99 Anti Mullerian Hormone (AMH/MIS) Elisa: A Diagnostic Tool in Neona-Tology And Paediatry

Abstract

Background: Dimorphic expression of the Anti-Müllerian hormone (AMH), also called Müllerian inhibiting substance (MIS), in ovary and testis is crucial for normal differentiation of reproductive structures. Its absence in the female embryo allows Müllerian ducts to form the uterus, oviducts and upper vagina. AMH assay in girls is restricted to granulosa cancer and evaluation of ovarian follicular status. In males, AMH is produced by the testes reflecting Sertoli cell maturation. AMH induces Müllerian duct regression and is involved in testicular differentiation and function. Clinical applications of AMH assay include external abnormal genitalia, precocious puberty and hypogonadotropic hypogonadism. Howether, AMH measurement belongs to specialised laboratories which performed home made assays. Recently, Immunotech® has developed an assay available in all clinical laboratories.We established usual AMH values for this assay and we improved its interest. Methods: AMH measurement required only 25 μl of plasma and 3 hours (detection range: 0–200 ng/ml; sensitivity: 0.3 ng/ml; within-assay and between-assaies coefficients of variation: below 6% and 9% respectively). Usual values were established on blood from, 48 eutrophic fetuses (18 to 37 weeks of gestation), 101 full-term healthy newborns, and 425 healthy infants aged from one day to 10 years. 88 children with external gonadal abnormalities (14 clitoral hypertrophy; 50 microphallus; 43 hypospadias; 25 cryptorchidism; 9 non palpable testis) were evaluated. Clinical overlap (ambiguous genitalia) was observed in 42 cases. Results: In female, AMH was undetectable before birth and then weakly produced (< 6 ng/ml). In males, AMH increases from fetal life, pickes up between 1 and 12 months of life (99.7 ng/ml) with wide interindividual variations and then decrase with no overlap with female values. In clitoral hypertorphia, isolated microphallus and isolated hypospadias, AMH concentrations were within the usual range in 90% of cases. AMH was decreased in 73% of isolated cryptorchidism cases and was undetectable in anorchia. In ambiguous genitalia, AMH concentrations were increased, decreased or normal. Conclusions: At birth, AMH levels seems useful when investigating ambiguous genitalia antenatally suspected. In children with isolated microphallus or hypospadias, normal AMH values exclude testis dysfunction. A single AMH measurement distinguishes between anorchia and cryptorchidism when testis palpation is abnormal. In ambiguous genitalia, AMH measurement must be combined with other investigations.