Fernholm R, Bramnert M, Hägg E, Hilding A, Baylink D J, Mohan S, Thorén M
Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden.
J Clin Endocrinol Metab. 2000 Nov;85(11):4104-12. doi: 10.1210/jcem.85.11.6949.
Although a specific GH deficiency (GHD) syndrome in the adult and the response to GH replacement therapy are well recognized, there are few data available on the effect of GH replacement therapy in elderly GH-deficient patients. We studied the effect of GH therapy on body composition and bone mineral density measured by dual energy x-ray absorptiometry, markers for bone metabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in 31 patients (6 women and 25 men; aged 60-79 yr; mean, 68 yr) with multiple pituitary hormone deficiencies. The GH response to arginine or insulin was below 3 microg/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg x week for 1 month, and after that it was 0.1 IU/kg x week divided into daily sc injections (0.75-1.25 IU/day). There were no changes in any of the measured variables during placebo treatment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within normal range. Lean body mass was increased, and the increase at 6 and 12 months correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly significant, reduction of total body fat. Mean bone mineral density was not different from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal peptide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) was significantly elevated for 12 months. Side-effects were mild, mostly attributed to fluid retention. In two patients with normal glucose tolerance at the start of the study, pathological glucose tolerance occurred in one patient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body composition and an increase in markers for bone metabolism. Side-effects are few, and elderly GHD patients can be offered treatment. As long-term risks are unknown, GH doses should be titrated to keep IGF-I within the age-related physiological range.
尽管成人特定的生长激素缺乏（GHD）综合征以及对生长激素替代疗法的反应已得到充分认识，但关于生长激素替代疗法对老年生长激素缺乏患者的影响的数据却很少。我们研究了生长激素疗法对31例（6名女性和25名男性；年龄60 - 79岁；平均68岁）患有多种垂体激素缺乏症患者的身体成分、通过双能X线吸收法测量的骨矿物质密度、骨代谢标志物、胰岛素样生长因子（IGFs）以及胰岛素样生长因子结合蛋白（IGFBPs）的影响。所有受试者对精氨酸或胰岛素的生长激素反应均低于3μg/L（9mU/L）。他们被随机分为生长激素组（优猛茁，礼来公司）或安慰剂组，为期6个月，随后进行12个月的开放治疗。剂量为0.05IU/kg×周，持续1个月，之后为0.1IU/kg×周分每日皮下注射（0.75 - 1.25IU/天）。在安慰剂治疗期间，任何测量变量均无变化。生长激素治疗使大多数患者的血清IGF - I恢复正常，并使IGFBP - 3和 - 5以及IGFBP - 4和IGF - II增加至正常范围内的值。瘦体重增加，6个月和12个月时的增加与IGF - I的增加相关（r分别为0.46；P = 0.010和r = 0.54；P = 0.003）。生长激素治疗使全身脂肪适度但高度显著地减少。平均骨矿物质密度与同年龄健康受试者无差异，且在观察期内未发生变化。骨形成标志物（血清中骨特异性碱性磷酸酶活性、骨钙素和I型前胶原羧基末端肽）在正常范围内增加，且在整个研究过程中水平持续稳定。骨吸收标志物（尿中吡啶啉）在12个月内显著升高。副作用轻微，主要归因于液体潴留。在研究开始时葡萄糖耐量正常的两名患者中，一名患者出现病理性葡萄糖耐量，一名患者葡萄糖耐量受损。总之，老年GHD患者对替代疗法的反应与年轻受试者相似，身体成分得到改善，骨代谢标志物增加。副作用较少，老年GHD患者可以接受治疗。由于长期风险未知，应调整生长激素剂量以使IGF - I保持在与年龄相关的生理范围内。
