最新研究发现，即使延迟至青春期给予生长激素(GH)治疗，仍可改善出生时小于胎龄的矮小儿童的成年身高。结果于8月17日在线发表于《临床内分泌和代谢杂志》(Journal of Clinical Endocrinology & Metabolism)。
来自荷兰Cutch生长研究基金会的Lem医师是本次研究的主要人员，他表示，我们的结果不会导致生长激素治疗延迟至青春期，因为儿童期和青春期身高正常有重要优势。然而，在临床实践中，当儿童在青春期出现身材矮小症时，也不能将他们排除在生长激素治疗之外。
约10%的出生时小于胎龄的儿童有持续性身材矮小症，生长激素可改善他们的生长和成年身高。但是据假设，作为骨骺成熟的方法，青春期生长激素治疗的效果有限。
Lem医师和同事在本次随机试验中纳入了121名这类儿童(年龄均≥8岁)，以比较标准生长激素剂量(1 mg/m2/天)和双倍生长激素剂量(2 mg/m2/天)。40名青春期开始时身高不足140 cm的儿童也接受了一种促性腺激素释放激素(GnRH)类似物治疗。
双倍剂量生长激素组女孩和男孩的成年身高均显著高于标准剂量生长激素组。青春期前开始生长激素治疗的儿童与青春期开始生长激素治疗的儿童的成年身高相似。
在84名于研究期达到成年身高的儿童中，中位身高从-2.9标准差评分(SDS)增至-1.7。
62%的儿童达到-2 标准差评分(SDS)以上的成年身高，70%达到目标身高范围的成年身高。身高增长范围从-0.7 至+3.3 标准差评分(SDS)。
生长激素联合或不联合其他GnRH类似物治疗可导致相似的成年身高标准差评分(SDS)，研究者指出，这表明，由于未达到成年身高预期而在青春期开始时接受其他GnRHa治疗的儿童获得的成年身高标准差评分(SDS)与不接受其他GnRHa治疗的儿童相当。”
接受双倍剂量生长激素治疗的青春期儿童的IGF-I显著高于接受标准剂量生长激素治疗的儿童。生长激素治疗总体上耐受良好，并且没有不良事件被归因于生长激素治疗。
Lem医师认为，在临床实践中，最好以标准剂量的生长激素(1 mg/m2/天)开始进行治疗，因为在此项研究中，青少年显示出用该剂量也可获得显著的身高增长。当儿童显示出追赶生长不足、青春期/骨龄快速进展或其他GnRH-a(人工合成的GnRH)治疗抑制性激素时，医师应考虑增加生长激素的剂量。
需要随访至成年期以研究生长激素治疗的极长期效果和以后成年期高IGF-I水平的可能效应。因此，Lem医师希望尽可能多地收集在此项研究中接受治疗的儿童的详细长期随访数据。”（生物谷Bioon.com）
doi:10.1210/jc.2012-1987
PMC:
PMID:
Adult Height in Short Children Born SGA Treated with Growth Hormone and Gonadotropin Releasing Hormone Analog: Results of a Randomized, Dose-Response GH Trial.
Lem AJ, van der Kaay DC, de Ridder MA, Bakker-van Waarde WM, van der Hulst FJ, Mulder JC, Noordam C, Odink RJ, Oostdijk W, Schroor EJ, Sulkers EJ, Westerlaken C, Hokken-Koelega AC.
Context:GH treatment is effective in improving height in short children born small for gestational age (SGA). GH is thought to have limited effect when started during adolescence.Objective:The aim of this study was to investigate GH treatment efficacy in short SGA children when treatment was started during adolescence; to assess whether GH 2 mg/m(2) · d during puberty improves adult height (AH) compared with 1 mg/m(2) · d; and to assess whether an additional 2-yr postponement of puberty by GnRH analog (GnRHa) improves AH in children who are short at the start of puberty (<140 cm), with a poor AH expectation.Patients and Design:In this longitudinal, randomized, dose-response GH trial, we included 121 short SGA children (60 boys) at least 8 yr of age. We performed intention-to-treat analyses on all children and uncensored case analyses on 84 children who reached AH. Besides, we evaluated growth during 2 yr of combined GH/GnRHa and subsequent GH treatment until AH in a subgroup of 40 pubertal children with a height of less than 140 cm at the start.Results:Short SGA children started treatment at a median age of 11.2 yr, when 46% had already started puberty. Median height increased from -2.9 at start to -1.7 sd score (SDS) at AH (P < 0.001). Treatment with GH 2 vs. 1 mg/m(2) · d during puberty resulted in significantly better AH (P = 0.001), also after correction for gender, age at start, height SDS at start, treatment years before puberty, and target height SDS. AH was similar in children who started puberty at less than 140 cm and received GH/GnRHa, compared with children who started puberty greater than 140 cm and received GH only (P = 0.795).Conclusion:When started in adolescence, GH treatment significantly improves AH in short SGA children, particularly with GH 2 mg/m(2) · d during puberty. When SGA children are short at the start of puberty, they can benefit from combined GH/GnRHa treatment.
