bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-217 New Methods for Primary Aldosteronism Screening by Exploring the Values of Different Indicators and in Combination with Predictive Model
Authors: Li Yuanmei , Wang Wen , Li Qianrui , Chen Tao , Mo Dan , Zhang Tingting , Zhou Fangli , Ren Yan , Tian Haoming
Published: May 2020

Background: Primary Aldosteronism (PA) is the most common cause of secondary hypertension. The endocrine society guidelines recommend case detection of PA by determining the aldosterone-renin ratio (ARR) under standard conditions, but the cut-off value of upright ARR varies greatly. In addition, as with all other biochemical tests, there are false positives and false negatives for upright ARR. In order to avoid false negative, some researchers have proposed plasma renin activity (PRA) < 1.0 ng/ml/h as a screening indicator. In order to avoid false positive caused by low PRA, Professor Young of the Mayo Clinic have proposed that the ARR combined with the plasma aldosterone concentration (PAC) > 15 ng / dL for PA screening. In 2019, Professor Young proposed PA screening positive when PAC≥10ng/dL and PRA<1.0 ng/ml/h. In addition, angiotensin II (AT-II) directly stimulates the synthesis of aldosterone. Compared with renin, the decrease of AT-II level and the increase of aldosterone to AT-II ratio (AA2R) may reflect the aldosterone autonomy secretion. However, whether these screening indicators are superior to upright ARR remains to be further verified. Therefore, either exploring the diagnostic efficacy of PAC, PRA, or AA2R as a screening indicator or even better developing a clinical prediction model combined with multiple indicators may provide a more accurate method for PA screening. Objective: To explore the value of different indicators and the logistic regression model (nomogram) for primary aldosteronism screening. Methods: The clinical data of 499 patients with PA and 479 patients with essential hypertension (EH) diagnosed by West China Hospital from 2009 to 2018 were retrospectively analyzed. The diagnostic performance of different screening methods was compared by plotting receiver operating characteristic curves (ROC). Results: The proportion of low potassium in PA group was higher than that in the EH group (86.20% vs. 36.50% P<0.001). The area under the ROC curve (AUC) of upright ARR was greater than that of upright AA2R, upright PRA, upright PAC, supine ARR, and lowest blood potassium (P<0.05); The AUC of logistic regression model (nomogram) [which consists of the upright PAC, the upright PRA, and the lowest blood potassium] was greater than that of upright ARR (96.3% vs. 94.6%, P<0.05). Conclusion: The upright ARR is the best single screening indicator; AA2R (radioimmunoassay) is not recommended for PA screening. Ultimately, the logistic regression model (nomogram) is superior to the upright ARR.
SUN-095 Understanding and Communication Around DSD According to the Mothers and Patients’ Perspectives
Authors: Quintao Lia Mesquita Lousada , Domenice Sorahia , Costa Elaine Maria Frade , Bachega Tania A , Fontenele Eveline Gadelha Pereira , Coutinho Debora Cabral , Batista Rafael Loch , Ferrari Maria Tereza Martins , Mendonca Berenice Bilharinho
Published: May 2020

Communication around DSD is complex. It involves diagnosis and treatment aspects and is influenced by the psychological status of the individuals and the cultural context. An adequate understanding by patients and relatives is essential for approach of DSD. Objetive: To evaluate the DSD care setting in three Brazilian tertiary centers in order to identify the barriers to an adequate understanding and an optimal communication. Methods: A guide with 69 questions, assessing the level of knowledge, the main doubts and difficulties around DSD was developed and guided individual interviews with 100 mothers and 53 adult patients with DSD. The main doubts were clarified and a self-assessment was requested to them before and after the interview on a scale from 0 to 10. Results: Mothers and patients mean age were, respectevily, 35.2 and 36.5 years. Both of them had a satisfactory educational level. Although 48% (p<0.01) of mothers and 68% (p:0.02) of patients were satisfied/very satisfied about their knowledge related to the DSD, 78% and 58%, respectively, of them still had doubts. The doubts were related to diagnosis, karyotype, medications, appearance of genitalia, surgery, sexual activity, fertility, genetic counseling, consequences of the condition and treatment on general health and condition influence on the child’s behavior and personality The unsatisfied mothers cited as barriers to an optimal understanding the complexity of the conditions, the difficult terms and the psychological stress at diagnosis. Patients also cited as barriers the absence of dialogue about the condition at home and some of them chose not to know. About 55% of mothers and 62% of patients didn’t even know the name of the condition; but positively 88% of them knew the necessary treatment. Regarding communication, 68% of mothers and 89% of patients didn’t feel comfortable talking to people about the DSD condition and around 68% of them underwent negative comments. Although 73% of patients would prefer to be first informed about their condition at childhood, 29% of mothers think that childhood is the best age for it. Among mothers and patients, the most and least appropriate term to name the DSD condition is, respectively, genital malformation and disease (p<0.01). Both of them have the stigma as the main concern. Conclusion: Even in a tertiary center with a multidisciplinary team, the mothers and patient’s knowledge about DSD conditions is scarce. The proper choice of the term to refer to DSD conditions should consider the families and patients perspectives. Communication about DSD is prejudiced by the lack of knowledge and the stigma suffered by these patients and families. Thus, due to complexity of this topic, continued educational action must be instituted as a strategy to modify this scenario.
MON-281 A Pilot Study: Comparing Prolactin Measurements Between Two Different Immunoassays
Authors: Woznick Walter K , Yang Almira , Gunsolus Ian , Sarvaideo Jenna Lynne
Published: May 2020

Hyperprolactinemia from a prolactin-secreting pituitary tumor is the most common endocrine disorder of the hypothalamic-pituitary axis. As suggested in the 2011 Endocrine Society Guidelines on Diagnosis and Treatment of Hyperprolactinemia, macroprolactin level should be assessed in patients with asymptomatic hyperprolactinemia. However, as discussed in prior studies comparing the performance of common prolactin immunoassays in a reference population of both males and females with and without known hyperprolactinemia or macroprolactinemia, there has been poor harmonization between assays and variable reactivity towards macroprolactin, resulting in significantly different normal ranges for total and monomeric prolactin between manufacturers. The goal of our analysis is to assess the concordance of the Roche and Siemens prolactin immunoassays using cases in which prolactin and macroprolactin testing was ordered on clinical indication. We hope to educate clinicians regarding potential variability between assays that may not be fully accounted for by using established, assay-specific reference ranges. We reviewed patients 18 years and older from any gender who underwent evaluation of prolactin levels as clinically indicated and had elevated serum prolactin on a Roche assay with a subsequent normal prolactin on a Siemens assay. Seven out of 18 patients had an elevated prolactin on the Roche assay and a normal prolactin on the subsequent Siemens assay that also tests for the presence of macroprolactin. The reasons for testing prolactin in the 7 patients were: secondary hypogonadism (4), pituitary microadenoma (1), oligomenorrhea (1) and baseline labs in a transgender female starting estrogen (1). Of the 7 cases we observed with discordant Roche and Siemens prolactin results, one of our 2 female patients and one of our 4 male patients would have shown concordant hyperprolactinemia results on both assays if the Siemens reference range was narrowed to align with published studies. This study demonstrates significant analytical discordance between prolactin immunoassays, leading to variable clinical interpretation regarding the presence of hyperprolactinemia. We suggest using a single prolactin immunoassay for routine measurement of prolactin as well as investigation of macroprolactin measurement to ensure comparable reactivity towards all forms of prolactin. References: (1) Vallette-Kasic et al., J Clin Endocrinol Metab. 2002 Feb;87(2):581-8. (2) Gibney et al., J Clin Endocrinol Metab. 2005 Jul;90(7):3927-32. (3) Luisa et al., Clinical chemistry 2008 Sept; 54:10 1673-1681 (4) Shlomo et al., J Clin Endocrinol Metab, February 2011, 96(2):273-288
SAT-611 Dietary Reduction of Branched-Chain Amino Acids
Authors: Karaman Rowan , Park Eunhae , Galusha Brittany M , Flores Victoria , Davis Dawn B , Lamming Dudley W
Published: May 2020

Background: One of the primary risk factors for the development of diabetes is obesity. Although moderate weight loss can lead to improvements in metabolic health, reduced-calorie diets are difficult to sustain. A number of groups have shown that low protein diets are associated with metabolic health in both rodents and humans. In particular, the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are associated with insulin resistance and diabetes in humans. Blood levels of the BCAAs decrease in humans fed a low protein diet, and we recently showed that reducing either dietary BCAAs or protein rapidly restored normal body composition and insulin sensitivity to diet-induced obese mice without reducing calorie intake. We are determining the effect of a low BCAA diet in humans with prediabetes and overweight/obesity.

Objectives: The primary outcome is the reduction of dietary BCAA intake by at least 50% in subjects in the low BCAA group while maintaining overall baseline calories. Secondary outcomes are compliance and tolerability of the low BCAA protein powder.

Method: This is a randomized, controlled, single-blind pilot study. The intervention arm uses a low BCAA protein powder to replace two meals per day for 60 days. The control arm uses a control protein powder with standard amounts of amino acids to replace two meals per day for 60 days. We are enrolling 16 males with the following criteria: ages 35 to 65, BMI 28 to 35, and hemoglobin A1c 5.7%-6.4% or fasting glucose 101-125 mg/dL. A registered dietitian reviews a 4-day food diary prior to diet initiation and creates an individualized meal plan based on those values in order to maintain baseline calories during the study diet. Baseline measurements prior to diet initiation include waist circumference, body mass index, fasting insulin and glucose, an oral glucose tolerance test, resting metabolic rate, body composition testing using dual energy x-ray absorptiometry, jumping mechanography to assess muscle function, and a stool sample to assess the microbiome. These tests are repeated after 60 days on the diet. Safety labs are performed while on the diet and 2-3 weeks after the end of the diet. Weekly safety telephone calls occur while on the diet. The food diaries are repeated after 30 and 60 days on the diet.

Results/Conclusion: Ten of sixteen subjects have completed the trial to date. One out of four subjects in the low BCAA group dropped out; the remainder successfully completed the study. BCAA intake was successfully reduced by 50%. Missed beverages were uncommon. No significant safety concerns or side effects have been noted. In conclusion, our early results suggest that replacement of two meals a day with a protein powder lacking BCAA for up to two months is a safe and feasible intervention. Ongoing analysis will determine if this intervention impacts metabolic health.
SAT-380 A Case of Primary Hyperparathyroidism on the Third Trimester of Pregnancy
Authors: Villapol Maria Alexandra Carranceja , Kanapi Maria Princess L
Published: May 2020

Introduction: This is the case of a pregnant woman on her 3rd trimester who was diagnosed with primary hyperparathyroidism. Since there are two patients involved, the potential complications that can be brought about by the diagnostic tests and the treatment had to be weighed against the benefits.

Case: The patient is SA, a 34-year old female on her 29th week of pregnancy, admitted due to a month history of abdominal pain described as intermittent, crampy, generalized, non-radiating, and mild-to-moderately severe in intensity. She was advised to do tests but did not comply. In the interim, there was recurrence of symptoms but with resolution. However, the crampy abdominal pain recurred, now localized at the right upper quadrant and epigastric areas, radiating to the right upper back, moderate in intensity, and with associated nausea and vomiting, leading to admission.

She was first managed under OB-Gynecology, given hydration, pain management and Betamethasone. She was also referred to Cardiology for blood pressure control, and Surgery for evaluation of the abdominal pain. Due to an increasing trend of her blood glucose, she was referred to Endocrinology and started on insulin. Mild bilateral nephrocalcinoses seen in an abdominal ultrasound prompted work-up showing an elevated serum ionized calcium at 1.88 meq/L (n 1.12-1.32 meq/L), elevated intact PTH at 451.13 pg/ml (n <67.9 pg/ml), and low Vitamin D at 10.96 ng/ml (n >30ng/ml). Parathyroid ultrasound showed nonthyroidal tissue measuring 0.4 x 0.6 cm at the right inferior area. Saline hydration and diuresis with Furosemide were started to manage the hypercalcemia. A multi-disciplinary meeting was held to discuss the options for management and risks involved. The goal was to deliver the baby in stable condition possibly to term, while keeping maternal calcium levels and blood pressure normal.

However on her 30th week of gestation, she had persistent elevated blood pressure and underwent emergency caesarian section. After delivery, the patient was advised against breastfeeding for adequate management of her hypercalcemia. She was started on Cinacalcet, Calcitonin, and Ibandronic Acid. A Parathyroid Sestamibi Scan done showed a parathyroid adenoma on the right inferior lobe, and she underwent right inferior parathyroidectomy, with left thyroidectomy and isthmusectomy. Findings showed a right inferior parathyroid adenoma and a benign follicular nodule on the left thyroid. She was started on Calcium Carbonate and Calcitriol, and discharged stable.

Conclusions: This case shows that when two lives are at stake every step of the management, whether diagnostic or therapeutic, must be communicated well to the patient and to the other members of the team. It is ultimately a choice made by the expectant mother but through the proper guidance and updated knowledge of the team, combined with a good clinical eye especially in the treatment of pregnant women.
SAT-596 POMC Expression in GABAergic Neurons Suppresses NPY Overexpression and Restores Food Intake in Obese Mice
Authors: Trotta Milagros , Bello Estefanía P , Alsina Ramiro , Tavella María B , Ferrán José L , Marcelo Rubinstein , Bumaschny Viviana Florencia
Published: May 2020

Hypothalamic arcuate proopiomelanocortin (Arc-POMC) neurons are involved in different physiological processes such as the regulation of energy balance, glucose homeostasis and stress induced analgesia. Since these neurons heterogeneously express different biological markers and project to many hypothalamic and extrahypothalamic areas, it is proposed that Arc-POMC neurons could be classified into different subpopulations having diverse physiological roles. The aim of the present study was to characterize the contribution of the subpopulation of Arc-POMC neurons co-secreting gamma-aminobutyric acid (GABA) neurotransmitter in the control of energy balance. Arc-Pomc expression restricted to GABAergic-POMC neurons was achieved by crossing a reversible Pomc-deficient mouse line (arcPomc-) with a tamoxifen-inducible Gad2-CreER transgenic line. Tamoxifen treatment of arcPomc-/-:Gad2-CreER mice at P60 resulted in Pomc expression in ~25 % of Arc-POMC neurons and ~23 % of Pomc mRNA levels, compared to Gad2-CreER control mice. Rescued mice normalized food intake, glycemia and fasting-induced hyperphagia, and significantly reduced body weight. Energy balance was also improved in arcPomc-/-:Gad2-CreER mice treated with tamoxifen at P25. Distribution analysis of rescued POMC immunoreactive fibers revealed that the DMH is a major target site of GABAergic-POMC neurons. Interestingly, the expression of the orexigenic neuropeptide Y (NPY) in the DMH was increased in arcPomc-/- obese mice but completely restored after Pomc rescue in arcPomc-/-:Gad2-CreER mice. Finally, we performed stereotactic intracerebral injections of fluorescent retrobeads into the DMH followed by in situ hybridization for Gad1 and found that ~75 % of Arc-POMC neurons projecting to the DMH are GABAergic. In conclusion, in the present study we show that the expression of Pomc in the subpopulation of Arc-GABAergic-POMC neurons is sufficient to maintain normal food intake. In addition, we found that DMH-NPY expression is negatively correlated with Pomc expression in GABAergic-POMC neurons, suggesting that food intake may be regulated by an Arc-GABAergic-POMC --> DMH-NPY pathway.
SUN-067 Pituitary Dysfunction in Children with Ectopic Posterior Pituitary
Authors: Naji Ghada , Poletto Erica , Kubicky Rita Ann
Published: May 2020

Background: Imaging studies aid in the detection of structural abnormalities that may be associated with pituitary dysfunction, such as ectopic posterior pituitary (EPP). The location of the ectopic lobe can vary, but it is most commonly located along the median eminence in the floor of the third ventricle. An EPP could result from complete or partial defective neural migration during embryogenesis, which could explain the different loci of EPP. Affected individuals have either severe isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiencies (CPHD); diabetes insipidus is not a feature, indicating that the EPP is functioning normally.

Aim: To detect the prevalence of IGHD or CPHD in children with EPP. In addition, to evaluate the association between the location of EPP and pituitary dysfunction.

Methods: A retrospective chart review of MRI reports at St. Christopher’s Hospital for Children (SCHC) from 2006-2018 that were found to have EPP. Pituitary hormone function was evaluated in the majority of the patient population.

Results: Of the 26 patients with EPP, [16 males (M) and 10 females (F)], mean chronologic age was 5.98+5.18 yrs, only 20 patients had an endocrine evaluation at SCHC. Of the 20 children, 14 had CPHD and 4 had IGHD.

Patients were classified into 3 groups (upper, middle & lower) according to EPP location along the pituitary stalk. Of the 21 patients with upper EPP, 17 had pituitary dysfunction (14 with CPHD, 3 with IGHD). Of the 4 children with middle EPP, only 1 had pituitary dysfunction which was IGHD. One patient had lower EPP with hyperprolactinemia. Diabetes insipidus was not identified in any of the children.

Conclusion: Our study supports previous reports that CPHD and IGHD are frequent in patients with EPP. Similarly, our data further demonstrate that no cases of diabetes insipidus have been reported in children with EPP.

In our study, EPP is most commonly located along the upper third of pituitary stalk at the median eminence level, with a higher prevalence of CPHD and IGHD, a finding similar to prior studies. No CPHD was reported in middle/lower but IGHD was found in the middle EPP group.
SUN-006 Light and Exercise Therapy Improves Depression in Women with Premenstrual Syndrome
Authors: Tsikirai Tino Michelle , Ramirez Francisco , Nedley Neil
Published: May 2020

Objective This study documents the effects that light and exercise therapy have in women experiencing premenstrual syndrome (PMS). Design Methods Study participants were fertile-aged females that were involved in a non-profit community depression and anxiety education program. Participants met in once a week and were taught about the effects of healthful cooking, regular exercise (at least 40 minutes of exercise five times a week), bright light exposure (20 - 40 minutes of exposure) from the sun or from a light box, and other healthy behaviors on their mental health. All participants took a 75-item questionnaire at the beginning and the end of the program to establish a baseline and measure changes in depression levels. The questionnaire measured depression level based on DSM-5 [The Diagnostic and Statistical Manual of Mental Disorders Volume 5] criteria. Participants were asked to provide their demographical information and patient history, including information about premenstrual syndrome. Depression was classified into 4 categories as none (0-6), mild (7-10), moderate (11-19) or severe (20 or more). Results From 1968 females 803 reported suffering from PMS mean age 38.8, SD 8.9. Baseline mean depression was 15.3, SD 15.3, median 16 and mode of 18. At the end from the 803, 280 established exercise and light therapy, that group had a depression average of 6.2 (SD 5.5), median 5, mode 0 and 83 (29.6%) of them reported no longer PMS symptoms. At the end those 125 did not established the exercise and light therapy had a depression average of 7.7 (SD 5.5), median 7 and mode 8 and 34 (27.2%) no longer reported PMS symptoms. Conclusions Women experiencing PMS exhibit improved mental health as a result of light and exercise therapy. Lifestyle intervention for maladies related to this syndrome may be an effective alternative to pharmaceutical medications.
SAT-494 An Unusual Presentation of Hypothyroidism
Authors: Sukumaran Anju
Published: May 2020

Introduction: Pediatric Endocrinologists see many children with congenital hypothyroidism. Complications from long standing untreated hypothyroidism reports are rare in children. This is a case report on an unusual presentation of hypothyroidism caused by noncompliance.Clinical Case: A 11-year-old boy with history for congenital hypothyroidism, lost for follow up for 10 months, presented to an outside hospital with pain on face, joints and all over his body. Initial labs showed elevated creatinine, liver enzymes and TSH >300 mcIU/mL with free T4 <0.1 ng/dL. He was transferred to University for further care. In our Emergency Room, patient had normal vitals. On exam he had puffy appearance, sluggish reflexes otherwise unremarkable exam. Chest X-ray was done due to cough and congestion symptoms and showed cardiomegaly. EKG showed low voltage complexes otherwise normal. ECHO obtained showed normal left ventricular function and small pericardial effusion. Cardiology recommended no intervention at this time. Endocrinology was consulted due to abnormal thyroid labs. Patient had normal mental status, no hypothermia or bradycardia or hypotension or hypoventilation. He had normal sodium. He had macrocytic anemia. Recommended to get creatinine kinase (CK) levels as he had elevated serum creatinine. CK levels came back at 3600 U/L. He was started on intravenous hydration and Synthroid. Doses were increased daily. Once serum creatinine trended down and glomerular filtration rate (GFR) normalized he was discharged home. CK was still elevated but trended down. He had Tanner 3 testes size on exam. His LH and testosterone levels were pubertal consistent with central puberty activation and not just macroorchidism. He was seen as outpatient a month after discharge. His thyroid levels were normal. Serum creatinine and CK had normalized and he continues to progress in puberty. Conclusion: Long standing untreated hypothyroidism can cause multiple organ dysfunctions. Our patient presented with cardiomegaly, acute kidney injury from rhabdomyolysis. It is important to look out for other system involvement as this happen rarely in children and myxedema coma can be life threatening.
SUN-673 Development of Euglycemic Diabetic Ketoacidosis in a Patient with Well-Controlled Type 2 Diabetes Mellitus on a Sodium-Glucose Transporter 2 Inhibitor
Authors: Narang Disha K , Anthony Pick , Anca Zegrean , Balu Simona , Mateo Tole
Published: May 2020

Background: We describe the case of a patient with euglycemic diabetic ketoacidosis (euDKA), in the setting of sodium-glucose cotransporter-2 (SGLT2) inhibitor use, complicated by non-anion gap metabolic acidosis and low-carbohydrate diet leading to admission.

Presentation: A 43-year-old woman with a history of type 2 diabetes mellitus treated with Metformin, with no prior history of DKA, was admitted with progressive dizziness, nausea, vomiting, malaise, palpitations, and dyspnea starting 3 days prior to admission. Her other history includes anemia due to uterine fibroids, hypertension, and hyperlipidemia. Hemoglobin A1C was 6.7%, however in the setting of anemia. She denied polyuria and polydipsia, and alcohol and drug use. She was started on a low-dose SGLT2i and pioglitazone 1 week prior to admission.

Labs revealed mild hyperglycemia (blood glucose 145 mg/dL), with mixed anion-gap and non-anion-gap metabolic acidosis, and respiratory alkalosis [arterial pH 6.97 (rr7.35-7.45), PCO2 <13.0 mmHg (rr 32-45 mmHg), bicarbonate 5mm/dL (rr 24-33 mg/dL), anion gap 22, B-hydroxybutyrate 12.52 mmol/L (rr 0-0.3 mmol/L), and chloride 108 mEq/L (rr 98-109 mEq/L)], with normal renal function, hepatic function, and lactate. Infectious work-up was negative, including chest x-ray and urinalysis.

She was diagnosed with euDKA due to SGLT2i. The SGLT2i was stopped and she was treated with insulin drip, intravenous fluids, and temporary bicarbonate drip given combined acidoses and severely low bicarbonate level, until her acidosis cleared. The patient noted that she had lately been eating a very low-carbohydrate diet in order to improve her glycemic control and promote weight loss.

Discussion: In this case, DKA was likely precipitated by ketogenesis from low-carbohydrate diet for 1 week while taking a low-dose SGLT2i. Additionally, the dual anti-hyperglycemic therapy with Metformin and SGLT2i contributed to high anion-gap metabolic acidosis, along with the presence of a non-anion-gap metabolic acidosis. The patient was successfully transitioned to Metformin and pioglitazone upon discharge. As the use of SGLT2i is becoming widespread across multiple disciplines, recognizing euDKA in the setting of profound acidemia and very low carbohydrate diet in patients who are overall lower risk is particularly important.
SAT-LB94 An Unusual Case of Acute Myocardial Infarction Revealing Underlying Polycythemia Secondary to Exogenous Bioidentical Testosterone Therapy
Authors: Fox Marissa , Epps Michelle , Jafari Jasmine , Roy Simi , Rahman Maisara
Published: May 2020

BACKGROUND: Many patients seeking testosterone therapy are turning to compound pharmacies for customized bioidentical testosterone replacement. These pharmacies market “bioidentical” hormone therapies as more effective and superior to traditional FDA-approved synthetic therapies. Bioidentical formulations are available as injections, creams, and subcutaneous pellet implants. Exogenous testosterone replacement is associated with polycythemia complicated by increased blood pressure, blood viscosity, and platelet aggregation (1). The ensuing hypercoagulable and prothrombotic changes predispose individuals to adverse cardiac events, including myocardial infarction.

CLINICAL CASE: A 66-year-old male with hypertension, type 2 diabetes, and hyperlipidemia presented with chest pain and dizziness. Initial EKG was unremarkable but troponin levels were elevated and the patient was admitted to telemetry. Lexiscan indicated anterior territory ischemia and coronary angiography revealed 95% stenosis of the left anterior descending artery (LAD). He underwent percutaneous coronary intervention (PCI) with stenting of the LAD. During the patient’s workup, he was noted to have elevated hemoglobin (20) and hematocrit (60) levels and was treated with 1g hydroxyurea as phlebotomy was unavailable. JAK2 mutation and EPO level screenings were ordered and unremarkable. The patient was noted to have multiple subcutaneous testosterone pellets in his buttocks which he stated were implanted three weeks prior. Serum total testosterone was elevated at 1226 ng/dL. Hematology was consulted and the patient continued daily 1g hydroxyurea. After discharge, the patient continued outpatient follow up with hematology and received plasmapheresis for management of polycythemia.

CONCLUSION: Considering polycythemia can arise secondary to exogenous testosterone use and is a known risk factor for cardiovascular events, it is likely this patient’s myocardial infarction was complicated by his use of exogenous bioidentical testosterone. Compound pharmacies providing bioidentical testosterone are not required to report adverse events, provide black box warnings, or show evidence-based safety and efficacy profiles for their products. The increasing availability and use of non-FDA-approved testosterone therapies warrants increased physician vigilance, particularly for patients with existing cardiac conditions or predisposition to hypercoagulable and prothrombotic states. The lack of regulation and research in the realm of compound pharmacy hormone products calls for further studies and reforms to protect patients from the risk of developing detrimental complications.

REFERENCE: (1) Xu, L., Freeman, G., Cowling, B. et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med11, 108 (2013).
MON-LB76 Impact of Age on Survival and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Cancer Patients
Authors: Buffet Camille
Published: May 2020

BACKGROUND

Age has been identified as a major prognostic factor in differentiated thyroid cancer (DTC). Prognostic factors of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) are poorly described. The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age.

PATIENTS AND METHOD

This single centre, retrospective study enrolled 155 patients diagnosed with a RAIR-DTC between 1991 and 2017. The primary end point was overall survival (OS). Secondary endpoints were progression free survival (PFS) and prognostic factors.

RESULTS

Median OS was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age (P = 0.47) with median OS at 8.3 years in patients < 65 (95% IC: 4.9-10), and 7.5 years in patients > 65 (IC: 4,9-11,3). PFS after RAIR-diagnosis was 2.1 years (95% IC: 0.8-3) in patients < 65, and 1 year in patients > 65 (95% IC: 0.34-0.68). In both groups, progressive disease despite 131I reduced OS, in comparison with other RAIR criteria. In patients < 65, an interval between the initial diagnosis of DTC and the diagnosis of RAIR metastatic disease more than 3 years was protective from poor OS (HR: 2.12; 95% CI: 1.05-4.27). In patients > 65, presence of a mediastinum metastasis at RAIR-diagnosis was a significant factor for decreased OS (HR: 0.22; 95% CI: 0.11-0.44).

No difference was found between groups regarding therapeutic management. One third of patients received tyrosine kinase inhibitors in both groups (< 65 years: 20 patients (28%), ≥ 65 years: 28 (33%), P = 0.49). They were also similar regarding the number of lines received or the median duration of treatment (< 65 years: 19.5 months (2-59), ≥ 65 years: 19 months (1-64), p= 0.35). At least one line of TKI was transitorily or definitively withdrawn due to toxicity in 40% of patients (< 65 years: 8/20 patients (40%), ≥ 65 years: 13/28 (46%), p= 0,037).

CONCLUSION

In RAIR-DTC patients, age was not predictive of the outcome. In our study, older patients seem to have benefited from intensive therapeutic management. Continual progress made in the management of RAIR-DTC, especially with the implementation of systemic therapies should probably make reconsider the natural history and conventional prognostic factors of RAIR-DTC.
SAT-LB9 Anti-Cancer Properties of RISUG Against Prostrate Cancer Cell Line PC-3 -Invitro Study
Authors: Singroul Pankaj , Singh Palak , Guha Sujoy K , Gupta Surabhi , Chaturvedi Pradeep Kumar
Published: May 2020

Cancer cell lines were initially established for understanding the genetic, functional, and epigenetic properties of cancer cells. The PC3 cell line is a human-derived prostate cancer cell line from the metastatic bone site of the grade IV adenocarcinoma patient. With the invention of RISUG-a polymeric male contraceptive, and studying its astonishing properties such as anti-microbial activity, there have been multiple hypotheses stating its anti-cancerous effect based on its physical and chemical nature[1]. This study focuses on understanding the effect of RISUG on prostate cancer cell line PC3 via MTT assay.For our study, 10 mg/ml working concentration of RISUG in DMSO (solvent) was used for the treatment to the cells. The dosage given to the cells for three varying incubation periods of 24 hours, 48 hours and 72 hours were analyzed for there viable cells post treatment. The dose was delivered with the media such that the final concentration of DMSO in the media is 1.5% (optimized) to avoid vehicle toxicity. The MTT assay was employed to study the cytotoxicity effect by measuring the amount of viable cells post treatment. The observations were statistically significant for the anti-cancerous effect of RISUG on PC3 prostate cancer cells for 72 hours, the optimized minimum incubation time/ time of action for RISUG to exhibit significant anti-cancer effect against PC3 cells. However, further in depth research is necessary for the understanding of the mechanism behind these actions.

Keywords: RISUG, Prostate Cancer, DMSO, Cell line,

Reference: 1. Subramanian, B., Agarwal, T., Basak, P., Maiti, T., & Guha, S. (2019). RISUG® based improved intrauterine contraceptive device (IIUCD) could impart protective effects against development of endometrial cancer. Medical Hypotheses, 124, 67-71. doi: 10.1016/j.mehy.2019.02.026
SAT-LB45 Chronic Opioid Use as a Cause of Severe Hypothyroidism: A Case Report
Authors: Slack Daniel , Brooks Danielle , Levine Alice C
Published: May 2020

Background: Hypogonadism and hypocortisolism are present in a sizeable proportion of chronic opioid users. (1) An association with hypothyroidism, however, has not been demonstrated.

Clinical Case: A 56-year old woman with chronic pain syndrome on opioids presented from a nursing home with decreased level of consciousness and was found to be hypotensive requiring ICU admission. Several weeks prior to her presentation, she was hospitalized for progressive weakness and was found to have evidence of panhypopituitarism: low TSH (0.209 uIU/mL, nl 0.400 – 4.200), low free T4 (0.76 ng/dL, nl 0.80 – 1.50), low LH (<0.12 mIU/mL, nl 10.9 – 58.6), low FSH (1.7 mIU/mL, nl 16.7 – 113.6), and abnormal ACTH stim test (ACTH 6.4 pg/mL, nl 7.2 – 63; cortisol 0-min 3.8 mcg/dL, nl 6.7 – 22.6; 60-min 13.10). She was discharged on levothyroxine 25 mcg daily and prednisone 7.5 mg daily. On admission, her exam was notable for symmetric, non-pitting edema of the lower extremities to the knees with peau d’orange appearance. Initial tests revealed profound hypothyroidism with low TSH (0.381 uIU/mL), low free T4 (0.60 ng/dL), undetectable total T4 (<0.9 mcg/dL, nl 5 – 12.2), and undetectable free T3 (<1.00 pg/mL, nl 2.5 – 3.9). Thyroglobulin and TPO antibodies were within normal limits. Thyroxine binding globulin was low (6 mcg/mL, nl 13 -39). Additional biochemical studies re-demonstrated panhypopituitarism with low LH (<0.12 mIU/mL) and FSH (0.9 mIU/mL). Cortisol was elevated (73.2 mcg/dL) as she had received hydrocortisone. Despite fluid resuscitation and use of vasopressors, her hypotension persisted and she remained in critical condition. She was treated as a case of myxedema coma and started on full replacement dose thyroid hormone with 120 mcg IV levothyroxine daily and liothyronine 5 mcg every 8 hours. Over the next several days, the patient’s hemodynamics and mental status improved dramatically. A contrast-enhanced pituitary-protocoled MRI was notable for a moderately flattened sella (pituitary 3.5 mm in height) and absence of usual T1 bright signal in the posterior lobe. A work-up for causes of panhypopituitarism was mostly unremarkable: low IgG 4 (0.82, neg <1.50), indeterminate quant gold, negative HIV, low serum iron (35 mcg/dL, nl 50 – 200). Urine toxicology was positive only for opioids, reflective of the patient’s chronic pain regimen consisting of MS-Contin 60 mg twice daily and methadone 10 mg twice daily.

Conclusion: This case demonstrates the potential for chronic opioid use to suppress the hypothalamic-pituitary-thyroid axis and highlights the importance of maintaining an index of suspicion for hypothyroidism in this population.

Reference: (1) de Vries, F., Bruin, M., Lobatto, DJ., Dekkers, OM., Schoones, JW., van Furth, WR., Pereira, AM., Karavitaki, N., Biermasz, NR., Najafabadi, AHZ. Opioids and their endocrine effects: A systematic review and meta-analysis. JCEM. 2019. Doi: 10.1210/clinem/dgz022
OR26-05 The Correction Factor for A1C in Anemic Patients
Authors: Villacreses Maria Chang , Karnchanasorn Rudruidee , Ou Horng-Yih , Feng Wei , Samoa Raynald , Chuang Lee-Ming , Chiu Ken C
Published: May 2020

Diabetes can be defined by hemoglobinA1c (A1c), fasting plasma glucose (FPG), and 2-hour plasma glucose (2hPG). Despite that A1c has a tendency for underestimation of the prevalence of diabetes and overestimation of the prevalence of normal glucose tolerance, A1c is the most convenient method, since no preparation required. However, various factors could affect A1c. The objective of this project is to identify the covariates that affect A1c. The study sample included 9,952 adults (age≥20 years old) from the 2005–2016 NHANES. Subjects with established diabetes were excluded, and we analyzed subject’s documented BMI, A1c, FPG, 2hPG, Hemoglobin (Hgb), race/ethnicity, age, education, poverty index, family history of diabetes, and tobacco and alcohol consumption to determine their impact on A1C measurement. Continuous data were expressed as means with standard deviation. Either t-test or ANOVA was used to examine the influence of covariates on continuous variables. We examined the relation of A1c with FPG, 2hPG, and other covariates. With backward regression analysis, we excluded the covariates without significant impact on A1c. All the analyses were conducted in SYSTAT 13, Systat Software, Inc. In the univariate analysis, A1c was significantly corelated with FPG (r=0.5692, P<0.0001) and 2hPG (r=0.5122, P<0.0001). In the backward regression analysis, education, poverty index, and family history of diabetes were excluded for their low impact on A1c. In addition to FPG and 2hPG, gender (r=-0.0527, P<0.0001), age (r=0.1746, P<0.0001), BMI (r=0.0978, P<0.0001), race/ethnicity (r=0.0478, P< 0.0001), current alcohol consumption (r=0.0542, P<0.0001), current smoker (r=-0.0806, P<0.0001), and Hgb (r=-0.1526, P<0.0001) had significant impact on A1c. Due to the significant difference in Hgb between gender, gender-based analyses were performed. In male gender, the impact of other covariates (age, BMI, race/ethnicity, current alcohol consumption, and current smoker) than FPG and 2hPG could be explained at least partially through their impact on Hgb (P<0.0001). Each 1 g/dL decrease of Hgb would falsely decrease A1c by 0.053% (P<0.0001). In female gender, the impact of covariates other than FPG and 2hPG on A1c could be explained by their impact on Hgb (p<0.0001) except for BMI. Each 1 g/dL decrease of Hgb would falsely decrease A1c by 0.047% (P<0.0001). In addition to FPG and 2hPG, A1c could be affected by gender, age, BMI, race/ethnicity, current alcohol consumption, and current smoker through their impact on Hgb, except for BMI in female gender. A1c will be falsely decreased by 0.053% in male gender and 0.047% in female gender for each 1 g/dL decrement of Hgb. Thus, A1c should be interpreted with caution in anemic patients. We propose using the gender specific correction factors for more accurate interpretation of A1c.
SAT-LB307 Case of the Broken Hearted
Authors: Namboodiri Divya , Khor Lynne , Champion Bernard , Shalaby Grant , Preda Veronica Angela
Published: May 2020

Phaeochromocytomas are rare neuroendocrine tumours which, usually present with headache, diaphoresis, episodic tachycardia and hypertension. Takotsubo-pattern cardiomyopathy is an unusual initial presentation of phaeochromocytomas, however has been reported1. Approximately 10% of phaeochromocytomas present with cardiomyopathy. It is associated with a high mortality risk and early intervention with surgery is the key to recovery. We report a case of a previously healthy, 68 year old man who presented with symptoms of left ventricular failure, and feeling anxious. Physical examination revealed signs of left ventricular failure, with a normal blood pressure and heart rate. A transthoracic echocardiogram (TTE) revealed dilated left ventricle with severe global hypokinesis and a left ventricular ejection fraction (LVEF) of 15%. A CTPA performed to exclude pulmonary embolism revealed an incidental right sided adrenal lesion measuring 3.9 X 3.4 X 3.7 cm. Subsequently a dedicated abdominal CT confirmed the adrenal lesion. Biochemistry revealed elevated 24 hour urine catecholamines and metanephrines and an elevated plasma metanephrines. Subsequently he proceeded to have adrenalectomy. Pre-operatively the patient was managed with alpha and beta blocking agents for 3 weeks prior to surgery. Post-operative course was uneventful and histopathology confirmed right sided phaeochromocytoma. TTE performed 12 months post-operatively showed a significant improvement in his LVEF to 40 % with subsequent TTE showing maintenance of LVEF. This case demonstrates highlights the unusual presentations of phaeochromocytomas and that early recognition and early intervention with surgery is the key to recovery to avoid catastrophic cardiac events.1. Chiang YL, Chen PC, Lee CC, et al. Adrenal pheochromocytoma presenting with Takotsubo-pattern cardiomyopathy and acute heart failure: A case report and literature review. Medicine (Baltimore)2016;95(36):e4846. doi: 10.1097/MD.0000000000004846 [published Online First: 2016/09/08]
SUN-LB138 Dynamic Structural Model of Testosterone Entry Into the Unliganded Androgen Receptor
Authors: Krylova Irina , Schaufele Fred J , Guilbert Christophe
Published: May 2020

Background: Crystallographic structures of nuclear receptor ligand binding domains provide a static model of a receptor stably wrapped around an internalized ligand. Understanding the dynamics of a receptor at different stages of ligand binding has been hampered by the paucity of crystal structures for unliganded nuclear receptors. Molecular dynamic models have been constructed for some nuclear receptors to fill that void.

Methods: The molecular simulation docking program MORDOR (MOlecular Recognition with a Driven dynamics OptimizeR)(1) was used to study the structural dynamics of the androgen receptor ligand binding domain (AR LBD) modeled from the static structure of the AR LBD bound to testosterone (T) (PDB ID: 2AM9). The goals of the study were to understand a) the dynamic interaction of the T in its binding pocket, b) AR LBD structural flexibilities that permit T entry/exit from the binding pocket and c) a model of the unliganded AR LBD.

Results: Modeling AR LBD structure flexibility over time revealed possible alternative dynamic structures, including those without ligand, overlaid against the canonical nuclear receptor structure. The model dynamically tracks the structural changes as a ligand enters into the ligand binding domain and nestles into the ligand binding pocket. The model predicted the appearance of alpha helices within the AR LBD that transiently fold/unfold during the ligand entry phases. Once in the pocket, the ligand itself remains very dynamic in a still flexible pocket. The model predicted also AR LBD amino acids that sequentially interact with the ligand during its dynamic entry into the AR LBD. Intriguingly, those AR amino acids include those mutated in castration-resistant prostate tumors that continue to grow during androgen suppression therapy. Functional studies showed those mutant ARs had a primary consequence of enhancing response to lower level T, and other androgens, consistent with their role in creating a higher affinity AR that can scavenge low-level androgens in an androgen-suppressed patient.

Conclusions: The molecular model of T binding to the AR LBD suggests a degree of structural dynamism not evident in the crystallographic structures commonly associated with nuclear receptors. Some AR mutations activating prostate tumor growth may do so by impacting androgen entry/exit, rather than by altering androgen fit into the ligand binding pocket.

Reference: (1) Guilbert C, James TL (2008) J Chem Inf Model. 2008 48(6): 1257-1268. doi: 10.1021/ci8000327
MON-LB60 Prolactin Response to Metformin in Cabergoline-Resistant Prolactinomas: A Prospective Study
Authors: Corrêa Portari Luiz Henrique , Correa-Silva Silvia Regina , Abucham Julio
Published: May 2020

Introduction: Prolactinomas are the most frequent pituitary-secreting tumors. Medical therapy with cabergoline (CAB), a dopamine agonist (DA), is the first line treatment, but 10% of prolactinomas are resistant to CAB. Recently, in vitro studies have shown anti-tumoral activity of metformin and other biguanids in human prolactinomas1, which prompted us to investigate that possibility in vivo. Aim: To evaluate the effect of metformin (MET) on Prolactin (PRL) secretion in patients with CAB resistant prolactinomas. Design and Setting: Prospective interventional study in a single referral center. Subjects: Ten patients (7 M; mean age: 44 ± 12y) with CAB resistant (PRL: 148 ± 125ng/ml; range: 38 - 386) prolactinomas (all macroadenomas) and metabolic syndrome on maximally tolerated CAB doses (4.3 ± 1.2 mg/week; range: 2.0-7.0) for ≥ 6 months (45 ± 39mo; range: 6-120). Intervention: Oral extended release metformin (p.o.) was prescribed according to patient’s tolerance (mean dose: 1.3 ± 0.4 g; range: 1.0-2.0). Main Outcome Measurements: Serum PRL (Elecsys, Roche, Indianapolis, USA), body weight (BW), fasting glycemia (FG) and HbA1C were evaluated before and at two time points during metformin treatment (30-60 and 120-180 days). Results: BW, FG, and/or HbA1C reductions were observed in 9/10 patients and mean FG decreased significantly (P=0.04). No significant changes were observed in serum PRL levels during metformin treatment [134 ± 124 ng/ml vs 138 ± 132 ng/ml vs 144 ± 129 ng/ml, before, at 30-60 days and at 120-180 days, respectively (P=0.499, mixed-effects analysis with the Geisser-Greenhouse correction)]. Individually, two patients exhibited a ≥ 50% decrease in PRL levels at a single timepoint (one at 30-60 days, with a further increase at 120-180 days and the other at 120-180 days). Conclusion: Metformin, at usual doses, did not inhibit prolactin secretion in patients with cabergoline-resistant prolactinomas. The discrepancy between our results and in vitro studies is not clear, but may be related to the much higher concentrations of metformin used in vitro1 as compared to the serum concentrations observed in patients during metformin treatment2. References: 1Gao J et al. Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts. J Cell Mol Med. 2018 22:6368-79; 2 Frid A et al. Novel assay of metformin levels in patients with type 2 diabetes and varying levels of renal function: clinical recommendations. Diabetes Care 2010 33:1291-3.