Overdiagnosis of 21-hydroxylase late onset congenital adrenal hyperplasia: correlation of corticotropin test and human leukocyte antigen typing

Objective To evaluate the reliability of the ACTH test as a means for detection of late onset congenital adrenal hyperplasia (CAH) and discriminating it from polycystic ovary syndrome (PCOS), by repeating the test after 6months of cyproterone acetate and ethinyl E 2 treatment. Design Follow-up comparison study. Setting Reproductive Endocrinology in an university tertiary center. Patients Thirty-one young women with hirsutism, oligoamenorrhea, and acne, 21 of them detected as late onset CAH, and 10 as non-late onset CAH (PCOS). Intervention Cyproterone acetate and ethinyl E 2 treatment for ≥6months. The ACTH test, before and after 6months of cyproterone acetate+ethinyl E 2 treatment, and human leukocyte antigen (HLA) typing. Main Outcome Measure The ACTH test interpretation correlated to HLA typing. Results By repeating the ACTH stimulation test in the 31 women (after cyproterone acetate+ethinyl E 2 administration), we found a diminution in the rate of accumulation of 17α-hydroxy-progesterone (Δ17-OHP)+P, in all 21-hydroxylase late onset CAH cases. As a result of treatment with cyproterone acetate+ethinyl E 2 , a decrease in the accumulation rate of 17-OHP+P, below the discriminative value for late onset CAH (6.5ng/dL per minute), was noted among 12 of 21 women defined primarily as late onset CAH. Among the nine other women, a decrease in the accumulation rate of 17-OHP+P was noted, however not Conclusions The interpretation of Δ17-OHP+P for the diagnosis of late onset CAH may be too sensitive as to the correct clinical diagnosis of late onset CAH. By repeating the ACTH test after 6months of treatment with cyproterone acetate+ethinyl E 2 , specificity and accuracy may be improved.