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 \g=m\gsynthetic ACTH (22 \m=+-\12 nmol/l to 349 \m=+-\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 \ m=+-\ 106 nmol/l) and only slightly increased after ACTH administration (657 \m=+-\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 (\g=D\4)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 \g=D\4to T. Plasma ACTH values were strongly elevated in patients with a complete defect in 21-hydroxylase (260 \ m=+-\50 pg/ml) but normal in patients with partial deficiency (< 40 pg/ml).In vitro testosterone 5\g=a\-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.

Detection of late-onset adrenal hyperplasia in girls with peripubertal virilization

“…The basal serum and blood-spot 17-OHP levels, as well as basal and post-ACTH testosterone and DHA-S levels in patients with mild 21-hydroxylase deficiency overlap those in other virilized females, which is in contrast to classic congenital adrenal hyperplasia (Bouchard et al 1981;Kuttenn et al 1985;Lobo & Goebelsmann 1980;New et al 1983;Scaronietal. 1986).…”

Late-Onset Adrenal Hyperplasia in North Indian Hirsute Women

“…In recent years there have been numerous reports of women with peripubertal onset of hirsutism and/or men strual disturbances due to 'attenuated' or 'late-onset' forms of adrenal hyperplasia [3][4][5][6][7][8][9][12][13][14][15]. The defects described include partial forms of 21 -hydroxylase, 1113-hydroxylase and 3(3-ol-dehydrogenase deficiencies [7,[16][17][18][19][20]; of these, 21-hydroxylase deficiency is generally considered to be the most common [11,16,23].…”

Congenital Adrenal Hyperplasia

“…The clinical presentation is characterized by virilization, menstrual disturbances, and endocrinological features consistent with 21-hydroxylase deficiency that begin in later childhood or early adulthood (Decourt et al 1957;Newmark et al 1977;Rosenwaks et al 1979;Bouchard et al 1981 ;B. Genetic females with the nonclassical, mild deficiency do not have prenatal virilization.…”