What Does AMH Tell Us in Pediatric Disorders of Sex Development?

Abstract

Disorders of sex development (DSD) are conditions where genetic, gonadal, and/or internal/external genital sexes are discordant. In many cases, serum testosterone determination is insufficient for the differential diagnosis. Anti-Müllerian hormone (AMH), a glycoprotein hormone produced in large amounts by immature testicular Sertoli cells, may be an extremely helpful parameter. In undervirilized 46,XY DSD, AMH is low in gonadal dysgenesis while it is normal or high in androgen insensitivity and androgen synthesis defects. Virilization of a 46,XX newborn indicates androgen action during fetal development, either from testicular tissue or from the adrenals or placenta. Recognizing congenital adrenal hyperplasia is usually quite easy, but other conditions may be more difficult to identify. In 46,XX newborns, serum AMH measurement can easily detect the existence of testicular tissue, leading to the diagnosis of ovotesticular DSD. In sex chromosomal DSD, where the gonads are more or less dysgenetic, AMH levels are indicative of the amount of functioning testicular tissue. Finally, in boys with a persistent Müllerian duct syndrome, undetectable or very low serum AMH suggests a mutation of the AMH gene, whereas normal AMH levels orient toward a mutation of the AMH receptor.

Clinical Utility of Anti-Mullerian Hormone in Pediatrics

“…AMH was first described in the context of dysregulated sexual differentiation, and the first clinical utility was in the diagnosis of differences of sexual development. While the presence of Mullerian duct derivatives reflects the lack of AMH secretion during the sixth to tenth weeks of fetal life, the serum AMH measurements after birth reflect not only Sertoli cell function in patients with DSD but also serve as a biomarker of the relative influence of FSH and androgens ( 53 ). FSH increases Sertoli cell mass and AMH secretion, but testosterone acting via the androgen receptors in Sertoli cells postnatally suppresses AMH ( 22 , 54 ).…”

“…One exception to this would be patients with AMH-negative PMDS due to AMH gene mutations, who also have undetectable AMH but nondescent of testes due to the presence of Mullerian-derived structures affecting descent. A pelvic ultrasound to detect Mullerian structures can distinguish this condition from anorchia due to testicular regression syndrome where Mullerian derivatives are absent ( 53 ).…”

Approach to the Virilizing Girl at Puberty

“…Elevated LH and FSH is consistent with primary gonadal failure. Furthermore, measurement of serum Anti-Müllerian hormone (AMH) help in classifying the different forms of DSDs with and without gonadal dysgenesis ( 32 ). Normally, AMH is produced in high amounts in immature Sertoli cells, but physiologically declines once pubertal testosterone production starts.…”

“…In 46,XY DSD, AMH is low in gonadal dysgenesis, but normal or elevated with defects of androgen synthesis or action. In chromosomal and 46,XY DSD with suspected gonadal dysgenesis, AMH levels indicate the existence of functional testicular tissue, ( 32 , 33 ). Granulosa cells of primary and small antral ovarian follicles produce only small amounts of AMH from late fetal life until menopause.…”

“…Granulosa cells of primary and small antral ovarian follicles produce only small amounts of AMH from late fetal life until menopause. In 46,XX DSD elevated AMH levels indicate ovotesticular DSD with usually functional ovarian tissue but dysgenetic testicular tissue ( 32 ). Tumor markers such as α-fetoprotein, β-human chorionic gonadotrophin, lactate dehydrogenase, inhibin, and cancer antigen 125 are positive in 50% to 80% of malignant ovarian lesions, but may also be positive in 20% of benign ovarian germ cell tumors ( 4 ).…”