Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity
Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity
复制标题
DOI：
10.1210/jc.2006-1610
复制
发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Underwood, Louis E.
中科院分区：
文献类型：
--
作者：
Chernausek, Steven D.;Backeljauw, Philippe F.;Underwood, Louis E.
内容：由于先天性或后天性GH作用缺陷而导致IGF-I严重缺乏的儿童身材矮小，不能通过GH治疗来纠正。目的：本研究的目的是检查重组人IGF-I（rhIGF-I）治疗严重IGF-I缺乏的矮小儿童的长期疗效和安全性。设计：76例因GH不敏感性导致IGF-I缺乏的儿童在主要开放标签设计下接受rhIGF-I治疗长达12年。这项研究是在一般临床研究中心进行的，并与内分泌学家合作。年龄大于2岁，身高和循环IGF-I浓度的SD评分小于年龄和性别的-2，以及GH抵抗的证据。干预：rhIGF-I以60 - 120 μ g/kg的剂量皮下给药，每日两次。主要结果测量：测量身高增长速度、骨骼成熟和不良事件。身高增速从基线时的平均2.8 cm/年增加到治疗第一年的8.0 cm/年（P < 0.0001），并取决于给药剂量。随后几年的身高速度较低，但在长达8年的时间里保持在基线以上。最常见的不良事件是低血糖症，在治疗前和治疗期间均观察到。49%的治疗受试者报告了该事件。下一个最常见的不良事件是注射部位脂肪肥大（32%）和扁桃体/腺样体肥大（22%）。结论：治疗rhIGF-I刺激线性生长的儿童严重IGF-I缺乏由于GH不敏感。不良事件很常见，但很少严重到足以中断或改变治疗。
Context: Children with severe IGF-I deficiency due to congenital or acquired defects in GH action have short stature that cannot be remedied by GH treatment.Objectives: The objective of the study was to examine the long-term efficacy and safety of recombinant human IGF-I (rhIGF-I) therapy for short children with severe IGF-I deficiency.Design: Seventy-six children with IGF-I deficiency due to GH insensitivity were treated with rhIGF-I for up to 12 yr under a predominantly open-label design.Setting: The study was conducted at general clinical research centers and with collaborating endocrinologists.Subjects: Entry criteria included: age older than 2 yr, SD scores for height and circulating IGF-I concentration less than -2 for age and sex, and evidence of resistance to GH.Intervention: rhIGF-I was administered sc in doses between 60 and 120 mu g/kg twice daily.Main Outcome Measures: Height velocity, skeletal maturation, and adverse events were measured.Results: Height velocity increased from 2.8 cm/yr on average at baseline to 8.0 cm/yr during the first year of treatment (P < 0.0001) and was dependent on the dose administered. Height velocities were lower during subsequent years but remained above baseline for up to 8 yr. The most common adverse event was hypoglycemia, which was observed both before and during therapy. It was reported by 49% of treated subjects. The next most common adverse events were injection site lipohypertrophy (32%) and tonsillar/adenoidal hypertrophy (22%).Conclusions: Treatment with rhIGF-I stimulates linear growth in children with severe IGF-I deficiency due to GH insensitivity. Adverse events are common but are rarely of sufficient severity to interrupt or modify treatment.