High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome.

OBJECTIVE Klinefelter's syndrome (KS) is associated with hypergonadotrophic hypogonadism in adulthood. However, limited information exists about the age at which hypogonadism occurs. The hypothalamic-pituitary-gonadal (HPG) axis is transiently activated during the first months of life, offering the opportunity to study testicular function by spontaneous, basal hormone levels. The aim of this study was to evaluate the HPG axis in KS infants. DESIGN Cross-sectional study. METHODS Ten KS infants aged 3.1 months (range 1.8-3.8) and 613 healthy controls aged 3.0 months (range 2.0-4.5). Serum levels of total and free testosterone (T), LH, FSH, inhibin B and sex hormone-binding globulin (SHBG) were determined. RESULTS KS infants had significantly higher concentrations of total T (5.0 (2.2-11.2) vs 3.4 (0.7-8.3) nmol/l, P = 0.02), free T (31.6 (18.2-61.8) vs 22.1 (4.3-48.4) pmol/l, P = 0.01), LH (3.3 (1.3-4.6) vs 1.7 (0.6-4.3) IU/l, P = 0.005) and FSH (1.7 (1.1-4.1) vs 1.2 (0.4-3.0) IU/l, P = 0.007) than controls. SHBG and inhibin B did not differ from controls. LH/T and LH/free T ratios were normal, whereas the FSH/inhibin B ratio was elevated (6.5 (2.7-16.9) vs 3.0 (0.78-11.4), P = 0.005) when compared to controls. The majority of KS infants had normal bivariate hormonal combinations. CONCLUSION We found increased FSH/inhibin B ratio as a possible sign of Sertoli cell dysfunction. However, serum levels of T were high normal suggesting an altered pituitary-gonadal set point.