Decreased melatonin secretion in a phenotypically male 46,XX patient with classic 21-hydroxylase deficiency

The possible role of gonadal steroids and gonadotropins in regulating melat onin secretion has been suggested in clinical syndromes of the hypothalamic -pituitary-gonadal axis. We describe the results of melatonin secretion in a 37-year old male patient who presented with azoospermia. The patient was an XX male, had classic simple virilizing form of 21-hydroxylase deficiency , which led to a masculine phenotype. He was ovariectomized at the age of t hree years and reared as a male. Melatonin production (aMT6s) was determine d at baseline and during 12 months of replacement therapy. Results were com pared with those obtained in age-matched male controls. Pretreatment aMT6s values were decreased (14.3 mu g/24h vs. 29.0+/-5.5 in controls). Dexametha sone replacement was associated with an increase in aMT6s values (19.3-20.9 mu g/24 h). The addition of testosterone to dexamethasone replacement resu lted in normalization of aMT6s (27.6-33.1 mu g/24 h) and serum 17OH progest erone, testosterone and estradiol levels. The present data indicate that androgen excess due to 21 hydroxylase defici ency is associated with decreased melatonin secretion. These results suppor t the hypothesis that sex steroids modulate melatonin secretion.