Abstract
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-Müllerian 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 (μmol/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.
Highlights
Silver-Russell syndrome (SRS) is a rare and heterogeneous syndrome affecting 1:30 000-100 000 births and is characterized by intrauterine growth restriction, short stature, relative macrocephaly with a prominent forehead, hemihypotrophy and a variety of minor malformations, including an increased risk of external genital malformations in boys [1,2,3]
From 6 years of age, androgens were determined by mass spectrometry, and anti-Müllerian hormone (AMH), inhibin B and sex hormone-binding globulin concentrations were analyzed by immunoassays
Depending on the adult height (AH) outcome, defined as AH adjusted for mid-parental height (MPH), subjects were retrospectively divided into one of two groups: eight subjects with AH >1 standard deviation score (SDS) below the MPH were defined as non-responders (NRs), and five subjects with AH ≤1 SDS below the MPH were defined as responders (Rs)
Summary
Silver-Russell syndrome (SRS) is a rare and heterogeneous syndrome affecting 1:30 000-100 000 births and is characterized by intrauterine growth restriction, short stature, relative macrocephaly with a prominent forehead, hemihypotrophy and a variety of minor malformations, including an increased risk of external genital malformations in boys [1,2,3]. Smeets et al reported a similar total height gain from the start of growth hormone (GH) treatment in SRS patients compared to that in non-SRS patients born small for gestational age (SGA). Small adult testicular volumes [5, 7] and Sertoli cell dysfunction [7] have been reported in males with SRS resulting in a risk of underestimating pubertal development when assessing testicular size and thereby, gonadal derived androgens might contribute to elevated androgen concentrations even at prepubertal testicular volumes. 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-Müllerian hormone (AMH) and inhibin B concentrations during childhood and puberty in this group of patients
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