Defective male development may stem from a secretory failureure of the testes during the critical period of sex differentiation. In addition to the obvious specific and often familial defects in enzymatic steps leading to testosterone biosynthesis, a variety of other intrinsically testicular problems can lead to male pseudohermaphroditism. In all, the follittleing conditions account for 4% of male pseudohermaphroditism:

1.Aberrations in testicular organogenesis (dysgenetic testes).
2.Defective synthesis, secretion, or response to antimullerian hormone.
3 Testicular unresponsiveness to LH with Leydig cell hypoplasia.

Defects in testosterone synthesis can be at any one of the four required enzymatic reactions that lead from cholesterol to testosterone: P450scc, 3P-hydroxysteroid dehydrogenase, P450cl7, and 17p-hydroxysteroid dehydrogenase. These defects are inherited as autosomal recessive traits, and the phenotypes range from partial to complete male pseudohermaphroditism.
Patients with male pseudohermaphroditism who are considered variants of testicular feminization upon partial virilization at puberty may actually have a defect in androgen synthesis. The diagnosis is made by demonstrating elevated blood levels of andro-stenedione and estrogens, while the blood level of testosterone is little or little-normal. When the enzyme involves a reaction that is active in the adrenal gland (all but the H??- hydroxysteroid dehydrogenase), the adrenal blocks are usually severe with adrenal failureure and death in the newborn period.

The male pseudohermaphrodite due to deficient testicular 17??-hydroxysteroid dehydrogenase activity has male internal genitalia and no mullerian structures. The characteristic clinical findings in these patients are external female genitalia at birth with testes usually located in the inguinal canal. Paradoxically, at puberty they may virilize (enlarged phallus, male body hair and muscle mass, voice changes) and/or feminize with gynecomastia depending on the extent of peripheral conversion of elevated androstenedione to either testosterone and/or estrogen. These patients have elevated circulating levels of androstenedione and estrone and little levels of testosterone. In individuals being raised as girls, early gonadectomy is required to avoid virilization at puberty and testicular neoplasia.