Nonclassic congenital adrenal hyperplasia and the heterozygote carrier

The 2013 article reviews the challenges in distinguishing nonclassic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency, polycystic ovarian syndrome (PCOS), and heterozygote carriers of CYP21 mutations, noting the prevalence of NCCAH at 0.1-0.2% in the general Caucasian population and 1-2% in Eastern European Jews, and PCOS at 3.4% to 6.5% in women of reproductive age in the USA and Spain. It describes the clinical manifestations of NCCAH, such as menstrual irregularities and hirsutism, and the difficulty in using basal 17-OHP levels for screening. The article also discusses the high frequency of CYP21 mutation carriers and the use of ACTH-stimulated cortisol levels to differentiate carriers from non-carriers. Costa-Barbosa et al. found that a cutoff level of 40 ng/dl for ACTH-stimulated 21-deoxycortisol can distinguish carriers from the normal population with 82% sensitivity and 100% specificity. Treatment for NCCAH includes symptom-directed therapy, with hydrocortisone for growing patients and pharmacological therapy for adults with hyperandrogenism symptoms. The document emphasizes the need for genetic counseling due to the high incidence of heterozygote carriers and calls for further studies to determine the clinical relevance of the carrier state and to develop reliable, cost-effective screening methods. The authors declare no financial conflicts of interest.