Pubertal Presentation of Congenital Δ5–-3β–Hydroxysteroid Dehydrogenase Deficiency*

Publisher Website
Google Scholar
Abstract
Partial deficiency of Δ5–3βhydroxysteroid dehydrogenase (3β-ol) was found in a 17-yr-old female with acne (onset at 8 yr), male-pattern hirsutism (beginning with feminization at 12 yr), and primary amenorrhea. Clitoromegaly, but not genital ambiguity, was found. Disproportionate elevations of Δ5–3βhydroxysteroids were demonstrated in all adrenal and ovarian steroidogenic paths. Plasma 17-hydroxypregnenolone (17-Preg) was 32,225 ng/dl, dehydroepiandrosterone (DHA) sulfate was 1,211 μg/dl, DHA was 7,853 ng/dl, and androstenediol was 406 ng/dl. These levels were all over 5 times greater than those of their immediate Δ4–3 keto-me abolites; the latter were nevertheless elevated (e. g.17-hydroxyprogesterone was 3,016 and androstenedione was 493ng/dl). Pregnenetriol and pregnanetriol excretion were 322 and 54 mg/day, respectively, patterns characteristic of 3β-ol deficiency. ACTH stimulated 17-Preg and DHA, though the plasma cortisol level (8.3 μxg/dl) did not rise. Dexamethasone administration reversed all of the abnormalities except that of 17-Preg, which remained modestly elevated (1,020 ng/dl). Menopausal gonadotropin stimulation elicited an estrogen surge at the expense of elevations in plasma DHA, androstenediol, and androstenedione. The addition of estrogen-progestin to dexamethasone brought plasma steroids to normal or below normal levels, although estrogen-progestin alone had no suppressive effect. Inefficient aldosterone secretion was indicated by high plasma renin. Corticoid therapy resulted in apparently ovulatory menstrual cycles. We postulate that the elevated levels of Δ43-ketosteroids resulted from the action of an intact hepatic 3β-ol isozyme on secreted Δ5-3β-hydroxysteroids. The elevated 11-deoxycortisol blood level (721 ng/dl) is hypothesized to result from comparable hepatic conversion of secreted 3/8, 17α21-trihydroxypregn-5-en-20-one. 16α-Hydroxylat on of Δ5-3β-hydroxysteroids was observed to be a prominent metabolic pathway, suggesting the persistence of fetal pathways of steroid metabolism. The hereditary nature of the disorder was supported by the mother’s abnormal response to ACTH; her 17-Preg level increased excessively relative to that of 17-hydroxyprogesterone.

This publication has 12 references indexed in Scilit: