11β-hydroxyandrostenedione and δ 5-androstenediol as markers of adrenal androgen production in patients with 21-hydroxylase–deficient nonclassic adrenal hyperplasia

Abstract

Objective: To determine the sensitivity of 11β-hydroxyandrostenedione (11-OHA4) and Δ 5-androstenediol (ADIOL) as markers of excessive adrenal androgen production. Design: Prospective study. Setting: Academic medical centers. Patient(s): Thirteen women with untreated 21-hydroxylase–deficient nonclassic adrenal hyperplasia (NCAH) and 18 healthy, eumenorrheic, nonhirsute controls matched for age and body mass index. Intervention(s): All subjects were studied before and after acute adrenal stimulation with 0.25 mg of IV ACTH-(1–24). Main Outcome Measure(s): Basal levels of total testosterone, sex hormone-binding globulin, DHEAS, and free testosterone were measured. Levels of androstenedione (A4), DHEA, 11-OHA4, and ADIOL were determined before (Steroid 0) and 60 minutes after (Steroid 60) acute ACTH-(1–24) stimulation. Result(s): Patients with NCAH had higher median basal levels of DHEAS and total and free testosterone than controls. Patients with NCAH had higher median A4 0, A4 60, DHEA 0, DHEA 60, 11-OHA4 0, ADIOL 0, and ADIOL 60 levels but similar 11-OHA4 60 levels compared with controls. Among patients with NCAH, 30%, 54%, 15%, and 85% had 11-OHA4 0, ADIOL 0, 11-OHA4 60, and ADIOL 60 levels, respectively, above the 95th percentile of controls. Conclusion(s): Overall, serum levels of 11-OHA4 did not appear to be a very sensitive marker of excessive adrenal androgen production, at least in patients with NCAH. Although ACTH-stimulated ADIOL levels were elevated in 85% of the patients studied, they did not appear to have any advantage over the measurement of A4 or DHEA levels.