bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-920 Familial Paraganglioma Syndrome: A Rare Case of Secondary Hypertension in Young People
Authors: Miranda Gonzalo 
Published: May 2020

Abstract
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 (&lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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&lt;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

Abstract
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&lt;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

Abstract
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&lt;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 &lt;=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 &lt;=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

Abstract
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

Abstract
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.