重组人生长激素治疗不同生长激素分泌状态青春前期矮小患儿追赶性生长模式分析

Analysis of catch-up growth pattern to recombinant human growth hormone treatment in prepubertal children with short stature and various secretory forms of growth hormone

目的比较不同生长激素（GH）分泌状态矮小患儿重组人生长激素（rhGH）治疗后的初始追赶性生长模式，初步探讨其机制。方法回顾性分析62例青春前期不同GH分泌状态矮小患儿对rhGH治疗1年半的追赶性生长模式并定期监测体格指标、促生长素轴的血清指标和骨龄。结果各组在初始追赶性生长的幅度相似，特发性矮小（ISS）组比完全性生长激素缺乏症（GHD）组更早出现生长减速，并与生长激素结合蛋白（GHBP）水平降低和胰岛素样生长因子结合蛋白3的标准差分数（SDS）增值较小显著相关。GH激发峰值（GHmax）〉7μg／L的部分性GHD组与ISS组有类同的生长追赶的模式。结论GH受体的降调节和受体后效应的降低可能是ISS组较早出现生长减速的机制。以GHmax7μg／L作为GHD诊断的界值并相应选择rhGH治疗剂量有更充分的依据和临床意义。

Objective To analyze the pattern of early catch-up growth in children with prepubertal short stature and various secretory forms of growth hormone（GH） following recombinant human growth hormone（rhGH） treatment and to explore the mechanism. Methods Sixty-two children with prepubertal short stature and various GH secretory forms were analyzed retrospectively, 27 with complete growth hormone deficiency （cGHD） , 23 with partial growth hormone deficiency （pGHD） and 12 with idiopathic short stature （ISS）. According to the GH peak value in GH provocative test, the group of pGHD was divided into pGHD-1 （5.0-6.9 μg/L） and pGHD-2 （7.0- 9.9 μg/L）. Height velocity, increase in height standard differentiation score （SDS） , was calculated; serum levels of somatotrophic axis hormone were detected and bone age was determined. Results The quick early catch-up growth in different groups were similar in the initial 6 months. While that in the ISS group persisted for shorter period and was correlated with lower level in serum GH-binding protein （ r = 0. 526, P = 0. 025 ） and △insulin-like growth factor-binding protein-3 （ IGFBP-3 ） SDS（ r = 0. 532 ,P = 0. 034 ） after rhGH treatment. The same doses of rhGH were applied to children with cGHD and pGHD. Children with pGHD-1 showed similar response to rhGH, regarding height velocity and △IGFBP-3 SDS, as compared with those of cGHD. However, children with pGHD-2 presented similar response with ISS, being worse than cGHD. Conclusion Downregulation of GH receptor and decrease in post-receptor effect seem to be the mechanism leading to early retardation in ISS. The incomplete catch- up growth in pGHD-2 may be caused by relatively inadequate rhGH dose. The cut-off value of GH provocative test in diagnosing GHD is more reasonable to be 7 μg/L.