ABSTRACT 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.
Kondo et al. (2026) studied this question.