目的 研究重组人生长激素(rhGH)对青春期前特发性矮身材(ISS)儿童生长速率(GV)、骨龄(BA)的影响及其量效-时效关系,为临床合理使用rhGH治疗ISS提供参考依据。方法 2011年1月-2016年6月选择青春期前ISS儿童108例,随机分为rhGH低剂量组[0.12 U/(kg·d),n=36]、中剂量组[0.18 U/(kg·d),n=36]和高剂量组[0.24 U/(kg·d),n=36],睡前皮下注射给药,疗程2年。评价治疗前后患儿的生活年龄(CA)、身高(Ht)、GV、BA、预测成年身高(PAH)及身高均值标准差积分(HtSDS)等指标。结果 rhGH治疗6、12、18、24个月,三组患儿的BA均明显进展,但三组BA/CA无明显变化(P>0.05),且BA、BA/CA差异无统计学意义(P>0.05)。三组患儿的Ht、GV、PAH、HtSDS均较治疗前显著升高(P<0.05),Ht、PAH、HtSDS均随时间推移逐步升高,GV在6个月时达到高峰,中、高剂量组的Ht、GV、PAH、HtSDS均显著高于低剂量组,高剂量组仅治疗6个月时GV显著高于中剂量组(P<0.05)。三组不良反应率依次为2.78%、2.78%、8.33%,组间比较差异无统计学意义(P>0.05),高剂量组1例促甲状腺激素(TSH)升高,经左旋甲状腺素治疗后缓解。结论 rhGH治疗青春期前ISS具有一定的促进GV增长作用,短期追赶生长可能存在剂量和时间依赖性,且对患儿的生长潜能影响较小,但过高剂量恐难以显著增效且长期用药可能存在甲状腺功能损伤风险。

Objectives To explore the dose-time effect of recombinant human growth hormone(rhGH) on growth velocity(GV) and bone age(BA) in preadolescent children with idiopathic short stature(ISS),in order to provide guidance of rational rhGH use in treating ISS. Methods A total of 108 preadolescent children with ISS were enrolled in this study from January 2011 to June 2016,and were randomly divided into three groups,including low-dose rhGH group [0.12 U/(kg·d),n=36],middle-dose rhGH group [0.18 U/(kg·d),n=36] and high-dose rhGH group [0.24 U/(kg·d),n=36]. All children were given rhGH by subcutaneous injection before sleep every day for 2 years. The chronological age(CA),height(Ht),GV,BA,predicted adult height(PAH) and height standard deviation score(HtSDS) of the children before and after treatment were evaluated. Results At 6,12,18 and 24 months after rhGH treatment,the BA of the three groups significantly increased(P<0.05),while the BA/CA showed no significant changes among three groups(P>0.05),and there were no significant differences on BA and BA/CA among three groups(P>0.05). The Ht,GV,PAH and HtSDS of the three groups at 6,12,18 and 24 months after rhGH treatment were significantly higher than those before treatment(P<0.05),the Ht,PAH and HtSDS all gradually increased with time,and the GV reached the peak at 6 months. The Ht,GV,PAH and HtSDS in the middle-dose and high-dose rhGH groups were significantly higher than those in the low-dose rhGH group at all time points(P<0.05),while the GV in high-dose rhGH group was significantly higher than that in the middle-dose rhGH group only at 6 months after treatment(P<0.05). The rates of adverse reaction in three groups were 2.78%,2.78% and 8.33%,respectively,and there was no significant difference among three groups(P>0.05). In high-dose rhGH group,thyroid-stimulating hormone(TSH) level in one case increased,and relieved after treatment with levothyroxine. Conclusions To a certain degree,rhGH is effective in promoting GV growth for preadolescent children with ISS. There may be dose- and time- dependence manner in short-term catch-up growth,and it has little influence on the growth potential of children. However,excessive doses may not be significantly synergistic,and long-term medication may have a risk of thyroid dysfunction.