基于体重和基于胰岛素样生长因子I（IGF-I）的生长激素（GH）给药方案在生长激素缺乏症儿童治疗中的比较及外显子3缺失型生长激素受体变异体的影响
Comparison between weight-based and IGF-I-based growth hormone (GH) dosing in the treatment of children with GH deficiency and influence of exon 3 deleted GH receptor variant.
作者信息
Marchisotti Frederico Guimarães, Jorge Alexander Augusto Lima, Montenegro Luciana Ribeiro, Berger Karina, de Carvalho Luciani Renata Silveira, Mendonca Berenice Bilharinho, Arnhold Ivo Jorge Prado
机构信息
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, Avenida Dr. Enéas de Carvalho Aguiar 155, São Paulo, CEP 05403-900, Brazil.
出版信息
Growth Horm IGF Res. 2009 Apr;19(2):179-86. doi: 10.1016/j.ghir.2008.10.001. Epub 2008 Nov 25.
OBJECTIVE
Compare the most frequently used weight-based GH dosing with an IGF-I level-based strategy in the treatment of children with severe GH deficiency. Additionally, analyse the influence of the GH receptor exon 3 polymorphism on IGF-I levels during GH therapy.
DESIGN
Thirty children with GH deficiency on treatment with GH for 4.3+/-3.2 yr in a single University Hospital were divided in group W (weight-based GH dosing) and group I (IGF-I-based dosing). In group I, GH doses were changed by 8.3 microg/kg d to maintain IGF-I levels between 0 and +2 SDS, whereas in group W the dose was fixed at 30 microg/kg d in prepubertal and 50 microg/kg d in pubertal patients. Growth velocity was measured after 1 yr, IGF-I and IGFBP3 levels quarterly. GH receptor exon 3 was genotyped by PCR.
RESULTS
Most patients in Group I reached target IGF-I levels after 6 months with a GH dose ranging between 25 and 66 microg/kg d (mean+/-SD, 38+/-8). Each change of 8.3 microg/kg d of GH dose, resulted in change of 1.17+/-0.6 SDS of IGF-I levels. Mean IGF-I levels were higher in Group I 0.8+/-0.5 SDS than in Group W -0.3+/-1.9 SDS (p<0.05), but growth velocities were similar, 6.8+/-2.6 cm/yr and 6.9+/-2.6 cm/yr (p=NS), respectively. Serum IGFBP3 levels were similar in both groups and were less useful to individualize GH therapy. Even treated with a similar mean GH dose, patients carrying at least one GH receptor d3-allele reached higher IGF-I levels (0.7+/-1.2 SDS) than those homozygous for the full-length allele (-0.3+/-1.2 SDS; p<0.05), however, growth velocities were not different.
CONCLUSIONS
By adjusting the GH dose, it was feasible to maintain IGF-I in the desired range (0-+2 SDS). Patients carrying at least one GH receptor d3-allele reached higher circulating IGF-I levels than those homozygous for the full-length allele. A multiple regression analysis failed to demonstrate an independent influence of IGF-I levels on GV during the 12 months of observation.
目的
比较在治疗重度生长激素缺乏症儿童时，最常用的基于体重的生长激素给药方案与基于胰岛素样生长因子-1（IGF-I）水平的给药策略。此外，分析生长激素受体外显子3多态性对生长激素治疗期间IGF-I水平的影响。
设计
在一家大学医院中，30名接受生长激素治疗4.3±3.2年的生长激素缺乏症儿童被分为W组（基于体重的生长激素给药）和I组（基于IGF-I的给药）。在I组中，生长激素剂量每8.3μg/kg·d进行调整，以维持IGF-I水平在0至+2标准差评分（SDS）之间，而在W组中，青春期前患者的剂量固定为30μg/kg·d，青春期患者为50μg/kg·d。1年后测量生长速度，每季度测量IGF-I和IGFBP3水平。通过聚合酶链反应（PCR）对生长激素受体外显子3进行基因分型。
结果
I组中的大多数患者在6个月后达到目标IGF-I水平，生长激素剂量范围在25至66μg/kg·d之间（均值±标准差，38±8）。生长激素剂量每改变8.3μg/kg·d，IGF-I水平改变1.17±0.6 SDS。I组的平均IGF-I水平为0.8±0.5 SDS，高于W组的-0.3±1.9 SDS（p<0.05），但生长速度相似，分别为6.8±2.6 cm/年和6.9±2.6 cm/年（p=无显著性差异）。两组的血清IGFBP3水平相似，对个体化生长激素治疗的作用较小。即使接受相似的平均生长激素剂量治疗，携带至少一个生长激素受体d3等位基因的患者达到的IGF-I水平（0.7±1.2 SDS）高于全长等位基因纯合子患者（-0.3±1.2 SDS；p<0.05），然而，生长速度并无差异。
结论
通过调整生长激素剂量，将IGF-I维持在期望范围内（0至+2 SDS）是可行的。携带至少一个生长激素受体d3等位基因的患者循环IGF-I水平高于全长等位基因纯合子患者。多元回归分析未能证明在12个月的观察期内IGF-I水平对生长速度有独立影响。
Zotero 插件