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Adrenal and Gonadal Activity, Androgen Concentrations, and Adult Height Outcomes in Boys With Silver-Russell Syndrome

Journal article
Authors Kjersti Kvernebo-Sunnergren
Carina Ankarberg-Lindgren
Jovanna Dahlgren
Published in Frontiers in Endocrinology
Volume 10
ISSN 1664-2392
Publication year 2019
Published at Institute of Clinical Sciences, Department of Pediatrics
Language en
Keywords small for gestation age, androgens, hypogonadism, anti-Mullerian, hormone, mass spectrometry, Silver-Russell syndrome, adult height, adrenarche, follicle-stimulating-hormone, anti-mullerian hormone, inhibin-b, premature adrenarche, luteinizing-hormone, testicular growth, receptor, gene, age, serum, testosterone, Endocrinology & Metabolism
Subject categories Pediatrics, Endocrinology and Diabetes


Background: We have previously shown that adult height (AH) in males with Silver-Russell syndrome (SRS) correlated negatively with prepubertal estradiol concentrations. We aimed to identify the source of estradiol by analyzing androgen secretion profiles and measuring anti-Mullerian hormone (AMH) and inhibin B concentrations during childhood and puberty in this group of patients. Methods: In a retrospective longitudinal single-center study, 13 males with SRS were classified as non-responders (NRs = 8) or responders (Rs = 5), depending on the AH outcome. From 6 years of age, androgens were determined by mass spectrometry, and AMH, inhibin B and sex hormone-binding globulin concentrations were analyzed by immunoassays. Results: AH outcome correlated negatively with dehydroepiandrosterone-sulfate (DHEAS) at 8 (r = -0.72), 10 (r = -0.79), and 12 years (r = -0.72); testosterone at 10 (r = -0.94), 12 (r = -0.70) and 14 years (r = -0.64); dihydrotestosterone (DHT) at 10 (r = -0.62) and 12 years; (r = -0.57) and AMH at 12 years (r = 0.62) of age. Compared with Rs, NRs had higher median concentrations of DHEAS (mu mol/L) at 10 years (2.9 vs. 1.0); androstenedione (nmol/L) at 10 (1.1 vs. 0.6) and 12 years (1.7 vs. 0.8); testosterone (nmol/L) at 10 (0.3 vs. 0.1), 12 (7.8 vs. 0.2) and 14 years (15.6 vs. 10.4); and DHT (pmol/L) at 10 (122 vs. 28) and 12 years (652 vs. 59) of age. AMH (ng/mL) was lower in NRs than in Rs at 12 years of age (11 vs. 50). No significant differences were observed in the inhibin B concentrations at any age. Conclusions: The elevated androgen concentrations before and during puberty, originated from both adrenal and gonadal secretion and correlated negatively with AH outcomes in males with SRS.

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