Pediatric Endocrinology, Mattel Children's Hospital at University of California, Los Angeles, 10833 Le Conte Avenue, MDCC 22-315, Los Angeles, California 90095, USA.
J Clin Endocrinol Metab. 2010 May;95(5):2089-98. doi: 10.1210/jc.2009-2139. Epub 2010 Mar 5.
We recently showed that, in IGF-based GH therapy, the IGF-I target chosen affects GH dose requirements, and higher IGF-I targets are associated with more robust growth parameters.
The objective of the study was to compare the response of GH-deficient (GHD) vs. idiopathic short-stature (ISS) children to IGF-based GH therapy.
This was a 2-yr, open-label, randomized trial.
The setting was multicenter and outpatient.
Prepubertal short children [height sd score (SDS) < -2] with low IGF-I levels (<or=-1 SDS), subclassified based on the peak stimulated serum GH concentration at baseline, into two subgroups: GHD (n = 63, GH < 7 ng/ml) and ISS (n = 102, GH >or= 7 ng/ml).
Patients were randomized 2:2:1 to three treatment groups: IGF-I target of 0 SDS (IGF0T), 2 SDS (IGF2T), or a conventional weight-based GH dosing of 40 microg/kg x d (Conv).
Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured.
ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 microg/kg x d, respectively), indicating that ISS represents a partial GH-insensitive state that manifests during treatment with higher doses of GH. GHD children grew more than those with ISS in both IGF-targeted dosage groups despite similar IGF-I levels (suggesting a degree of IGF insensitivity in ISS subjects): Delta height SDS of 2.04 +/- 0.17 for GHD and 1.33 +/- 0.09 for ISS groups in IGF2T, 1.41 +/- 0.13 for children with GHD, and 0.84 +/- 0.07 for those with ISS in IGF0T.
IGF-based GH dosing is clinically feasible in both GHD and ISS patients, although GH dose requirements and auxological outcomes are distinct between these groups. This suggests a degree of both GH and IGF insensitivity in subjects with ISS that requires specific management strategies to optimize growth during GH therapy.
我们最近表明，在基于 IGF 的 GH 治疗中，所选的 IGF-I 靶标会影响 GH 剂量需求，而较高的 IGF-I 靶标与更显著的生长参数相关。
本研究的目的是比较生长激素缺乏症（GHD）和特发性身材矮小（ISS）儿童对基于 IGF 的 GH 治疗的反应。
这是一项为期 2 年、开放标签、随机试验。
该试验为多中心、门诊设置。
青春期前矮小儿童（身高标准差评分 [SDS] < -2），IGF-I 水平低（< -1 SDS），根据基线时最高刺激血清 GH 浓度进行分类，分为两个亚组：GHD（n = 63，GH < 7 ng/ml）和 ISS（n = 102，GH >or= 7 ng/ml）。
患者随机分为 2:2:1 三组治疗组：IGF-I 目标为 0 SDS（IGF0T）、2 SDS（IGF2T）或常规体重基础 GH 剂量 40 microg/kg x d（Conv）。
身高 SDS、IGF-I SDS 和 GH 剂量的变化。
在 IGF2T 组（而非 IGF0T 组），ISS 患者需要的 GH 剂量高于 GHD 患者（中位数分别为 119 和 65 microg/kg x d），表明 ISS 代表 GH 不敏感的部分状态，在较高剂量 GH 治疗期间表现出来。在两种 IGF 靶向剂量组中，GHD 患儿的生长速度均高于 ISS 患儿，尽管 IGF-I 水平相似（表明 ISS 患者存在一定程度的 IGF 不敏感性）：IGF2T 组 GHD 患儿的身高 SDS 变化为 2.04 +/- 0.17，ISS 组为 1.33 +/- 0.09；IGF0T 组 GHD 患儿为 1.41 +/- 0.13，ISS 患儿为 0.84 +/- 0.07。
基于 IGF 的 GH 给药在 GHD 和 ISS 患者中均具有临床可行性，尽管两组的 GH 剂量需求和生长参数结果不同。这表明 ISS 患者存在一定程度的 GH 和 IGF 不敏感性，需要特定的管理策略来优化 GH 治疗期间的生长。
