Decreased nocturnal melatonin secretion in patients with Klinefelter's syndrome

OBJECTIVE We have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion which decreases to normal levels during testosterone treatment. The results suggested that sex steroids, rather than LH, modulate pineal melatonin in an inverse fashion. The purpose of this study was to characterize circulating melatonin levels in untreated males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS). DESIGNS Prospective, controlled. SUBJECTS Eleven patients with Klinefelter's syndrome and seven controls. Patients were subdivided into two groups: (1) with low testosterone, and (2) with normal testosterone levels. MEASUREMENTS Serum samples for melatonin concentrations were obtained every 15 minutes from 1000 to 0700 h in a controlled light-dark environment. RESULTS All patients had elevated FSH, LH and oestradiol (E(2)) levels. Mean (+/- SD) dark time nocturnal melatonin levels were significantly lower in low testosterone KS (92 +/- 19 pmol/l) compared with 146 +/- 42 pmol/l in normal testosterone KS and 179 +/- 59 pmol/l in controls (P < 0.02). A similar pattern was observed for the mean (+/- SD) peak melatonin levels (165 +/- 41, 236 +/- 59 and 293 +/- 89 pmol/l) in low testosterone KS, normal testosterone KS and controls, respectively (P < 0.01). Integrated nocturnal melatonin secretion values (AUC) were also lower in low testosterone KS (64 +/- 13) compared with 96 +/- 26 in normal testosterone KS and 116 +/- 39 pmol/min l x 10(3) in controls (P < 002). The time of melatonin peak and the time of the nocturnal melatonin rise as well as the light-time mean (+/- SD) serum melatonin levels were similar in all three groups. No correlations were found between melatonin and LH, FSH, or Ea levels. CONCLUSIONS Melatonin secretion is decreased in male patients with low testosterone hypergonadotrophic hypogonadism whereas in normal testosterone Klinefelter's syndrome patients, melatonin secretory profiles are normal. The results suggest that the suppression of melatonin secretion in these patients is mediated by GnRH (either directly or indirectly) and/or oestradiol.