Insulin infusion amplifies 17 alpha-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.

Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.

Peripheral and ovarian venous concentrations of various steroid hormones in virilizing ovarian tumors.

The ovarian-peripheral gradients of various delta4 and delta5 steroids were determined for a patient with virilizing arrhenoblastoma. The high peripheral testosterone level accompanying this tumor results from increased precursor supply from both the delta4 and delta5 pathways, with the delta5 pathway predominating, and from negligible aromatase activity. A review of 45 cases of androgen-producing ovarian tumors with measurement of peripheral venous testosterone, and of 24 cases with measurement of ovarian venous testosterone, and a comparison with findings in 159 patients with hirsutism of functional origin reveal the following 1) An androgen-producing tumor must be ruled out when peripheral testosterone exceeds 2 ng/ml; 2) an ovarian venous testosterone level exceeding 20 ng/ml generally accompanies a tumor, particularly when the tumor is less than 5 cm in diameter; and 3) virtually all (98%) of the tumors reviewed were accompanied by virilization, regardless of the peripheral concentration of testosterone.

[Screening for congenital adrenal hyperplasia in Hungary]. / A congenitalis adrenalis hyperplasia célzott szürése Magyarországon.

Measurement of blood-spot 17-hydroxyprogesterone (17-OHP) concentration was used to identify cases of congenital adrenal hyperplasia (CAH) among patients with inappropriate virilization and/or salt wasting. Between 1978 to 1986 61 cases with 21-hydroxylase deficiency among 707 patients (278 newborns, 204 infants and 225 children) were identified. The incidence of classical CAH was calculated for a seven year prospective trial period using the blood-spot 17-OHP method in selective screening. There were 38 salt-losers and 14 simple virilizers in 968,303 live births giving an incidence of 1 in 18,000 for CAH in the Hungarian population. The use of a central laboratory facility to measure the blood-spot 17-OHP concentrations is proposed as a valuable initial method to investigate patients at risk for CAH in countries where blood steroid assays are not readily available in hospitals.