生长激素治疗特发性矮小儿童随访至接近成年终身高的治疗效果分析

doi:10.3969/j.issn.1006-7795.2018.01.017

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (1): 92-97.doi: 10.3969/j.issn.1006-7795.2018.01.017

生长激素治疗特发性矮小儿童随访至接近成年终身高的治疗效果分析

吴迪¹, 冯国双², 巩纯秀¹

1. 首都医科大学附属北京儿童医院内分泌遗传代谢科国家儿童医学中心, 北京 100045;
2. 首都医科大学附属北京儿童医院临床流行病与循证医学中心国家儿童医学中心, 北京 100045

收稿日期:2017-06-02 出版日期:2018-01-21 发布日期:2018-01-27
通讯作者: 巩纯秀 E-mail:chunxiugong@sina.com
基金资助:
国家自然科学基金（81670713）。

Analysis of effect of growth hormone treatment on idiopathic short status children to near-adult height

Wu Di¹, Feng Guoshuang², Gong Chunxiu¹

1. Department of Endocrine Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China;
2. Center for Clinical Epidemiology and Evidence Based Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China

Received:2017-06-02 Online:2018-01-21 Published:2018-01-27
Supported by:
This study was supported by National Natural Science Foundation of China(81670713).

摘要/Abstract

摘要： 目的评价用生长激素治疗的特发性矮小（idiopathic short status，ISS）年长儿随访至接近成年终身高的治疗效果，并分析相关影响因素。方法随访曾予生长激素治疗、目前已停药并达接近成年终身高的ISS患者。主要评价指标为接近成年终身高标准差积分（near-adult height standard deviation scores，NAHtSDS）与遗传靶身高（target height，TH），也叫父母中位身高（mid-parent height，MPH），标准差积分（standard deviation scores，SDS）的差值，即△HtSDS，并分析相关影响因素。结果生长激素治疗初始HtSDS男女分别为-3.31，-2.86。接近成年终身高HtSDS分别为-1.98，-1.39。男女患儿接近成年终身高SDS与用药初始SDS相比，差异有统计学意义（P=0.000）。以遗传靶身高HtSDS为标准，采用非劣效检验分析接近成年终身高与遗传靶身高接近程度，提示ISS男性患儿接近成年终身高低于遗传靶身高，女性患儿接近成年终身高不劣于遗传靶身高。55.7%（59/106例）ISS男性患儿、71.4%（50/70例）ISS女性患儿其接近成年终身高HtSDS>-2 SD，即达到正常、非矮小身高。这部分人群，男性患儿和女性患儿在<1年和 ≥ 1年的疗程内，其接近成年终身高与遗传靶身高HtSDS相比，均具有非劣效性。采用多重线性回归，以△HtSDS为因变量，分析性别、用药初始年龄、用药初始HtSDS、用药初始骨龄、疗程对△HtSDS的影响。性别、用药初始HtSDS、疗程对△HtSDS的影响差异有统计学意义（P值分别为0.005，0.000，0.027）。结论本研究ISS年长儿，应用生长激素治疗，大部分可达到正常人群身高。女性患儿、用药初始HtSDS高、长疗程，有助于其达到或接近遗传靶身高。

关键词: 特发性矮小, 生长激素, 接近成年终身高, 遗传靶身高, 身高标准差积分

Abstract: Objective To evaluate the effects of growth hormone(GH) treatment in idiopathic short status (ISS) children with baseline height ≤ -2 SD on near-adult height(NAH) outcomes.Methods ISS children were included in the current analyses if they had a baseline height ≤ -2 SD and were treated by GH and had been discontinued and attained adult height or NAH. The main outcome measures included near-adult height(NAH)standard deviation scores-target HtSDS in response to GH treatment(△HtSDS=NAHtSDS-T HtSDS), and analysis of correlation with △HtSDS.Results A total of 176 cases of ISS into the group, 106 males and 70 females. Mean chronological age at baseline of male and female were (12.9±2.12)years and (12.1±1.72)years, bone age were (9.5 ±2.53) years and (10.1 ±2.16) years, respectively. The current average ages were 16.74 years and 16.56 years. The follow-up period was 0.27-8.80 years. Mean HtSDS baseline to NAH male:-3.31 to -1.98 and female:-2.86 to -1.39. There were significant difference between baseline to NAH of HtSDS, both male and female were P=0.000. Analysis of non-inferiority test showed that male NAHtSDS were shorter than target HtSDS, while female were not shorter than target HtSDS. Percentages of patients reaching near-adult height>-2SD were male55.7% (59/106),female 71.4% (50/70). Baseline HtSDS, sex and duration of treatment were significantly correlated with △ HtSDS, P values were 0.005, 0.000, 0.027, when analyzed by multiple linear regression.Conclusion Despite a relatively advanced children age, the majority of GH-treated patients in this study attained mean near-adult HtSDS within the normal range(HtSDS>-2SD). Female, higher baseline HtSDS, longer duration of GH treatment would likely have resulted in greater adult height achieved in ISS children.

Key words: idiopathic short status (ISS), growth hormone (GH), near-adult height (NAH), target height (TH), height standard deviation scores (HtSDS)

中图分类号:

R725.8

吴迪, 冯国双, 巩纯秀. 生长激素治疗特发性矮小儿童随访至接近成年终身高的治疗效果分析[J]. 首都医科大学学报, 2018, 39(1): 92-97.

Wu Di, Feng Guoshuang, Gong Chunxiu. Analysis of effect of growth hormone treatment on idiopathic short status children to near-adult height[J]. Journal of Capital Medical University, 2018, 39(1): 92-97.

参考文献

[1] Cohen L E. Idiopathic short stature:a clinical review[J]. JAMA,2014,311(17):1787-1796.
[2] Sotos J F, Tokar N J. Growth hormone significantly increases the adult height of children with idiopathic short stature:comparison of subgroups and benefit[J]. Int J Pediatr Endocrinol, 2014, 2014(1):15.
[3] Rothenbuhler A, Linglart A, Bougnères P. A randomized pilot trial of growth hormone with anastrozole versus growth hormone alone, starting at the very end of puberty in adolescents with idiopathic short stature[J]. Int J Pediatr Endocrinol,2015,2015(1):4.
[4] Kelnar C J. Growth hormone for short children-whom should we be treating and why?[J]. J R Coll Physicians Edinb,2012,42(1):32-33.
[5] Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short status:systematic review[J]. BMJ,2011,342:c7157.
[6] Straetemans S, De Schepper J, Thomas M, et al. Validation of prediction models for near adult height in children with idiopathic growth hormone deficiency treated with growth hormone:A Belgian Registry Study[J].Horm Res Paediatr,2016,86(3):161-168.
[7] Ross J L, Lee PA Gut R, Germak J. Increased height standard deviation scores in response to growth hormone therapy to near-adult height in older children with delayed skeletal maturation:results from the ANSWER Program[J].Int J Pediatr Endocrinol,2015,2015(1):1.
[8] 中华医学会儿科分会内分泌遗传代谢学组. 矮身材儿童指南[J]. 中华儿科杂志, 2008,46(6):428-430.
[9] Wit J M, Clayton P E, Rogol A D, et al. Idiopathic short stature:definition, epidemiology, and diagnostic evaluation[J]. Growth Horm IGF Res,2008,18(2):89-110.
[10] Schena L, Meazza C, Pagani S,et al. Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children[J].J Pediatr Endocrinol Metab, 2017,30(2):197-201.
[11] Ross J L, Lee P A, Gut R, et al. Attaining genetic height potential:analysis of height outcomes from the ANSWER program in children treated with growth hormone over 5 years[J]. Growth Horm IGF Res,2015,25(6):286-293.
[12] Rothenbuhler A, Ormières B, Kalifa G, et al. A pilot study of growth hormone administration in boys with predicted adult short stature and near-ending growth[J].Growth Horm IGF Res, 2015,25(2):96-102.
[13] Coutant R, Rouleaus S, Despert F, et al. Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature:the influence of pituitary magnetic resonance imaging findings[J]. J Clin Endocrinol Metab,2001,86(10):4649-4654.
[14] Leschek E W, Rose S R, Yanovski J A, et al. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature:a randomized, double-blind, placebo-controlled trial[J]. J Clin Endocrinol Metab,2004,89(7):3140-3148.
[15] Cohen P, Bright G M, Rogol A D, et al. Effects of dose and gender on the growth and growth factor response to GH in GH-deficient children:implications for efficacy and safety[J]. J Clin Endocrinol Metab,2002,87(1):90-98.
[16] Rose S R, Shulman D I, Larsson P, et al. Gender does not influence prepubertal growth velocity during standard growyh hormone therapy-analysis of United States KIGS data[J]. J Pediatr Endocrinol Metab,2005,18(11):1045-1051.
[17] Savendahl L, Blankenstein O, Oliver I, et al. Gender influences short-term growth hormone treatment response in children[J]. Horm Res Paediatr,2012,77(3):188-194.

生长激素治疗特发性矮小儿童随访至接近成年终身高的治疗效果分析

Analysis of effect of growth hormone treatment on idiopathic short status children to near-adult height

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价

[1]	胡旭昀, 吴迪, 李孟婷, 陈佳佳, 李晓侨, 苏畅, 陈少科, 沈亦平, 巩纯秀. 身材矮小合并短指(趾)畸形3例家系的基因突变与表型分析并文献复习[J]. 首都医科大学学报, 2018, 39(6): 937-944.
[2]	毕智勇;贾旺;贾桂军. 垂体生长激素腺瘤经蝶入路手术预后因素分析[J]. 首都医科大学学报, 2011, 32(5): 688-691.
[3]	贾旺;贾桂军;钱柯;毕智勇;倪明. 青春期生长激素腺瘤的显微外科治疗[J]. 首都医科大学学报, 2010, 31(6): 808-811.
[4]	周华;许媛;何伟. 重症病人甲状腺功能状态及其相关激素改变[J]. 首都医科大学学报, 2007, 28(5): 587-591.
[5]	李群;王捷;徐秀英;李继红. 60例肢端肥大症患者心脏结构和功能改变[J]. 首都医科大学学报, 2006, 27(2): 214-217.
[6]	文煜冰;刘惠兰;黄丽荣;姚英. 重组人类生长激素改善蛋白质营养不良机制的研究[J]. 首都医科大学学报, 2005, 26(4): 467-470.
[7]	熊峰;宁惠娟;金瑞;徐健;谢贤春;吉中和;郎振为;段钟平. 重组人生长激素对急性肝坏死小鼠肝脏的组织学影响[J]. 首都医科大学学报, 2005, 26(2): 175-178.
[8]	华琦;王育琴;王力红;王拥军. 儿童期单纯肥胖症内分泌系统的变化及临床意义[J]. 首都医科大学学报, 1998, 19(1): 34-36.
[9]	王蓬文;杨佩荪;刘国贞;汪红焱. 谷氨酸单钠对大鼠垂体生长激素细胞发育的影响[J]. 首都医科大学学报, 1997, 18(3): 214-217.
[10]	郭春远;刘传弟;盛树力;高林;陈雁江;刘延津;胡晓愚. 生长激素释放多肽通过与生长激素释放因子不同的受体起作用[J]. 首都医科大学学报, 1990, 11(4): 289-294.