Disorders of Testosterone Action in 46 XY DSD

Disorders of androgen action constitute the largest subgroup of 46XY DSD. These children suffer from inadequate testosterone action on the developing gonadal structures in the embryo. The defects in androgen action leads to defective masculinization of internal and external genitalia and functional deficits later. The most common cause of defective testosterone action is androgen insensitivity syndrome due to anomalous testosterone receptors and deficiency of 5-alpha reductase which converts testosterone to its active form, dihydrotestosterone. These defects can have a variable range of severity leading to a wide spectrum of phenotypic manifestations. Thus, the timing and mode of presentation in these children are highly variable. The most severe form of 46 XY DSD can present as a completely female phenotype. They may be investigated and further diagnosed due to inguinal hernia with prolapsing testis or primary amenorrhea at puberty. On the other end of the phenotypic spectrum is an undervirilized male with small clitoris-like phallus, undescended gonads, unfused bifid scrotum, and possibly variable degree of hypospadias and/or a blind vaginal pouch. These children may be suspected to have DSD in neonatal period or infancy and may be investigated with karyotyping and further hormonal studies. Decision about the sex of rearing in these children need multifactorial consideration, including extent of virilization, male pattern genetic imprinting, and virilization potential at puberty. In general, children with complete androgen insensitivity (CAIS) are better reared as females, whereas those with partial androgen insensitivity (PAIS) and 5-alpha-reductase deficiency have better potential for virilization and may be assigned the male gender. Estrogen or testosterone supplementation at puberty and feminizing or masculinizing genitoplasty are required according to the gender assignment.