Soriano-Guillén Leandro, Lahlou Najiba, Chauvet Geneviève, Roger Marc, Chaussain Jean Louis, Carel Jean Claude
Department of Pediatric Endocrinology and Institut National de la Santé et de la Recherche Médicale, U561, Groupe Hospitalier Cochin-Saint Vincent de Paul, Faculté Cochin, Université Paris V, 82 avenue Denfert Rochereau, 75014 Paris, France.
J Clin Endocrinol Metab. 2005 Jan;90(1):147-51. doi: 10.1210/jc.2004-1438. Epub 2004 Nov 2.
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.
家族性男性限局性性早熟是一种由促黄体生成素（LH）受体激活突变引起的罕见性早熟病因，可导致过早出现男性化和身材矮小。目前已提出两种治疗方法：细胞色素P450抑制剂酮康唑，或螺内酯与睾酮内酯联合治疗。迄今为止，尚未有关于这两种治疗后成人身高的报道。在本研究中，我们报告了5例接受酮康唑治疗患者的结果，中位剂量为16.2 mg/kg.d，中位治疗时间为6.2年。成人身高为173 cm（中位数；四分位间距，14），与目标身高（175 cm；四分位间距，9）相似，且显著高于治疗前预测身高（165 cm；四分位间距，12；P < 0.01）。治疗期间，58次睾酮测量中有39次（68%）低于0.5 ng/ml（1.7 nmol/L），58次中有9次（15%）在0.5至1 ng/ml（3.5 nmol/L）之间，58次中有10次（17%）高于1 ng/ml。我们观察到10岁后促性腺激素释放激素（GnRH）刺激的LH水平有生理性升高，且无一例患者出现促性腺轴过早激活。肝脏耐受性良好，仅有1例患者血清转氨酶有短暂轻度升高。我们得出结论，酮康唑是治疗家族性男性限局性性早熟的一种有效且耐受性良好的长期治疗方法，应作为一线治疗方案推荐。
