through December 2017. Samples were determined on Afirma report as benign, suspicious, or insufficient and rate of insufficiency was determined. 95 indeterminate nodule FNA washings were sent for Afirma GEC. 93 (97.9%) samples were sufficient for RNA, with 47 (49.5%) reported as suspicious and 46 (48.4%) reported as benign, 2 (2.1%) samples were insufficient for RNA. 97.9% of our samples were sufficient when using FNA washings alone. Our experience suggests that the technique used at our clinical practice is an acceptable alternative to using an additional 2 passes for dedicated samples in collecting RNA for Afirma GEC. This method decreases need for call back for a second biopsy, is less time consuming, and potentially more cost effective. Limitations in our study are a small sample size limited to a single institution, differing number of FNA washings per total passes among practitioners, and variability of experience between providers. In conclusion thyroid nodule FNA washings are an acceptable alternative to dedicated FNA when obtaining tissue samples for genetic expression classifier analysis. Further studies with a larger sample size across different institutions are necessary.

1.Prathima S, Thyroid Research and Practice, January-April 2016; Vol 13: Issue 1; p 9-14

Yang SE et al, Cancer Cytopathology, February 2016, p 100-109

2. Alexander EK. Kennedy GC. Baloch ZW.et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med. 2012;367(8):705–715.
MON-107 Diabetic Ketoacidosis at Type 1 Diabetes Diagnosis in Children from a Large Centre (Hangzhou, China)
Authors: Peng Wei , Jin Binghan , Yuan Jinna , Dong Guanping , Lin Hu , Huang Ke , Wu Wei , Derraik José G B , Fu Junfen
Published: May 2020

Objective: To review the clinical symptoms and biochemical parameters associated with diabetic ketoacidosis (DKA) in children newly diagnosed with type 1 diabetes (T1D) in our single medical centre over 10 years. Methods: Participants were children aged <16 years diagnosed with T1D between 1 January 2009 and 31 December 2018 at the Children’s Hospital, at Zhejiang University School of Medicine (Hangzhou, China). DKA occurrence was assessed by blood gases using pH and bicarbonate. The severity of DKA was categorized according to ISPAD 2014 guidelines, as mild, moderate, or severe. The child’s history prior to diagnosis was recorded, and patients underwent a number of clinical assessments, including anthropometry, biochemical parameters, and OGTT. The demographic and clinical characteristics of children with and without DKA were compared. Results: 681 patients (314 boys and 367 girls) were diagnosed with T1D over the study period. 341 (50.1%) had DKA at diagnosis, with yearly rates ranging from 45.0% to 56.8%. Eight cases had missing data on severity, but 120 had mild (36.0%), 100 moderate (30.0%), and 113 severe (33.9%) DKA. Children with DKA were younger than those without DKA (7.2 vs 8.2 years, respectively; p=0.001), and were more likely to report vomiting (13.2% vs 1.5%; p<0.001), loss of appetite (3.2% vs 0.9%; p=0.031), fatigue (39.3% vs 5.6%; p<0.001), and abdominal pain (9.1% vs 1.5%; p<0.001) prior to T1D diagnosis. The classical symptoms of diabetes were similar in children with and without DKA, such as polyuria (86.8% vs 90.3%, respectively; p=0.153), polydipsia (90.6% vs 91.5%; p=0.696), polyphagia (26.4% vs 30.3%; p=0.259), and weight loss (50.7% vs 50.6%; p=0.970). Children with DKA had higher blood lipids and fasting insulin levels at presentation, but displayed similar HbA1c levels. Conclusions: We report a high incidence of DKA at our centre (50%) among children diagnosed with T1D. As most children displayed classical symptoms of diabetes, it is important to increase community awareness of the disease to ensure an early diagnosis and lower the risk of children presenting with DKA.
OR24-02 Identification of Membrane Proteins That Enhance the Responsiveness of the Ghrelin Receptor
Authors: Prins Karina , Visser Jenny A , Huisman Martin , Mies Rosinda , Neggers Sebastian J C M M , der Lely Aart Jan Van , Delhanty Patric J
Published: May 2020

Ghrelin, a 28-amino acid peptide gut hormone, occurs in acylated (AG) and unacylated (UAG) variants. AG is a GH secretagogue as well as being orexigenic and diabetogenic, acting via the growth hormone secretagogue receptor (GHSR1a) in the hypothalamus and pituitary. UAG counteracts these metabolic effects through unknown mechanisms. While screening for potential UAG receptor(s) we discovered previously uncharacterised interactions of AG and UAG with five cell membrane proteins (MPs), three of which are known to modulate metabolism. Here, we studied if two of these MPs (MP1 & 2) could modulate GHSR1a signalling by expressing their transgenes in HEK293 cells. As GHSR1a is coupled with calcium signalling via Gq proteins, aequorin luminescence was used to evaluate Ca2+ influx into the cells. Transfected cells were treated with either AG, UAG, or soluble parts of the MPs, or combinations thereof.

MP2 markedly enhanced the efficacy (~5.5-fold), but not the potency, of AG-induced Ca2+ influx, whereas MP1 had no effect on Ca2+ influx. Neither MP1 nor MP2 overexpression altered cellular GHSR1a levels. In the absence of GHSR1a, MP2 was unable to stimulate an AG-induced Ca2+ influx. UAG treatment (100nM) had no effect on GHSR1a-mediated Ca2+ influx in the presence or absence of MP2. MP2 is post-translationally modified and we suspected this to be important for its activity. However, removal or blockade of these modifications had no effect on the ability of MP2 to enhance GHSR1a signalling. Moreover, incubating the cells with soluble ectodomain of MP2 did not alter its effect on GHSR1a signalling. Nevertheless, induction of ectodomain shedding with PMA (0.4-1µM) dose-dependently reduced the AG-induced Ca2+ response to 0.5-0.2 of control levels (DMSO) in MP2-GHSR1a co-transfected cells. Unlike MP2, which has a transmembrane and intracellular domain, MP1 is attached to the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor and lacks an intracellular domain. Since MP1 is otherwise structurally similar to MP2, we suspected that the intracellular domain of MP2 may be important for its function. Therefore, we expressed chimeras of MP2 and MP1 in which the GPI linkage site and the transmembrane/intracellular domains were exchanged. The MP2 ectodomain with a GPI-anchor had similar stimulatory effects on GHSR1a signalling as full-length MP2, whereas the MP1 ectodomain with MP2 transmembrane and intracellular domain only enhanced GHSR1a signalling by approximately 3-fold.

In conclusion, we have identified a membrane protein as a novel component of the ghrelin signalling pathway that markedly enhances the response of the ghrelin receptor to AG. Our current data suggest its ectodomain is important in mediating this effect. Studies are ongoing to fully delineate the mode of interaction and to determine the role of MP2 in ghrelin signalling in vivo.
SUN-373 Addressing the Burden of Hip Fracture in Older Men
Authors: Khan Mehreen , Hamann Kendal , Chandra Malini , Hui Rita , Fulchino Lisa , Lo Joan Chia-Mei
Published: May 2020

INTRODUCTION: Men have a lower incidence of hip fracture compared to women. However, hip fractures comprise a greater proportion of overall fractures in men and result in greater morbidity and mortality. In 2015, a new high-risk fracture prevention program was implemented in our medical group, targeting men aged 70-85y with hip, pelvic, humerus, wrist or vertebral fracture for osteoporosis treatment within 6 months of the fracture event. In this study, we examined patient characteristics, site of hip fracture, treatment initiation and time to treatment initiation in men who experienced a hip fracture before and after implementation of this new fracture prevention program.

METHODS: This study examines data from 1114 men age 70-85y (81% white race) who experienced a hip fracture during 2013-2014 (N=527) and 2015-2016 (N = 587), based on a principal hospital discharge diagnosis, excluding men who had received osteoporosis treatment in the prior year. Initiation of osteoporosis treatment within 6 months following the hip fracture and time to initiation of osteoporosis treatment (bisphosphonate, teriparatide, denosumab) were examined. The following covariates were ascertained using data from electronic health records and databases: age, race/ethnicity, smoking status, body mass index (BMI), and history of diabetes mellitus with diabetes pharmacotherapy. A Charlson Comorbidity Index was derived using health record data form the prior year. The site of hip fracture was classified as femoral neck or pertrochanter. Subgroups were compared using the Chi-square test.

RESULTS: Among the 1114 men with hip fracture (mean age 79 ± 4 years), half (54%) experienced a fracture in the femoral neck and the remainder (46%) in the pertrochanter. Nearly 1 in 5 (17%) men were current smokers, 13% were obese (BMI ≥30 kg/m2), 25% had diabetes mellitus, and 42% had a comorbidity index ≥3. One fourth (24%) had a clinical fracture diagnosed in the past 2 years. Osteoporosis treatment initiation post-hip fracture increased from 16% in 2013-2014 to 29% in 2015-2016 with implementation of the high-risk program targeting men (p<0.01). Time to treatment examination of 2013-2014 vs 2015-2016 revealed that the largest increase in treatment initiation was seen at 2-4 months (4% vs 12%, p<0.01) whereas non-significant differences were seen at ≤2 (7% vs 10%) and 4-6 (4% vs 7%) months following hip fracture.

CONCLUSION: Implementing targeted post-hip fracture intervention in men dramatically increased osteoporosis treatment following fracture, with the largest intervention seen 2-4 months after fracture. The high burden of prevalent fractures, smoking, and diabetes highlights the need for post-fracture intervention and counseling for modifiable risk factors.