bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-013 Cardiometabolic Profile of Brazilian Women with Polycystic Ovary Syndrome (PCOS): A Systematic Review and Meta-Analysis
Authors: Marchesan Lucas Bandeira , Ramos Ramon Bossardi , Oliveira Monica , Spritzer Poli Mara
Published: May 2020

Introduction. PCOS is a frequent endocrine disease and its clinical expression may be influenced by ethnicity and sociocultural backgrounds. Despite its high prevalence, few studies are available regarding clinical characteristics of Brazilian women with PCOS. The aim of this study was to summarize the available evidence regarding metabolic risks in PCOS population in Brazil trough a systematic review and meta-analysis. Materials and Methods. We systematically searched EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials for studies published until July 31, 2019. Results. Eleven cross-sectional and case-control studies were selected for the present meta-analysis, including 898 women diagnosed with PCOS and 2176 controls. All used the Rotterdam criteria for the diagnosis of PCOS. Compared to controls, BMI was higher in PCOS [standardized mean difference (SMD) 0.67 (95% CI 0.29, 1.05) I²=91%], as well as waist circumference [SMD 0.88 (0.40, 1.37) I²=93%]. Systolic and diastolic blood pressure were higher in PCOS, SMD 0.66 (0.30, 1.01) I²=83%, SMD 0.55 (0.24, 0.87) I²=81%, respectively. Glucose and HOMA-IR were higher in PCOS, SMD 0.22 (0.02, 0.41) I²= 57%, SMD 0.78 (0.52, 1.04) I² =26% respectively. Regarding lipid profile, PCOS had higher values for triglyceride [SMD= 0.39 (0.14, 0.64, I² =63%)], total cholesterol [SMD 0.36 (0.15, 0.57, I²=57%)] and LDL [SMD 0.44 (0.11, 0.78, I²=82%)] and lower values for HDL [SMD -0.56 (-0.78, -0.34) I²=68%]. Conclusions. Even though the studies considered were observational, including mostly small samples, the evidence from this meta-analysis indicates women with PCOS from different regions of Brazil present worse cardiometabolic profile than women without PCOS. This systematic review and meta-analysis is registered in PROSPERO (CRD42016038537).
SUN-916 Novel Germline p.Gly42Arg MEN1 Missense Mutation in a Family Harboring Very Aggressive Pancreatic Tumor, Hyperparathyroidism and Pituitary Tumor
Authors: Naves Luciana Ansaneli , Santana Lidiana B , Miranda Isabella Santiago M , Rosa Isabella Naves , Mesquita Pedro G , Santa Rita Ticiane H , Sousa Claudia F , Barra Gustavo Barcelos
Published: May 2020

Background.Pancreatic neuroendocrine tumors ocurs in 30-80% of patients with MEN-1, and may be non-functioning and hormone secreting tumors. Non-functioning GEP-NETs are increasingly recognised due to advanced imaging modalities such as endoscopic ultrasound thus became the most common type in MEN1 patients. Several mutations MENIN gene were described, although patients with missense mutations are considered as low-impact mutation carriers.Case report.Index case, female, 47 years old, menarche at age of 16yo, amenorrhea until 23yo, when started continuous oral contraceptives. At age of 45 presented dizziness, paresthesia, cramps, had the diagnosis of Hyperparathyroidism related to multinodular parathyroid hyperplasia (Calcium 14mg/dL, PTH 117 pg/mL) and macroprolactinoma (prolactin 235 ng/mL; pituitary tumor 1.2 X 1.0 cm). All siblings and her mother were recruited and one brother, aged 45 years confirmed the diagnosis of hyperparathyroidism and nephrocalcinosis. Their mother, aged 77 years old, presented abdominal pain, and had the diagnosis of aggressivepancreatic tumor compressing bile duct causing intra and extra-pancreatic dilation, associated with metastatic lymph nodes. She was sunmitted to total pancreato-gastrectomy with esophagus jejunum anastomosis. Genetic screening:MEN1genetic screening for mutations was performed in all patients. In these probands, MLPA analysis was performed to detect large deletions of the MEN1gene, using SALSA MLPA probemix kit P017-D1 according to the manufacturer’s instructions (MRC-Holland, Amsterdam, The Netherlands).DNA was extracted from EDTA-Whole blood using MagNA Pure 24 (Roche). Sequencing libraries were qualified/quantified using TapeStation4200 (Agilent). Test method included coding regions ±10bp flanking intronic sequences of 3921 genes enriched using Kappa HyperPlus Library Preparation Kit (Roche) and SeqCap EZ inherited disease panel (Roche) and sequenced (2x75-bp Mid Output V2 Reagent) using NextSeq-500 (Illumina) (estimated mean coverage-100X). Read alignment, variant calling, variant filtration and annotation were performed with Varstation. SNVs and small indels (20bp) with total-read-depth,10X and variant-read-frequency more than20% found on AIP, APC, CDC73, CDKN1B, DICER1, FH, MAX, MEN1, MET, NF1, PRKAR1A, PTEN, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53, VHL, WRN genes were analyzed.A missense mutation in exon 2, MEN1:c.124G.C:p.(GLY42Arg) was detected. Discussion and conclusion:MEN1-associated GEP-NETs seem to have a low proliferation rate and long survival has been reported, they should be of particular attention, since they are still the principal cause of death in MEN1 patients.Early screening and diagnosis are crucial for MEN-1 phenotypes.
SUN-336 Obesity and Impaired Glucose Metabolism in Adult Patients with X-Linked Hypophosphatemia
Authors: Lecoq Anne-Lise , Trabado Séverine , Schilbach Katharina , Rothenbuhler Anya , Barosi Anna , Debza Yahya , Linglart Agnes , Bidlingmaier Martin , Kamenicky Peter
Published: May 2020

Background: X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Epidemiologic studies suggest a relationship between FGF23, obesity and metabolic syndrome. However, the prevalence of metabolic complications in adult XLH patients is not known.

Study design: We conducted a prospective cohort study (CNIL 2171036 v 0) in a single tertiary referral center.

Subjects: Patients were adult subjects with XLH, defined as hypophosphatemia due to renal phosphate wasting with either documented PHEX mutation (92%) and/or family history of rickets. Healthy controls were selected among adult participants of the AcroCut cohort and matched for sex, age and body mass index (BMI).

Methods: Prevalence of obesity and diabetes in patients was compared with the general French population (ObEpi 2012; Bonaldi C. et al., Bulletin épidemiologique hebdomadaire 2016) and prevalence of glucose intolerance in patients, assessed by standard 75-g OGTT, was compared to matched controls. Resistance to insulin was evaluated with HOMA-IR index.

Results: 107 patients (79 women and 28 men) were recruited. Median age at evaluation was 35.5 years (range 16.9-74.2) and median BMI was 25 kg/m2 (range 18-48). Thirty-eight (35.5%) patients were overweight (29 women) and 22 (20.5%) patients were obese (16 women). Distribution of normal weight, overweight and obesity in adult XLH patients differed from that seen in the general French population. We observed an excess of overweight and obesity (+20%, 95% CI [+6; +33], P=0.013) in comparison to general population, especially in younger age categories (under 45 years of age). Three (2.8%) out of the 107 patients were treated for diabetes which did not differ from the expected frequency of type 2 diabetes of 5% in the French population. Twelve (13%) out of 90 patients with available OGTT were glucose intolerant or diabetic compared to ten (12%) of the 82 matched controls (P=0.995). Decreased insulin sensitivity assessed by HOMA-IR was found in fourteen (15.6%) adult XLH patients. Comparison of insulin and glucose curves obtained during the OGTT in patients and matched controls are planned to analyze insulin sensitivity in both populations.

Conclusion: Adult XLH patients are prone to develop overweight and obesity, particularly adolescents and young adults. This excess of weight does not seem to result in increased prevalence of metabolic disorders. Insulin sensitivity, yet, needs to be further evaluated in these patients and compared to appropriate controls. FGF23 concentrations will also be assessed to search for determinants of insulin sensitivity in patients. Lifestyle recommendations to prevent obesity, promoting physical activity, are thus essential in the management of XLH patients.
SUN-178 Clinical and Anatomopathological Characteristics of Two Atypical Aldosterone-Producing Adenomas
Authors: Goldbaum Tatiana Silva , Balancin Marcelo L , Ledesma Felipe L , Maciel Ana Alice Wolf , de Freitas Thaís Castanheira , Yamauchi Fernando , Srougi Victor , Tanno Fabio Y , Chambo Jose L , Latronico Ana Claudia , Mendonca Berenice Bilharinho , Fragoso Maria Candida Barisson Villares , Zerbini Maria Claudia N , Almeida Madson Q
Published: May 2020

Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small (<2 cm in diameter) benign appearing nodules on computed tomography (CT). Up to 70% of APAs may harbor KCNJ5 somatic mutations.

Clinical Cases: Case 1. A 33-yr-old man was referred to investigate resistant hypertension (HT). Biochemical evaluation revealed normal K levels, aldosterone (A) of 14.7 ng/dl, renin of 2.1 mUI/L (normal, 4.4-46.1) and A/R ratio of 24.8. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation revealed a non-suppressible cortisol after an overnight 1 mg low-dose dexamethasone suppression (8.3 μg/dL), abnormal midnight salivary cortisol, and normal urinary free cortisol, plasma DHEAS and ACTH levels. Computed tomography (CT) scan showed a well-limited mass in left adrenal, measuring 5.8 cm with pre-contrast density of 30 HU and absolute wash-out of 72%. After left laparoscopic adrenalectomy, hydrocortisone was started and adrenal insufficiency confirmed by basal cortisol <3 μg/dL. He presented biochemical cure of PA and improvement in HT control. Histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 1 (clear cells <25%). CYP11B2 staining was positive in 10% and Ki67 in 5% of tumor cells. Case 2. A 58 yr-old woman was referred to investigate an adrenal mass. She had resistant HT and hypokalemia since 2010. Biochemical evaluation revealed hypokalemia (2.8 mEq/L), A of 16.9 ng/dl, renin <1.6 mUI/L and A/R ratio of 10.6. Confirmatory testing confirmed PA diagnosis. Hypercortisolism investigation was negative. CT scan showed a heterogeneous solid mass in the right adrenal, measuring 5.5 cm with pre-contrast density of 30 HU and absolute wash-out of 77%. After laparoscopic right adrenalectomy, histologic examination revealed an encapsulated tumor with glomerulosa-like cells predominance and a Weiss score 2 (clear cells < 25% and > 1/3 diffuse architecture). CYP11B2 staining was positive in 30% and Ki67 in 5% of the cells. She presented biochemical cure of PA and improvement in HT control. Genetic investigation for somatic KCNJ5, ATP1A1, ATP2B3 and CTNNB1 was negative in both cases.

Conclusion: We describe two rare cases of APAs that presented as large and suspicious tumors, without somatic mutations in genes associated with APAs.
MON-256 A Late-Onset Case of Sheehan’s Syndrome Presenting as Life Threatening Adrenal Insufficiency
Authors: Bhat Salman Zahoor , Goyal Itivrita , Batra Manav
Published: May 2020

OBJECTIVE

Sheehan’s syndrome or postpartum pituitary necrosis, is an important but rare cause of hypopituitarism, caused due to severe postpartum hemorrhage. Seen more commonly in the developing world, it is less common in developed countries due to advanced obstetric practices. It can present acutely but more frequently has an insidious course (onset 10-20 years later) with variable hormonal deficiencies. Here, we report a late-onset case of Sheehan’s syndrome, 24 years after the incident event, presenting as life threatening adrenal failure.

CASE PRESENTATION

A 48-year-old female with no significant past medical history was admitted to the hospital after being found unresponsive at home. She had not seen a physician for many years. She complained of weakness and lethargy for a week and recently established care with a primary care physician. The patient was severely hypotensive in the emergency department and had an elevated temperature of 101°F. Physical examination showed no significant abnormalities. CBC and metabolic panel were not significantly altered. CSF analysis and CSF/blood cultures were negative for any infection. TSH was 4.29 mIU/mL (0.27-4.20) but the total and free T4 (fT4) were severely low at 1.1 mcg/mL (4.6-12) and 0.24 ng/dL (0.93-1.70) respectively. On further questioning, patient reported severe postpartum hemorrhage 24 years ago, needing multiple units of blood transfusion. This was followed by inability to lactate and menstruate but was never worked up as she had not seen any physician all these years. Pituitary hormonal panel was obtained, demonstrating multiple hormonal deficiencies with fT4 severely low at 0.24 ng/dL, ACTH of 2.6 pg/mL (7.2-63.3), prolactin (PRL) 1 ng/mL (4.8-23.3) and insulin like growth factor-1 (IGF-1) low at 10 ng/mL (56-194). Cortisol level was elevated in the hospital due to administration of high dose IV steroids but a morning cortisol level obtained 1 week prior by her primary was 1.5 mcg/dL (10-20). Estradiol levels were low with FSH and LH levels inappropriately normal. MRI of the pituitary was obtained which showed an empty sella turcica. Patient was diagnosed as late-onset Sheehan’s syndrome. She was started on hormone replacement with hydrocortisone followed by levothyroxine and had marked improvement in her symptoms. She continues to do well.

CONCLUSION

Our patient presented late due to lack of medical care and awareness. A great number of patients with Sheehan’s diseasae go undiagnosed due to subtle clinical presentations, thus delaying treatment. It is imperative to diagnose this condition timely with appropriate obstetric/gynecological history and clinical suspicion to avoid late manifestations of the disease, especially adrenal crisis. Patients at risk need long term follow-up. Early treatment is necessary to improve quality of life and reduce morbidity and mortality associated with this condition.
MON-004 Ovarian Steroid Cell Tumor, Not Otherwise Specified (NOS): A Case Report and Clinical Review
Authors: Lobaton Miry , Malanco Luz M , Trejo Liliana
Published: May 2020

Background: Ovarian tumors are divided into non functioning and functioning, within the last group, we can find those with endocrine activity that produce androgenization. Ovarian cell tumors, not otherwise specified (SCT-NOS) is a rare type of ovarian sex cordomal tumor and represents the 60% of this tumors, which compromise less than 0.1% of the ovarian tumors. (1)

Clinical Case: We here present a 28 year old woman who was referred to the Endocrine Clinic due to secondary amenorrhea and virilization signs. At the age of twelve a diagnosis of polycystic ovarian syndrome (POS) was made and treated with combined oral anticonceptive (COA). Menses became regular only with medication. Six months after she stopped medication, amenorrhea and virilization signs worsened. Biochemically she had levels of serum total testosterone 6.8 ng/mL (0.02-0.45) and free testosterone 42 pg/mL (0.1-6.4) since only pelvic ultrasonography has been made by physician, a transvaginal ultrasound and abdomen – pelvic CT scan showed a anexial tumor. After analysis of biochemical and imaging results a multidisciplinary team performed a surgical extirpation of the primary lesion, which was diagnosed by histopathology as a tumor of lipoidic cells NOS. A month after the surgery, menses became regular.

Conclusion: The purpose of this article is to present the available information about this kind of tumors and the treatment recommended. It is mandatory to follow a correct approach among a multidisciplinary team, in order to get the correct diagnosis at the proper time.

(1) Zang L, Ye M, Yang G, Li J, Liu M, Du J et al. Accessory ovarian steroid cell tumor producing testosterone and cortisol. Medicine. 2017;96(37):e7998.
SAT-564 Effectiveness of Treatment with Mineralocorticoid Receptor Antagonistsin Primary Aldosteronism
Authors: Tezuka Yuta , Turcu Adina
Published: May 2020

Background: Medical treatment with mineralocorticoid receptor antagonists (MRAs) is preferred for patients with primary aldosteronism (PA) who are not surgical candidates. Adequate mineralocorticoid receptor blockade, as suggested by renin elevation above suppression levels, has been associated with lower rates of cardiovascular and renal complications as compared with PA with sustained renin suppression.

Objectives: To assess the timeline and rates of achieving target renin levels in patients with PA and low renin hypertension treated with MRAs.

Patients and Methods: We conducted a retrospective cohort study of adult patients with hypertension who were treated with MRAs in an academic center between 2003-2019. Of these, we included patients who had suppressed renin at baseline, and repeated renin measurement(s) during MRAs therapy. Renin suppression was defined as plasma renin activity (PRA) 1.0 ng/mL/h or direct renin concentration (DRC) 8.0 pg/mL. We excluded patients with adrenal cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. Mann-Whitney test, Wilcoxon signed rank test, Chi-Square test and multiple logistic regression analysis were employed, as appropriate.

Results: So far, 89 patients (45 men), median age 56 (range, 19-84), have been included. Of these, 46% had confirmed PA; 25% had positive PA screening, but no confirmatory tests; and 29% had other forms of low-renin hypertension. On average, patients were on 2.9 1.6 antihypertensive agents; 62% of patients were prescribed beta blockers, and 38% were on K+ supplements. Overall, renin (PRA in 69 cases, and DRC in 20 cases) increased after MRA treatment (from 0.40 [0.10, 0.60] ng/mL/h to 1.10 [0.60, 2.23] ng/mL/h; and from 2.1 [2.1, 3.7] pg/mL to 5.7 [2.9, 16.7] pg/mL, respectively, p<0.0001 for both). The cumulative proportions of patients in whom renin reached target levels during MRA treatment were: 25% at 2 weeks; 38.9% at 1 month; 34.2% at 3 months; 39.5% at 6 months; and 47.2% at 1 year. Age, sex, race, blood pressure, use of beta blockers, renal function, serum K+ and aldosterone concentrations were similar between patients with target vs. suppressed renin. Multiple logistic regression analysis suggested that after adjusting for age and sex, higher MRA dose and higher BMI were associated with higher likelihood of achieving target renin during MRA therapy (odds ratio (95%CI): 1.021 (1.001-1.041) and 1.097 (1.008-1.193), respectively, p<0.05 for both); conversely, beta blockers use tended to be less often associated with target renin (odds ratio, 0.37 (0.13-1.008), p=0.052).

Conclusion: Although raising renin above suppression levels is important for reducing the cardiovascular risk associated with PA, this goal is achieved in less than half of patients, even after one year of treatment with MRAs, in an academic setting. Strategies for optimizing PA treatment are critically needed.
MON-163 A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of a Selective Glucocorticoid Receptor Modulator, Relacorilant, in Patients with Autonomous Cortisol Secretion Due to Cortisol-Secreting Adrenal Adenoma(s)/Hyperplasia
Authors: Auchus Richard Joseph , Grauer Andreas , Moraitis Andreas
Published: May 2020

Relacorilant is a highly selective glucocorticoid receptor antagonist that modulates the effects of excess cortisol without interacting with the mineralocorticoid or progesterone receptor. A Phase 2 relacorilant study in patients with endogenous Cushing syndrome (CS) demonstrated improvements in glycemic control and hypertension with no instances of drug-related hypokalemia or antiprogesterone effects.

An international, multicenter, Phase 3 clinical trial of relacorilant is currently underway to evaluate the efficacy and safety of relacorilant in CS of various etiologies with evidence of hypercortisolism documented through two independent biochemical tests and at least two clinical signs and symptoms of CS. It uses a randomized-withdrawal design after 22-weeks (22wk) of open-label treatment with relacorilant (GRACE Study: NCT03697109).

Here we introduce a double-blind, randomized, placebo-controlled study in patients with less severe CS secondary to adrenal adenoma(s) or hyperplasia. Approximately 130 eligible patients 18-80 years old with a radiologically confirmed adrenal lesion, a biochemical diagnosis of autonomous cortisol secretion and either impaired glucose tolerance/diabetes mellitus (IGT/DM) or hypertension will receive relacorilant (100 mg/day, titrated to 400 mg/day, as tolerated) or placebo over 22WK.

Biochemical criteria for entry into the study include a serum cortisol >1.8 µg/dL after dexamethasone suppression testing (DST) and low (<10 pg/dL) or suppressed morning ACTH levels. Patients must be stable on their antidiabetic and/or antihypertensive agents for at least 4 weeks prior to the first dose of relacorilant.

The primary efficacy endpoints are the between-treatment difference in change from Baseline to 22wk in AUCglucose for the IGT/DM group and mean systolic blood pressure (based on ambulatory blood pressure monitoring) for the hypertension group. Secondary endpoints include changes in weight, waist circumference, quality of life and coagulation markers. The safety analysis will be performed for all patients who received at least one dose of study drug.

This will be the first randomized, double-blind, placebo-controlled study to test if patients with adrenal autonomous hypercortisolism benefit from medical treatment.
SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study
Authors: Even-Zohar Naomi , Sofer Yael , Yaish Iris , Serebro Merav , Tordjman Karen , Greenman Yona
Published: May 2020

Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.
SUN-709 MiR-200c Expression Profiles in Plasma of 46,XY DSD Patients of Unknown Etiology
Authors: Elias Felipe Martins , Gomes Nathalia Lisboa , Nishi Mirian Yumie , Batista Rafael Loch , Bissegatto Debora Delmonte , Sircili Maria Helena , Ferrari Maria Tereza , Costa Elaine Maria Frade , Mendonca Berenice Bilharinho , Domenice Sorahia
Published: May 2020

Introduction: Despite the use of robust techniques for diagnosis, such as arrays and large-scale sequencing of patients with differences of sex development (DSD), the etiology of a great number of DSD patients remains unclear. Investigation of alternative signaling pathways and epigenetic factors is scarce in 46,XY DSD patients. The ZEB proteins have been related to the occurrence of hypospadias in humans, a feature often observed in the atypical genitalia of patients with 46,XY DSD. Additionally, miR-200c has been reported to regulate ZEB. Objective: To evaluate the expression of miR-200c in plasma samples of 46,XY DSD patients with unknown etiology. Methods: Plasma miR-200c of six adult 46,XY DSD patients with unknown etiology (age 18-33, mean 19±8) and 15 adult male controls (age 18-55, mean 29±10 yo) were analyzed. External Masculinization Score (EMS) was used to describe the undervirilization degree of patients’ external genitalia and to classify them in two groups with low EMS (LEMS: 0-4.9 points) and high EMS (HEMS: 5-10 points). All patients presented atypical genitalia with hypospadias. miR-200c was selected based on its targeting to ZEB1 and in silico analysis; miR-23a was used as internal normalization control. RNA was extracted from plasma samples with Magmax Mirvana Total RNA isolation kit. cDNA was synthesized using TaqMan Advanced miRNA cDNA Synthesis Kit and qPCR was performed using TaqMan Advanced miRNA. The data analysis of qPCR results of patients, of each individualized patient and also the EMS groups were compared with the control group by statistical test. Results: LEMS group presented lower expression values of miR-200c when compared to HEMS group (P=0.0001) and control group (p=0.0009), but no difference was observed when comparing HEMS group and controls, the two patients with lower miR-200c expression presented the lowest EMS (EMS- 3 and 3.5). Altogether, patients presented lower values of miR-200c, although not significantly (p=0.09). Discussion: These findings corroborate with previous literature data correlating miR200-c, ZEB1 and hypospadias. The regulatory loop of miR-200c/Zeb1 was previously demonstrated in rats with hypospadias, confirming that low expression of miR-200c induce a higher Zeb1 expression. The ZEB1 upregulation in penile tissue is positively correlated with the severity of hypospadias in animal models and humans. In the present study, 46,XY DSD patients with severe genital undervirilization had lower miR-200c expression in plasma. Conclusion: Plasma miRNA expression patterns may be a new strategy research in 46,XY DSD, contributing for understanding the processes involved in the external genitalia development.
OR16-03 Metabolic Effects Of Hypothalamic Pomc Neurons Generated Postnatally From Tanycytes On A Pomc Null Genetic Background
Authors: Gahlot Surbhi , Wittmann Gabor , Lechan Ronald M , Low Malcolm J
Published: May 2020

Hypothalamic proopiomelanocortin (POMC) neurons are an integral part of the central melanocortin system and regulate feeding and energy balance in vertebrates. Tanycytes are radial glial-like cells lining the third ventricle that contain a subpopulation of adult stem cells, which can differentiate under specific circumstances into glia and neurons, including POMC neurons. However, the capacity of these stem cell-derived neurons to fully mature and integrate into existing neural circuits of physiological relevance is unknown. This study systematically tested whether Pomc mRNA-positive cells newly generated from tanycyte precursors can differentiate into melanocortin-secreting POMC neurons, integrate into the normal anatomical projection pathways of these cells and rescue the obesity phenotype caused by the loss of Pomc expression in ArcPomcfneo/fneo mice. We generated an inducible compound genetic mouse model by crossing RaxCreERT2 with the Cre-dependent ArcPomcfneo/fneo and LSL-syp-tdTomato alleles. Rax is expressed exclusively in postnatal tanycytes, thereby limiting tamoxifen-induced recombination of the two floxed alleles by CreERT2 to tanycytes. As expected, tamoxifen treatment of the mice at age 4–5 wk recapitulated endogenous Rax expression 16 wk later as observed by red fluorescent tdTomato expression in all tanycytes. In addition, Cre recombinase-mediated deletion of the floxed-neomycin cassette from the neuronal enhancer region of the ArcPomcfneo alleles relieved their constitutive transcriptional silencing. Consequently, tamoxifen treatment consistently generated a significant number of newly generated POMC neurons from tanycytes (~10% of the POMC neurons in a WT mouse), identified by Pomc FISH and POMC/α-MSH immunofluorescence in the soma and established terminal projections to hypothalamic nuclei including the PVH and DMH involved in energy homeostasis. A subpopulation of these neurons also expressed the synaptophysin-tDTomato reporter. We performed serial body weight, food intake, body composition, oral GTT and insulin measurements with the RaxCreERT2/+, ArcPomcfneo/fneo mice and found no significant differences in any of these metabolic variables compared to untreated obese ArcPomcfneo/fneo mice. These data are consistent with previous studies from our lab suggesting that Pomc expression has to be at least ~30% of normal to mitigate the obesity phenotype in Pomc-null mice. In conclusion, we demonstrated that tanycytes are capable of generating mature Pomc-expressing neurons in the hypothalamus of adult mice. However, we propose that determining the underlying mechanisms involved in the generation of hypothalamic POMC neurons from tanycytes and interventions to increase their number, might lead to a novel approach to treat obesity. Nothing to Disclose: SG, GW, RML, MJL
MON-434 Encapsulated Follicular-Variant of Micropapillary Carcinoma Presenting with Distant Bony Metastasis
Authors: Berlioz Ana Ramirez , Patel Richa , Chinnakotla Bhavana , Acevedo Camila Margarita Manrique , Liu John
Published: May 2020

INTRODUCTION The incidence of thyroid cancer has risen steadily over the last decades, in part due to increasing diagnosis of apparently low-risk well-differentiated cancers. The outcomes of well-differentiated thyroid cancers, including follicular variant papillary thyroid carcinoma (PTC), are believed to be quite favorable, with a largely indolent benign course. We examine an encapsulated follicular-variant of micropapillary carcinoma presenting with distant bony metastasis. CASE 55-year-old lady presented to clinic after biopsy of iliac crest (IC) mass revealed thyroid tissue. One year prior she started having dull pain at right hip, attributed to increased physical activity. She noticed a tender “lump” on her right hip. CT revealed destructive right iliac 8 cm mass with extraosseous soft tissue component, central necrosis, and eccentric calcifications; and right ovarian cyst. Right IC biopsy was consistent with thyroid tissue with positive Thyroglobulin and TTF-1 immunostains. Physical exam was normal, except for mild tachycardia, hypertension, right flank large rounded mass fixed to IC, tender to palpation without erythema or warmth on overlying skin. Thyroid ultrasound showed normal thyroid gland except 5.58 x 6.22 x 7.76 mm left lobe nodule without increased vascularity but with coarse peripheral calcification. FNA was unsatisfactory. Thyroid function tests revealed undetectable TSH, elevated FT4, FT3, and markedly elevated thyroglobulin and TSI. PET/CT scan showed focal area of mild FDG avidity, corresponding to the right iliac crest mass, without additional areas of FDG avidity suggestive of metastatic disease or primary neoplastic process. Three weeks after presentation, patient began having symptoms of hyperthyroidism. As FT4 and FT3 continued to rise, she was started on propranolol and methimazole. Due to inadequate response, methimazole was switched to high dose propylthiouracil with mild improvement. Thyroid uptake and scan and SPECT-CT revealed increased thyroid uptake and thyromegaly consistent with Graves’ disease and redemonstrated large right IC lesion with increased uptake in the periphery and central photopenia, suggesting metastatic thyroid malignancy. Pathology from total thyroidectomy reported encapsulated follicular variant of PTC, confined to the left lobe of the thyroid, without extrathyroidal extension, greatest tumor dimension 0.6cm. As metastasis to the IC were unlikely to have originated from this small encapsulated thyroid cancer, it was recommended to proceed with right oophorectomy for suspected malignant struma ovarii and IC lesion debulking. Surgical pathology revealed right ovary and fallopian tube without pathologic changes or features of teratoma and tissue from right iliac mass consistent with PTC. Patient is off all antithyroid medications and remains biochemically euthyroid, awaiting radioactive iodine therapy.
MON-443 SPECT/CT Localization of Incidental Diverticular Bleed After Radioiodine (i131) Therapy for Metastatic Thyroid Cancer
Authors: Doshi Sejal B , Kardan Arash
Published: May 2020

Background: Radioiodine therapy for patients with metastatic papillary and follicular thyroid cancer status post total thyroidectomy improves overall survival and is standard of care. Physiologic and pathologic biodistribution of I131 is dependent on tissue sodium iodine symporter expression with nonspecific radioiodine distribution seen secondary to physiologic routes of excretion.

Clinical Case: Whole body scintigraphy (WBS) was performed seven days after I131 therapy in a 37-year-old male treated for metastatic papillary thyroid cancer with extension to a thyroglossal duct cyst at the time of surgery. His post-procedural course was uncomplicated with the exception of self-limited hematochezia six days after ablation. WBS images demonstrated a focus more superiorly in the neck concordant with metastatic thyroglossal duct cyst involvement. Activity was also present in the small and large bowel distribution reflecting normal routes of radioiodine excretion. WBS images depicted a discrete focus of radioiodine activity in the right lower quadrant, which SPECT/CT further localizes as activity in the sigmoid colon. Non-contrast CT images demonstrate an associated linear pattern of hyperdense hyperattenuation in the colonic lumen consistent with fresh blood. It is well established that the physiologic and pathologic biodistribution of I131 is dependent on tissue sodium-iodine symporter expression with additional distribution secondary to normal routes of excretion. Nonspecific radioiodine localization has been described at sites of inflammation secondary to vasodilation and increased vascular permeability resulting in leakage and accumulation in tissues. Sodium-iodine expression is found in many tissues, including salivary glands, lactating mammary glands, gastric mucosa, thymus, and small bowel; however, they are not expressed in the colon, nasopharyngeal mucosa, or orbital fibroblasts. I131 localization has been previously described within numerous body diverticula, such as Zenker’s and Meckel’s diverticula; however, radioiodine activity in association with an acute colonic diverticular bleed has not been reported.

Conclusion: We propose that the isolated focus of radioiodine activity in the sigmoid colon associated with transient self-limited bleed could be either related to preexisting diverticulitis leading to I131 accumulation secondary to hyperemia, increased vascular capillary permeability, and subsequent aggravation of colonic mucosa resulting in a transient bleed or due to incidental nonspecific pooling of radioiodine in a colonic diverticulum resulting in secondary mucosal irritation with subsequent minor bleeding. To our knowledge this is the first reported case of SPECT/CT localization of radioiodine to an isolated colonic diverticular bleed in a patient status post I131 therapy for metastatic papillary thyroid cancer.
MON-246 A Diagnostic Dilemma of Primary Versus Secondary Thyroid and Adrenal Hormone Insufficiencies: A Unique Case of Widely Metastatic Renal Cell Carcinoma After Brain Radiation
Authors: Gugger Aristea Sideri , Stamatiades George Alexiades , Majumdar Sachin K
Published: May 2020

Background Identifying the etiology of hormonal insufficiency is important for correct diagnosis and for appropriate hormone supplementation. Usually multiple hormone deficiencies are driven by pituitary pathology, but here we present a case that poses a unique diagnostic and therapeutic dilemma. Clinical Case A 55 y/o lady with HTN and recently diagnosed metastatic Renal Cell Carcinoma (RCC) presented with weakness, dizziness, altered mental status, polydipsia and polyuria. Her metastases included the bilateral adrenal glands, thyroid, brain, and she had a sellar lesion displacing the pituitary as well as infundibular thickening. She had been treated with dexamethasone due to vasogenic edema, whole brain radiation, and was going to start immunotherapy (Ipilumimab&Nivolumimab). On exam she had relative hypotension and tachycardia (BP 115/58, HR 108). She was diagnosed with non-PTH mediated hypercalcemia (Ca 13.9/ 15.3 corrected for albumin 2.3, PTH 6.5, PTH-RP 69, Vitamin D-25 19.4). Her calcium normalized after fluid resuscitation and bisphosphonate treatment, but weakness and hypotension persisted. We tested thyroid and adrenal function given the location of her lesions, recent whole brain radiation, and recent steroid use. Her TSH was 0.017 (0.270 - 4.200 µIU/mL), fT4 0.84 (0.80 - 1.50 ng/dL), T3 0.59 (72.0 - 153.0 ng/dL), ACTH was 1.7 (7.2-63.3 pg/ml), cortisol 1.3 (6.0 - 18.4 ug/dL), aldosterone 3 (< or = 28 ng/dL), renin 7.87 (0.25 - 5.82 ng/mL/h), renin/aldosterone 0.4 (0.9 - 28.9). At 30 minutes after cosyntropin administration cortisol was 7.7 ug/dL, aldosterone 26 ng/dL, and at 60 minutes cortisol was 10.3 ug/dL. Hydrocortisone was initiated while tapering off dexamethasone, and levothyroxine was offered but declined. She opted to postpone further workup. Conclusion This patient presents a dilemma in identifying the primary causes of hormonal abnormalities given potential pituitary and primary thyroid and adrenal disease. The thyroid abnormalities could represent sick euthyroid physiology with lower T4 to T3 conversion or the effects of steroids which can also suppress TSH vs. hypothalamic or pituitary disease. Primary hypothyroidism from gland destruction was unlikely. The low ACTH and cortisol levels were expected since she was on dexamethasone, but low aldosterone with raised renin activity was concerning for primary adrenal insufficiency. However, after cosyntropin the suboptimal cortisol yet preserved aldosterone response supported secondary or tertiary adrenal insufficiency, and only cortisol was supplemented. Understanding her endocrine disease had implications for longer term management given that replacement may only need to be temporary and adrenal recovery might be possible. Further, the use of a 30 minute aldosterone level can be helpful in cases where multiple factors and discrepant laboratory findings may exist.
OR15-02 Mental Health Implications and Determinants of When Youth Present to a Gender Clinic
Authors: Sorbara Julia , Chiniara Lyne , Ngo Hazel , Thompson Shelby , Palmert Mark Raney
Published: May 2020

Background/Aims: Gender incongruent (GI) youth experience high rates of mental health comorbidities. While gender-affirming medical care (GAMC) provides psychological benefit, GI youth often present to care at older ages. The goals of this study were to 1) assess the relationship between age at presentation to GAMC and rates of mental health comorbidities, 2) identify factors influencing when youth present to GAMC, and 3) determine whether older presenting youth face more barriers to care.

Methods: We performed a cross-sectional chart review of patients presenting to GAMC. Subjects were classified a priori as younger presenting youth (YPY): <15 years of age at presentation or older presenting youth (OPY): > 15 years of age. Self-reported rates of mental health comorbidities and medication use were compared between groups. Binary logistic regression analysis was used to identify determinants of mental health comorbidities. Covariates included pubertal stage at presentation, social transition status, and assigned sex. Next, we performed a sequential exploratory mixed-methods study. Factors influencing age at presentation to GAMC were explored through 24 semi-structured interviews with OPY, YPY, and their caregivers (OPY-C and YPY-C). Thematic analysis identified themes with differential representation between OPY/OPY-C and YPY/YPY-C. From these themes, a questionnaire was designed and distributed to youth and caregivers presenting for follow-up. Responses were compared between OPY and YPY and between OPY-C and YPY-C.

Results: Of 300 youth, there were184 OPY and 116 YPY. Upon presentation, more OPY than YPY reported a diagnosis of depression (46% vs. 30%), had self-harmed (40% vs. 28%), had considered suicide (52% vs. 40%), had attempted suicide (17% vs. 9%), and required psychoactive medications (36% vs. 23%), all p < .05. After controlling for covariates, late puberty (Tanner stage 4 or 5) was associated with depressive disorders (OR 5.49 [95% CI: 1.14, 26.32]) and anxiety disorders (OR 4.18 [95% CI: 1.22, 14.49]) while older age remained associated only with psychoactive medication use (OR 1.31 [95% CI: 1.05, 1.63]). Six themes were identified from interviews that influenced age at first clinic visit, including individual, environmental, and healthcare system factors. 101/152 youth and 102/147 caregivers completed questionnaires. While OPY/OPY-C did not endorse more barriers to care than YPY/YPY-C, more OPY than YPY had religious families (54% vs 28%, p=.01) while more YPY than OPY had LGBTQ+ family members (46% vs. 20%, p=.006).

Conclusions: Older age and late pubertal stage are associated with worse mental health among GI youth presenting to GAMC. Our findings emphasize the importance of timely access to GAMC for GI youth and highlight familial environment as a factor that influences when youth present to gender-affirmative care.
MON-162 Utility of 24-Hour Urine Cortisone for the Diagnosis of Cushing’s Syndrome
Authors: McGlotten Raven , Paul Namrata , Soldin Steven , Nieman Lynnette K
Published: May 2020

Background: Obesity, diabetes and hypertension are common in the general population, and do not discriminate between patients (pts) with or without Cushing’s syndrome (CS). Thus, Endocrine Society guidelines recommend biochemical testing in pts with multiple features compatible with the diagnosis (1). A 24-hour (d) urine cortisol (UF) is one of the recommended screening tests. However, tandem mass spectrometry (MS/MS) measurement of UF may be less sensitive than immunoassay because of antibody cross-reactivity with cortisol-like compounds. Cortisone (E), the product of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) inactivation of cortisol, can be measured in the urine (UE) by MS/MS and might improve the sensitivity of UF alone. The goal of this study was to compare the diagnostic utility of UE, UF, their sum (UF+UE) and their ratio (rUF/UE) for the detection of CS.

Methods: We retrospectively reviewed 35 pts evaluated for CS from 1/2017 to 9/2019. UF (reference range (RR), 3.5-45 ug/d) and UE (RR 17-129 ug/d) were measured by MS/MS. CS etiology was later confirmed in 24 pts by pathology and/or tumor localization [14 female; 14 Cushing’s disease, 7 ectopic ACTH secretion (EAS), 3 presumed EAS awaiting surgery; 46 UF and UEs], and was excluded (noCS) in 11 pts followed over time [8 female; 65 UF and UEs with salivary cortisol and/or dexamethasone suppression]. For CS patients with multiple results, the sample with the lowest UF was compared with all available samples from the NoCS group.

Results: Using a single result for each CS pt, the median (range) for UF, UE, UF+UE and rUF/UE were 281 ug/d (34 - 32,444), 358 ug/d (171 - 802), 642 ug/d (232 - 33246) and 0.78 (0.13 - 40.5). By contrast, using all observations in noCS pts, median (range) for UF, UE, UF+UE and rUF/UE were 13.6 ug/d (2.2 - 88.8), 79.5 ug/d (4.9 - 253), 98.2 ug/d (7.1 - 342) and 0.2 (0.05-0.67).

Using the upper RR (or their sum) as a criterion for abnormality, all CS pts had abnormal UE and UF+UE; 45/46 had abnormal UF. In noCS samples, abnormal values were seen in 12/65 UF (3 pts), 14/65 UE (4 pts), and 13/65 UF+UE (3 pts).

The rUF/UE was < 0.70 in all noCS pts and in 9/24 CS patients. Within this group, the UF+UE was > 230 ug/d in two noCS patients (2/3 and 2/7 samples/pt), and in all 9 CS patients, including two with normal UF and two with UF <50% above the RR. Alternatively, a UE > 170 ug/d identified the same noCS and CS patients.

Conclusion: UF remains an important tool for screening of CS. The addition of UE and UF+UE may provide additional information to discriminate CS from noCS in patients with rUF/UE < 0.70. In contrast to CS pts, noCS pt consistently had UF+UE > 230 ug/d or UE > 170/d, underscoring the importance of multiple samples. Additional study, especially of pts with mild hypercortisolism, is needed to determine optimal diagnostic criteria.

1.Nieman L et al. J Clin Endocrinol Metab 93:1526, 2008
SUN-168 Case Series of ACTH-Secreting Pheochromocytoma: Diagnosis and Management
Authors: Tran Anh , Failor Richard A , Hirsch Irl B
Published: May 2020

INTRO

ACTH-secreting pheochromocytoma is rare, posing challenges in diagnosis and management. Here we report two cases with different presentations and pre-operative approaches.

CASES

Patient 1 A 59 yo female who presented for basal cell carcinoma resection experienced hypertensive crisis intra-op and NSTEMI due to stress cardiomyopathy. The patient reported spells of palpitations, diaphoresis, tremors and pallor since 2015. She had elevated plasma metanephrine (M) 19.4 (0-0.49nmol/L), normetanephrine (NM) 24.7 (0-0.89nmol/L), 24-hour urine M 18711 (30-180mcg) and NM 11897 (128-484mcg). Imaging demonstrated a 5.6 x 5.5 x 5.8cm left adrenal mass. After pre-operative alpha and beta blockade, patient underwent left adrenalectomy.

Pre-op 24-hour urine cortisol was checked as part of secondary HTN evaluation and found to be elevated at 219 (3.5-45mcg). She did not have any features of Cushing’s and this was initially felt to be an appropriate stress response. Due to persistent post-op hypotension and a low 10PM random cortisol level of 3.4mcg/dL, which was inappropriate given patient’s clinical status, hydrocortisone was started with subsequent hemodynamic improvement. Our suspicion was that she had an ACTH-secreting pheochromocytoma, which would have resulted in hypercortisolism pre-op, and secondary AI post-op. Pathology report later confirmed ectopic ACTH production with 25% cells positive with immunostaining.

Patient 2 A 48 yo female was admitted for hypertensive urgency with symptoms of palpitations, facial and abdominal swelling, easy bruising and proximal muscle weakness. Her labs showed elevated 24-hour urine epinephrine 115 (0-20mcg), norepinephrine 366 (0-135mcg), plasma M 288 (0-62pg/mL) and NM 475 (0-145pg/mL), and an AM cortisol was 47.9mcg/dL. Aldosterone and renin levels were <1ng/dL and 0.775ng/mL/hr. Imaging revealed 3.4 x 3.1cm right adrenal mass with portal venous phase of 53 HU and no washout. AM cortisol level post 1mg dexamethasone was 62.6mcg/dL with an ACTH level of 222pg/mL. An ACTH-producing pheochromocytoma was suspected. Despite progressive uptitration of alpha and beta blockade, her BP remained poorly controlled. Her blood glucose also increased to 300s range. Ketoconazole 400mg BID was subsequently added to the regimen with rapid and marked improvement in BP and glycemic control. She underwent right adrenalectomy. Post-op plasma M, NM and ACTH were <0.20nmol/L, 0.36nmol/L and <5pg/mL.

DISCUSSION

Within the past 6 months, we have seen 2 cases of ACTH-secreting pheochromocytoma with different clinical symptoms and pre-op courses. Ectopic ACTH secretion may not cause classic Cushingoid features as in patient 1. Failure to recognize ectopic ACTH pre-op can lead to post-op complications such as AI. Patient 2 demonstrates that treatment of the hypercortisolemia may be necessary in order to adequately control BP and glucose levels prior to surgery.