Inhibin B and Anti-Müllerian Hormone, But Not Testosterone Levels, Are Normal in Infants with Nonmosaic Klinefelter Syndrome

Abstract

Klinefelter syndrome is a major cause of infertility in the male. Nevertheless, pregnancies were recently obtained by intracytoplasmic injection of sperm retrieved by surgery or ejaculation, underscoring the need to understand the role of Sertoli and Leydig cell secretions during development. In 18 infants with prenatally diagnosed homogenous 47,XXY karyotype, blood samples were taken from birth to 3 yr of age. Inhibin B (INHB), anti-Müllerian hormone (AMH), testosterone, FSH, and LH levels were compared with those in six adolescents with XXY karyotype and reference values established in 215 control infants. In XXY infants FSH, LH, INHB, and AMH did not differ from controls. Testosterone levels during the first trimester exhibited a physiological increase but were lower than in controls (P = 0.0001). Significant correlations were found between testosterone and LH (P < 0001), between INHB and FSH (P = 0.0011), and between AMH and INHB (P = 0.025). In XXY adolescents, AMH and INHB were undetectable. Our findings demonstrate that testosterone secretion is impaired in infants with Klinefelter syndrome. By contrast, INHB and AMH secretions were not altered, which raises the question of the mechanism(s) governing the decline of Sertoli cell function after puberty.

Are Adolescent Boys with Klinefelter Syndrome Androgen Deficient? A Longitudinal Study of Finnish 47,XXY Boys

“…Thus, impaired T secretion is not an evident feature of KS boys during puberty. In fact, to our knowledge, only two studies on KS boys have demonstrated diminished T secretion before puberty (30,31), but these studies comprised infant KS boys, and the results cannot therefore be directly extrapolated to peripubertal and pubertal KS subjects.…”

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

“…The mini-puberty represents a window suitable for studying the function of the pituitary-gonadal axis at this young age by measuring the spontaneous, basal hormone levels (32). Although controversies exist as to whether the HPG axis is impaired in KS infants (16,33,34,35), the latest and largest study on the mini-puberty in KS demonstrated normal testosterone concentrations (35). Importantly, however, the testosterone concentrations were below the median of the controls, which may indicate a subtle Leydig cell dysfunction, although this was not supported by an elevation of LH concentrations (35).…”

Prepubertal gynecomastia in Peutz-Jeghers syndrome: incomplete penetrance in a familial case and management with an aromatase inhibitor

“…Anti-Mullerian hormone (AMH) was measured with a solid phase sandwich assay (DSL-France, Cergy-Pontoise, France). Details of the assays used and their precision profiles have been described previously (6,7). Immunoreactive inhibin-a was measured by RIA using antiserum 1989 raised against purified 31 kDa bovine inhibin, kindly donated by D M de Kretzer (Monash University, Clayton, Australia) (8).…”