Anti-müllerian hormone and its clinical use in pediatrics with special emphasis on disorders of sex development

Abstract

Using measurements of circulating anti-Müllerian hormone (AMH) in diagnosing and managing reproductive disorders in pediatric patients requires thorough knowledge on normative values according to age and gender. We provide age- and sex-specific reference ranges for the Immunotech assay and conversion factors for the DSL and Generation II assays. With this tool in hand, the pediatrician can use serum concentrations of AMH when determining the presence of testicular tissue in patients with bilaterally absent testes or more severe Disorders of Sex Development (DSD). Furthermore, AMH can be used as a marker of premature ovarian insufficiency (POI) in both Turner Syndrome patients and in girls with cancer after treatment with alkylating gonadotoxic agents. Lastly, its usefulness has been proposed in the diagnosis of polycystic ovarian syndrome (PCOS) and ovarian granulosa cell tumors and in the evaluation of patients with hypogonadotropic hypogonadism.

Figure 1

Mutations of the AMH gene (Case 1) and the AMH-RII gene (Case 2) in two families with boys presenting with PMDS. Two missense mutations in exons 1 and 2 (substitution of alanine by proline and of tyrosine by cysteine, resp.) were found in the AMH gene in two brothers presenting with AMH-negative PMDS. A homozygous missense mutation in exon 9 (substitution of aspartic acid by tyrosine) in the AMH-RII gene was found in two brothers presenting with AMH-positive PMDS.

Figure 2

Serum AMH in 1953 healthy subjects (926 females and 1027 males) according to age. Females: red circles, males: blue circles. Longitudinal values during infancy are connected with grey lines. The red and blue curves represent the female and male reference ranges, respectively (median, ±2SD). The figure was redrawn from our previously published data using Immunotech Coulter enzyme immunometric assay in all subjects [–13]. Please note the logarithmic y-axis. The y-axes for the DSL and Gen II assays were created using the following formulas: AMH (IOT) pmol/L = 2.0 × AMH (DSL) ug/L × 7.14 pmol/ug and AMH (IOT) pmol/L = 0.74 × AMH (Gen II) ug/L × 7.14 pmol/ug.

Figure 3

Immunohistochemical staining of AMH in testis tissue. GW: gestational week. Scale bar corresponds to 100 μm.