Holmes S J, Shalet S M
Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK.
Clin Endocrinol (Oxf). 1995 Aug;43(2):143-9. doi: 10.1111/j.1365-2265.1995.tb01908.x.
Although the nature of the side-effects of GH replacement in adults are well described, the factors influencing their development are ill understood. The aim of this study was to determine whether there were any characteristics of adults with GH deficiency that predicted whether or not they developed side-effects of GH replacement.
A 12-month study (double blind placebo controlled for the first 6 months and open for the second 6 months) of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) in adults.
Sixty-three adults (27 men, 36 women, aged 34.9 +/- 1.4 (mean +/- SE, range 20.1-59.5 years)) with GH deficiency (peak serum GH response to provocative testing of less than 10 mU/l) who took part in a 12-month study of GH replacement. Twenty-five patients (40%) did not develop side-effects, 19 patients (30%) developed side-effects which did not necessitate a reduction in dose of GH, and 19 patients (30%) required a reduction in dose of GH because of side-effects.
The three groups of patients were compared according to age, height, weight and body mass index (BMI) at entry into the study and to pretreatment peak serum GH response to provocative testing. They were also compared according to serum concentration of insulin-like growth factor (IGF)-I and IGF binding protein-3, and age-adjusted serum IGF-I standard deviation score (SDS), at entry into the study and by change in these measurements after 6 months of GH replacement. The patient's sex, whether GH deficiency was of childhood or adult onset, estimated duration of GH deficiency, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder and previous therapeutic interventions were also compared in the three groups of patients.
Those patients who required a reduction in dose of GH because of side-effects were more likely to have a peak serum GH response of greater than 1 mU/l (P = 0.005) and to have adult onset GH deficiency (P = 0.04) than those who did not develop side-effects or who did not require a reduction in dose of GH because of side-effects. In addition, those who needed a reduction in GH dose were older (P = 0.002), heavier (P = 0.04) and had a greater BMI (P = 0.003) than those who did not develop side-effects. Those who developed side-effects but did not require a reduction in dose of GH had a greater increment in IGF-I SDS after 6 months of GH replacement than those who did not develop side-effects (P = 0.03).
Side-effects of GH replacement are more likely to occur in older patients, in those with a peak serum GH response to provocative testing of greater then 1 mU/l, in those with a greater increment in serum IGF-I SDS whilst receiving GH replacement, in those with greater weight and BMI, and those with adult onset GH deficiency.
虽然成人生长激素（GH）替代治疗的副作用性质已得到充分描述，但对其发生发展的影响因素却了解甚少。本研究的目的是确定生长激素缺乏的成年人是否存在某些特征，这些特征可以预测他们是否会出现生长激素替代治疗的副作用。
一项为期12个月的研究（前6个月为双盲安慰剂对照，后6个月为开放试验），对成年人进行生长激素替代治疗（第一个月为0.125IU/kg/周，之后为0.25IU/kg/周）。
63名生长激素缺乏的成年人（27名男性，36名女性，年龄34.9±1.4（平均±标准误，范围20.1 - 59.5岁）），其血清生长激素对激发试验的峰值反应低于10mU/l，参与了一项为期12个月的生长激素替代治疗研究。25名患者（40%）未出现副作用，19名患者（30%）出现副作用但无需减少生长激素剂量，19名患者（30%）因副作用需要减少生长激素剂量。
根据研究入组时的年龄、身高、体重和体重指数（BMI）以及治疗前血清生长激素对激发试验的峰值反应，对三组患者进行比较。还根据研究入组时以及生长激素替代治疗6个月后这些测量值的变化，比较三组患者的胰岛素样生长因子（IGF）-I和IGF结合蛋白-3的血清浓度以及年龄校正后的血清IGF-I标准差评分（SDS）。还对三组患者的性别、生长激素缺乏是儿童期还是成人期发病、估计的生长激素缺乏持续时间、是否存在其他垂体激素缺乏、潜在的病理疾病以及先前的治疗干预进行了比较。
因副作用需要减少生长激素剂量的患者，与未出现副作用或无需因副作用减少生长激素剂量的患者相比，血清生长激素峰值反应大于1mU/l的可能性更高（P = 0.005），且成人期发病的生长激素缺乏的可能性更高（P = 0.04）。此外，需要减少生长激素剂量的患者比未出现副作用的患者年龄更大（P = 0.002）、体重更重（P = 0.04）且BMI更高（P = 0.003）。出现副作用但无需减少生长激素剂量的患者，在生长激素替代治疗6个月后，其IGF-I SDS的增量比未出现副作用的患者更大（P = 0.03）。
生长激素替代治疗的副作用更可能发生在年龄较大的患者、血清生长激素对激发试验的峰值反应大于1mU/l的患者、接受生长激素替代治疗时血清IGF-I SDS增量较大的患者、体重和BMI较高的患者以及成人期发病的生长激素缺乏患者中。
