长效重组人生长激素治疗儿童生长激素缺乏症的疗效与安全性

Efficacy and Safety of Polyethylene Glycol Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency

关键词:  生长激素缺乏症  聚乙二醇重组人生长激素  重组人生长激素  疗效  安全性

Key words:  GHD  PEG-rhGH  rhGH  efficacy  safety

摘要:

目的 比较聚乙二醇重组人生长激素（PEG-rhGH）与重组人生长激素（rhGH）治疗儿童生长激素缺乏症（GHD）的疗效及其对体质指数（BMI）、甲状腺功能、糖代谢的影响，为临床个体化用药提供参考。方法 采用回顾性分析，纳入90名GHD儿童，其中PEG-rhGH组和rhGH组各45例，分析两组身高、身高标准差积分（Ht SDS）、年化生长速率、身高标准差积分变化量（△Ht SDS）、胰岛素样生长因子?1（IGF?1）、BMI、甲状腺功能、空腹血糖、空腹胰岛素等指标变化。结果 线性混合效应模型分析显示，两组患儿身高和Ht SDS均较治疗前显著改善（P<0.001）。治疗前12个月内两组身高无显著差异（P>0.05），从第15个月开始，rhGH组身高显著优于PEG-rhGH组，并在第21与第24个月保持此差异（P<0.05）。两组间Ht SDS无显著差异（P>0.05）。在生长动力方面，两组年化生长速率均在治疗的前3个月达到峰值（12.44 vs 11.96 cm·Y-1）；在治疗7-9个月时，rhGH组年化生长速率显著高于PEG-rhGH组（P=0.034），该时间段内△Ht SDS亦显著更优（P=0.038），其余时间段两组间无显著差异（P>0.05）。PEG-rhGH组治疗后BMI显著升高，在12个月与rhGH组差异显著（P=0.005），24个月时差异消失。两组治疗前后T4、TSH、胰岛素水平无显著变化（P>0.05），T3、空腹血糖随时间变化显著但均在正常范围。结论 PEG-rhGH与rhGH均能有效促进GHD患儿生长，且在实现标准化追赶生长（Ht SDS）上疗效相当。rhGH在7-9个月呈现更强的生长动力并累积为15个月以后的绝对身高优势；两种药物对甲状腺功能及糖代谢影响较小，安全性良好。

Abstract:

OBJECTIVE To compare the efficacy of polyethylene glycol recombinant human growth hormone (PEG-rhGH) versus recombinant human growth hormone (rhGH) in children with growth hormone deficiency (GHD) and their effects on body mass index (BMI), thyroid function, and glucose metabolism, so as to provide references for individualized clinical medication. METHODS In this retrospective study, 90 children with GHD were enrolled, including 45 cases each in the PEG-rhGH and rhGH groups. Changes in height, height standard deviation score (Ht SDS), annualized growth velocity, change in Ht SDS (ΔHt SDS), insulin-like growth factor-1 (IGF-1), BMI, thyroid function, fasting blood glucose, and fasting insulin were analyzed. RESULTS Linear mixed-effects model analysis revealed significant improvements in height and Ht SDS in both groups after treatment (P<0.001). No significant difference in height was observed between the two groups within the first 12 months of treatment (P>0.05). Starting from the 15th month, the rhGH group showed significantly greater height than the PEG-rhGH group, and this difference was maintained at the 21st and 24th months (P<0.05). No significant difference in Ht SDS was found between the groups (P>0.05). Regarding growth dynamics, the annualized growth velocity peaked within the first 3 months in both groups (12.44 vs. 11.96 cm/year). During the 7-9 month treatment period, the rhGH group exhibited a significantly higher annualized growth velocity than the PEG-rhGH group (P=0.034), accompanied by a greater ΔHt SDS (P=0.038). No significant intergroup differences were observed in other periods (P>0.05). BMI increased significantly after treatment in the PEG-rhGH group, showing a significant difference compared to the rhGH group at 12 months (P=0.005), which disappeared by 24 months. No significant changes were observed in T4, TSH, or insulin levels between the two groups before and after treatment (P>0.05). Although significant changes in T3 and fasting blood glucose were noted within groups, all values remained within the normal range. CONCLUSION Both PEG-rhGH and rhGH effectively promote growth in children with GHD and demonstrate comparable efficacy in Ht SDS. Daily rhGH exhibits stronger growth dynamics at 7-9 months, translating into an absolute height advantage from 15 months onward. Both medications have minimal impact on thyroid function and glucose metabolism, demonstrating good safety profiles.