Ambiguous genitalia in the newborn.

Ambiguous genitalia in the newborn need immediate and rational management. This complex situation requires a strategy of clinical, hormonal, genetic, molecular, and radiographic investigation to determine the etiology of the intersex state and orient the therapeutic approach. Physical examination is key to diagnosis. Careful palpation to locate gonads at the genital folds or in the inguinal region provides the first element for diagnostic orientation. If gonads are absent, a diagnosis of female pseudohermaphroditism seems advisable; if gonads are palpated, a diagnosis of male pseudohermaphroditism is more appropriate. Karyotyping is systematic while polymerase chain reaction (PCR) analysis of the SRY gene provides information about the presence of a Y chromosome within 1 day. Hormonal investigation should be based on clinical and genetic orientation. Substantially elevated plasma 17-OH progesterone will confirm the diagnosis of congenital adrenal hyperplasia due to deficiency in 21-hydroxylase. Testicular stimulation with human chorionic gonadotropin (hCG) will determine the functional value of testicular tissue. Exploration of the genitourinary axis is principally carried out by ultrasound and genitography. By the end of these investigations, the medical team should be able to give a precise diagnosis. Female pseudohermaphroditism may be due to excess fetal androgens (congenital adrenal hyperplasia), increased androgen production of maternal origin, or placental androgen excess. In male pseudohermaphroditism, if testosterone rises normally after hCG stimulation, androgen resistance is indicated. If it does not rise after this test, either testicular dysgenesis or disturbance in testosterone biosynthesis may be responsible. The assignment of sex for rearing must be guided by the etiology of the genital malformation, the anatomic condition, and family considerations. In cases of female pseudohermaphroditism, the newborn should always be declared to be of female sex at birth. In cases of male pseudohermaphroditism, great care should be taken in the declaration of male sex: the potential for reconstructive surgery and the pubertal "programmed" response of the external genitalia to endogenous and exogenous testosterone are determinant. Management of ambiguous genitalia in the newborn requires an entire multidisciplinary team in every step of the diagnostic procedure, the choice of sex assignment, and the treatment strategy.