Variable Degree of Growth Hormone (GH) and Insulin-Like Growth Factor (IGF) Sensitivity in Children with Idiopathic Short Stature Compared with GH-Deficient Patients: Evidence from an IGF-Based Dosing Study of Short Children
Variable Degree of Growth Hormone (GH) and Insulin-Like Growth Factor (IGF) Sensitivity in Children with Idiopathic Short Stature Compared with GH-Deficient Patients: Evidence from an IGF-Based Dosing Study of Short Children
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DOI：
10.1210/jc.2009-2139
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发表时间：
2010-05-01
影响因子：
5.8
通讯作者：
Rosenfeld, Ron G.
中科院分区：
文献类型：
--
作者：
Cohen, Pinchas;Germak, John;Rosenfeld, Ron G.
内容：我们最近发现，在基于IGF的GH治疗中，选择的IGF-I目标影响GH剂量需求，更高的IGF-I目标与更稳健的生长参数相关。目的：本研究的目的是比较GH缺乏（GHD）与特发性身材矮小（ISS）儿童对基于IGF的GH治疗的反应。设计：这是一项为期2年的开放标签随机试验。设置：患者：青春期前矮小儿童[身高SD评分（SDS）< -2]，IGF-I水平低（≤ 7 ng/ml）。干预：患者以2：2：1的比例随机分为三个治疗组：IGF-I目标为0 SDS（IGF 0 T）、2 SDS（IGF 2 T）或常规的基于体重的GH剂量为40 μ g/kg。结果：ISS受试者需要的GH剂量高于IGF 2 T组（而非IGF 0 T组）GHD患者（中位数为119和65 μ g/kg）。d），表明ISS代表在用较高剂量的GH治疗期间表现的部分GH不敏感状态。尽管IGF-I水平相似，但在两个IGF靶向剂量组中，GHD儿童的生长速度均高于ISS儿童（表明ISS受试者中存在一定程度的IGF不敏感性）：IGF 2 T中GHD组的Δ身高SDS为2.04 +/- 0.17，ISS组为1.33 +/- 0.09，GHD儿童为1.41 +/- 0.13，IGF 0 T组ISS组为0.84 ± 0.07。结论：以IGF为基础的GH给药在GHD和ISS患者中均具有临床可行性，但GHD和ISS患者的GH剂量需求和生长发育结局不同。这表明ISS受试者存在一定程度的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。（临床内分泌代谢杂志95：2089-2098，2010）
Context: 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.Objective: 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.Design: This was a 2-yr, open-label, randomized trial.Setting: The setting was multicenter and outpatient.Patients: Prepubertal short children [height SD score (SDS) < -2] with low IGF-I levels (= 7 ng/ml).Interventions: 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 mu g/kg . d (Conv).Main Outcome Measures: Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured.Results: ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 mu g/kg . 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.Conclusion: 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. (J Clin Endocrinol Metab 95: 2089-2098, 2010)