Detection of Late-Onset 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia in Adolescents

Abstract

Because severe hirsutism is difficult to reverse, the evaluation of the adolescent girl with progressive hirsutism should aim at the pathophysiology of androgen excess in order to select appropriate therapies. A prospective study was undertaken to determine the occurrence of late-onset 21-hydroxylase deficiency among adolescents with androgen excess. Twenty-two young women (mean age 17.3 +/- 2.6 years) with androgen excess had serum 17-hydroxyprogesterone measured before and after bolus intravenous infusion of synthetic ACTH (Cortrosyn), 0.25 mg. Two patients, aged 13 and 19 years old, had elevated base line 17-hydroxyprogesterone and 30- and 60-minute responses to Cortrosyn consistent with 21-hydroxylase deficiency. Chromosome 6p haplotypes provided supportive evidence of 21-hydroxylase deficiency. The base line androgen levels, clinical presentation, and a four-day dexamethasone test did not distinguish patients with 21-hydroxylase deficiency from other hirsute adolescents. The Cortrosyn test identifies a population of adolescents who need long-term corticosteroid therapy. The use of major histocompatibility complex haplotypes could be of help in identifying affected siblings prior to the development of significant hirsutism.