长效与短效重组人生长激素治疗特发性矮小症患儿的临床研究

Clinical trial of long-acting and short-acting recombinant human growth hormone in the treatment of children with idiopathic short stature

目的观察长效重组人生长激素(rhGH)与短效rhGH治疗特发性矮小症(ISS)患儿的临床疗效,及其对生长发育指标、血清甲状腺功能指标和胰岛素水平的影响。方法将ISS患儿随机分为长效组和短效组。长效组给予皮下注射聚乙二醇重组人生长激素注射液(0.2 mg·kg^(-1)·w^(-1),qw),短效组给予每晚睡前30 min皮下注射重组人生长激素注射液(0.15 U·kg^(-1)·d^(-1))。2组患儿均持续治疗12个月。比较2组患儿的生长发育[生长速度(GV)和身高标准积分(Ht SDS)]、甲状腺功能、空腹胰岛素(FINS)、胰岛素样生长因子-1(IGF-1),以及药物不良反应的发生情况。结果本研究共入组68例,因治疗过程中失访、个人原因私自中断治疗脱落4例,最终长效组和短效组分别纳入33例和31例进行统计分析。治疗6个月后,长效组和短效组的GV分别为(4.53±0.56)和(3.97±0.48)cm·year^(-1),Ht SDS分别为-2.45±0.23和-2.66±0.21,IGF-1分别为(551.62±41.48)和(524.36±37.84)mg·mL^(-1);治疗12个月,长效组和短效组的GV分别为(9.44±0.82)和(8.46±0.77)cm·year^(-1),Ht SDS分别为-1.68±0.19和-1.91±0.20,IGF-1分别为(642.46±36.49)和(593.14±40.12)mg·mL^(-1),在统计学上差异均有统计学意义(均P<0.05)。治疗后,2组患儿的FT3、FT4、TSH和FINS水平比较,在统计学上差异均无统计学意义(均P>0.05)。长效组和短效组的总药物不良反应发生率分别为6.06%(2例/33例)和12.90%(4例/31例),在统计学上差异无统计学意义(P>0.05)。结论长效rhGH对ISS患儿近期的生长发育促进效果优于短效rhGH治疗,更能提高血清IGF-1水平,对ISS患儿甲状腺功能无明显影响,安全性好。

Objective To observe clinical curative effect of longacting recombinant human growth hormone(rhGH)and short-acting rhGH,and their influences on growth and development indexes,serum thyroid function indexes and insulin in children with idiopathic short stature(ISS).Methods The children with ISS were randomly divided into long-acting group[subcutaneous injection of polyethylene glycol recombinant human growth hormone(0.2 mg·kg^(-1)·w^(-1),qw)]and short-acting group[subcutaneous injection of recombinant human growth hormone(0.15 U·kg^(-1)·d^(-1))at 30 min before sleep every night].All children were treated for 12 months.The growth and development[growth velocity(GV),height standard deviation of points(Ht SDS)],thyroid function,fasting insulin(FINS)and insulin-like growth factor-1(IGF-1)were compared between the two groups.The occurrence of adverse reactions was recorded.Results In the 68 children,there were 4 cases with loss to follow-up and shedding due to personal reasons.Finally,there were 33 cases in long-acting group and 31 cases in short-acting group for statistical analysis.After 6 months of treatment,GV in long-acting group and short-acting group were(4.53±0.56)and(3.97±0.48)cm·year^(-1),Ht SDS were-2.45±0.23 and-2.66±0.21,IGF-1 levels were(551.62±41.48)and(524.36±37.84)mg·mL^(-1),respectively.After 12 months of treatment,GV in longacting group and the short-acting group were(9.44±0.82)and(8.46±0.77)cm·year^(-1),Ht SDS were-1.68±0.19 and-1.91±0.20,IGF-1 levels were(642.46±36.49)and(593.14±40.12)mg·mL^(-1),differences were statistically significant(allP<0.05).There were no significant differences in FT3,FT4,TSH and FINS between the two groups after treatment(allP>0.05).There was no significant difference in the total incidences of adverse drug reactions between long-acting group and short-acting group[6.06%(2 cases/33 cases)vs12.90%(4 cases/31 cases),P>0.05].Conclusion Compared with short-acting rhGH,promotion effect of long-acting rhGH is better on short-term growth and development in ISS children,which can increase level of serum IGF-1 and has no obvious effects on thyroid function,with good safety.