bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 < 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 > 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

•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 <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

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<100, 101-125, 126-200, >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 <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

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<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<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<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

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 <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

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

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.
SUN-920 Familial Paraganglioma Syndrome: A Rare Case of Secondary Hypertension in Young People
Authors: Miranda Gonzalo
Published: May 2020

Paragangliomas are rare tumors originating in the autonomic nervous system, whose clinical manifestations are the result of excessive production of catecholamines.

We present a case of a 26-year-old female with 5 years of disease characterized by episodic profuse sweating, headaches and high blood pressure refractory to antihypertensive treatment. She also had intermittent palpitations which intensified 1 month before admission. Patient was cataloged with diagnosis of endocrine hypertension. She had elevated urinary fractionated metanephrines, elevated plasma normethanephrin and plasma chromogranin A (CgA). Subsequently, an abdominal CT study was performed, finding a solid ovarian mass of defined edges located in retroperitoneal space, an intercave region immediately preceding the L2-L3 intervertebral disc that measured 26.2 x 23.9 x 28.8 mm. It was also found bilateral tumours at cervical level of 14 mm in right side and 10 mm in left side, suggestive of paranganglioma by magnetic resonance imaging (MRI).

With a suspected diagnosis of paraganglioma of Zuckerkandl’s organ, beta and alpha-adrenergic blockage were carried out and surgical intervention was done by a block resection of the tumour. Anatomopathological diagnosis confirmed the suspicion of well-delimited capsulated paraganglioma of 2.0 X 1.0 X 0.3 cm, with low mitotic index (<2) and a result of positive sinaptophisin by immunohistochemistry. She reached complete remission and normal determinations in urine of catecholamines and methanephrines. Currently the patient is in follow-up with favorable evolution and succinate dehydrogenase type B (SDHB) gene test is pending.

Despite infrequency of paragangliomas, it is important to take them into account in the differential diagnosis of hypertension, especially in young patients, due to their malignant potential and the effects of catecholamine secretion on the cardiovascular system.
SUN-591 PAPP-A Inhibition - a Novel Anti-Obesity Therapeutic Approach
Authors: Ramakrishna Akhila , Conover Cheryl A
Published: May 2020

Background: Adipose tissue is a heterogeneous endocrine organ with tremendous capability for expansion. The antithetical pathogenicity of visceral adipose tissue (VAT), compared to subcutaneous adipose tissue (SAT), has been linked to the metabolic stress of enlarging mature adipocytes and a limited ability to recruit new adipocytes. One of the major distinguishing features of VAT preadipocytes is the high expression of Pregnancy Associated Plasma Protein–A (PAPP-A) when compared to SAT. PAPP-A is a zinc metalloprotease that is secreted, and can associate with the cell surface in an autocrine or paracrine fashion. It is the only known physiological IGFBP-4 (Insulin-like Growth Factor Binding Protein) protease. It cleaves the IGF/IGFBP-4 complex, releasing IGF, making it more bio-available for receptor engagement and downstream signaling. The role of IGFs in adipogenic differentiation is well established. While there is quantitative depot-specific variability in PAPP-A expression among preadipocytes, mature adipocytes do not express any PAPP-A. These findings suggest that there may be a relationship between PAPP-A inhibition and adipogenic differentiation and maturation. Similar to human VAT, PAPP-A expression is highest in visceral fat in murine models. The PAPP-A KO mice, when fed a high fat diet, showed restrained visceral adiposity and decreased visceral adipocyte size, suggesting that PAPP-A could regulate adipogenesis locally in tissues that express high PAPP-A.

Hypothesis: PAPP-A inhibition is a novel anti-obesity treatment strategy. Methods/Results: We fed 20 male and 20 female wild type mice 42% high fat diet (HFD) starting at 10 weeks of age. Concomitantly, we treated 10 mice in each group with either mAb-PA1/41 (a PAPP-A neutralizing monoclonal antibody) or IgG2a (control isotope), intraperitoneally at a dose of 30 mg/kg weekly for the duration of the HFD. At the end of 15 weeks, the mice were sacrificed and the adipose tissue, serum and solid organs were harvested.

Compared to the control (IgG2a) mice, the mAb-PA1/41 treated male and female mice gained 40% less weight (P = 0.03) and had smaller visceral fat depots (mesenteric and pericardial). Also, when we looked at individual adipocyte size, the drug treated mice had 45% smaller mesenteric adipocytes (P = 0.002) and 44% smaller pericardial adipocytes (P= 0.003). Also, the visceral depots in the drug treated mice had 30% more cells (P = 0.006). In both groups, there was decreased liver lipid content (P=0.005). The mAb-PA1/41 treatment had no significant effect on subcutaneous fat depots.

Conclusion: Pharmacologic inhibition of PAPP-A decreased weight gain, visceral fat depot weight, visceral adipocyte size, hepatic lipid deposition and increased visceral adipocyte cell number in both male and female mice that were fed a high fat diet.
MON-519 In Silico Analysis of rs1042522 and rs1042522 Polymorphic Variants of TP53 Gene
Authors: Bó Izabela Dal , Teodoro Larissa , Peres Karina Colombera , Teixeira Elisangela Souza , Bufalo Natassia Elena , Ward Laura Sterian
Published: May 2020

The TP53 gene encodes the p53 protein which is a nuclear phosphoprotein that plays a key role in cell cycle regulation, especially in the transition from G0 to G1. It is located on chromosome 17 at position p13.1 and found at very low levels in normal cells, but it is expressed in large quantities in damaged cells. The most frequent alterations in the TP53 gene are point mutations that cause alteration in the base sequence, resulting in a defective protein. The most frequent alteration occurs in codon 72 (rs1042522). P72R shows an exon 4 polymorphism of the TP53 gene where it there is a substitution of an arginine (Arg) by a proline (Pro). This variant is associated with sporadic thyroid cancer. In addition, codon 72 variants decrease p53’s ability to activate apoptosis and are associated with some autoimmune diseases like Graves’ disease. The codon variant 47 (rs1800371) P47S has a rare polymorphism in the p53 N-terminal transactivation domain that replaces the serine-like wild-type proline (Ser). This variant is associated with impaired pro-apoptotic p53 activity therefore also increasing the risk of cancer. In order to better understand the role of SNPs (rs1042522) and (rs1800371), based on data obtained from the NCBI dbSNP database and UniProt, we evaluated the effect of amino acid alteration on protein structure. We used bioinformatics tools such as SIFT (Sorting Intolerant from Tolerant), Align GVGD, PolyPhen-2, SNAP (Screening for nonacceptable polymorphisms), PANTHER (Protein Analysis Through Evalutionary Relationships), PredictSNP, nsSNPAnalyzer, PROVEAN, SNP & GO, PMut and MuPRO. Rs1042522 and rs1800371 bioinformatic analysis suggested that the amino acid change alters protein structure (Align GVGD tool), decreases the stability (MuPro tool) and function (SNAP) of the protein. SNPs & GO confirmed an association of these polymorphisms with different diseases. We conclude that SNPs rs1042522 and rs1800371 are important in the process of tumorigenesis, corroborating findings from our group and others that suggest that they difficult the action of p53 protein.
SUN-734 The Role of Chromatin-Associated LncRNA161 in Estrogen-Dependent Transcription
Authors: Le Ilene , Choudhari Ramesh , Yang Barbara , Ramos Enrique I , Sedano Melina , Gadad Shrikanth S
Published: May 2020

Long noncoding RNAs (lncRNAs) have been identified to play a role in the progression of many different types of cancer. Some biological processes that are involved with lncRNA include but are not limited to chromatin organization, transcriptional and post-transcriptional gene expression, and protein and transcript trafficking. When lncRNAs are aberrantly expressed, disruption in the biological processes can cause tumor proliferation and progression leading to cancers. Studies have shown the role of lncRNAs in association with breast cancers. While estrogen receptor alpha positive (ERα+) breast cancer responds well to anti-estrogen treatment, the cancer can become refractory. With breast cancer as one of the leading causes of mortality in women, deeper understanding of lncRNAs can establish it as a potential therapeutic target. It will be determined the functional mechanisms by which lncRNAs, specifically lncRNA161, drives hormone-resistance in breast cancer. LncRNA161 was selected from a comprehensive list of lncRNAs due to it being expressed in reproductive tissue, being tamoxifen resistant, being robustly regulated by estrogen, and its association with the chromatin. It was determined that lncRNA161 was upregulated in breast cancers. When lncRNA161 was treated with estrogen, there was transcriptional activation and localization to the chromatin. Subsequent knockdown of lncRNA161 affected other genes in the estrogen signaling pathway. Overexpression of lncRNA161 demonstrated increased proliferation, and knockdown showed decreased proliferation indicating a role of lncRNA161 in tumor proliferation and progression in breast cancer. Altogether, the results suggest lncRNA161’s involvement in the estrogen signaling pathway and establish it as a potential therapeutic target in hormone-refractory breast cancer. Supported by grant from the Cancer Prevention and Research Institute of Texas to S.S.G.
OR20-07 Placentas from Obese Women Are Resistant to the Effect of Insulin on Triglyceride Content Ex Vivo
Authors: Anam Anika K , Cooke Katherine , O’Bryan Jane , Vijayakumar Pavithra , Vatner Daniel , Flannery Clare Ann
Published: May 2020

Background: Obesity affects 25% of pregnant women and is associated with a higher risk of neonatal complications, such as macrosomia and increased adiposity. The placenta may contribute to neonatal adiposity by accumulating and transferring excess lipid in response to maternal hyperinsulinemia. We previously found that insulin promotes a 3-fold increase in placental triglyceride (TG) content in lean women. We hypothesized that obese women have higher placental insulin resistance compared to lean women[FC1] with respect to TG content. Methods: Healthy, lean women (n=12; mean age 34±1 yrs; BMI 22±0.4 kg/m2) and non-diabetic, obese women (n=9; mean age 32±2 yrs; BMI 33±0.4 kg/m2, p<0.0001) consented for placenta collection at elective c-section under fasting conditions. Placental villous explants were immediately flash frozen or cultured for 24 hours, starved, then treated for 48 hours with 0.1nM, 1nM, 10nM, or 100nM of insulin, or vehicle. Lipids were extracted from basal and treated explants using a chloroform-methanol separation protocol. TG content was quantified by spectrophotometer and normalized to weight. Data were analyzed by two-way ANOVA. Results: Basal placenta tissue from obese women contained a 1.5-fold higher level of TG compared to lean women (9.4±0.5 vs 5.7±0.5 mcg/mg, p=0.001). Placental response to insulin in lean women peaked at 1nM insulin (20.2±3.3 mcg/mg), and plateaued at higher doses of 10nM (18.6±3.3 mcg/mg) and 100nM (22.8±2.8 mcg/mg, p=NS respectively). In contrast, placenta explants from obese women required the highest insulin dose of 100 nM for maximal response (23.6±3.2 mcg/mg), and showed a gradual dose response from 0.1 nM insulin (9.5±2), 1nM (14.8±2), 10 nM (16.9±3). At 100nM insulin, the difference in TG content was variable, but on average was 2-fold higher than vehicle treated placenta (vs 11.8±2.5[FC2] [AA3] mcg/mg, p=0.002). Conclusion: Our findings indicate that placenta from obese women develop insulin resistance similar to peripheral tissues, which can be overcome by high insulin doses. This placental insulin resistance likely occurs in response to chronic hyperinsulinemia, leading to interference of insulin signaling pathways, and may protect the neonate from excessive nutrient flux.
SUN-935 Invasive Neuroendocrine Breast Carcinoma Presenting as Liver Metastases
Authors: Das Dhriti , Fields Steven , Cortes Anais
Published: May 2020

Introduction:

Primary neuroendocrine carcinoma of the breast is rare and must be differentiated from metastatic neuroendocrine carcinoma from the gastrointestinal tract.

Clinical Case:

A 66-year-old white female presented to the outpatient clinic complaining of abdominal fullness with unintentional weight loss of over 30 pounds over 3 months. She had no nausea, vomiting, diarrhea, or constipation. During initial evaluation, she had hepatomegaly with the liver edge palpable 4 cm below the costal margin. Laboratory studies are within normal limits except for elevated alkaline phosphatase at 369 U/L (n<130 U/L).

A CT scan of the abdomen and pelvis with contrast showed extensive malignant lesions involving the liver consistent with prior hepatocellular carcinoma versus metastatic disease. Patient had a colonoscopy and esophagogastroduodenoscopy in an attempt to identify a primary gastrointestinal malignancy, but both studies were unremarkable. Ultrasound guided biopsy of the liver masses revealed malignant cells with morphologic features that were suggestive of metastatic neuroendocrine carcinoma.

The patient was started on monthly intramuscular octreotide 30 mg. She had a Gallium-68 dotatate scan showing increased uptake in the area of several large heterogeneous necrotic tumors throughout the liver, and in the left sixth posterolateral rib. The maximum uptake was noted in a 3.7 cm x 3.5 cm ovoid mass in the right breast. The patient admitted to noticing a mass in her right breast which decreased in size after her initial dose of octreotide. She had not had a mammogram in several years and refused a breast exam during initial evaluation. The patient was sent for mammography and ultrasound as well as for biopsy of the breast lesion.

Results of the breast biopsy showed intermediate grade neuroendocrine tumor of the breast. The patient underwent right total mastectomy with lymph node staging, and intraoperative pathology identified neuroendocrine carcinoma of intermediate grade in the right breast and right axillary lymph nodes, and macrometastatic carcinoma in a right axillary tail lymph node. Immunohistochemistry showed the malignant cells were chromogranin and synaptophysin positive. They were also estrogen receptor positive. The cells were negative for progesterone receptor and human epidermal growth factor receptor 2.

The patient follows up regularly with oncology and continues to receive monthly doses of octreotide. She was also started on exemestane and had Yittrium-90 radioembolization of liver metastases.

Conclusion:

Patients with neuroendocrine carcinoma of the breast rarely present with clinical conditions related to hormonal hypersecretion as in neuroendocrine carcinoma of the GI tract but respond to treatment with somatostatin analogs.
SAT-395 Correlations Between Biochemical Parameters and Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP) Patients
Authors: Santos Lívia Marcela , Ohe Monique Nakayama , Pallone Sthefanie Giovanna , Kunii Ilda Sizue , Silva Renata Elen Costa , Pereira Bruno Gabriel , Nacaguma Isabela Ohki , Vieira Jose Gilberto , Lazaretti-Castro Marise
Published: May 2020

Background: Vitamin D deficiency is common among PHP patients. While data are limited, some studies suggest that vitamin D deficiency may exacerbates skeletal disease in PHP. TBS is a software-based method for assessment of trabecular bone structure of the spine, based on analysis of pixels obtained in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS, vitamin D status, clinical and laboratorial measurements in a PHP group of patients in a search for a more accurate bone fragility test for risk assessment in this group of patients.

Methods: From June/2017 to January/2019, patients who met the criteria for PHP diagnosis were included in this study. Control group was composed by age and sex-matched healthy individuals. Overall, 64 PHP and 63 controls were enrolled. Bone mineral density (BMD) measured by DXA (Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, and TBS values (InSight™) were determined in both groups. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured. None were in use of Vitamin D supplementation.

Results: As expected, PHP patients had lower BMD values than controls in all sites (p<0.0001). TBS measurements were also reduced in PHP patients compared to controls (1233 vs 1280, p=0.0444). TBS values were inversely correlated with total calcium (CaT) and phosphorus measurements were positively correlated in the PHP patients. 25(OH)D measurements didn’t differ between groups (PHP 22.5 vs. controls 19.8 ng/mL, p=0.1699). There was a positive correlation between 25(OH)D and TBS in both PHP and controls (r= 0,3088, p= 0,0138 and r= 0,3708, p= 0,003 respectively). Considering individuals with vitamin D deficiency (25(OH)D levels <=20 ng/mL), a negative correlation between TBS and CaT measurements among PHP patients (r= -0,4391, p=0,0172) was observeed, while in controls there was a positive correlation between TBS and 25(OH)D (r= 0,3504, p= 0,0362).

Conclusion: Serum total calcium presents negative correlation and phosphorus a positive one with TBS in PHP patients. We also found a correlation between TBS and 25(OH)D, both in PHP and in controls. 25(OH)D <=20 ng/mL is an independent risk factor determining degraded TBS among PHP patients and controls.
SAT-710 Comparative Histopathology of Endocrine Glands in Phthalate Exposed Male Wistar Rats Unveil the Vulnerability of Adrenal Gland and Augmented by Molecular Docking
Authors: Ahmad Shahzad , Raisuddin Sheikh
Published: May 2020

Limited research has been conducted on adrenal gland as a target of endocrine-disrupting chemicals (EDCs). Moreover, studies on steroidogenesis as the target of EDCs has also attracted lesser attention compared to other metabolic pathways. We studied the effects of two extensively used phthalate esters viz., di-ethyl hexyl phthalate (DEHP) and di-butyl phthalate (DBP) on the adrenal gland in Wistar rats and checked its susceptibility against the exposure of these extensively used phthalates categorized as EDCs. Male rats were divided into seven groups (n = 6). Group I (control) received only corn oil (as a vehicle). Group II, III and IV were treated daily with DEHP at the dose of 250, 750 and 1500 mg/kg-BW respectively per os for 14 days. Group V, VI and VII were treated with a daily dose of DBP 100, 500 and 1000 mg/kg-BW respectively per os for 14 days. The comparative histological observation of endocrine glands i.e., pituitary, pineal, thyroid, parathyroid, adrenal gland and testes unveil that changes in adrenal gland towards the DEHP and DBP were more remarkable compared to other endocrine glands. Glucocorticoid biosynthesis pathway in the adrenal gland was analyzed by molecular docking of DEHP and DBP with the enzyme proteins involved in the pathway using Maestro Schrodinger 9.4 software. It showed the potential of DEHP and DBP to inhibit these proteins comparable to the known inhibitors of enzymes involved. The present study used a novel approach of in silico and in vivo to elucidate the sensitivity of adrenal gland towards EDCs through the analysis of the sensitivity of adrenal steroidogenesis on exposure to two widely distributed phthalates with environmental and human health risk potential.
SAT-255 Pituitary Adenoma With TSH and GH Co Secretion
Authors: Riquelme Romina , Romero Fabiola , Infante Maria de Jesus , Cabrera Francisco , Gonzalez Elena , Galeano Sandra , Arzamendia Sady , Espinoza Grecia , Valinotti Elizabeth , Ayala Alejandro
Published: May 2020

Introduction:

Thyrotropinomas are rare pituitary adenomas, representing 2% of pituitary tumors.

They are characterized by autonomous secretion of thyrotropin (TSH) and elevated levels of peripheral hormones.

A third can secrete other hormones, including growth hormone (GH).

We present the case of a patient with hypersecretion TSH and GH with clinical manifestations.

Clinical case:

44-year-old woman with a history of palpitations and weight loss of 8 kilos of 3 months of evolution, as well as decreased visual acuity and headache.

Physical exam: tachycardia, fine tremor, prognathism, thickening of the lips, increase in the base of the nose, hands and feet.

TSH; 8.8mU / L (0.4-4), FT4: 35.59pg / ml (8-17), GH: 3.93 (less than 1.88), IGF-1: 716ng / ml (101-267), ANTI TPO negative, FSH, LH, Estradiol, Prolactin, Cortisol in range. Thyroid profile is repeated: TSH: 12.92mIU / ml (0.34-4.94); FT4 and T3 high.

Campimetry: left temporal hemianopia

Pituitary MRI: a heterogeneous 51x42x47mm Turkish chair mass with sphenoid sinus invasion and right cavernosum with vascular structures encompassing.

Thyroid ultrasound: normal

Methimazole and octeotride LAR are initiated and in June 2018, a transcranial approach and partial resection of the pituitary macroadenoma is performed.

In August 2019, hormonal profile IGF1: 470 ng / ml, TSH: 2.7 uUI / ml, T3 207 ng / dl.

Pituitary MRI showing evidence of selar, sphenoid expansive lesion with bilateral carotid invasion, bitemporal hemiapnosia, acromegalics facial features and acral growth without signs of hyperthyroidism.

Neurosurgery decides to perform a tranesphenoidal approach and partial tumor resection without postoperative complications; The immunohistochemical study reveals GH positive, nonspecific TSH, KI 7% P53 20%. LAR octeotride is suspended.

In September 2019, the homonal profile reports IGF1 177ng / ml, TSH: 4.39 uUI / ml, FT4 7.14 ug / dl and T3 50ng / dl, the signs of acromegaly disappear.

Discussion.

Thyrotropinomas are rare, even more so if they are multi-hormonal, usually they secrete one hormone or another or they are silent. Thyrotropic and somatotropic cells share common transcription factors: Pit-1 and Prop-1.

Most of these tumors are silent or manifest clinically with TSH secretion. The case presented has the particularity of expressing clinical characteristics of both GH and TSH secretion.

Preoperative treatment with somatostatin analogues can reduce tumor size and control hormonal hypersecretion. Radiation therapy is an alternative in case of unsatisfactory results after surgery.

Multi-hormonality predicts a higher risk of recurrence than the secretory tumors of only one hormone, so monitoring these patients is essential.
OR29-04 TGFβ Regulates Bone Perilacunar/Canalicular Remodeling in a Sexually Dimorphic Manner
Authors: Dole Neha , Alliston Tamara
Published: May 2020

Sexual dimorphism in the material properties of bone extracellular matrix (ECM) and geometry, which are parameters of bone quality have been recognized (Alswat, 2017; Nieves et al., 2005). However, the molecular mechanisms responsible for dimorphic bone quality remain unclear, limiting our ability to therapeutically target fragility, which is determined by bone quality. Recently, using male mice, we found that systemic or osteocyte-intrinsic inhibition of TGFβ signaling (TβRIIocy-/-), suppresses perilacunar/canalicular remodeling (PLR) and compromises bone quality (Dole et al., 2017). Since we previously demonstrated that female bone mass is more sensitive to TGFβ (Mohammad et al., 2009), we hypothesized that loss of osteocytic TGFβ in females will lead to more severe deterioration of PLR and bone quality.

Analysis of female bones, however, surprisingly revealed sexual dimorphism in the TGFβ regulation of osteocyte function. While the male TβRIIocy-/- mice demonstrated reduced trabecular bone mass and repression in expression of requisite PLR genes, including matrix metalloproteinases (Mmp2, Mmp13, and Mmp14), cathepsin K (Ctsk), and tartrate-resistant acid phosphatase (Acp5/TRAP) (Qing et al., 2012), the female TβRIIocy-/- bones were intact. With absence of osteocytic TGFβ signaling, the canaliculi of male TβRIIocy-/- osteocytes were truncated and a severe deterioration of lacuno-canalicular network (LCN) was observed. Unlike the male TβRIIocy-/- mice that exhibited poor bone quality, female TβRIIocy-/- bones were completely protected from bone quality defects and macromechanical bone fragility. Thus, TGFβ-dependent regulation PLR and bone quality is sexually dimorphic.

Since, lactation is a potent PLR agonist, we also evaluated the lactation-induced PLR response of TβRIIocy-/- female mice. Compared to WT, lactation-induced bone loss and upregulation of PLR genes was significantly attenuated in the TβRIIocy-/- female mice. Lactation-mediated increases in osteocyte lacunar volume were suppressed in TβRIIocy-/- bones as well. This mitigation in PLR of lactating TβRIIocy-/- mice was analogous to that observed in mice with osteocyte-specific ablation of parathyroid hormone type I receptor (PTHR1) (Qing et al., 2012). Remarkably, lactation-inducible PTHR1 expression was also diminished in TβRIIocy-/- osteocytes. Therefore, osteocyte-intrinsic TGFβ signaling is critical for the maximal induction of PLR during lactation, and TGFβ is an upstream regulator of PTHR1-dependent activation of osteocytic PLR. Indeed, we also found sexual dimorphism in the regulation of osteocytic PTHR1 expression by TGFβ, such that male, but not female, TβRIIocy-/- mice had reduced PTHR1 compared to WT.

In summary, we identify a novel PTH-dependent mechanism that protects female bone against the severe bone fragility that results from suppressed TGFβ signaling in osteocytes.
SAT-LB76 Impact of Glucocorticoid Cosecretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease
Authors: Handgriff Laura , Adolf Christian , Heinrich Daniel , Braun Leah , Ladurner Roland , Ricke Jens , Seidensticker Max , Bidlingmaier Martin , Reincke Martin
Published: May 2020

Context: Excess aldosterone is associated with the increased risk of cardio- and cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects.The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation.

Patients and Methods: 97 PA patients (43 with unilateral, 54 with bilateral PA) from the database of the German Conn’s Registry were included. Anti-TPO and anti-TG levels were measured pre and 6 to 12 months post therapeutic intervention. Patients were assessed for ACS according to their 24h urinary cortisol excretion, late night salivary cortisol and low-dose dexamethason suppression test.

Results: Abnormal test results in line with ACS were identified in 74.2% of patients. Significant increases in anti-TPO levels were observed in adrenalectomized patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy.

Conclusion: ACS appears to be a relevant factor in PA affecting thyroid autoimmune disease. The biochemical and clinical course maybe be exacerbated after resolution of hypercortisolism by adrenalectomy in PA.