A Decade-Long Diagnostic Challenge: A Case of Nonclassical 21-Hydroxylase Deficiency Mistaken for Polycystic Ovary Syndrome.

We report a rare case of nonclassical 21-hydroxylase deficiency (NC21-OHD) diagnosed in adulthood after being misdiagnosed as polycystic ovary syndrome (PCOS) for 9 years. A 27-year-old Japanese woman presented with longstanding amenorrhea, hirsutism, and polycystic ovarian morphology on ultrasonography but did not exhibit withdrawal bleeding after standard estrogen/progestin (E/P) therapy. Hormonal evaluation revealed a low luteinizing hormone (LH) level, elevated testosterone (T), and a significantly increased 17α-hydroxyprogesterone level, which further increased following adrenocorticotropic hormone stimulation. Genetic analysis identified compound heterozygous mutations in the CYP21A2 gene (c.92C>T; c.293-13C>G), confirming the diagnosis of NC21-OHD. This case underscores the importance of considering NC21-OHD in adolescents and young adults with atypical PCOS features, such as severe hirsutism, abnormal hormonal profiles (low LH with markedly elevated T levels), and resistance to standard E/P therapy.