来曲唑治疗青春期特发性矮身材男童的临床观察

Clinical effect of letrozole in treatment of idiopathic short stature in adolescent boys

目的评估来曲唑用于青春期特发性矮身材(ISS)男童的治疗效果及安全性。方法回顾性收集16例骨龄≥ 14岁青春期ISS男童的病例资料,其中8例初始应用重组人生长激素(rhGH)治疗,骨龄14~15.5岁时开始rhGH联合来曲唑治疗;另8例首诊时骨龄≥ 14岁,即应用rhGH联合来曲唑治疗。其中16例均治疗满6个月,12例治疗满1年,5例治疗满1.5年。分析ISS患儿治疗后骨龄增长、预期成年身高(PAH)、成年终身高、性激素水平及不良反应。结果治疗6个月、1年及1.5年时中位骨龄分别较治疗前增加0岁、0.5岁、0.5岁,均显著低于年龄增加(P < 0.05);PAH均较治疗前显著增加(P < 0.05);7例达终身高,较治疗前PAH显著增加(P < 0.05)。与治疗前相比,治疗后各时间点促黄体生成素、卵泡刺激素及睾酮水平均显著升高(P < 0.05);治疗1年时雌二醇水平降低,胰岛素水平升高(P < 0.05)。治疗6个月、1年时胰岛素样生长因子-1较治疗前显著升高(P < 0.05)。治疗中监测血糖、血脂、尿酸、甲状腺功能指标与治疗前比较差异均无统计学意义(P > 0.05)。结论青春期大骨龄ISS男童应用rhGH联合来曲唑治疗,可延缓骨龄增长,改善PAH及成年终身高,且未见明显不良反应,安全有效。

Objective To evaluate the therapeutic effect and safety of letrozole in the treatment of adolescent boys with idiopathic short stature (ISS).Methods A retrospective analysis was performed for the clinical data of 16 adolescent boys with ISS who had a bone age of ≥ 14 years. Among these boys, 8 were initially treated with recombinant human growth hormone (rhGH), followed by rhGH combined with letrozole during a bone age of 14-15.5 years. The other 8 boys were initially treated with rhGH combined with letrozole since their bone age was ≥ 14 years at diagnosis. Of the 16 boys, 16 were treated for not less than 6 months, 12 were treated for not less than 1 year, and 5 were treated for not less than 1.5 years. The increase in bone age, predicted adult height (PAH), final adult height, sex hormones, and adverse reactions after treatment were analyzed.Results After 6 months, 1 year, and 1.5 years of treatment, median bone age was increased by 0 year, 0.5 year, and 0.5 year respectively, which was significantly lower than the increase in age (P < 0.05). There was a significant increase in PAH after treatment (P < 0.05). Seven boys reached final height, which was significantly higher than PAH before treatment (P < 0.05). All the 16 boys had significant increases in luteinizing hormone, follicle-stimulating hormone, and testosterone levels after treatment (P < 0.05), with a significant reduction in the estradiol level and a significant increase in the insulin level at 1 year of treatment (P < 0.05). There was a significant increase in the insulin-like growth factor-1 level at 6 months and 1 year of treatment (P < 0.05). There were no significant changes in blood glucose, blood lipids, uric acid, and the three indices for thyroid function as monitored during treatment (P > 0.05).Conclusions In adolescent boys with ISS and a high bone age, rhGH combined with letrozole can safely and effectively delay the increase in bone age and improve PAH and final adult height, with little adverse effect.