bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-937 A Case of Two Pathologies: Primary Hyperaldosteronism with a History of Pheochromocytoma
Authors: Akamnonu Chukwuka , Parikh Sahil , Wondisford Fredric Edward 
Published: May 2020

Abstract
Background: In patients with system based diseases, multiple pathologies coexisting in the same organ can go undiagnosed. We present a case of a patient with long standing hypertension recently diagnosed with Primary hyperaldosteronism in the setting of known Pheochromocytoma. Case: A 43 year old male with a history of Von Hippel Lindau (VHL), Pheochromocytoma status post right subtotal adrenalectomy 18 years ago, renal cell carcinoma, prediabetes, bilateral renal cysts, and hypertension presented to the clinic for evaluation of suspected hyperaldosteronism. The patient had a history of medication refractory hypertension associated with hypokalemia requiring potassium supplementation. The patient’s VHL disease involved the pancreas, adrenal, brain and spine which required surgery to remove tumors in these areas. His Pheochromocytoma resolved status post subtotal adrenalectomy. Recent imaging and laboratory work up showed a stable left adrenal nodule (unchanged over the years), unremarkable right adrenal status post subtotal adrenalectomy with normal serum and urine metanephrines. In September 2019 he was seen by his Cardiologist for persistent Atrial Fibrillation and subsequent workup for suspected hyperaldosteronism showed a morning plasma aldosterone of 44.4ng/dL (normal range 4–21 ng/dL), plasma renin activity of &lt;0.6 ng/ml/hr (normal range 0.6–4.3 ng/mL), 24 hour urine aldosterone of 21mcg/24hr (normal range 3–20 mcg/24hr), Urine sodium excretion of 236 mmol/24hr (normal range 40-217mmol/24hr), and potassium of 3.5mmol/L (normal range 3.6–5.0 mmol/L). The diagnosis of Primary hyperaldosteronism was confirmed and the patient was subsequently scheduled for adrenal venous sampling. Conclusion: This case demonstrates how multiple adrenal pathologies can present in the same individual. There is paucity of data in the literature as to the existence of both Pheochromocytoma and primary hyperaldosteronism in the same individual or the pathophysiological connection between them. When the diagnosis of a disease affecting a specific organ has already been made, the discovery of a secondary pathologic process affecting such organ may end up getting delayed. Clinicians should be aware of this possibility.
SAT-254 Desmopressin Stimulation Test in a Pregnant Patient with Cushing’s Syndrome
Authors: Warachit Wasita , Porntharukchareon Thachanun , Sunthornyothin Sarat 
Published: May 2020

Abstract
Background: Cushing’s syndrome (CS) in pregnancy is a rare condition. Accurate diagnosis and appropriate treatment are necessary due to increased morbidity and mortality in the fetus and mother with active CS. However, hormonal changes during pregnancy and limitations in terms of teratogenicity complicates the diagnosis of CS. Clinical case: A 27-year-old female presented at gestational age (GA) of 8 weeks with a 2-month history of proximal muscle weakness. She had 20-kg weight gain in 2 years before hypertension, prediabetes and pulmonary tuberculosis developed at the age of 25. On physical examination, her blood pressure was 160/100 mmHg. She had moon face, buffalo hump, wide purplish striae and hirsutism without signs of virilization. At GA 9 weeks, her morning cortisol was 32 μ;g/dL (883 nmol/L). Her salivary cortisol was 0.7 μ;g/dL (19 nmol/L) and a mean 24-hour urinary free cortisol was 237 μ;g/d (654 nmol/d), which were above reference ranges. Adrenocorticotropic hormone (ACTH) were 48 pg/mL (11 pmol/L) and 40 pg/mL (9 pmol/L). Dehydroepiandrosterone sulphate was 378 μ;g/dL (10 nmol/L). A non-gadolinium enhanced magnetic resonance imaging (MRI) at GA 12 weeks did not reveal a pituitary mass. Desmopressin stimulation test was carried out at GA 14 weeks. Her baseline cortisol was 31 μ;g/dL (855 nmol/L) and ACTH was 35 pg/mL (8 pmol/L). Her ACTH increased 70% at 15 minutes after desmopressin stimulation, with an absolute difference between basal and peak ACTH of 24 pg/mL (5 pmol/L). MRI pituitary gland with gadolinium at GA 14 weeks revealed an 8-mm adenoma at right inferolateral aspect of pituitary gland. Transsphenoidal surgery with selective adenomectomy was done at GA 18 weeks without immediate complications. Pathological findings showed a segment of pituitary adenoma with ACTH positive cells. After surgery, her morning cortisol was 6 μ;g/dL (166 nmol/L). Hydrocortisone supplement was given and had been continued throughout pregnancy. She successfully gave birth to a term 2300-gram male infant. One year after delivery, she had spontaneous pregnancy and also delivered a term 3300-gram male infant. Cushing’s syndrome had been in remission for 2 years of follow-up. Conclusion: Hormonal changes during pregnancy lead to an increased in ACTH after 7 weeks of gestation. Desmopressin test can be a safe and reliable test to differentiate between ACTH-dependent and ACTH-independent CS. Because a non-gadolinium enhanced MRI may not always detect pituitary microadenoma, this raises the necessity of the use of MRI with gadolinium as an initial imaging in pregnant patients with ACTH-dependent CS. References: Brue T, Amodru V, Castinetti F. Management of Cushing’s syndrome during pregnancy: solved and unsolved questions. Eur J Endocrinol. 2018;178(6):R259-266.
MON-514 Detection of RAS Mutations and RET/PTC Fusions in Thyroid Cancer Using Microfluidic Digital PCR
Authors: Ylli Dorina , Patel Aneeta , Mendoca-Torres Maria Cecilia , Costello John , Bikas Athanasios , Wartofsky Leonard , Burman Kenneth D , Jensen Kirk , Vasko Vasyl V 
Published: May 2020

Abstract
Background:
The identification of somatic mutations and gene fusions is crucial for guiding therapeutic decisions in patients with thyroid cancer. Microfluidic digital PCR is currently considered as a technique of choice for highly sensitive detection of gene mutations/fusion. We recently demonstrated that dPCR is a useful tool for detection of BRAFV600E and TERT promoter mutations in thyroid tumors.
Objectives:
This study aimed to determine the analytic and clinical validity of dPCR for detection of RAS mutations and RET/PTC fusions in thyroid cancer tissue.
Material and Methods:
Thyroid tissues from 75 patients with PTCs (58 classical PTC (CPTC) and 17 follicular variant (FVPTC) were used for DNA and RNA extraction. The rare mutation SNP genotyping assays which were multiplexed for detection of mutant and wild type NRASQ61; as well as RET/PTC1 and RET/PTC3 were synthesized by Thermo Fisher Scientific. Digital PCR was performed using a QuantStudio 3D Digital PCR platform. QuantStudio Software was used for relative and quantitative data analysis.
Results:
NRASQ61 was detected in 0/58 CPTC and in 6/17 (35%) FVPTC. The ratios of mutant/total varying from 11.7% to 61.5%. Among patients with FVPTC there were no significant associations between the presence of NRASQ61 and patient’s age, sex, multifocal growth, extra-thyroidal invasion and lymph node metastases. The ratios mutant/total correlated with tumor size in patients harboring NRASQ61. In 23 cases, RET/PTC1 and RET/PTC3 transcripts were examined. RET/PTC1 and RET/PTC3 transcripts were detected in 3 and 1 case, respectively. RET/PTCs were detected in CPTC, but not in FVPTC. RET/PTC positive tumors were characterized by multi-focal patterns of growth, presence of extra-thyroidal invasion, and presence of lymph node metastases (4 of 4 cases with RET/PTC). There were not RET/PTCs positive tumors harboring simultaneously anomalies in RAS oncogene.
Conclusions:
Microfluidic digital PCR allows specific, sensitive and rapid detection of RAS mutations and RET/PTC fusions in thyroid tissue samples. Implementation of dPCR-based assays may facilitate analysis of thyroid tumors and support research in patients with thyroid cancer.
SUN-540 Inflammasome Components After Bariatric Surgery: Novel Targets for a Chronic Disease
Authors: Herrera-Martinez Aura D , Aguayo Vicente Herrero , Sez Prudencio , López-Cánovas Juan L , L-López Fernando , Gahete Manuel David , Molina Puerta María J , Continente Alfonso Calañas , Membrives Antonio , Jiménez Concepción Muñoz , Rebollo-Román Ángel , Alcántara Laguna María D , Castano Justo Pastor , Gálvez-Moreno María A , Luque Raúl M 
Published: May 2020

Abstract
Background: Obesity is a metabolic chronic disease with important associated morbidity and mortality. Bariatric surgery (BS) is the most effective treatment for keeping long-term weight loss in severe obesity and consequently decreases obesity-related complications including inflammation. Aim: to explore changes in the inflammasome components after BS and their relations with clinical and biochemical parameters at baseline and six months after surgery. Patients and methods: 22 patients that underwent BS (sleeve gastrectomy and roux-en-Y gastric bypass) were included. Epidemiological, clinical, anthropometric and biochemical evaluation was performed. Four groups of inflammasome components and inflammatory associated factors were evaluated: NOD-like receptors; inflammasome activation components; cytoquines and inflammation/apoptosis related components; and cell-cycle and DNA-damage regulators. Clinical-molecular correlations and associations were for the first time performed in a cohort of patients with morbid obesity that underwent BS. Results: The four groups of inflammasome components were dysregulated after BS. The mRNA expression of several factors was markedly decreased after BS, specially CXCL3, CCL8, TLR4, NLRC4 and NLRP12. Most changes were independent of the performed surgical technique. Inflammasome components displayed several clinical and biochemical correlations including the presence of baseline metabolic comorbidities (type2 diabetes, dyslipidemia and hypetension) and the body composition. Conclusion: the regulation of several inflammasome system components may explain the improvement and reversion of some obesity-related comorbidities after BS.
MON-118 Reducing Unnecessary Repeat HbA1c Testing in a Tertiary Academic Hospital
Authors: Rajeswaran Vamana , Alexander Lisa , Alwithenani Raad , Jaskolka Diana , Usmani Shirine , Tran Susan , Khan Sarah , Yip Paul , Mukerji Geetha 
Published: May 2020

Abstract
Background
Glycated hemoglobin (HbA1c) is a surrogate marker of glycemia over the preceding three months, where the last 30 days contributes to 50% of the value (1). Therefore guidelines often recommend repeating HbA1c only after 3 months in most situations (2), but repeat testing of HbA1c is often conducted earlier when not warranted (3). We aimed to conduct a Quality Improvement (QI) initiative to reduce unnecessary repeat testing of HbA1c at a large tertiary care academic hospital in Toronto, Ontario by 50% by May 2020.
Methods:
The Model for Improvement Quality Improvement (QI) framework was used in the design of the QI project to reduce repeat HbA1c. Problem characterization was conducted to understand root causes and iterative Plan-Do-Study-Act cycles were used to develop a change intervention. Unnecessary HbA1c tests were the primary outcome and defined as repeat HbA1c testing within 60 days; the top three specialities that ordered unnecessary HbA1c tests were targeted for education prior to implementation of the change intervention.
Results:
Baseline data on all HbA1c tests in 2018 revealed repeat testing in approximately 10% of 15,290 HbA1c tests, with estimated potential savings of more than $11,000 based on the provincial reimbursement rate. The top 3 ordering specialities targeted for education included Nephrology (n=410 repeat HbA1c tests), Cardiology (n=246 repeat HbA1c tests), and Endocrinology (n=136 repeat HbA1C tests). Root cause analysis revealed that providers often ordered repeat HbA1c tests due to being unaware of prior results and a knowledge gap of testing recommendations. A laboratory forced function will be implemented on December 1, 2019 to cancel any repeat HbA1c tests within 60 days and calls to the lab to add HbA1c testing will be tracked.
Conclusions:
Repeat HbA1c testing is frequent in hospital settings and can be an important target for QI efforts. A forced function to cancel processing of repeat HbA1c may be an appropriate QI intervention to reduce repeat testing to promote high-value care. Ongoing data analysis will be conducted to assess the impact of this intervention.
References
(1)
Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM, Sacks DB. Tests of Glycemia in Diabetes. Diabetes Care 2004;27(7): 1761-1773.
(2)
Berard LD, Siemens R, Woo V. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Monitoring Glycemic Control. Can J Diabetes 2018;42(Suppl 1):S47-S53.
(3)
Chami N, Simons JE, Sweetman A, Don-Wauchope AC. Rates of inappropriate laboratory test utilization in Ontario. Clinical Biochemistry 2017;50: 822-827.
SUN-915 Diffuse Large B Cell Lymphoma Presents with Femur Fracture and Involvement of Thyroid Gland
Authors: McNierney Dakota A , Vazquez Bianca , Shahlapour Mahmood , Rahman Samina , Horani Mohamad Hosam 
Published: May 2020

Abstract
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common type of Non-Hodgkin Lymphoma worldwide. It is an aggressive lymphoma that arises from germinal center or post-germinal center B cells. Patients typically present with a rapidly enlarging symptomatic mass, most usually nodal enlargement in the neck or abdomen, but may present with a mass lesion anywhere in the body. However, multiple sites of involvement occur less frequently. We report a case of a 74- year-old woman who initially presented to the hospital for evaluation of a right distal femoral fracture which resulted from a fall at home. Lytic lesions were found in the distal femur and proximal fibula. She was also found to have hypercalcemia with a calcium level of 12.2. A CT- guided biopsy confirmed the diagnosis of Diffuse Large B-Cell Lymphoma with non-germinal center phenotype. A radical resection of the right femur was performed, and a distal femoral replacement hinged knee arthroplasty was done successfully. A venous port was also placed for chemotherapy administration. The patient was admitted to inpatient rehab with plans to initiate chemotherapy. 6 weeks later, the patient presented to the emergency department (ED) with a chief complaint of difficulty hearing, ear discomfort, dysphagia, and dyspnea for 3 weeks. These symptoms prompted her medical oncologist to send her to the ED and postpone chemotherapy that was to begin on that day. Physical examination found the patient to have neck fullness, large palpable lymph nodes, and stridor. Upon evaluation she was also found to have impaired renal function (Blood urea nitrogen 41, Cr 3.10), severe hypercalcemia (Corrected calcium 16.2), and hypokalemia (Potassium 2.8). An EKG demonstrated sinus rhythm and non-specific t-wave abnormality. A chest radiograph showed an enlarged thyroid extending into the superior mediastinum. There was also tracheal narrowing, and tracheal deviation to the left. She was admitted to the Intensive Care Unit (ICU) for treatment of hypercalcemia and stridor. The patient was aggressively treated with fluid management. She also received loop diuretics, steroids, and calcitonin. Once stabilized, a fine needle aspiration of the thyroid gland identified further involvement by diffuse B-Cell Lymphoma. The medical oncologist then initiated R-CHOP chemotherapy. The stridor resolved and the patient’s symptoms significantly improved. After two weeks in the ICU she was discharged to a rehab facility where chemotherapy was continued. This is a rare case of rapidly growing non-germinal center DLBCL that presented with involvement of both the bone and thyroid gland causing life-threatening symptoms. Upon reviewing the literature, there has been no documented cases of DLBCL simultaneously involving the bone and thyroid gland. The patient responded well to R- CHOP chemotherapy and continues to receive treatment in an outpatient facility.
SUN-043 Galactorrhea and Hyperprolactinemia in a Transgender Female
Authors: Unnithan Rachna , Elson Diane Frances , Shenker Yoram 
Published: May 2020

Abstract
Background: Galactorrhea is a rare manifestation of hyper-prolactinemia in males and post-menopausal females, however the hormonal milieu of the transgender female may increase its incidence
Clinical Case: A 43 year old transgender female presented with three years of bilateral breast discharge. She had chronic, stable headaches and fatigue, but no vision changes or other symptoms. Notably, she had breast augmentation surgery with saline breast implants placed shortly before the galactorrhea commenced. She was on a stable dose of estradiol tablets 1 mg twice daily for six years. On physical exam she had pronounced bilateral breast discharge of a milky quality with nipple compression. Prolactin levels were checked several times and were 40-50 ng/mL, TSH was 2.36 uIU/mL. An MRI showed a left inferior pituitary lesion measuring 6 mm x 3 mm x 5 mm with no mass effect on adjacent structures. Her breast discharge was not bothersome to her, and her pituitary lesion was small. It was unclear whether there was a relationship between her prolactin levels and the lesion seen on MRI, as we expected more pronounced prolactin elevation with a prolactinoma. Instead, given the timing of her symptoms in relation to her breast augmentation surgery, her galactorrhea and hyper-prolactinemia were thought to be the result of nipple irritation related to her breast implants combined with a hyper-estrogenemic state.
Clinical Lessons: In the setting of a prolactin secreting micro-adenoma, galactorrhea in a male is highly unusual. This case highlights the importance of recognizing that the unique medical and surgical characteristics of male to female transgender patients can lead to hyper-prolactinemia and galactorrhea.
Reference: Reisman T, Goldstein Z. Case report: induced lactation in a transgender woman. Transgender Health. 2018;3(1):24-26.
SAT-420 Interaction Between Gene Polymorphisms and Urine Iodine Levels on Susceptibility to TPOAb Positivity in the Chinese Population
Authors: Han Bing 
Published: May 2020

Abstract
Objective: Hashimoto thyroiditis, characterized by positive thyroid peroxidase antibodies (TPOAbs), is caused by the interaction of genetic and environment factors. The aim of this study was to clarify the interaction of gene polymorphisms and iodine intake in the incidence of TPOAb positivity. Methods: 1733 subjects were included in this study. Genomic DNA was extracted from peripheral blood white cells. Seven SNPs (rs10944479, rs11675434, rs1230666, rs3094228, rs653178, rs9277555 and rs301799) were selected for genotyping. Thyroid hormones and autoimmune antibodies (TPOAb and TGAb) were determined using the electrochemiluminescence immunoassay method. Results: The mean TSH level in TPOAb-positive subjects was higher than in TPOAb-negative subjects (P&lt;0.001). There were no significant differences in urine iodine and blood iodine between these two groups. Genotype GG of rs9277555 and genotype TT of rs11675434 were associated with an increased risk of TPOAb positivity. Logistic regression analysis showed rs9277555 was associated with TPOAb positivity in all models. Furthermore, rs9277555 was also associated with TPOAb levels in linear regression analysis. The cross-validation consistency and the testing accuracy indicated that there were no significant differences between SNPs and urine iodine interaction. Conclusion: rs9277555 was associated with an increased risk of TPOAb positivity in a Chinese Han population. Furthermore, there was no gene polymorphisms-iodine intake interactions in our cohort.
OR06-06 Pituitary Tumors and Immortalized Cell Lines Generated by Cre-Inducible Expression of SV40 T-Antigen
Authors: Mortensen Amanda Helen , Daly Alexandre , Dudley Lindsey Anne , Camper Sally Ann 
Published: May 2020

Abstract
Pituitary and hypothalamic cell lines have been developed by targeted oncogenesis. This involved using cell-specific transcriptional regulatory sequences to drive expression of large and small SV40 T-antigens in transgenic mice. Invariably, tumors develop in some of the mice, and the cells in these tumors can sometimes be adapted to grow in culture into stable, immortalized cell lines that maintain some of the features of differentiated cells. Cell lines that represent pre-gonadotropes (αT3-1), gonadotropes (LβT2), precursors to the POU1F1 lineage (GHFT1, Pit1-zero), differentiated cells of the POU1F1 lineage (Pit1-triple, TaT1, and Pit1-PRL), and GnRH neurons (GT1-1) have been made by this approach. Tumors often develop early and cause infertility or death. To increase the opportunity for generating cell lines and to make it feasible to follow the process of tumorigenesis, we developed a mouse strain that expresses SV40 T-antigens in response to cre-recombinase. Using CRISPR/Cas9 we inserted an 8 kb cassette with coding sequences for SV40 T-antigens and IRES-GFP into the Rosa26 locus, downstream from a stop sequence flanked by loxP sites: Rosa26LSL-SV40-GFP. 30% of the progeny born from hybrid zygotes injected with template DNA, CRISPR/Cas9, and sgRNA had correctly targeted the Rosa26 locus. These mice were mated with previously established Prop1-cre and Tshb-cre transgenic lines. The majority of Rosa26LSL-SV40-GFP/+; Prop1-cre and Rosa26LSL-SV40-GFP/+; Tshb-cre mice developed dwarfism and large tumors by 4 wks. The pituitaries of Rosa26LSL-SV40-GFP/+; Tshb-cre mice appear grossly normal at birth, but they are enlarged and showing evidence of increased vascularization by 2 wks. Flow-sorted GFP-positive cells from Rosa26LSL-SV40-GFP/+; Prop1-cre and Rosa26LSL-SV40-GFP/+; Tshb-cre mice express Prop1 and TSH, respectively. Tumors from Rosa26LSL-SV40-GFP/+; Tshb-cre mice were adapted to growth in cell culture. We have established a thyrotrope-like cell line that expresses Cga and Pou1f1. These studies demonstrate the utility of the novel, Rosa26LSL-SV40-GFP mouse line for reliable targeted oncogenesis and development of unique cell lines.
The authors have nothing to disclose.