Recent reports have thrown doubt on the role of measurements of plasma
5 alpha-androstane-3 alpha,17 beta-diol glucuronide (3 alpha-diolG) as a marker of peripheral
androgen metabolism in women with
polycystic ovarian syndrome and idiopathic
hirsutism. It has been suggested that a plasma profile of C19
steroid glucuronides may be more informative. While preliminary data indicates that both 3 alpha-diolG and
androsterone G (ADTG) may arise from adrenal
steroid precursors, there have been no reports of C19
steroid glucuronides in women with non-classical, or
late-onset congenital adrenal hyperplasia (NC-CAH), who constitute a significant proportion of the hirsute female population. We therefore measured plasma levels of 3 alpha-diolG, ADTG and
dihydrotestosterone G (DHTG) before and following a standard
Cortrosyn test in 15 symptomatic and 3 asymptomatic NC-CAH patients, 5 heterozygote carriers for
21-hydroxylase deficiency (NCHETS) and 18 normal women. The effects of chronic
glucocorticoid (GCR)
therapy (greater than 3 months) on the C19
steroid glucuronide profile in the symptomatic patients was also investigated. Baseline plasma levels of all 3
glucuronides were significantly (P less than 0.001) higher in symptomatic patients compared with either normals or NCHETS. However, the order of discrimination was ADTG greater than 3 alpha-diolG greater than DHTG. There were no significant differences between
steroid glucuronide levels for NCHET and normal women and the C19
steroid glucuronide concentrations for the asymptomatic NC-CAH patients were greater than 2 SD above the normal means. Moderate clinical improvement was observed in all patients receiving oral GCR
therapy and was accompanied by approx. 80% suppression of the plasma levels of all 3 C19
steroid glucuronides. This contrasts with a mean suppression of
androstenedione of only 50%. However, plasma levels of the C19
steroid glucuronides were not significantly increased in response to a short
ACTH stimulation test. This may be explained by the fact that the
androgen glucuronides are thought to be peripherally formed metabolites derived from unconjugated glandular secreted
androgen precursors and thus their synthesis at 60 min following adrenal stimulation may lag substantially behind that of their respective precursors. There were significant linear correlations between the levels of all 3
glucuronides, but neither correlated with Ferriman-Gallway scores, body mass index or
17-hydroxyprogesterone levels.(ABSTRACT TRUNCATED AT 400 WORDS)