Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Abstract

Premature adrenarche (PA), the early rise in adrenal androgen (AA) production, can manifest with different clinical signs of androgen effect. Premature pubarche defined as appearance of pubic hair before the age of 8/9 years in girls/boys, is the most prominent clinical sign of PA and often erroneously described as a synonym of PA. Our aim was to determine the association of circulating AA concentrations with different prepubertal signs of androgen action (SAA). Secondly, we tested whether adrenomedullary function is altered in children with SAA, as it is in congenital adrenal hyperplasia (CAH) also causing adrenal hyperandrogenism. We examined 73 Finnish prepubertal children with any hyperandrogenic sign(s) having appeared before the age of 8/9 years (girls/boys) (35 with pubic and/or axillary hair=PAH; 38 without=nonPAH), and 98 age- and sex-matched controls. Circulating adrenal steroid and catecholamine concentrations were measured and correlated with clinical parameters. None of the children with SAA had CAH or virilizing tumor. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione concentrations overlapped between the SAA and control children, and they were lower in the nonPAH than PAH group (P<0.01). SAA children had similar plasma epinephrine but higher norepinephrine (NE) concentrations than their controls (mean (95% confidence interval) 1.61 (1.44, 1.77) versus 1.39 (1.30, 1.49) nmol/l, P=0.03). PA forms a continuum with more pronounced increase in circulating androgens in children with PAH than in those without. Some children show SAA with fairly low androgen concentrations. The clinical significance of elevated NE concentrations associated with SAA needs to be confirmed in further studies.