Evaluation of Gonadal Function in 107 Intersex Patients by Means of Serum Antimüllerian Hormone Measurement¹

Abstract

Fetal male sexual differentiation is driven by two testicular hormones: testosterone (synthesized by interstitial Leydig cells) and antimüllerian hormone (AMH; produced by Sertoli cells present in the seminiferous tubules). Intersex states result either from gonadal dysgenesis, in which both Leydig and Sertoli cell populations are affected, or from impaired secretion or action of either testosterone or AMH. Until now, only Leydig cell function has been assessed in children with ambiguous genitalia, by means of testosterone assay. To determine whether serum AMH would help in the diagnosis of intersex conditions, we assayed serum AMH levels in 107 patients with ambiguous genitalia of various etiologies. In XY patients, AMH was low when the intersex condition was caused by abnormal testicular determination (including pure and partial gonadal dysgenesis) but was normal or elevated in patients with impaired testosterone secretion, whereas serum testosterone was low in both groups. AMH was also elevated during the first year of life and at puberty in intersex states caused by androgen insensitivity. In 46,XX patients with a normal male phenotype or ambiguous genitalia, in whom the diagnosis of female pseudohermaphroditism had been excluded, serum AMH levels higher than 75 pmol/L were indicative of the presence of testicular tissue and correlated with the mass of functional testicular parenchyma. In conclusion, serum AMH determination is a powerful tool to assess Sertoli cell function in children with intersex states, and it helps to distinguish between defects of male sexual differentiation caused by abnormal testicular determination and those resulting from isolated impairment of testosterone secretion or action.

GATA4 variant identified by whole‐exome sequencing in a Japanese family with atrial septal defect: Implications for male sex development

“…In this regard, although well‐masculinized external genitalia and normal LH and testosterone productions indicate well‐preserved Leydig cell function, slightly increased FSH values and obviously low AMH values may suggest more or less compromised Sertoli cell function in the two boys 17, 18, 19. In particular, serum AMH is s a reliable marker of Sertoli cell function 18.…”

“…In this regard, although well‐masculinized external genitalia and normal LH and testosterone productions indicate well‐preserved Leydig cell function, slightly increased FSH values and obviously low AMH values may suggest more or less compromised Sertoli cell function in the two boys 17, 18, 19. In particular, serum AMH is s a reliable marker of Sertoli cell function 18. However, since GATA4 binds to the AMH promoter and enhances AMH expression synergically with NR5A1,6 the GATA4 p.(R284H) variant may have primarily impaired AMH expression, with no clinically discernible deleterious effect on other Sertoli cell function including Sertoli‐germ cell interaction.…”

“…AMH: anti‐Müllerian hormone; ASD: atrial septal defect; CHD: congenital heart disease; FSH: follicle‐stimulating hormone; LH: luteinizing hormone.The values in parentheses represent the age‐ and sex‐matched normal range 17, 18a

Peak value during a GnRH stimulation test (GnRH 100 μg/m 2 bolus iv; blood sampling at 0, 30, 60, 90, and 120 min).

b

Basal and stimulated values in an hCG test (3,000 IU/m 2 per dose [max.

…”

Anti-Müllerian hormone: A unique biochemical marker of gonadal development and fertility in humans

“…AMH leve ls re main hi gh du ri ng the who le pre pu ber tal pha se and are downre gu lated in pu ber ty by in crea sed tes tos te ro ne le ve ls. Se rum AMH le ve ls in ma les, ac cor di ng to age, are shown in tab le 1 (15). The as ses sme nt of AMH (a nd in hi bin B) can be useful in the diff e ren tial diag no sis of con sti tu tio nal de lay of growth and pu ber ty when AMH se rum leve ls re main at hi gh pre pu ber tal va lues, whi le low AMH (a nd in hi bin B) le ve ls at the age of physio logi cal pu ber ty are in di ca ti ve for the con ge ni tal hypo go na di sm (9).…”

How vulnerable is the developing testis to the external environment?

“…A number of peptide hormones are produced by the Sertoli cell, including anti-mullerian hormone (AMH) and inhibin. Measurement of serum AMH concentrations have been proposed as a marker of testicular function in infancy as well as indicating whether testes are present in bilateral cryptorchidism and intersex disorders 21. Inhibin is a glycoprotein, which is produced predominantly in men by the Sertoli cells.…”