Division of Pediatric Endocrinology, Department of Pediatrics, Mattel Children's Hospital, University of California at Los Angeles, Los Angeles, CA, USA.
Pituitary. 2012 Jun;15(2):126-34. doi: 10.1007/s11102-011-0343-y.
The optimal dosing of growth hormone (GH) therapy is challenging due to high inter-individual variability in subcutaneous GH absorption and sensitivity to the drug. Optimal dosing would maximize patient gains in height, body composition, and metabolic outcomes while minimizing GH adverse events. The pulsatile secretion of GH, however, does not allow direct assessment of circulating GH levels as a measure of response to GH therapy. Insulin-like growth factor (IGF-I), a key marker of GH activity, has been shown to be useful in monitoring and adjusting GH dose during treatment of GH deficiency (GHD). Traditionally, monitoring IGF-I levels in response to GH therapy has been recommended for assessment of treatment compliance and safety. More recently, GH treatment guidelines have stated that IGF-I levels should also be used to guide GH dosing. This review examines whether individualized GH dosing based on the IGF-I response to GH therapy provides a better method for determining the GH replacement needs of pediatric and adult patients compared with conventional GH dosing, and whether IGF-I-based dosing improves outcomes such as height and body composition, with reduced side effects. Because IGF-I measurement presents its own difficulties, the current state of IGF-I assays is also discussed. The reviewed studies show that the use of GH dose adjustments based on IGF-I responses to GH therapy successfully reduces adverse events in adults with GHD and results in greater positive height attainment in children, without increasing adverse events. Long-term outcome studies are needed, as are internationally accepted guidelines for IGF-I measurement.
由于皮下 GH 吸收和对药物的敏感性存在高度个体差异，因此生长激素（GH）治疗的最佳剂量颇具挑战性。最佳剂量方案旨在使患者的身高、身体成分和代谢结果最大化获益，同时使 GH 不良反应最小化。然而，GH 的脉冲式分泌不允许直接评估循环 GH 水平作为 GH 治疗反应的衡量标准。胰岛素样生长因子（IGF-I）是 GH 活性的关键标志物，已被证明在治疗 GH 缺乏症（GHD）时监测和调整 GH 剂量有用。传统上，监测 IGF-I 水平以评估 GH 治疗的反应已被推荐用于评估治疗依从性和安全性。最近，GH 治疗指南指出，IGF-I 水平也应用于指导 GH 剂量。本综述探讨了基于 GH 治疗对 IGF-I 的反应进行个体化 GH 剂量是否为儿科和成年患者确定 GH 替代需求提供了一种优于常规 GH 剂量的更好方法，以及 IGF-I 剂量是否改善了身高和身体成分等结果，同时减少了副作用。由于 IGF-I 的测量存在自身的困难，因此还讨论了目前 IGF-I 检测方法的现状。综述研究表明，基于 GH 治疗对 IGF-I 的反应调整 GH 剂量可成功减少 GHD 成年患者的不良反应，并使儿童获得更大的身高增益，而不会增加不良反应。需要进行长期的结局研究，并制定国际认可的 IGF-I 测量指南。
