Postnatal Virilization Mimicking 21-Hydroxylase Deficiency in 3 Very Premature Infants

Abstract

Premature infants are known to have elevated 17-hydroxyprogesterone and adrenal androgen concentrations immediately after birth, but the levels decrease rapidly. Virilization of normal premature female infants as a result of these high androgens has not been described. Three premature female infants born at 24 to 25 weeks’ gestation, with birth weights 550 to 880 g and significant neonatal complications were noted to develop clitoromegaly 2 weeks to 3 months after birth. All 3 had elevated 17-hydroxyprogesterone >100 nmol/L and testosterone >3 nmol/L concentrations. All were treated as simple virilizing 21-hydroxylase deficiency, but subsequent genetic analysis revealed no CYP21 mutations. Follow-up after discontinuation of treatment revealed no recurrent virilization and normal adrenal steroid levels. Postnatal virilization in sick premature girls may occur, and investigations may suggest 21-hydroxylase deficiency. Genetic analysis of CYP21 should be performed before the diagnosis is confirmed. Further studies are needed to better document the natural history and possible causes of postnatal adrenal androgen secretion in sick premature infants.