小剂量甲状腺素干预对青春前期特发性矮小患儿生长激素敏感性的影响

Effects of levothyroxine on recombinant human growth hormone sensitivity in prepubertal chil-dren with idiopathic short stature

目的：探讨青春前期特发性矮小（ISS）患儿甲状腺功能正常，但游离甲状腺素（FT4）处于正常低值时，小剂量甲状腺素（L-T4）对ISS患儿重组人生长激素（rhGH）敏感性的影响。方法选取86例甲状腺功能正常，但血清FT4浓度处于正常值的第3～25百分位之间，首次确诊为ISS的青春前期患儿进行前瞻性研究，根据治疗方案不同随机分为两组，即：rhGH＋L-T4组和rhGH组。 rhGH＋L-T4组给予rhGH[0.15～0.20 U／（kg· d）]＋L-T4（0.5～1.5μg／kg）干预，rhGH组给予rhGH（[0.15～0.20 U／（kg· d）]＋安慰剂干预，观察治疗4个月后患儿治疗期间净获身高（ΔHt）、体质量指数（BMI）、年龄的身高标准差分值（HtSDS-CA）、胰岛素样生长因子-1（IGF-1）、胰岛素样生长因子结合蛋白-3（ IGFBP-3）、促甲状腺素（ TSH ）、FT4等各项指标的变化。结果经治疗4个月后， rhGH＋L-T4组患儿ΔHt、FT4和IGF-1较rhGH组增高，且差异有统计学意义（ t ＝5.025，49.332，4.050， P均＜0.05）；HtSDS-CA较rhGH组稍增高，但差异未见统计学意义（ t＝1.517，P＝0.133）；BMI、TSH和IGFBP-3与rhGH组相比差异未见统计学意义（t＝0.544，－1.440，0.974，P均＞0.05）。结论对于甲状腺功能正常、FT4处于正常低值的青春前期ISS患儿，小剂量甲状腺素短期干预可增强生长激素敏感性，且不会增加肥胖发生率，其机制可能与调控GH-IGF-1信号传导通路的IGF-1水平有关。

Objective To evaluate the effects of levothyroxine （ L-T4 ） on recombinant human growth hormone growth （ rhGH ） sensitivity in prepubertal children with idiopathic short stature （ ISS ） . Methods Eighty-six prepubertal children with ISS and free T4 （ FT4 ） concentrations between the 3 rd and the 25 th percentiles were enrolled in this study to receive either 4-month rhGH plus L-T4 or 4-month rhGH plus placebo treatment.Delta height （ end beginning stature） , the standard deviation score of height for chronological age（HtSDSca）, body mass index（BMI）, IGF-1, IGFBP-3, TSH and FT4 were investigated during treatment.Results After 4-month thyroid supplementation and/or rhGH ad-ministration, rhGH plus L-T4 group had significantly increase in delta height, FT4 and IGF-1 concentra-tions compared with rhGH plus placebo group （ t=5.025 , 49.332 , 4.050 , P〈0.05 ） , and they exhibi-ted a slightly increase in HtSDS-CA （t=1.517,P=0.133）.Howerver, there was no obviously signifi-cant change in BMI, TSH and IGFBP-3（t=0.544, -1.440, 0.974, P〉0.05）.Conclusions Sup-plementation with L-T4 for 4-month promotes sensitivity of rhGH and does not increase the obesty rate in prepubertal ISS children with low-normal FT4 , and the mechanism can be connected with IGF-1 which involved GH-IGF-1 pathway.