Chanoine J P, Vanderschueren-Lodeweyckx M, Maes M, Thiry-Counson G, Craen M, Van Vliet G
Department of Pediatrics, Universities of Brussels, Belgium.
J Clin Endocrinol Metab. 1991 Dec;73(6):1269-75. doi: 10.1210/jcem-73-6-1269.
Forty prepubertal subjects (25 boys and 15 girls) with idiopathic short stature, aged 3.8-14.6 yr, were randomly allocated to receive sc injections of recombinant human GH (hGH) 6 days/week at a dose of 3 IU (1.25 mg)/m2.day either in the morning or in the evening. After 6 months of therapy, each subject was switched over to the other schedule of injection. After 12 months, treatment was stopped, and the subjects were followed for 6 months. For the whole group, regardless of the time of injection, height velocity (centimeters per yr) was 4.3 +/- 0.9 before hGH treatment, 8.3 +/- 1.9 during the first 6 months of treatment, and 6.9 +/- 1.6 during the last 6 months of treatment. Thirty-three of 38 subjects (87%) who completed 12 months of therapy presented an increase in height velocity greater than 2 cm/yr. Two patients (5%) developed antibodies to hGH and were among the nonresponders. There was no significant difference in growth response according to the schedule of injections. GH-releasing hormone (GHRH) testing was performed before and after 6 and 12 months of hGH therapy. When the last hGH injection was performed 12 h before the GHRH test, there was a 36% decrease in the maximum GH response (P less than 0.01) and a 33% decrease (P less than 0.01) in the GH secretory area compared to those before therapy. When the last hGH injection was performed 24 h or more before the GHRH test, no significant differences were observed. Insulin-like growth factor-I levels were not significantly different when measured 12 or 24 h after hGH. During the 6 months after discontinuation of hGH therapy, catch-down growth was observed in 44% of the subjects. We conclude that the schedule of injection does not influence the growth response, which wanes after 6 months; this waning effect is not related to declining insulin-like growth factor-I levels or GH autofeedback, suggesting a peripheral mechanism. Likewise, the catch-down phenomenon after hGH is discontinued is not related to a persistent diminution of pituitary responsiveness to GHRH.
40名患有特发性身材矮小的青春期前受试者（25名男孩和15名女孩），年龄在3.8至14.6岁之间，被随机分配接受重组人生长激素（hGH）的皮下注射，每周6天，剂量为3 IU（1.25 mg）/m²·天，分别在早晨或晚上注射。治疗6个月后，每个受试者转换为另一种注射时间表。12个月后，停止治疗，并对受试者随访6个月。对于整个组，无论注射时间如何，hGH治疗前身高增长速度（厘米/年）为4.3±0.9，治疗的前6个月为8.3±1.9，治疗的后6个月为6.9±1.6。完成12个月治疗的38名受试者中有33名（87%）身高增长速度增加超过2厘米/年。两名患者（5%）产生了hGH抗体，且属于无反应者。根据注射时间表，生长反应无显著差异。在hGH治疗6个月和12个月前后进行了生长激素释放激素（GHRH）测试。当在GHRH测试前12小时进行最后一次hGH注射时，与治疗前相比，最大GH反应降低了36%（P<0.01），GH分泌面积降低了33%（P<0.01）。当在GHRH测试前24小时或更长时间进行最后一次hGH注射时，未观察到显著差异。hGH注射后12小时或24小时测量时，胰岛素样生长因子-I水平无显著差异。在停止hGH治疗后的6个月内，44%的受试者出现了追赶生长。我们得出结论，注射时间表不影响生长反应，生长反应在6个月后减弱；这种减弱效应与胰岛素样生长因子-I水平下降或GH自身反馈无关，提示存在外周机制。同样，hGH停用后的追赶现象与垂体对GHRH反应性的持续降低无关。
