A Prospective Study of the Prevalence of Nonclassical Congenital Adrenal Hyperplasia among Women Presenting with Hyperandrogenic Symptoms and Signs

Abstract

The diagnosis of the polycystic ovary syndrome requires the exclusion of nonclassical congenital adrenal hyperplasia (NCAH). Our objective was to evaluate the actual prevalences of 21-hydroxylase and 11beta-hydroxylase deficiencies among women presenting with hyperandrogenic complaints. This study was performed at an academic hospital. A total of 270 consecutive unselected women presenting with hyperandrogenic symptoms were prospectively recruited. Basal and ACTH-stimulated 11-deoxycortisol and 17-hydroxyprogesterone concentrations were measured. The prevalences of 21-hydroxylase and 11beta-hydroxylase deficiencies were calculated, and the diagnostic performance of basal serum 17-hydroxyprogesterone levels for the screening of NCAH was evaluated by receiver operating characteristic curve analysis. Six of the 270 patients had 21-hydroxylase-deficient NCAH that was confirmed by CYP21 genotyping, whereas no patient was diagnosed with 11beta-hydroxylase deficiency, for an overall NCAH prevalence of 2.2% (95% confidence limits 0.5-3.9%). According to receiver operating characteristic analysis, a single basal serum 17-hydroxyprogesterone determination has a 0.97 (95% confidence interval: 0.934-1.008) chance of detecting NCAH in hyperandrogenic women. In our experience, the most appropriate cutoff value for the detection of NCAH is a 17-hydroxyprogesterone above 1.7 ng/ml, showing a 100% sensitivity and a 88.6% specificity. Five of the six 21-hydroxylase-deficient NCAH patients carried a severe CYP21 allele requiring genetic counseling and highlighting the importance of excluding this disorder among hyperandrogenic patients. The prevalence of NCAH among hyperandrogenic patients from Spain is 2.2%. Basal serum 17-hydroxyprogesterone measurements have an excellent diagnostic performance, yet the cutoff value should be established in each laboratory to avoid false-negative results.