Duck S C, Schwarz H P, Costin G, Rapaport R, Arslanian S, Hayek A, Connors M, Jaramillo J
Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226.
J Clin Endocrinol Metab. 1992 Oct;75(4):1115-20. doi: 10.1210/jcem.75.4.1400880.
The purpose of this study was to determine the efficacy and safety of GH-releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty previously untreated prepubertal children with GHRH deficiency were treated for 1 yr in a multicenter, open label, company-sponsored study with at least 20 micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main effects were enhancement of linear growth, advancement in bone age, and alteration in general blood chemistries and hormonal values. The mean velocity of the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at 1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/- 2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for the second 6 months. The high dose group increased their mean linear growth velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/- 1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year of therapy. No adverse changes in general biochemical, hormonal, or pituitary radiographic analyses were noted. No change in fasting glucose or insulin concentrations, or excessive generation of insulin-like growth factor-I concentrations occurred. We conclude that GHRH in a daily dose of 20-40 micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH-responsive GH-deficient patients. It was well tolerated without side-effects. Glucose intolerance was not noted.
本研究的目的是确定生长激素释放激素[GHRH-(1-44)]疗法对生长激素缺乏儿童的疗效和安全性。在一项多中心、开放标签、由公司资助的研究中，20名先前未经治疗的青春期前生长激素释放激素缺乏儿童接受了为期1年的治疗，皮下注射至少20微克/千克GHRH-(1-44)，一半在睡前注射，一半在醒来时注射。主要效果包括线性生长增强、骨龄进展以及一般血液化学和激素值的改变。治疗1年后，整个组的平均生长速度从3.6±1.1厘米/年增加到8.1±1.5厘米/年（P<10⁻⁴）。治疗6个月后，16名儿童的平均生长速度为9.4±2.0厘米/年，并继续使用该剂量。4名生长速度为5.5±1.7厘米/年的患者，在第二个6个月将剂量增加至每日40微克/千克。高剂量组在使用较高剂量的第二个6个月期间，平均线性生长速度增加至7.6±0.4厘米/年（P<10⁻²）。这与继续每日接受20微克/千克治疗的16名受试者在治疗第二个6个月的平均速度（7.6±1.2厘米/年）相等。治疗第一年骨龄的平均进展为1.3±0.6岁。在一般生化、激素或垂体影像学分析中未发现不良变化。空腹血糖或胰岛素浓度没有变化，也没有出现胰岛素样生长因子-I浓度过度生成的情况。我们得出结论，每日剂量为20-40微克/千克的GHRH治疗1年，对大多数生长激素释放激素反应性生长激素缺乏患者增加生长速度有效。耐受性良好，无副作用。未发现葡萄糖不耐受情况。
