The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. Controlled clinical study. Tertiary care institutional hospital. Forty hirsute women and 13 healthy control women. The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.