Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.
Side effects resulting from the use of growth hormone and insulin-like growth factor-I as combined therapy to frail elderly patients.
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DOI：
10.1093/gerona/53a.3.m183
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发表时间：
1998-05
期刊：
影响因子：
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通讯作者：
D. Sullivan;W. Carter;W. R. Warr;L. H. Williams
中科院分区：
文献类型：
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作者：
D. Sullivan;W. Carter;W. R. Warr;L. H. Williams
背景：本研究旨在探讨血清胰岛素样生长因子-I(IGF-I)浓度与重组人生长激素(RhGH)和重组人胰岛素样生长因子-I(rhIGF-I)治疗副作用发生率的关系。方法13例高危、营养不良的老年男性开始皮下注射重组人生长激素和重组人胰岛素样生长因子-I，疗程15天。重组人生长激素的剂量保持在0.0125毫克/公斤/天，而重组人胰岛素样生长因子-I的剂量从10微克/公斤逐步增加到目标剂量40微克/公斤，每天两次。结果9名受试者完成了方案，达到了两种激素的全部目标剂量。液体滞留、男性乳房发育症和立位性低血压是最常见的并发症。激素注射使血清胰岛素样生长因子-I(从72.7±40.9升至483.7±251.4 g/ml，p=.001)和胰岛素样生长因子结合蛋白-3(从1.82±0.66增至2.72±1.18 mg/L，p=.012)升高，血清白蛋白(从34.3±/-5.5降至31.4+/-4.6g/L，p=.009)降低。最初血清IGF-I浓度升高的幅度是严重直立性低血压、弥漫性肌痛和药物性肝炎的重要危险因素。血清IGF-I浓度与液体滞留或女性乳房发育症之间没有关联。结论应用指定剂量的合成代谢药物rhGH和rhIGF-I治疗营养不良的老年衰弱患者，可能会出现液体滞留、乳房发育和立位性低血压等不良反应。尽管这些药物具有治疗前景，但在这一高危人群中必须谨慎使用。
BACKGROUND The objective of this study was to examine the relationship between serum IGF-I concentration and the incidence of side effects of therapy with recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor-I (rhIGF-I). METHODS Thirteen high-risk, undernourished elderly males were started on a 15-day course of rhGH and rhIGF-I by subcutaneous injection. The dose of rhGH was held constant at .0125 mg/kg/day, whereas the dose of rhIGF-I was increased in a stepwise fashion from 10 micrograms/kg to the targeted dose of 40 micrograms/kg twice a day. RESULTS Nine subjects completed the protocol and reached the full target dose of both hormones. Fluid retention, gynecomastia, and orthostatic hypotension were the most common complications. The hormone injections increased the serum concentration of IGF-I (from 72.7 +/- 40.9 to 483.7 +/- 251.4 eta g/ml, p = .001) and IGFBP-3 (from 1.82 +/- 0.66 to 2.72 +/- 1.18 mg/L, p = .012), and decreased serum albumin (from 34.3 +/- 5.5 to 31.4 +/- 4.6 g/L, p = .009). The magnitude of the initial increase in the serum IGF-I concentration was a powerful risk factor for severe orthostatic hypotension, diffuse myalgias, and drug-induced hepatitis. There was no association between the serum IGF-I concentration and fluid retention or gynecomastia. CONCLUSIONS Treatment of the undernourished frail elderly with the anabolic agents rhGH and rhIGF-I at the specified dosages may produce undesirable side effects including fluid retention, gynecomastia, and orthostatic hypotension. Although these agents hold therapeutic promise, they must be used with caution in this high-risk population.