Absence of Nonclassical Congenital Adrenal Hyperplasia in Patients with Precocious Adrenarche

Abstract

We studied 31 patients (28 girls and 3 boys), ranging in age from 3.2-7.9 yr, with precocious adrenarche defined by the presence of early sexual hair development, no signs of virilization, and bone age within +3 SD of the mean for chronological age. To determine if this symptom complex stemmed from any form of nonclassical (late-onset) congenital adrenal hyperplasia, an ACTH stimulation test was performed on each patient using a standard 0.25-mg dose of Cortrosyn, given as an iv bolus. Twelve pubertal children (7 girls and 5 boys) and 18 prepubertal children (11 girls and 7 boys) served as normal controls. Baseline and stimulated 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol, dehydroepiandrosterone, androstenedione, testosterone, and cortisol levels were measured. Using published nomogram standards for serum 17-OHP response to ACTH, no child with precocious adrenarche was diagnosed as having nonclassical 21-hydroxylase deficiency. Eight girls, however, had a stimulated 17-OHP value that exceeded the mean response for pubertal and prepubertal controls by more than +2 SD [range, 295-670 ng/dL (8.94-20.3 nmol/L)]. Stimulated 11-deoxycortisol values [< 400 ng/dL (11.6 nmol/L)] ruled out any cases of nonclassical 11.beta.-hydroxylase deficiency. No patient had nonclassical 3.beta.-hydroxysteroid dehydrogenase deficiency, as defined by both the stimulated 17-OHPreg and the 17-OHPreg/17-OHP ratio to be more than +2 SD above the mean for pubertal children [1354 ng/dL (41.0 nmol/L) and 10.4, respectively]. In conclusion, we could not provide any biochemical evidence for nonclassical congenital adrenal hyperplasia in a large group of children with precocious adrenarche.