Identification of nonclassical 21-hydroxylase deficiency in girls with precocious pubarche

Abstract

Recent studies have described mild adrenal enzymatic defects in patients presenting with precocious pubarche. In order to identify these defects we have evaluated basal and ACTH- (25 IU iv) stimulated serum adrenal steroid levels in 19 girls, 2- to 8.3-year-old, with precocius pubarche (pubic hair Tanner II-III). Two patients had clitorial enlargement. Bone age was moderatly advanced in 10 patients and 2 to 3.7 yr in four others. Four patients had high basal serum levels of 17-hydroxyprogesterone (17OHP) (525 + 202 ng/dl, mean +SD), compatible with the diagnosis of nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NCCAH-21OH), which was confirmed by an increased response of 17OHP to ACTH (3425 +/- 953 ng/dl). Fifteen patients had moderately elevated basal 17OHP levels (56 + 38 ng/dl) but a normal 170HP response (191 +/- 71 ng/dl) to ACTH, compatible with the diagnosis of idiopathic precocious pubarche (IPP). The cortisol response to ACTH was normal in both groups. Basal values of DHEA-S were 651 +/- 256 and 506 + 462 ng/ml and of DHEA 380 +/- 24 ng/dl and 205 +/- 102 ng/dl, in NCCAH-210H and IPP, respectively. We conclude that: i) clinical findings and baseline levels of DHEA-S and DHEA in IPP can be indistinguishable from the late onset 21 hydroxylase deficiency; ii) baseline levels of 17OHP are sufficient for the diagnosis of NCCAH-21OH; iii) the ACTH stimulation test is indicated only when baseline levels of 17OHP are moderately elevated (100-300 ng/dl).