Johannsson G, Bjarnason R, Bramnert M, Carlsson L M, Degerblad M, Manhem P, Rośen T, Thorén M, Bengtsson B A
Research Center for Endocrinology and Metabolism, Sahlgrenska University Hospital,
J Clin Endocrinol Metab. 1996 Apr;81(4):1575-81. doi: 10.1210/jcem.81.4.8636370.
The aim of the present trial was to study the individual responsiveness to GH treatment in terms of body composition and to search for possible predictors of the response in GH-deficient adults. Sixty-eight patients (44 men and 24 women) with a mean age of 44.3 (1.2) yr and verified GH deficiency participated in a 2-phase treatment trial with an initial randomized, double blind, placebo-controlled, 6-month period, followed by an open treatment period, thereby ensuring all patients 12 months of GH treatment. Recombinant human GH was administered sc daily at bedtime, with a target dose of 12 micrograms/kg x day. GHBP was measured by ligand-mediated immunofunctional assay, and serum insulin-like growth factor I (IGF-I) was determined by RIA after acid-ethanol extraction, using a truncated IGF-I analog as the radioligand. Lean body mass (LBM) and body fat (BF) were determined by dual energy x-ray absorptiometry, and total body water (TBW) was determined by bioelectrical impedance. During the placebo control period, serum IGF-I,LBM, and TBW increased (P < 0.001), whereas BF decreased (P < 0.001) and serum GHBP was unchanged in the group treated with GH compared with the patients treated with placebo. After 12 months of GH treatment, the individual changes in BF ranged from -12.5 to 4.3 kg and from -4.5 to 10.1 kg in LBM. Age (P < 0.05) and baseline GHBP level (P < 0.01) were inversely correlated with the increase in LBM. The GH-induced increment in IGF-I and TBW was greater in men than in women (P < 0.01), whereas the decreases in BF were similar in men and women. This trial demonstrates the variability in responsiveness to GH administration in GH-deficient adults. The best response to GH was obtained in younger patients with low GHBP levels. Furthermore, men responded better than women.
本试验的目的是研究生长激素(GH)治疗对身体成分的个体反应性,并寻找生长激素缺乏的成年人中可能的反应预测因素。68例患者(44例男性和24例女性),平均年龄44.3(1.2)岁,经证实存在生长激素缺乏,参与了一项两阶段治疗试验,初始阶段为随机、双盲、安慰剂对照的6个月疗程,随后是开放治疗期,从而确保所有患者接受12个月的生长激素治疗。重组人生长激素于睡前皮下注射,每日一次,目标剂量为12微克/千克·天。采用配体介导免疫功能测定法测量生长激素结合蛋白(GHBP),酸乙醇提取后,使用截短的胰岛素样生长因子I(IGF-I)类似物作为放射性配体,通过放射免疫分析法(RIA)测定血清IGF-I。通过双能X线吸收法测定瘦体重(LBM)和体脂(BF),通过生物电阻抗法测定总体水(TBW)。在安慰剂对照期,与接受安慰剂治疗的患者相比,接受生长激素治疗的组中血清IGF-I、LBM和TBW升高(P<0.001),而BF降低(P<0.001),血清GHBP无变化。生长激素治疗12个月后,BF的个体变化范围为-12.5至4.3千克,LBM的个体变化范围为-4.5至10.1千克。年龄(P<0.05)和基线GHBP水平(P<0.01)与LBM的增加呈负相关。生长激素诱导的IGF-I和TBW的增加在男性中大于女性(P<0.01),而BF的减少在男性和女性中相似。本试验证明了生长激素缺乏的成年人对生长激素给药反应的变异性。在GHBP水平低的年轻患者中获得了对生长激素的最佳反应。此外,男性的反应优于女性。