bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
Background: Aldosterone producing adenomas (APAs) are the most common cause of unilateral primary aldosteronism (PA). In most cases, APAs present as small (&lt;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 &lt;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 &lt;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 &lt;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 &lt; 25% and &gt; 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

Abstract
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

Abstract
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

Abstract
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&lt;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&lt;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

Abstract
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 &gt;1.8 µg/dL after dexamethasone suppression testing (DST) and low (&lt;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

Abstract
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 (&lt;20 mg/day), compared with high dose (&gt;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

Abstract
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.