重组人生长激素对青春期前特发性矮身材儿童的生长速率、骨龄的影响及其量效-时效关系

doi:10.11852/zgetbjzz2018-1526

摘要/Abstract

摘要： 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。

关键词: 特发性矮身材, 重组人生长激素, 生长速率, 骨龄, 量效关系, 时效关系

Abstract: 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.

Key words: idiopathicshortstature, recombinanthumangrowthhormone, growthvelocity, boneage, dose-effectrelationship, time-effectrelationship

中图分类号:

R725.8

彭艳松, 邹芙蓉. 重组人生长激素对青春期前特发性矮身材儿童的生长速率、骨龄的影响及其量效-时效关系[J]. 中国儿童保健杂志, 2019, 27(11): 1228-1231.

PENG Yan-song, ZOU Fu-rong. Dose- and time-effect relationship of recombinant human growth hormone on growth velocity and bone age in preadolescent children with idiopathic short stature[J]. journal1, 2019, 27(11): 1228-1231.

参考文献

[1] 郭春艳,贺波,呼延佳,等.儿童矮身材病因及其骨龄发育情况374例分析[J].中国妇幼健康研究,2015,26(1):3-5.
[2] 郭春艳,贺波,呼延佳,等.重组人生长激素对身材矮小儿童增高疗效的相关影响因素分析[J]. 中国儿童保健杂志,2015,23(2):147-149.
[3] 李俊利,袁鹰.基因重组人生长激素治疗青春前期矮身材的效果[J].青岛大学医学院学报,2016,52(5):532-535.
[4] 张雪霜,熊丰,朱岷,等.重组人生长激素治疗不同病因矮小症患儿效果观察[J].第三军医大学学报,2016,38(16):1889-1894.
[5] 中华医学会儿科学分会内分泌遗传代谢学组.矮身材儿童诊治指南[J].中华儿科杂志,2008,46(6):428-430.
[6] Cohen P,Rogol AD,Deal CL,et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature:a summary of the Growth Hormone Research Society,the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology Workshop [J]. J Clin Endocrinol Metab,2008,93(11):4210-4217.
[7] 颜纯,王慕逖.小儿内分泌学[M].2版.北京:人民卫生出版社,2006:78-79.
[8] 叶义言.中国儿童骨龄评分法[M].北京:人民卫生出版社,2005:84-151.
[9] 沈永年,罗小平.儿科内分泌遗传代谢性疾病诊疗手册[M].上海:上海科学技术文献出版社,2010:8-9.
[10] 徐雪梅,庞军.基因重组人生长激素治疗青春期前特发性矮小症的量效和时效关系研究[J].中国药房,2015,26(17):2372-2375.
[11] 胡玉娟,董文科,王伟,等.不同剂量重组人生长激素治疗特发性矮小症的疗效观察[J]. 第三军医大学学报,2014,36(16):1734-1737.
[12] Bang P,Bjerknes R,Dahlgren J,et al.Acomparison of different definitions of growth response in short prepubertal children treated with growth hormone[J]. Horm Res Paediatr,2011,75(5):335-345.
[13] van-Gool SA,Kamp GA,Odink RJ,et al.High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height[J]. Eur J Endocrinol,2010,162(4):653-660.
[14] 张本金,吕有道,邓春晖.不同剂量重组人生长激素治疗青春期前ISS患者的临床疗效分析[J].重庆医学,2016,45(6):813-815.
[15] 桂林艳,王璞.青春期前特发性矮身材儿童的生长激素应用剂量研究[J].中国儿童保健杂志,2018,26(4):451-452.
[16] Society GHR.Consensus guidelines for the diagnosis and treatment of growth hormone(GH ) deficiency in childhood and adoleseence:summary statement of the G H research society[J].J Clin Endocrinol Metab,2010,85(7):3990-3993.
[17] 薛颖,高怡青,王淑琴,等.不同剂量基因重组人生长激素治疗儿童生长激素缺乏症线性生长随访及代谢变化[J].中国妇幼保健,2014,29(22):3605-3608.
[18] 任巧,任娟娟,王晓静.重组人生长激素治疗矮身材青春期早发育患儿的近期疗效及安全性[J]. 安徽医学,2018,39(1):108-110.
[19] Curtò L,Giovinazzo S,Alibrandi A,et al.Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults:a retrospective cohort study [J]. Eur J Endocrinol,2015,172(5):543-552.