MULLERIAN INHIBITING SUBSTANCE IN THE DIAGNOSIS AND MANAGEMENT OF INTERSEX AND GONADAL ABNORMALITIES

Müllerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme-linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with male pseudohermaphroditism, and eight other intersex patients with undescended testes, dysgenetic gonads, or ovotestes. In these latter patients, serial MIS values were also helpful to confirm complete removal of gonadal tissue postoperatively. MIS may be a more sensitive marker for the presence of testicular tissue than serum testosterone levels, both before and after the neonatal androgen surge, and, consequently, may obviate the need for human chorionic gonadotropin stimulation in the evaluation of certain intersex disorders. In patients with the persistent Müllerian duct syndrome, MIS values were useful in differentiating the underlying etiology of the disorder. Four patients with undetectable levels have presumptive MIS gene mutations, while 7 others with MIS values of 2 to 45 ng/mL may have bioinactive hormone or MIS receptor defects. Finally, two young girls with ovarian granulosa cell tumors had elevated MIS values that fell from 18 to 2 ng/mL and from 6.5 to 1 ng/mL during postoperative follow-up. The MIS level in the latter patient has recently increased to 7.2 ng/mL, raising the question of residual tumor. Data in adults with similar sex cord tumors suggest that serum MIS can be followed in these patients as a marker for persistent or recurrent disease. Thus, the determination of serum MIS concentrations is useful in the diagnosis and management of patients with a variety of intersex and gonadal abnormalities. © 1993.