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Saturday 01 January 2005

Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty.

By: Soriano-Guillen L, Lahlou N, Chauvet G, Roger M, Chaussain JL, Carel JC.

J Clin Endocrinol Metab 2005 Jan;90(1):147-51

Familial male-limited precocious puberty is a rare cause of precocious puberty due to activating mutations of the LH receptor, leading to early onset virilization and short stature. Two therapeutic approaches have been proposed: the P450 cytochrome inhibitor ketoconazole or combined treatment with spironolactone and testolactone. Results on adult heights have not been reported to date after these two treatments, and in this study we present results from five patients treated with ketoconazole at a median dose of 16.2 mg/kg.d for a median of 6.2 yr. Adult height was 173 cm (median; interquartile range, 14), similar to target height (175 cm; interquartile range, 9) and significantly higher than pretreatment predicted height (165 cm; interquartile range, 12; P < 0.01). During treatment, 39 of 58 (68%) testosterone measurements were less than 0.5 ng/ml (1.7 nmol/liter), nine of 58 (15%) were between 0.5 and 1 ng/ml (3.5 nmol/liter), and 10 of 58 (17%) were above 1 ng/ml. We observed a physiological increase in GnRH-stimulated LH levels after the age of 10 yr, and none of the patients had early activation of the gonadotropic axis. Liver tolerance was excellent, and only one patient had a transient and modest increase in serum transaminases. We conclude that ketoconazole is an efficient and well tolerated long-term treatment of familial male-limited precocious puberty that should be proposed as a first line therapy.

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