bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-635 Results of a Preclinical Pilot Study Evaluating 24-Hour Subcutaneous Infusion of the GLP-1 Analogue Liraglutide Delivered via the H-Patch Wearable Device
Authors: Barnes Jessica W , Lucera Erick 
Published: May 2020

Abstract
Nonalcoholic fatty liver disease (NAFLD) affects an estimated 30% of Americans, is the most common cause of chronic liver disease in the US, and a leading cause of liver-related morbidity/mortality worldwide1. Currently, there are no FDA-approved drugs specifically tailored to NAFLD or its big brother, non-alcoholic steatohepatitis (NASH). Glucagon-like peptide 1 (GLP-1) is an incretin peptide hormone, secreted in the distal ileum and proximal colon by L cells. Besides stimulating the pancreas to cause beta cell proliferation and enhance insulin biosynthesis, GLP-1 interacts with receptors in other parts of the GI tract, lung, kidney and CNS. Thus, GLP-1’s metabolic functions include delayed gastric emptying, appetite suppression, enhanced liver glucose uptake, peripheral insulin sensitivity, as well as glucose-dependent insulin secretion while inhibiting the release of glucagon from α-cells. While GLP-1 receptor agonists such as exenatide and liraglutide have been approved for type 2 diabetes, a meta-analysis of several studies has shown promise in patients with NASH. Effects including decreased serum ALT levels, improvement in hepatic fat content and fibrosis, and weight loss making GLP-1 therapeutics potentially attractive for use in patients with NASH and metabolic syndrome2-5. While subcutaneous injection is an avenue for administration, continuous infusion offers many benefits for native GLP-1 and GLP-1 analogues. We investigated the pharmacokinetics (PK) of a GLP-1 analogue (liraglutide) delivered over a single 24h period using the wearable h-Patch™ subcutaneous infusion device in dogs. Liraglutide (1800ug) was infused at a static rate over 24h delivered with PK evaluated at time points to 72h from the start of infusion. Liraglutide levels were detectable in blood detected within 30m of the beginning of infusion, peaked above the upper level of quantitation of the LC/MS/MS analysis (316ng/ml upper level of quantitation), and gradually decreased with quantifiable levels still detected 48h after completion of h-Patch™ infusion. The h-Patch™ provides a simple all-in-one delivery device with no exposed needle, no programming or infusion set required, additionally it can be configured to deliver two payload in separate reservoirs offering the potential option of an insulin/GLP-1 infusion combination. These preliminary encouraging results of liraglutide infusion via the h-Patch warrant further investigation in a variety of indications including diabetes, NASH, and obesity as a monotherapy and in combination with other complementary therapeutics. 1. Liver Int. 2017; 37(S1):97-103. 2. Lancet. 2016; 387(10019):679-690. 3. J Gastroenterol Hepatol. 2016; 31(1):23-31. 4. Clin Ther. 2007; 29(1):139-153. 5. Aliment Pharmacol Ther. 2013; 37(2):234-242.
MON-182 Increased Risk of Bleeding and Excessive Anticoagulation Using Standard Dose Low Molecular Weight Heparin (LMWH) in Cushing’s Syndrome
Authors: Haykal Rasha , McGlotten Raven , Bolan Charles , Kalsi Shelley , Nieman Lynnette K 
Published: May 2020

Abstract
Background: Cushing’s Syndrome (CS) is a hypercoagulable state with increased risk of venous thrombosis events (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT). In the absence of clear recommendations (1), a standard dose of low molecular weight heparin (LMWH) is given: 1 mg/kg q12h (with dose reduction for CrCl &lt; 30ml/min and low BMI). Here we report an excessive level of anticoagulation (based on standard LMWH anti-Xa levels) using standard dosing requirements in 8 of 11 patients with CS complicated by VTE who received treatment with Enoxaparin.
Methods: We retrospectively studied 6 women and 5 men with active hypercortisolism and VTE (6 PE and 5 DVT) treated with Enoxaparin given at doses below every 12 hours. Self-declared race/ethnicity were 7 white (one Hispanic), 2 unknown, 1 Asian, and 1 African. Anticoagulation therapy was monitored 4 hours after administration with measurement of LMWH anti-Xa (therapeutic range: 0.5-1.2 IU/mL).
Results: The (subsequent) etiology of CS was ectopic ACTH secretion in 6 patients (3 pulmonary NET, 3 occult) and Cushing’s disease in 5. Median age was 53 years (range 24 - 74); median BMI 34.7 kg/M2 (range 24.9 - 52.9). Median urine cortisol was 659 mcg/24h (range 122 - 32,444; nl reference range 3.5 - 45). All had CrCl &gt; 60 ml/min. 6 patients were taking a CYP3A4 inhibitor (Ketoconazole: n=5 or Mifepristone: n=1). 6/7 patients who received an initial dose of 1 mg/kg had supratherapeutic anti-Xa levels, from 1.4 - 2 IU/ml; five were on a CYP3A4 inhibitor. One died from a massive retroperitoneal bleed leading to organ failure. The other five required dose reduction; the median dose at which anti-Xa levels were at goal was 0.56 mg/kg (range 0.36 - 0.87 mg/kg). The sixth patient had an initial anti-Xa level of 0.2 IU/ml, which normalized on a dose of 1.1 mg/kg.
One patient started at 1.3 mg/kg exhibited an anti-Xa level of 1.7 IU/ml, with appropriate anti-Xa levels at a dose of 0.6 mg/kg. 3 patients started at reduced treatment doses (0.68, 0.78 and 0.87 mg/kg) exhibited therapeutic anti-Xa levels. In summary, therapeutic anti-Xa levels were achieved at a dose of approximately 1 mg/kg in only three patients (0.87, 0.96, 1.12 mg/kg); others required reduction of the usual recommended dose to between 0.36 and 0.78 mg/kg. CYP3A4 inhibitors were used in 5/8 patients with elevated anti-Xa levels.
Conclusions: Patients with Cushing’s syndrome appear to require lower than standard dose of enoxaparin; which may be only partly explained by concomitant CYP3A4 inhibitors. We suggest that anti-Xa levels be more closely monitored in CS patients to avoid morbidity and mortality caused by PE or bleeding. Further studies are needed to determine if this risk is present in patients receiving supraphysiologic doses of exogenous glucocorticoids.
1. Wagner J et al. Front Endocrinol (Lausanne). 9: 805, 2018
MON-339 Secondary Hyperparathyroidism Due to Decrease 1 Alpha Hydroxylase Activity
Authors: Bahlol Maimoona , Sacerdote Alan Scott , Bahtiyar Gul 
Published: May 2020

Abstract
•Our patient is a 63-year-old African American female with medical history significant for hypertension, class 1 obesity, osteoarthritis of knees who initially presented to the adult ambulatory clinic on 9/19/2013 with complaints of body aches and bone pain. Labs were remarkable for a serum calcium level of 9.8 mg/dl, serum phosphorous of 4.7 mg/dl, and serum parathyroid hormone level of 166 pg/ml (15-65 pg/ml), normal GFR and serum vitamin 25-OH D of 62. A DEXA scan was performed which showed mild osteopenia wof 1.0 (0.8-1.8), serum 1,25 - OH vitamin D of &lt;8 pg/ml, normal alpha and beta carotene level, negative endomysial antibodies and normal magnesium level. A diagnosis of secondary hyperparathyroidism with unclear etiology was made. Same treatment was continued and a follow up in 3 months with repeat labs was advised. Repeat PTH went up to 281pg/ml but serum calcium and phosphate remained normal. Based on normal serum 25 OH vitamin D and low 1, 25 OH vitamin D, patient was started on calcitriol 0.25 mg daily. On next follow up in 3 months PTH decreased to 203pg/ml and 1, 25 OH vitamin D level normalized (35pg/ml). MEN was excluded with normal serum free metanephrine and gastrin levels. On subsequent visits DEXA scan normalized and PTH further trended downward to 101.7 pg/ml. Patient was discharged from endocrine clinic back to the PCP. • •Patient continued to follow up in adult medicine clinic but calcitriol fall off of patient’s medication list likely due to an error. Patient was off of calcitriol for 6 months but continue to take calcium vitamin D.PTH trended up to 186pg/ml and then to 350pg/ml. A referral to endocrinology was made again and a parathyroid sestamibi scan was obtained which did not reveal any abnormal uptake. Serum calcium, phosphate, magnesium and vitamin OH 25 vitamin D remained normal. •Patient was started back on calcitriol 0.5 mg daily and PTH again started to trend downward. The last PTH was down to 82 on March 20th 2019 with normal serum calcium, phosphate, magnesium and eGFR. The final diagnosis was secondary hyperparathyroidism due to decrease 1 alpha hydroxylase activityith a T score of −1.5 at left forearm. A diagnosis of primary hyperparathyroidism was made by the PCP and patient was started on calcium vitamin D and Fosamax and was referred to endocrinology for further evaluation. • •Further testing in the endocrine clinic revealed 24-hour urine calcium of 49 mg (100-300) and urine creatinine. This case report concludes that low 1-alpha hydroxylase activity should be considered as a cause of secondary hyperparathyroidism in a patient with normal GFR and 25-OH vitamin D level
SUN-342 Effect of Hyperglycemia on Bone Mineral Density and Fracture in Pre-Liver Transplant Recipients
Authors: Abate Ejigayehu G , McKenna Amanda 
Published: May 2020

Abstract
The liver plays an important role in bone and mineral metabolism of patients with end-stage liver disease. These patients are known to have an increased risk of osteoporosis and fractures before liver transplant (LT) with reported fracture incidence of 10-56%. The cause is multifactorial, which includes their underlying liver disease, chronic illness, vitamin D deficiency, and hyponatremia. The impact of hyperglycemia and diabetes mellitus on bone health in liver transplant recipients is not known. Hypothesis: Hyperglycemia increases risk of fracture and osteoporosis in pre- LT patients undergoing LT. Methods: To answer this question, we did a retrospective chart review of consecutive first time, single organ LT recipients at our institution from 2011-2014, who had BMD performed prior to transplantation. We identified 393 patients but included only 209 patients who carried a diagnosis of hyperglycemia or diabetes (type 2 DM, type 1 DM, steroid induced DM and hyperglycemia). BMD was defined based on WHO criteria as Normal, osteopenia and osteoporosis. Hemoglobin A1C was divided into 4 quartiles (A1C ≤5.6%, 5.7-6.4%, 6.5-7.9%, and ≥8%); fasting blood glucose was defined as any venous glucose checked before 9am and labeled as a fasting lab in the chart. Fasting blood glucose was divided into those with BG&lt;100, 101-125, 126-200, &gt;200 mg/dL. We chose labs closest to the transplant date. Pre LT fracture was compared with hemoglobin A1C and BMD as well as fasting glucose. STATA statistical program was used to calculate Fisher T-test. Results: Baseline characteristics of our cohort were as follows. Median BMI was 27.9 (16.2, 45.6). Majority had hepatitis C (33%), NASH 12%, and alcoholic liver disease 23%. Average MELD score was 15 (6-40). Average wait time to transplant was 90 days. 29% of patients had normal BMD, 46% osteopenia and 25% osteoporosis. From the total 209 patients reviewed, 17 had a fracture prior to transplant of which 14/17 had vertebral fractures. The only variable that correlated with risk of fracture was hemoglobin A1C. Higher level of Hemoglobin A1C correlated with the presence of fracture p= 0.04. BMD did not correlate with fracture p= 0.28. There was no association between BMD and Fasting glucose level p=0.55. There was no correlation between fasting glucose and risk of fracture p=0.44. Discussion: This study suggests that a correlation between the presence of pre LT fracture and HgA1C exists. Other factors such as BMD and fasting BG did not correlate with fracture. Those with higher hemoglobin A1C prior to liver transplant might be at risk for fracture compared to those without diabetes or hyperglycemia (A1C &lt;5.7). Benefit of diabetes control for bone health in this population is not known, however we speculate that those with lower A1C, thus better glucose control, have a lower risk of fracture thus aggressive glucose control should be part of the pre transplant care.
SAT-597 Hypothalamic ESR1 Gene Knockdown Elicits Intermittent Decrement in Postprandial Energy Expenditure Associated with Obesity Onset in Female Rhesus Monkeys
Authors: Willging Molly , Levine Jon E , Greinwald Emily , Flowers Matthew T , Colman Ricki J , Abbott David Howard 
Published: May 2020

Abstract
Declining serum estradiol (E2) levels during the menopausal transition are associated with increased central adiposity and heightened risk for metabolic disease. Estrogenic effects on adiposity and metabolism in female rodents are primarily mediated by estrogen receptor alpha (ESR1) activation in ventromedial (VMN) and arcuate (ARC) nuclei within the mediobasal hypothalamus (MBH). The role of hypothalamic ESR1 in the menopausal transition, and in regulating body weight, body composition and energy homeostasis in female primates, however, remains unclear. To investigate the involvement of ESR1 in regulating female primate body weight, we employed RNAi technology to assess ESR1 gene knockdown throughout the MBH of adult, full-grown, ovary intact female rhesus macaques. Using MRI-guided stereotaxic targeting, adeno-associated viral vector 8 (AAV8) expressing shRNA-ESR1 (ERαKD) (n=6), or a scrambled control sequence (n=4), were infused bilaterally into the MBH to knockdown ESR1 expression. Results: ERαKD females exhibited a ~22% (+2.0 ± 0.1 kg) increase in body weight to attain 10.4±0.9 kg after ~12-24 months (mo) (p&lt;0.05), compared to ~12% increase in controls (+ 1.1±0.1 kg) attaining 9.1±1.0 kg body mass. The divergence in body weights between female groups, however, began at 6 mo. Daily calorie consumption at ~26 mo was comparable between groups. Assessments at ~28 months enabled customized metabolism cage analysis of energy expenditure (EE) corrected for fat-free mass and respiratory exchange ratio (RER). Postprandial EE (hours (h) 1-5 after once daily feeding) was inconsistently diminished in ERαKD compared to control females (1st day: ERαKD 0.087±0.001 vs. Control 0.104±0.002 kcal/min/kg, p&lt;0.0002; 2nd day: ERαKD 0.092±0.0004 vs. Control 0.095±0.002 kcal/min/kg, NS). Overnight fasted RER (hours -1 to -2 prior to feeding) tended (p&lt;0.06) to remain higher in ERαKD (1st day, 0.757±0.010, 2nd day, 0.732±0.031) compared to control females (1st day, 0.728±0.007, 2nd day, 0.728±0.060) suggesting constrained switching between lipids and other carbon sources for energy metabolism during fasting in ERαKD females. We found no significant differences in 24 hr, 12 hr light or 12 hr dark EE and RER. Overall, these findings highlight MBH ESR1 roles in regulating body weight, energy expenditure and carbon sources utilized in daily energy metabolism, and suggest a discrete MBH location for development of therapeutic targeting to combat female obesity.
SAT-464 A Case of Impending Thyroid Storm in a Patient with Subacute Thyroiditis Following an Influenza Vaccine
Authors: Stefan Simona , Hillary Whitlatch B 
Published: May 2020

Abstract
Introduction: Thyroid storm is a rare, potentially fatal condition, affecting 1% of individuals with thyrotoxicosis. Although it can theoretically be seen in any cause of thyrotoxicosis, the most likely underlying etiology is Graves’ disease. The rarity of thyroid storm due to thyroiditis makes the diagnosis challenging as the clinical and biochemical features overlap Grave’s disease. Here we describe a rare case of severe thyrotoxicosis in a woman due to subacute thyroiditis that developed after receiving an influenza vaccine.
Case report: A 30 year-old Caucasian female with no known past medical history presented to the ED with worsening sore throat, odynophagia and anterior neck pain. Symptoms began 4 weeks ago prior to presentation, 1 day after receiving an influenza vaccine. Other symptoms included loss of appetite, chills, fever, fatigue, malaise, abdominal pain, diarrhea, palpitations, heat intolerance and 5lbs weight loss. She was treated by her primary care provider for suspected pharyngitis with a course of corticosteroids and antibiotics. Two weeks later, given worsening symptoms, was referred to the emergency room. On exam, she appeared anxious and was tachycardic (124 beats per minute) and tachypneic (28 breaths per minute). She had no lid lag, stare, thyromegaly or thyroid bruit. However, there was significant tenderness on palpation of the anterior neck. Laboratory evaluation was notable for TSH &lt;0.01 uIU/mL (0.39 - 4.0.8), free T4 5.19 ng/dL (0.58 - 1.64), free T3 10 pg/ml (2.53-3.87), ESR 95 mm/hr (0-20) and CRP 9.339 mg/dl (0.0-0.9) consistent with thyrotoxicosis. Given Burh-Wartofsky score of 45, there was a concern for impending thyroid storm. She received hydrocortisone, methimazole and beta blockers and was admitted to the intensive care unit. She responded dramatically to treatment and was discharged within 24 hours on prednisone and metoprolol. The 24-hour radioactive iodine uptake (RAIU) was 2.7% 2 weeks post admission, consistent with a diagnosis of subacute thyroiditis. TSI was negative. Family history was negative for autoimmune disease. She continued on beta blockers with a steroid taper for 8 weeks. Thyroid function tests and inflammatory markers normalized within 3 months.
Conclusion:
Aside from the described patient, only three other cases of thyrotoxic crisis due to subacute thyroiditis have been reported in the literature. This case underscores the importance of thoroughly investigating the etiology of severe thyrotoxcosis, given the management and prognosis varies depending on underlying cause. Thyroiditis should be considering in the differential diagnosis of thyroid storm in patients who do not have a personal or family history of autoimmunity and present with neck tenderness in the setting of a precipitating event. Subacute thyroiditis is very uncommon after influenza vaccine, there have been 4 reported cases.
SUN-416 Fatigue and Quality of Life Among Thyroid Cancer Survivors
Authors: Yukari Maki 
Published: May 2020

Abstract
BACKGROUND Fatigue among thyroid cancer survivors is an important issue that needs to be appreciated and managed appropriately. Although several studies have reported potential factors that might be related to postoperative fatigue, the associations have yet to be inconclusive. The purpose of the present study was to estimate the prevalence of clinical fatigue in patients with papillary thyroid carcinoma and to reveal predictive factors, including their quality of life. METHODS A cross-sectional survey was conducted on patients with papillary thyroid carcinoma. Patients who underwent non-curative surgery, or those with recurrent or metastatic PTC, or those with other malignancies were excluded. The primary outcome was fatigue measured by the Cancer Fatigue Scale (CFS), and the secondary outcome was quality of life (QoL) quantified using the SF-36 v2. The following explanatory variables were collected; gender, age, employment status, marital status, co-morbidities, time since initial surgery, types of surgery, replacement of thyroid hormone, use of radioactive iodine, and the level of thyrotropin. The prevalence of clinical fatigue was estimated with the cut-off value of 18/19 of the CFS score. Correlations between the CFS score and the explanatory variables were examined using uni-variable analyses as well as multi-variable analysis. RESULTS Three hundred twenty-one patients participated in the survey. Of them, 258 respondents (80%) were female. The median age was 58 years, and the median time from initial surgery was 6.4 years. The mean and the standard deviation of the CFS score were 17.9 and 9.3, respectively (range: 0-48). The prevalence of clinical fatigue was 42% [95%CI: 36-47%]. Among the variables explored, having a job and scores of the mental component summary, the physical component summary, and the role/social component summary of the SF-36 were inversely associated with the CFS score in both uni- and multivariable analyses. CONCLUSION Postoperative fatigue was common in thyroid cancer survivors. Patients with a job and better QoL, in particular, those with good mental health, maybe at low-risk of developing the burden.
MON-061 A Case of Central Precocious Puberty Patient with Arnold Chiari Malformation, Type I
Authors: Kim Dae Hyun , Choi Ju-hee 
Published: May 2020

Abstract
Central precocious puberty (CPP) is caused by early activation of Hypothalamo-Hypophyseal-Gonal (H-P-G) axis. Although the cause of CPP is idiopathic in most cases, small portions of CPP are caused by intracranial lesion such as hypothalamic hamartomas, postencephalitic scars, tubercular meningitis, head trauma, hydrocephalus, tuberous sclerosis, arachnoid cyst, etc. Type I Chiari malformation is a disorder characterized by a displacement of the cerebellar tonsils through the foramen magnum into the upper cervical spinal canal with various neurologic symptom. There have been some reported cases of Arnold-Chiari type I malformations with CPP, however this association is not yet completely understood. We would like to introduce a case of girl experiencing Arnold Chiari type I malformation as well as CPP, who presented with progressive breast budding and acceleration of growth. A 8-year-old girl was presented with 6month history of breast budding and acceleration of growth (5cm/7month). Her family history demonstrated that her mother had been treated with prolactinoma and experienced early menarche. On physical examination, she showed Tanner stage 2(B2, P1). She did not exhibit any neurological signs or symptoms. Thyroid gland was not enlarged and No abnormal skin pigmentation or bony abnormalities were identified. Her height was 124.9cm (37th percentile), weight was 22.4kg (14th percentile), while midparental height was calculated to be 159cm (father: 174cm, mother: 157cm). Her bone age was assessed to be 10 years of age. Luteinizing hormone(LH) showed pubertal response (peak LH: 9.9IU/L) in Luteinizing Hormone Releasing Hormone (LHRH) stimulation test. The abdominopelvic US revealed pubertal response of uterus(length 4.1cm, endometrial echogenicity) without any other abnormality. We performed brain Magnetic Resonance Imaging(MRI) for rule out intracranial lesion, which showed Arnold-Chiari type 1 malformation (downward displacement of the cerebellar tonsil by 6 mm). Following diagnosis, Her parents wanted further neurologic evaluation and treatment in Canada, beacause she was Canadian. In conclusion, Arnold-Chiari type 1 malformation can be a possible cause of CPP without neurological symptoms in children, more cases are needed to clarify the relationship and evaluate reasonable causes of Arnold-Chiari type 1 malformation in the brain, especially in young patients with precocious puberty.