A 46,XX karyotype in a newborn with ambiguous genitalia suggests that the affected child is a genetic female who was exposed to excessive amounts of androgens during fetal life. Marked elevation of plasma 17-hydroxypregnenolone, 17-hydroxyprogesterone and androstenedione, along with male levels of testosterone, are characteristic of 21-hydroxylase deficiency. High values of corticosterone and 11-deoxycortisol, along with elevated androgens, indicates 11β-hydroxylase deficiency.

When excess maternal androgen production is the underlying cause for masculinization of a female fetus, the source of these steroids is eliminated postnatally. Thus, the various steroids studied in affected newborns will be in the normal female range despite masculinization of the genitalia.

In ovotesticular DSD with a 46,XX chromosome complement, masculinization arises from androgens secreted by the testicular portion of the gonads. Androgen production is similar to that produced by normal testes except that the amount is usually smaller. The degree of masculinization of the genitalia is thus related to the amount of functioning testicular tissue present.

On occasion, translocation of the pseudo-autosomal part of the Y chromosome along with a mutated SRY gene to an X chromosome occurs. The result is partial masculinization of the genitalia in a 46,XX newborn.

Very low values of MIS are expected in 46,XX newborns with masculinized genitalia that is attributed to CAH or excess maternal androgen production during gestation. MIS is higher in newborns with ovotesticular DSD, due to the extent of Sertoli cell development in the testicular portion of their gonads.

A 46,XY karyotype suggests that one is dealing with a genetic male who was under-masculinized during fetal development (Figure 2). Laboratory findings of normal or elevated testosterone and dihydrotestosterone suggest a diagnosis of androgen insensitivity syndrome. Similar laboratory results are expected with a timing defect. MIS is elevated in PAIS, but should be normal in a baby with a timing defect in relation to normal male values. If testosterone levels are normal but DHT levels are low, a diagnosis of steroid 5α- reductase deficiency can be made. Low levels of testosterone and DHT, along with marked elevation of some androgen precursors, indicates a deficiency of one of the enzymes required for androgen biosynthesis. For example, if the elevated precursors include androstenedione and 17-hydroxyprogesterone, then the defective enzyme is 17-ketosteroid reductase. In all cases of testosterone biosynthetic defects, MIS levels are similar to those in unaffected male infants. Finally, when all androgens and their precursors are below normal levels one is dealing with either gonadal dysgenesis or 46,XY ovotesticular DSD. In these cases, MIS values should also be low. In contrast, for babies affected by Leydig cell hypoplasia, androgens and their precursors are low, while MIS values should be in the normal male range.