重组人生长激素治疗特发性矮小12个月疗效评估

目的 分析重组人生长激素(rhGH)对特发性矮小（ISS）患儿的治疗效果和影响因素，为寻求优化治疗效果的途径提供参考依据。 方法 回顾性分析2003年2月至2011年7月在首都儿科研究所生长发育门诊确诊为ISS患儿的临床资料，依据是否予rhGH治疗分为rhGH组和对照组。以身高标准差变化（ΔHtSDS）和生长速度（GV）作为评估指标进行疗效和影响因素分析。分析治疗期间骨龄、身高年龄及胰岛素样生长因子(IGF-1)水平的变化。 结果 rhGH组35例，对照组33例进入分析。①rhGH组治疗前、治疗后12个月HtSDS呈增长趋势(P<0.05)；对照组均未见升高趋势。治疗后0～3个月的ΔHtSDS水平为(0.22±0.13)，治疗后~6、~9和~12个月分别为(0.20±0.10)、(0.12±0.14)和(0.14±0.15)，呈降低趋势，但差异无统计学意义。治疗后0～3个月GV为(10.78±2.70) cm·year-1，治疗后~6、~9和~12个月分别为(10.52±2.44)、(8.31±2.78)和(8.50±2.29) cm·year-1，呈降低趋势，但差异无统计学意义。治疗后0~6个月ΔHtSDS和GV水平均显著高于～12个月［ΔHtSDS :(0.43±0.20) vs (0.27±0.24), GV: (10.48±2.17) vs (8.48±2.39) cm·year-1］。②治疗后12个月的ΔHtSDS水平与治疗开始时的年龄呈负相关，与治疗后0～3个月的ΔHtSDS呈正相关；治疗后12个月的GV水平与治疗前的GH峰值和治疗后3个月的GV水平呈负相关。③治疗后1年青春期前、青春早中期和青春后期ΔHtSDS差异总体上有统计学意义（P=0.016），其中青春期前显著高于青春早中期和青春后期；GV差异无统计学意义。④rhGH组治疗后12个月的骨龄变化差异无统计学意义，身高年龄显著高于对照组。⑤rhGH组IGF-1水平在治疗后1个月升高较明显，之后升高趋势减缓。 结论 rhGH用于ISS患儿的治疗应尽量选择青春期前；治疗后3个月的效果可作为第1年治疗效果的预测因素；rhGH治疗不会使ISS患儿骨龄明显提前。

Effect of recombinant human growth hormone therapy on idiopathic short stature patients: 12 months follow-up

Objective To analyze the effect of GH therapy on idiopathic short stature (ISS) patients and the influential factors. Methods Patients who accepted rhGH therapy and regularly revisited were chosen as rhGH group, and patients who didn′t accept rhGH therapy as control group. Growth velocity (GV) and increment in height SDS (ΔHtSDS) were used as outcome variables of growth responses to rhGH therapy. Then the effect and influential factors or the changes on those untreated such as bone age, height age were retrospectively analyzed during the follow-up. Results Thirty-five patients were recruited in rhGH group and 33 patients in control group. The ΔHtSDS and GV of patients in rhGH group during the first 3 months, -6 months, -9 months, -12 months were (0.22±0.13), (0.20±0.10), (0.12±0.14), (0.14±0.15) and (10.78±2.70) cm, (10.52±2.44)cm, (8.31±2.78)cm, (8.50±2.29) cm respectively. The height increments in the first 6 months and 6-12 months were 5.24 cm (0.43 SDS) and 4.24 cm (0.26 SDS), it was 9.54 cm (0.68 SDS) in the first year and 7.00 cm (0.17 SDS) in the second year. According to the simple correlation analysis, it was found that ΔHtSDS in the first year was negatively correlated with patients′ age and positively correlated with ΔHtSDS in 3 months after treatment, GV levels in first year were negatively correlated with the peak of GH level and GV in 3 months after treatment. There were significant differences in ΔHtSDS among prepubertal, midpubertal and postpubertal children one year after treatment(P=0.016), ΔHtSDS was significantly higher in prepuberty than midpuberty and postpuberty. But there was no significant difference in GV. Besides, the increment of height age in rhGH group was significantly larger than control group, but there was no significant difference in increment of bone age between two groups. The levels of IGF-1 elevated in rhGH group signigicantly 1 month after treatment and slowed down afterwards. Conclusions For ISS patients, therapy should be started at an earlier age ,at least before the puberty in order to achieve better cost-effect ratio. The therapeutic effect in the first 3 months may be a good predictor of one year therapeutic efficacy. While the rhGH therapy didn′t significantly accelerate the increment of bone age of patients.