DECREASED NOCTURNAL MELATONIN SECRETION IN PATIENTS WITH KLINEFELTERS-SYNDROME

OBJECTIVE We have recently demonstrated that GnRH deficient male patie nts have increased nocturnal melatonin secretion which decreases to no rmal 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 mel atonin levels in untreated males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS). DESIGNS Prospective, controlled. S UBJECTS 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 f or melatonin concentrations were obtained every 15 minutes from 1000 t o 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 testos terone 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 simil ar pattern was observed for the mean (+/- SD) peak melatonin levels (1 65 +/- 41, 236 +/- 59 and 293 +/- 89 pmol/l) in low testosterone KS, n ormal testosterone KS and controls, respectively (P < 0.01). Integrate d nocturnal melatonin secretion values (AUC) were also lower in low te stosterone KS (64 +/- 13) compared with 96 +/- 26 in normal testostero ne KS and 116 +/- 39 pmol/min l x 10(3) in controls (P < 002). The tim e of melatonin peak and the time of the nocturnal melatonin rise as we ll 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 i n male patients with low testosterone hypergonadotrophic hypogonadism whereas in normal testosterone Klinefelter's syndrome patients, melato nin secretory profiles are normal. The results suggest that the suppre ssion of melatonin secretion in these patients is mediated by GnRH (ei ther directly or indirectly) and/or oestradiol.