Adrenal hyperandrogenism in adolescent girls with a history of low birthweight and precocious pubarche

OBJECTIVE Girls with precocious pubarche (PP) are at increased risk for ova rian dysfunction, hyperinsulinism and dyslipidaemia in adolescence, in part icular when PP is preceded by reduced fetal growth. However, it is not know n whether PP girls still have adrenal hyperandrogenism after puberty and if so, which fraction of PP girls develops so-called functional adrenal hyper androgenism (FAH), an entity characterized by ACTH-dependent 17-ketosteroid excess. PATIENTS AND DESIGN Data were longitudinally collected from 47 girls with P P: at birth (weight for gestational age), at diagnosis of PP (age 6.7 +/- 1 .1 years) and in adolescence (age 15.0 +/- 1.9 years). MEASUREMENTS Serum dehydroepiandrosterone sulphate (DHEAS) and androstenedi one were measured at PP diagnosis, as well as the 17-hydroxyprogesterone (1 7-OHP) response to ACTH; postpubertal evaluation included assessment of adr enal and ovarian function, and of insulin responses to a glucose load. PP g irls were considered to have FAH in adolescence if both DHEA and androstene dione responses to ACTH were excessive (> 1500 ng/dl and > 350 ng/dl, respe ctively). RESULTS At diagnosis of PP, girls had high DHEAS and androstenedione levels , as well as high 17-OHP responses to ACTH. In adolescence, PP girls had a normal BMI, presented with mild hirsutism and had high baseline and post-AC TH concentrations of most adrenal androgens, low SHBG levels and tended to have hyperinsulinemia and to present biological signs of ovarian hyperandro genism. More than a third of the PP cohort developed FAH in adolescence. Ne ither baseline DHEAS, androstenedione, nor post-ACTH 17-OHP values at diagn osis of PP predicted the development of FAH in adolescence. In PP girls, on ly a low weight at birth was found to be significantly associated with subs equent FAH. CONCLUSIONS These longitudinal findings in girls with PP point to the possi bility of an endocrine sequence of prenatal onset: low weight at birth, PP in childhood and adrenal hyperandrogenism in adolescence. The pathophysiolo gical mechanisms underpinning this newly recognized sequence remain to be i dentified.