Altered sensitivity to low dose dexamethasone in a subset of patients with premature adrenarche

During adrenarche, levels of adrenal androgens increase. Although the regulatory mechanisms of adrenarche and premature adrenarche (PA) are not fully understood, it has been suggested that, unlike the cortisol (F) response to glucocorticoid suppression, which is not age dependent, before adrenarche the major adrenal androgen, dehydroepiandrosterone sulfate, is not suppressible by glucocorticoid. As these studies were performed using long term, high dose glucocorticoids, we sought to evaluate the F and adrenal androgen or androgen precursor suppression in response to low dose glucocorticoids [a single evening dose of dexamethasone (DEX), 0.3 mg/m2]. Twenty-four children (aged 1.3-8.75 yr; 4 males and 20 females) known to have PA, as determined by their response to ACTH-(1-24) (Cortrosyn; 0.25 mg, given by iv bolus), were studied. The children with PA could be divided into two groups, as defined by their morning F level after DEX administration: group I (n = 12), F levels below 5 micrograms/dL; and group II (n = 12), F levels of 5 micrograms/dL or more. Although the mean baseline values of F, testosterone, dehydroepiandrosterone, delta 4-androstenedione, 17-hydroxyprogesterone, and delta 5-17-hydroxypregnenolone did not differ between groups I and II, the mean levels in group I vs. group II of dehydroepiandrosterone, delta 4-androstenedione, and delta 5-17-hydroxypregnenolone were significantly greater in response to ACTH and lower in response to DEX (P < 0.05). Although no clinical difference was noted between the 2 groups, the mean SD for bone age adjusted for chronological age was greater and approached significance in group I, suggesting a greater degree of biological maturity in this group. These results suggest an increased sensitivity of the hypothalamic-pituitary-adrenal axis to changes in ACTH secretion in this subgroup of patients with PA.