The longitudinal study of adrenal maturation during gonadal suppression: Evidence that adrenarche is a gradual process

The physical changes that herald the onset of puberty result from the combi nation of adrenarche and gonadarche. To examine adrenal maturation and asso ciated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during longterm pituitary-gonad al suppression. Beginning at the mean age of 2.9 yr, dehydroepiandrosterone sulfate levels, linear growth, skeletal maturation, body mass index, and s econdary sexual development were evaluated at 3- to 6-month intervals for u p to 12.3 yr. In 12 of the girls, levels of dehydroepiandrosterone, androst enedione, 17-hydroxypregnenolone, and 17 alpha -hydroxyprogesterone were de termined before and after acute ACTH stimulation every 6 months to investig ate the maturation of adrenal steroidogenic enzyme activity. Serum dehydroepiandrosterone sulfate levels rose progressively throughout t he study. An exponential model fit the longitudinal datasets well and indic ated that dehydroepiandrosterone sulfate levels increased approximately 22% /yr from the youngest age onward. Increasing activity of 17-20 lyase (CYP17 ) and decreasing activity of 3 beta -hydroxysteroid dehydrogenase were also evident in preadrenarchal subjects. When controlled for chronological age, no significant associations were noted between weight, body mass index, or body surface area and dehydroepiandrosterone sulfate levels. However, simi lar analyses revealed modest correlations of both height and growth velocit y with dehydroepiandrosterone sulfate levels. Our results suggest that adrenarche is not the result of sudden rapid chang es in adrenal enzyme activities or adrenal androgen concentrations; rather, adrenarche may be a gradual maturational process that begins in early chil dhood.