Context: Klinefelter syndrome (KS) is the most common sex chromosome disorder and a major cause of male infertility. In adult patients, serum inhibin B and anti-Mullerian-hormone (AMH) are undetectable, testosterone secretion is often impaired, and the tubules are depleted of germ cells. Before puberty, inhibin B, AMH, and testosterone levels are within the normal range.
Objective: Sertoli and Leydig cell secretions, including insulin-like peptide-3 (INSL3), were evaluated in infants with nonmosaic XXY karyotype to assess testicular function soon after birth.
Design: The study was conducted in four University Pediatric Departments from the United States and France.
Subjects: Sixty-eight prenatally diagnosed infants aged 2-750 d were enrolled.
Main outcome measures: Serum FSH, LH, inhibin B, AMH, and INSL3 were measured by immunoassay, and testosterone was measured by tandem mass-spectrometry.
Results: In infants with KS, INSL3 levels transiently increased at 2-3 months of age and were significantly correlated with testosterone (Spearman r = 0.57) and LH (Spearman r = 0.73) levels. They did not differ from controls. Testosterone levels were within the normal range, but most of them were below the median of controls. Inhibin B and AMH levels were also within normal range. Inhibin B was correlated with FSH (Spearman r = 0.49). AMH was not correlated with FSH or testosterone. FSH levels were above normal in 25% of patients, despite normal inhibin B levels.
Conclusions: In infants with KS, Leydig cells are normally sensitive to the LH proliferative effect. In contrast, the Sertoli cell sensitivity to FSH is questionable, which may be prophetic of the postpubertal Sertoli cell resistance to FSH.