bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-009 Variable Presentation of Two Patients with Gestational Trophoblastic Disease and Hyperthyroidism
Authors: Chale-Matsau Bettina , Mokoena Samantha , Kemp Tanja , Pillay Tahir S 
Published: May 2020

Abstract
Background: Gestational trophoblastic disease (GTD) represents a group of tumours caused by abnormal proliferation of trophoblastic cells, including molar pregnancy. Elevated β-hCG levels are an established marker for the presence of the disease and useful for monitoring. Due to the shared structural homology of β-hCG and TSH, hyperthyroidism can occur.
Clinical Cases: We present two patients with GTD associated with hyperthyroidisim. Case 1, a 20 year old female (G1P0) presented to the emergency department complaining of vaginal bleeding associated with abdominal pain. She was estimated to be 13 weeks. Laboratory evaluation were β-hCG 648 324 IU/L, TSH 0.06 (0.35 - 4.94 mIU/L, free T4 23.2 (9.0 - 19.0 pmol/L, Hb 8.0 (11.6 - 16.4 g/dL). Ultrasound revealed molar pregnancy. She underwent uterine evacuation, thereafter complicated with thyroid storm (Burch Wartofsky score = 45). Post- operative vitals were BP 192/112, pulse rate 120 bpm and temperature 360C. She was managed in high care on labetolol, carbimazole, lugol’s iodine and hydrocortisone.
She was subsequently referred to Medical Oncology for further management. Histology sample obtained in theatre confirmed complete molar pregnancy.
Her staging CT scan indicated the presence of small lung nodules, suggesting metastatic disease. The patient’s FIGO/WHO score was III: 2. At the time of preparing this study, she had already received 7 weeks of methotrexate intramuscularly and still had detectable β-hCG levels.
Case 2 was a 31 year old female presented similarly. This was her second pregnancy (G2P1), 12 weeks by dates. Her vitals were BP 141/74, pulse rate 110 bpm and temperature 36oC. The Ultrasound revealed larger for gestational age uterus with cystic structures in utero. Her quantitative β-hCG was significantly elevated (&gt; 1 500 000 IU/L) she was thyrotoxic [TSH (&lt;0.1 (0.34 - 4.94 mIU/L) free T4 (47.2 (9.0 - 19.0 pmol/L)], however did not develop thyroid storm (Burch Wartofsky score = 20). This patient also underwent uterine evacuation and did well post operatively. She was treated for her thyrotoxicosis with carbimazole, propranolol and thiamine. Further management was by Medical Oncology. Histological examination was in keeping with a partial mole.
Her staging CT scan showed no metastasis, and had a FIGO/WHO score of 1: 4 due to her pre-treatment hCG of &gt;1.5 million IU/L. She received 7 cycles of intramuscular methotrexate from which she achieved and maintained suppressed β-hCG levels (&lt;1 IU/L).
Conclusions: This study has demonstrated that the β-hCG levels may not always correlate with disease severity and prognosis.
When comparing the two patients Case 1 had lower levels of β-hCG and of free T4 than Case 2, however was clinically more unwell, developed thyroid storm and had metastatic disease. Case 2 had hCG levels almost double those of Case 1, wsa stable and her levels decreased much quicker reaching undetectable levels
OR12-03 Mineralocorticoid and Glucocorticoid Receptors Adopt Distinct Quaternary Structures and Can Form Heteromultimers That Affect Chromatin-Binding Profiles
Authors: de la Rosa Diego Alvarez , Johnson Thomas A , Fettweis Gregory , Hager Gordon L 
Published: May 2020

Abstract
The mineralocorticoid and glucocorticoid receptors (MR and GR) are evolutionarily related nuclear receptors with high sequence conservation and a shared hormone response element (HRE). Both receptors are activated by glucocorticoids, but MR can be selectively activated by aldosterone. Using the imaging technique Number & Brightness (N&B) it has recently been proposed that liganded GR dimers form tetramers upon binding to HREs in live cells. We now show that agonist-bound MR adopts a tetrameric organization in the nucleoplasm and forms complexes with an average of 7 receptor units upon binding an HRE. Interestingly, MR antagonists eplerenone and spironolactone induced intermediate oligomerization arrangements, strongly suggesting that higher order oligomerization is essential for receptor activity. Site-directed mutagenesis and deletion analysis suggest that the N-terminus of MR is a main determinant of higher order oligomerization. Both with corticosterone and aldosterone, GR can incorporate into MR complexes partially displacing MR monomers. Genome-wide chromatin binding studies suggest that the presence of GR in the same cells profoundly change MR interaction with distinct sets of enhancers in a ligand-dependent way, contributing to receptor-specific signaling. Certain genes respond to only one receptor while others respond to both receptors. The interaction of these two closely related receptors has important implications for the mechanisms for glucocorticoid signaling and transcription factors in general.
SAT-725 Alterations in the Phenotype and Epigenomic Landscape of Luminal Breast Cancer Following Long-Term Nanomolar Exposure to Bisphenol a (BPA)
Authors: Liwag Jason Tan , Velarde Michael Cu , Bagamasbad Pia Dano 
Published: May 2020

Abstract
Breast cancer (BCa) is the leading cause of female cancer-related death worldwide. Luminal BCa accounts for at least 70% of all BCa and is characterized by its hormone dependence, particularly to estrogen. Endocrine disruptors may function to exert the pro-tumorigenic effects of estrogen in proxy following environmental exposure. Bisphenol A (BPA) is a ubiquitous endocrine disruptor shown to increase risk towards developing BCa in multiple in vivo mammalian models and in vitro human breast models. Despite this, there is limited information on the phenotypic and epigenetic effects of nanomolar BPA following long-term exposure particularly in the context of BCa stem cell population, which accumulate the ‘cellular insult’ and are likely to pass such information down through epigenetic mechanisms. We hypothesize that BPA affects the epigenome, in part, by altering the regulation of DNA methyltransferases (DNMTs) since BPA disrupts transcriptional and translational regulation of DNMTs in various other tissue types such as the brain, testis and prostate. In this study, MCF7 cells were chronically (&gt;4 weeks) cultured with nanomolar doses of BPA, and subsequently subjected to phenotypic assays and gene expression analysis in monolayer or mammosphere culture. Gene expression analysis revealed a downregulation of DNMT3A and ESR1 following long-term exposure to BPA in mammosphere culture of MCF7 cells, but not in monolayer culture. This is accompanied by alterations in mammosphere morphology, reduction in mammosphere size, an increase in the mammosphere number, and an increase in the CD49f+ population, indicating a positive contribution of BPA to stemness. However, there are no significant changes in proliferation, apoptotic rate, and metastasis in both monolayer and mammosphere culture. Future analysis includes assessment of genome-wide alterations in DNA methylation patterns in these chronically exposed MCF7 mammospheres, as well as identifying estrogen responsiveness, chemotherapeutic response, and self-renewal properties of these cancer cells.
SUN-423 Impact of Hyperthyroidism and Its Treatment on the Outcome of Mental Health, Occupational Functioning and Quality of Life - a Prospective Study
Authors: Chopra Roopa , Kalaria Tejas Kumar , Gherman-Ciolac Carolina , Raghavan Rajeev , Viswanath Ananth , Buch Harit , Kar Nilamadhab 
Published: May 2020

Abstract
Hyperthyroidism is known to be associated with psychiatric symptoms such as anxiety and depression, impartment of functioning and poor quality of life (QOL).
It was intended to study the outcome of anxiety, depression, ability to work and QOL following the treatment of hyperthyroidism in endocrine clinic.
In a prospective study, all newly referred hyperthyroidism patients with fully supressed TSH (&lt;0.004 mIU/L) were followed up three monthly for more than a year. Besides the thyroid status and clinical assessment, they were assessed using Patient Health Questionnaire (PHQ)-9 for depression, Generalised Anxiety Disorder (GAD)-7 questionnaire for anxiety; EuroQoL (ED5D) for QOL and Work and Social Adjustment Scale (WSAS) to measure functional impairment.
There were 177 participants (77.9% females), with a mean age of 50.1±15.6 years (range 16-86). Majority (88.7%) were having Grave’s disease and 11.3% had thyroid nodular disease; 10.2% had recurrent hyperthyroidism. At the baseline, anxiety was considered severe in 27.7%; similarly depression was moderately severe in 13.7% and severe in 14.9%. Although these decreased over time, considerable proportions continued to have these symptoms even after a year of treatment. A little over a quarter (26.6%) had beta-blockers at baseline and 9.0% had antidepressants; these proportions decreased reflecting symptomatic improvement. Proportions not-working changed from 28% to 18.2% within a year. WSAS suggested that the proportion with significant impairment changed from 46.7% to 34.6% (mean score change from 11.6 to 5.1). The EuroQoL mean score was 59.6 at the initial assessment which increased gradually to over 80. Most of these outcome parameters correlated with the improvement in thyroid status; however for many patients, mental health symptoms and functional impairments continued even after the thyroid tests became normal.
Considerable proportion of patients with hyperthyroidism had anxiety, depression, functional impartment and poor quality of life; most of which improved with the course of anti-thyroid treatment; however a considerable proportion continued to have symptoms and impairments even after a year. This suggests the need for additional psychiatric intervention, probably early in the treatment to decrease the morbidity and improve QOL. Use of specific screening measures for psychiatric symptoms in the endocrinology clinics may be useful.
References
(1) Demet et al, Arch Med Res. 2002 Nov-Dec;33(6):552-6.
SAT-191 A Case of Hypoplastic Left Heart Syndrome and Paraganglioma
Authors: Bowes Christa , Subauste Angela 
Published: May 2020

Abstract
INTRODUCTION:
Cyanotic heart disease and paragangliomas are two rare diagnosis. Co-occurrence of congenital cyanotic heart disease and pheochromocytomas/paragangliomas has been described, but the mechanism is unclear. In those patients where immediate cyanosis resulting from the congenital heart disease happens right after birth there is an association with an earlier detection of tumor compared to those with cyanotic heart disease later in life (26.6 years vs 46.3 years respectively) [1]. The objective of this case is to highlight this association, as a high degree of suspicion needs to be had when caring for individuals with cyanotic heart disease to pursue evaluation of these tumors. CASE: A 23-year-old man with a chief complaint of diffuse abdominal pain was found to have a 2.6 x 2.8 cm smoothly marginated soft tissue mass in the right lower quadrant on abdominal computed tomography. Patient had a known history of hypoplastic left heart syndrome (mitral atresia-aortic atresia) who had undergone a three-stage Norwood repair in childhood. In his adulthood was diagnosed with Central Adrenal Insufficiency, and Type 2 Diabetes Mellitus. At the time of presentation patient was short of breath, tachycardic (heart rate 115), and tender to palpation of his right lower quadrant. Plasma normetanephrines were 3.8 nmol/L (normal &lt; 0.9 nmol/L), 24-hour urinary excretion of normetanephrine was 1117 mcg/24h (normal 103-390 mcg/24h). Plasma metanephrine levels were normal. A nuclear medicine whole body scan with metaiodobenzylguanidine (MIBG) scan confirmed a MIBG avid tumor in the right lower quadrant. Preoperative management was initiated with oral doxazosin. He underwent laparoscopic surgery with removal of a 3 cm pelvis mass resected from the retroperitoneal tissue deep to the peritoneum along the gonadal vein and ureter. Final pathology confirmed the diagnosis of a paraganglioma. Postoperatively, plasma normetanephrines were corrected at 0.86 nmol/L. Patient underwent genetic testing that was negative for FH, MAX, MEN1, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127 and VHL. CONCLUSION: Multidisciplinary approach to these patients is essential given their complex hemodynamics. Long term follow up is necessary to monitor for tumor recurrence, review of case reports may suggest a higher risk of recurrence [1]. Of these case reports there has been no strong genetic association found, the most popular theory is a causal relationship from their cyanotic heart disease. References:
Zhao B, Zhou Y, Zhao Y et al (2018) Co-occurrence of pheochromocytoma-paraganglioma and cyanotic congenital heart disease: A case report and literature review. Front Endocrinol. https://doi.org/10.3389/fendo.2018.00165
SAT-723 Effects of Organohalogenated Endocrine Disrupting Chemicals on Cell Proliferation and Gene Expression in GH3 Somatolactotropes
Authors: Ringrose Sophie , Grammatopoulos Kyriakos , Welch Natalie , Simbi Bigboy , Niessen Stijn J , McGonnell Imelda M , Scudder Christopher J , Fowkes Robert C 
Published: May 2020

Abstract
Endocrine Disrupting Chemicals (EDCs) are substances that have been increasingly implicated in many serious pathologies, such as tumor formation, metabolic, growth and reproductive disorders. The economic and health burden of exposure to these compounds has an annual predicted cost in excess of €150 billion, across the EU regions alone. Of the growing list of compounds that act as EDCs, the organohalogenated compounds (OHCs), polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) have been associated with an increased risk of pituitary disease. We have previously reported that feline patients with hypersomatotropism (acromegaly) are exposed to elevated levels of PBDEs and PCBs in their environment. However, the mechanisms by which these compounds might directly influence somatotroph function have yet to be established. In this study, we use the GH3 rat somatolactotrope cell line to investigate how two PCB congeners - 138 and 153 - influence cell proliferation (using a Crystal Violet assay) and somatotrope gene expression (using a multiplex RT-qPCR approach to examine expression of Esr1, Esr2, Sstr1, Sstr2, Sstr3, Sstr4, Sstr5, Insr, Tshr, Pou1f1, Ghrhr2, Gh). GH3 cells were treated with Phenol Red-free media in the absence or presence of either PCB138 or 153 (-10 to -6 M), or in combination (-10 to -6M) for up to 72h. Treatment with either PCB alone, or in combination, caused significant concentration-dependent, biphasic changes in cell proliferation at each time point, but with a different profile of response on each day (significantly increased at high pM/low nM concentrations); there was no evidence of toxicity at maximum concentrations (-6M). Gene expression changes were determined in GH3 cells treated in the absence or presence of either -8M or -6M PCB138 or 153 for 24h. Differential effects of these compounds were seen on the expression of Sstr3, Sstr4, Sstr5 and Insr; all other gene transcripts were unaffected. These findings reveal that GH3 cells exposed to physiologically relevant concentrations of PCB138 and 153, alone or in combination, show concentration-dependent increases in cell proliferation; furthermore, the expression of genes associated with therapeutic targets for the treatment of acromegaly (i.e. SSTRs) are differentially affected by exposure to PCB138 and 153. Our data indicate a potential mechanism for EDCs in the onset of acromegaly, that require further, in vivo, investigations.
MON-444 The Case of a Rare Anaplastic Thyroid Cancer Variant with Rhabdoid Features
Authors: Foster Jennifer , Diedrich Veronica , Leonard Talayna , Shahlapour Mahmood , Horani Mohamad Hosam 
Published: May 2020

Abstract
Introduction: We present a very rare case of a variant of anaplastic carcinoma, a high-grade thyroid carcinoma with rhabdoid features. Less than 15 cases have been reported in English literature over the last 20 years. The prognosis of thyroid cancer with this variant phenotype is unfortunately very poor with a mean survival time of only 6 months after diagnosis. Treatment includes surgery, often a total thyroidectomy due to the rapid rate of growth of this tumor type. The benefits of chemotherapy and radiation are not yet apparent.
Case presentation: A 49 year old female with history of breast cancer status-post recent chemoradiation therapy presented to the emergency department for a rapidly enlarging, right-sided neck mass. The mass had been present for approximately one month, but it was estimated to have grown from 3cm to 5cm within the two weeks prior. The patient was being followed by her ENT specialist and had a recent outpatient CT scan done. The results of the CT revealed a large thyroid tumor partially obstructing the esophagus and given the rapid progression of symptoms, she was instructed to go straight to the ED for emergent admission. Upon arrival, the patient reported not having consumed any solids or liquids for the past day due to concerns of aspiration and increasing neck pain. She had complaints of worsening dysphagia. Initial lab work revealed low thyroglobulin (1.4 ng/mL), elevated T4 (15.42 nmol/L) presumably due to Tamoxifen exposure, and elevated PTH (96.9 pg/mL), likely primary hyperparathyroidism. She was admitted and endocrine was consulted for further evaluation. The patient underwent a fine-needle aspiration biopsy showing high-grade anaplastic carcinoma with extensive necrosis and rhabdoid features. The tumor was eventually classified as stage 4B with gross extra thyroidal extension to the adventitial layers of the esophagus, thus it was determined to be unresectable. It was recommended at that time she have a percutaneous tracheostomy and feeding tube to protect her airway. However, the patient requested to be discharged so that she could obtain a second opinion regarding treatment options and prognosis. She subsequently underwent a total thyroidectomy at another hospital.
Conclusion: It remains unclear whether this patient’s history of breast cancer treated with chemoradiation therapy played a role in the development of this rare thyroid carcinoma. Some cases of the rhabdoid phenotype are documented to have transformed from papillary thyroid carcinoma, for which radiation therapy is a well-known risk factor. Future studies should use molecular markers, such as BRAF V600E mutations common to papillary and anaplastic thyroid carcinomas, to help differentiate between types of thyroid cancers and avoid delayed treatment options for rapidly metastasizing thyroid tumors.
SUN-695 Should Vitamin B12 Status Monitoring Be Implemented for Patients Taking Metformin?
Authors: Hoskyns Wesley , Shahlapour Mahmood , Brooks Ryan , McNierney Dakota , Kihara Sylvia , Horani Mohamad Hosam 
Published: May 2020

Abstract
Introduction : Cobalamin (vitamin B12) is used in multiple metabolic processes, functioning primarily as a coenzyme with Methylmalonyl-CoA mutase and Methionine synthase in humans. Without functioning enzyme, substrate levels build up which are neurotoxic, leading to neurological debilitation. Lack of enzyme also halts cellular replication processes causing severe anemia. Since numerous studies have found decreased cobalamin levels in patients who regularly take metformin1, then could regular monitoring of cobalamin levels in such patients prevent these outcomes?
Case Presentation : We present a 50-year-old female who reported to the ED with general weakness and shortness of breath after having a seizure. Her medical history included type 2 diabetes mellitus being treated with metformin and a history of seizures controlled by carbamazepine since childhood.
Neurological exam abnormalities consisted of DTRs that were 1/4 on all proximal and distal upper and lower extremities and absent fine sensory and vibratory sensation on ankles and feet bilaterally. Patient was also ataxic. Hgb A1c was 14%. Head CT, chest x-ray, EKG, and cardiac markers found no abnormalities. CBC found a profound pancytopenia with WBC 1.6, RBC 1.27, Hgb 5.2, MCV 119, MCH 40.9, MCHC 34.3, RDW 18.2, and platelets 113. Blood smear was normal. Bone marrow sample showed normochromic macrocytic cells with no other abnormalities. Folate level was normal and cobalamin was found to be low (61.5 pmol/L). Intrinsic factor antibodies were negative. Extensive autoimmune workup was also negative.
Discussion: Our patient’s neurological symptoms and pancytopenia were found to be due to multiple factors. R. Pawlak, found that metformin use had a 2.45 (p &lt; 0.0001) times higher odds of developing B12 deficiency in comparison to non-metformin users1. This was also supported by a systemic review of the impact of metformin
Carbamazepine is known for its effects on decreasing the absorption of folate and has statistically been found to decrease cobalamin significantly as well.
There are several B12 assessment methods available to providers, including serum/plasma B12, Mean Corpuscular Volume (MCV), Homocysteine (Hcy), Holotranscobalamin II (holoTCII), and serum and urinary Methylmalonic Acid (MMA). Urinary MMA has been found to be the most specific and sensitive of these markers when adjusted by kidney function (through serum creatinine levels) and while fasting
Conclusion : Currently, there are no screening guidelines by the U.S.P.S.T.F or American Diabetes Association for cobalamin deficiency. However, neurologic deficits and macrocytic anemia could be prevented through monitoring cobalamin levels in diabetics receiving metformin treatment. This monitoring might be needed more in patients with seizure disorderon Carbamazebin.