The masculinized female and investigation of abnormal sexual development

The congenital adrenal hyperplasias are the commonest cause of ambiguity of the external genitalia at birth, although sexual differentiation in these disorders is strictly normal. The masculinized genetic female is invariably the result of 21-hydroxylase deficiency. The molecular features are well characterized and the phenotypic correlates are generally concordant. Prenatal treatment by maternal dexamethasone administration can successfully prevent virilization of the external genitalia in an affected female fetus. Placental aromatase is a rare and recently characterized alternative cause of a masculinized female which should be considered in the absence of fetal adrenal hyperplasia and maternal androgen-secreting tumours. The investigation of abnormal sexual development requires an initial karyotype analysis and serum 17OH progesterone measurement to determine whether 21-hydroxylase deficiency is the likeliest cause. Thereafter, the presence of a 46,XY karyotype determines the mode of investigation according to androgen production and action. Obtaining appropriate samples for DNA, biochemical and immunohistochemical analyses is essential if the diagnostic yield for the investigation of abnormal sexual development is to be improved.