The elevated levels of 17α-hydroxyprogesterone present in all forms of 21-hydroxylase deficiency are rapidly suppressed by administration of exogenous corticoids. Even a single dose of a glucocorticoid such as dexamethasone will suppress 17α-hydroxyprogesterone in CAH but not in virilizing ovarian and adrenal neoplasms.
Hirsutism It is suggested that androgen-receptor blockade may be preferable to glucocorticoids as primary treatment of nonclassic 21-hydroxylase deficiency (97). Although menses usually (but not always) become regular shortly after beginning therapy with glucocorticoids, the hirsutism in this disorder is remarkably refractory to glucocorticoids.
Distinguishing nonclassic forms of CAH from idiopathic hirsutism may be problematic.
Individuals with idiopathic hirsutism have regular ovulatory menses, thus effectively eliminating PCOS from consideration. Confusion can be created by the fact that some women with nonclassic CAH may continue to ovulate. Basal levels of 17α-hydroxyprogesterone are normal in idiopathic hirsutism, as is the response to adrenocorticotropic hormone stimulation. Idiopathic hirsutism represents enhanced androgen action at the hair follicle (98).
Mixed Gonadal Dysgenesis The term mixed gonadal dysgenesis is used to designate those individuals with asymmetric gonadal development, with a germ cell tumor or a testis on one side and an undifferentiated streak, rudimentary gonad, or no gonad on the other side. Most individuals with this rare disorder have a mosaic karyotype of 45,X/46,XY and are raised as girls who experience virilization at puberty. Gonadectomy is indicated to remove the source of androgens and eliminate any risk for neoplasia.
Rare Forms of Male Pseudohermaphroditism
Individuals who have rare forms of male pseudohermaphroditism, especially 5α-reductase deficiency (the so-called penis at 12 syndrome) and the Reifenstein syndrome, generally have ambiguous female genitalia with variable virilization at puberty. Cushing syndrome may occur rarely during the pubertal years, as may adrenal or ovarian androgen-secreting neoplasms.
Ambiguous external genitalia in a newborn constitutes a major diagnostic challenge. Prompt evaluation is of critical importance to identify a possible life-threatening disorder and to assign the appropriate gender. The prime diagnosis until ruled out is CAH because it is the only condition that is life-threatening. Extreme sensitivity is required in interacting with the family, and no attempt should be made to guess the sex of the baby. The incidence of genital ambiguity is 1 in 4,500, although some degree of male undervirilization, or female virilization may be present in as many as 2% of live births (99,100).
Physical Signs During the 3 to 4 days required for evaluation, it is important to be supportive of the parents. Many clinicians believe that it is important not to attach any unusual significance to the genital ambiguity and to treat the abnormality as just another “birth defect.” Physicians should emphasize that the child should undergo normal psychosexual development regardless of the sex-of-rearing selected. Either a name compatible with either sex should be chosen or the naming of the infant should be delayed until the studies are completed.