Congenital adrenal hyperplasia due to partial 21-hydroxylase deficiency. A study of five cases

Abstract. Five women with post pubertal hirsutism due to a partial 21-hydroxylase deficiency were studied. These patients had no abnormalities of the external genitalia. They were compared to 3 adult women with a complete defect in 21-hydroxylase. The diagnosis of 21-hydroxylase deficiency was substantiated by the dramatic increase in 17-hydroxyprogesterone (17-OHP) after im injection of 250 μg synthetic ACTH (22 ± 12 nmol/l to 349 ± 153 nmol/l). However, in adult women with 21-hydroxylase deficiency recognized at birth and presenting abnormalities of the external genitalia, plasma 17-OHP was elevated in basal conditions (512 ± 106 nmol/l) and only slightly increased after ACTH administration (657 ± 133 nmol/l). Plasma cortisol levels determinated at 08.00 h were lower than normal in both groups but only slightly in groups with partial 21-hydroxylase deficiency. After ACTH stimulation, plasma cortisol levels remained lower than normal in all patients but with a noticeable increase in patients with partial defect. The differences noted between precocious and delayed onset virilization gave an indication of the importance of the enzyme defect. Plasma testosterone (T) and androstenedione (Δ4) levels were elevated both in basal conditions and after ACTH administration. However, in patients with delayed onset of hirsutism most circulating T seems to originate from peripheral conversion of Δ4 to T. Plasma ACTH values were strongly elevated in patients with a complete defect in 21-hydroxylase (260 ± 50 pg/ml) but normal in patients with partial deficiency (< 40 pg/ml). In vitro testosterone 5α-reductase activity was determined in pubic skin homogenates from 4 patients with partial 21-hydroxylase deficiency. The amount of dihydrotestosterone + androstanediols formed from incubated [3H]testosterone was in the normal range for women. Virilization of patients with partial 21-hydroxylase deficiency therefore seems to be essentially due to an increase in active androgen production and not to exaggerated skin 'utilization' of pre-androgens as observed in idiopathic hirsutism.