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

Summary:

The possible role of gonadal steroids and gonadotropins in regulating melatonin 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 three years and reared as a male. Melatonin production (aMT6s) was determined at baseline and during 12 months of replacement therapy. Results were compared with those obtained in age-matched male controls. Pretreatment aMT6s values were decreased (14.3 μg/24 h vs. 29.0 ± 5.5 in controls). Dexamethasone replacement was associated with an increase in aMT6s values (19.3-20.9 μg/24 h). The addition of testosterone to dexamethasone replacement resulted in normalization of aMT6s (27.6-33.1 μg/24 h) and serum 17OH progesterone, testosterone and estradiol levels.

The present data indicate that androgen excess due to 21 hydroxylase deficiency is associated with decreased melatonin secretion. These results support the hypothesis that sex steroids modulate melatonin secretion.

Key words:

Sulphatoxymelatonin - adrenal androgens - testosterone - dexamethasone - congenital adrenal hyperplasia

References

• 1 Bagatell C J, Dahl K D, Bremner W J. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in man is partially mediated by aromatization to estradiol.  J of Andrology. 15 15-21 1994; 
• 2 Berga S L, Mortola J F, Yen S SE. Amplification of nocturnal melatonin secretion in women with functional amenorrhea.  J Clin Endocrinol and Metab. 66 242-244 1988; 
• 3 Brzezinski A, Lynch H J, Seibel M M, Deng M H, Wurtman R J. The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women.  J Clin Endocrinol Metab. 166 891-895 1988; 
• 4 Delfs T M, Baar S S, Fock C, Schumacher M, Olcese J, Zimmermann R C. Sex steroids do not alter melatonin secretion in the human.  Human Reprod. 9 49-54 1994; 
• 5 Finkelstein J S, Whitcomb R W, O'Dea L L, Langcopes C, Schoenfeld D A, Crowley W F. Sex steroid control of gonadotropin secretion in the human male. Effects of testosterone administration in normal and gonadotropin-releasing hormone deficient men.  J Clin Endocrinol Metab. 123 609-620 1991; 
• 6 Kadva A, Djahanbakach O, Monson J, Di W L, Silman R. Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea.  J Clin Endocrinol Metab. 83 3653-3662 1988; 
• 7 Luboshitzky R, Dharan M, Goldman D, Hiss Y, Herer P, Lavie P. Immunohistochemical localization of gonadotropin and gonadal steroid receptors in human pineal glands.  J Clin Endocrinol Metab. 82 977-981 1997 b; 
• 8 Luboshitzky R, Lavi S, Thuma I, Lavie P. Increased nocturnal melatonin secretion in male patients with hypogonadotropic hypogonadism and delayed puberty.  J Clin Endocrinol Metab. 80 2144-2148 1995 a; 
• 9 Luboshitzky R, Lavi S, Thuma I, Lavie P. Testosterone treatment alters melatonin concentrations in male patients with gonadotropin-releasing hormone deficiency.  J Clin Endocrinol Metab. 81 770-774 1996 b; 
• 10 Luboshitzky R, Tiosano D, Ben-Harush M, Thuma I, Ayash A, Lavie P, Etzioni A. Pseudo-precocious puberty in a male patient and the melatonin-testosterone relationship.  J Ped Endocrinol Metab. 8 295-299 1995 b; 
• 11 Luboshitzky R, Wagner O, Lavi S, Herer P, Lavie P. Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment.  Clin Endocrinol. 47 463-469 1997 a; 
• 12 Luboshitzky R, Wagner O, Lavi S, Herer P, Lavie P. Decreased nocturnal melatonin secretion in patients with Klinefelter's syndrome.  Clin Endocrinol. 45 749-754 1996 a; 
• 13 Okatani Y, Sagara Y. Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhea: relation to endogenous oestrogen concentration.  Clin Endocrinol. 41 736-770 1994; 
• 14 Rajmil O, Puig-Domingo M, Tortosa F, Viader M, Petterson A G, Schwarzstein D, De Leiva A. Melatonin concentration before and during testosterone replacement in primary hypogonatic men.  Europ J Endocrinol. 137 48-52 1997; 
• 15 Speiser F W, White P C. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency.  Clin Endocrinol. 49 411-417 1998; 
• 16 Terzolo M, Piovesan A, Ali A, Codegone A, Pia A, Reimondo G, Torto M, Paccotti P, Borretta G, Angeli A. Circadian profile of serum melatonin in patients with Cushing's syndrome or acromegaly.  J Endocrinol Invest. 18 17-24 1995; 
• 17 Waldhauser F, Boepple P A, Schemper M, Mansfield M J, Crowley W F. Serum melatonin in central precocious puberty is lower than in age-matched prepubertal children.  J Clin Endocrinol Metab. 73 793-796 1991; 
• 18 Waldhauser F, Frisch H, Krautgasser-Gasparotti A, Schober E, Bielmayer C. Serum melatonin is not affected by glucocorticoid replacement in congenital adrenal hyperplasia.  Acta Endocrinol. 111 355-359 1986; 

1 * data are the mean ± SD; D = Dexamethasone; T = Testosterone