矮小症儿童脂质运载蛋白2水平及重组人生长激素治疗后脂质运载蛋白2、胰岛素样生长因子1的变化

doi:10.3877/cma.j.issn.2095-655X.2025.01.006

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摘要目的探讨脂质运载蛋白2（LCN2）在矮小症儿童血清中的水平以及应用重组人生长激素（rhGH）治疗后血清LCN2、胰岛素样生长因子1（IGF-1）的变化。方法选择2020年1月至2023年10月就诊于济宁医学院附属医院内分泌遗传代谢科的440例矮小症患者，根据病因不同将其分为生长激素缺乏症(GHD)组（n=334）和特发性矮小症(ISS)组（n=106），其中GHD组根据生长激素峰值不同进一步分为完全性GHD（n=161）和部分性GHD（n=173）。收集3组患者在应用rhGH治疗前的临床特征及血清学参数，分析LCN2在区分完全性GHD、部分GHD、ISS患者中的诊断效能。对其中2023年1~10月就诊的82例患者随访治疗6个月以及12个月，观察血清LCN2、IGF-1等指标的变化情况及临床治疗效果；并对治疗前后不同时期血清LCN2水平与临床特征及血清学参数进行相关性分析。结果治疗前ISS组血清LCN2水平［337.69(276.35，449.28)μg/L］显著高于完全性GHD组［238.81(188.70，350.62)μg/L］和部分性GHD组［278.95(211.45，393.29)μg/L］，差异具有统计学意义(H=10.464，P＜0.01)。rhGH治疗12个月后，3组患儿身高标准差积分（SDS）均较治疗前、治疗6个月后呈明显增长趋势(H=66.167，41.040，19.142；均P＜0.01)。3组患者血清LCN2的表达水平均随着治疗时间的延长呈显著下降趋势（H=60.500,44.720,38.095），IGF-1水平（H=55.056，40.106，35.524）、IGF-1 SDS（H=43.167，38.480，33.429）均较治疗前逐渐增加，均差异具有统计学意义（均P＜0.01）。完全性GHD、部分GHD、ISS患者治疗前、治疗6个月时LCN2与IGF-1呈明显负相关（r=-0.219，-0.461，-0.443，-0.575，-0.443，-0.457；均P＜0.05)。LCN2在区分ISS与完全性GHD的受试者操作特征（ROC）曲线下面积(AUC)为0.709，特异度为63.98%，敏感度为75.47%；区分ISS与部分性GHD的ROC曲线AUC为0.628，特异度为38.73%，敏感度为85.85%；区分完全性与部分性GHD的ROC曲线AUC为0.588，特异度为48.45%，敏感度为69.36%。结论GHD和ISS儿童在应用rhGH治疗后临床疗效确切，血清LCN2水平可作为身材矮小儿童诊断及治疗后的一项疗效监测与评估的指标。

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关键词 ：生长激素缺乏症, 特发性矮小症, 重组人生长激素, 胰岛素样生长因子-1, 脂质运载蛋白2

Abstract：ObjectiveTo study the expression of serum lipocalin-2 (LCN2) in children with short stature and the application of recombinant human growth hormone (rhGH) in children with short stature, as well as the changes of LCN2 and insulin-like growth factor 1 (IGF-1) serum level after rhGH treatment. MethodsA total of 440 patients with short stature admitted to the Department of Endocrinology, Genetics and Metabolism of the Affiliated Hospital of Jining Medical University from January 2020 to October 2023 were analyzed. Patients were divided into growth hormone deficiency (GHD) group (n=334) and idiopathic short stature (ISS) group (n=106). GHD group was further divided into complete GHD group (n=161) and partial GHD group (n=173) according to the peak value of growth hormone. The clinical characteristics and serological parameters of the three groups before rhGH treatment were collected. The diagnostic efficacy of LCN2 in differentiating patients with complete GHD, partial GHD and ISS was analyzed. A subgroup of 82 patients (treated January-October 2023) underwent 6 month and 12 month follow-up to monitor therapeutic responses and changes of indicators (LCN2 and IGF-1 serum levels). The correlation between LCN2 serum levels and clinical features and serological parameters at different periods before and after treatment was analyzed. ResultsBefore treatment, the LCN2 serum levels in the ISS group ［337.69(276.35, 449.28)μg/L］ were significantly higher than those in the complete GHD group ［238.81(188.70, 350.62)μg/L］ and the partial GHD group ［278.95(211.45, 393.29)μg/L］, with the differences being statistically significant (H=10.464, P＜0.01). After 12 months of rhGH treatment, the height standard deviation score (SDS) of children in all three groups showed a significant upward trend compared to baseline and six months treatment (H=66.167, 41.040, 19.142, all P＜0.01). The expression level of LCN2 decreased significantly with the extension of treatment time (H=60.500, 44.720, 38.095), while IGF-1 level (H=55.056, 40.106, 35.524) and IGF-1 SDS (H=43.167, 38.480, 33.429) gradually increased compared with those before treatment, with statistically significant differences (all P＜0.05). LCN2 and IGF-1 levels showed a significant negative correlation in patients with complete GHD, partial GHD, and ISS both before treatment and at 6 months of treatment (r=-0.219, -0.461, -0.443, -0.575, -0.443, -0.457, all P＜0.05). The area under the curve (AUC) of LCN2 in distinguishing ISS children from complete GHD was 0.709, with a specificity of 63.98% and a sensitivity of 75.47%. The AUC of LCN2 in distinguishing ISS children from partial GHD was 0.628, with a specificity 38.73% and a sensitivity of 85.85%. The AUC for distinguishing complete GHD from partial GHD was 0.588, with a specificity of 48.45% and a sensitivity of 69.36%. ConclusionsrhGH treatment is effective in children with GHD and ISS. The serum level of LCN2 can be used as an indicator for the diagnosis and treatment of children with short stature.

Key words： Growth hormone deficiency Idiopathic short stature Recombinant human growth hormone Insulin-like growth factor-1 Lipocalin-2

收稿日期: 2024-12-16

基金资助:济宁市重点研发计划项目（2023YXNS029）

通讯作者: 张梅, Email: zhangmeijn@163.com

引用本文:

朱昱颖赵倩倩李艳英潘珂鑫马兆慧张梅. 矮小症儿童脂质运载蛋白2水平及重组人生长激素治疗后脂质运载蛋白2、胰岛素样生长因子1的变化[J]. 中华诊断学电子杂志, 2025, 13(1): 38-44.
Zhu Yuying1, Zhao Qianqian2, Li Yanying2, Pan Kexin1, Ma Zhaohui1, Zhang Mei2.. The level of LCN2 in children with short stature and the changes of LCN2 and IGF-1 after treatment with recombinant human growth hormone. zhzdx, 2025, 13(1): 38-44.

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