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 6 months of cyproterone acetate and ethinyl E₂ 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 E₂ treatment for ≤6 months. The ACTH test, before and after 6 months of cyproterone acetate + ethinyl E₂ 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 E₂ administration), we found a diminution in the rate of accumulation of 17α-hydroxyprogesterone (Δ17- OHP) + P, in all 21-hydroxylase late onset CAH cases. As a result of treatment with cyproterone acetate + ethinyl E₂, a decrease in the accumulation rate of 17-OHP + P, below the discriminative value for late onset CAH (6.5 ng/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 <6.5 ng/dL per minute. 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 6 months of treatment with cyproterone acetate + ethinyl E₂, specificity and accuracy may be improved.