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胰岛素样生长因子生成试验及临床应用价值分析

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【摘要】 目的 胰岛素样生长因子(insulin-like growth factor,IGF)生成试验是临床常用的内分泌动态试验,常被视为评估GH不敏感综合征(GH insensitive syndrome,GHIS)矮小患者GH-IGF1生长轴功能技术之一。本文旨在观察:(1)IGF生成试验中的IGF1反应值(△IGF1)是否能够反映rhGH促生长效应;(2)IGF生成试验对GHD、ISS与GHIS三类患者是否具有临床鉴别价值。方法 对27例身材矮小患儿的IGF生成试验做一回顾性分析,平均年龄10.2岁(5.8~15.0岁),均处于青春发育期前期(Tanner Ⅰ期),其中原发性生长激素缺乏(GHD)15例、特发性矮小(ISS)11例和GH不敏感综合征(GHIS)即Laron综合征1例。IGF生成试验相关参数检测包括:血清GH峰值、IGF1和生长激素结合蛋白(GHBP)。依据生长速率(GV)探索△IGF1诊断敏感性和特异性的切点。结果 GHD与ISS患者血清IGF1SDS基础值和△%IGF1差异具有显著性(t=2.17,P=0.003;t=2.23,P=0.03)。GHD组患儿基础IGF1SDS与△%IGF1和△GV呈负相关(r=-0.79,P=0.001及r=-0.59,P=0.028);GH峰值与△IGF1、△GV呈负相关(r=-0.78,P=0.001及r=-0.64,P=0.01);△%IGF1与△GV呈正相关(r=0.63,P=0.015)。ISS组患者△IGF1与HtSDS及IGF1基础值呈负相关(r=-0.61,P=0.047;r=-0.64,P=0.036);由ROC曲线可见△IGF1对ISS患儿判断GH疗效具有较高敏感性和特异性的切点约为165.9μg/L。结论 (1)IGF生成试验是完全性GHI可靠的实验诊断;(2)IGF生成试验具有一定的预测rhGH促生长效应的作用;(3)本文未能对部分性GHI提供临床诊断信息。

【关键词】 生长调节素类,生成试验,分析
  
Insulin-like growth factor generation test and its clinical value
  
【Abstract】 Objective The insulin-like growth factor(IGF)generation test has been used to assess growth hormone(GH)responsiveness in children with short stature in clinic.The aim of this study was to seek a cutting value (1) in effect of prediction for growth promoting with recombinant human GH(rhGH) therapy in children with idiopathic short stature(ISS) and (2) in differential diagnosis between GH deficiency (GHD) ISS and GH insensitive syndrome(GHIS).Methods Twenty-seven pre-pubertal children with short stature(including 15 GHD,11 ISS and 1 GHIS),mean age 10.2 years(5.8~15.0),were retrospectively studied.All the patients received rhGH treatment over one year except the GHIS patient.Serum GH peak value,IGF1 and GH binding protein(GHBP) levels were measured.The diagnostic cut-off line of IGF1 responding levels(△IGF1)during standard IGF generation test was sought on the basis of growth velocity(GV).Results Among the GHD and ISS groups,distinct differences were shown in serum basal IGF1SDS levels(t=2.17,P=0.003)and △%IGF1 levels(t=2.23,P=0.03).In GHD group we found negative relationships between the basal IGF1SDS and △%IGF1(r=-0.79,P=0.001),between the basal IGF1SDS and △GV(r=-0.59,P=0.028),between GH peak level and the △IGF1 level(r=-0.78,P=0.001)and between GH peak level and △GV(r=-0.64,P=0.01).Positive relationship was shown between △%IGF1 and △GV(r=0.63,P=0.015)in GHD patients.In ISS group,negative relationships were shown between △IGF1 and HtSDS(r=-0.61,P=0.047)and between △IGF1 and basal IGF1 value (r=-0.64,P=0.036).The ROC plot showed that the best cut-off line of △IGF1 for prediction of rhGH therapeutic effect was likely 165.9μg/L.Conclusion (1) The IGF generation test is a reliable clinical laboratory diagnostic parameter for complete GHI;(2) IGF generation test was suspected valuable in prediction of growth promoting effect in short stature with rhGH treatment;(3) The diagnostic value of IGF generaton test for partial GH insensitivity need to be clarified.
  
【Key words】 somatomedins;diagnosis;growth hormone insensitive syndrome
目录:
  1 资料与方法

  2 结果

  3 讨论


参考文献:
1 Rosenfeld RG,Albertsson-Wikland K,Cassorla F,et al.Diagnostic controversy:the diagnosis of childhood growth hormone deficiency revised.J Clin Endocrinol Metab,1995,80:1532-1540.
  2 Blair JC,Camacho-Hubner C.Standard and low-dose IGF1 generation tests and spontaneous growth hormone secretion in children with idiopathic short stature.Clinical Endocrinol,2004,60(2):163-168.
  3 Attie KM,Carlsson LM,Rundle AC,et al.Evidence for partial growth hormone insensitivity among patients with idiopathic short stature.The national Cooperative Growth Study.J Pediatr,1995,127:244-250.
  4 Cotteril AM,Camacho-Hubner C,Woods,et al.The insulin-like growth factor 1 generation test in the investigation of short stature.Acta Paediatr.1994,399:128-130.
  5 Goddard AD,Dowd P,Chernausek S,et al.Partial growth-hormone insensitivity:the role of growth-hormone receptor mutations in idiopathic stature.J Paediatr,1997,131:51-55.
  6 Buckway CK,Guevara-Aguirre J,Pratt KL,et al.The IGF-1 generation test revisted:a marker of GH sensitivity.J Clin Endocrinol Metab,2001,86:5176-5183.
  7 Buckway CK,Selva KA,Pratt KL,et al.Insulin like growth factor binding protein-3 generation as a measure of GH sensitivity.J Clin Endocrinol Metab,2002,87:4754-4765.
  8 Darendelilre F,Ocal C,Bas F,et al.Evaluation of insulin like growth factor(IGF)-1 and IGF binding protein-3 generation test in short stature.J Clin Endocrinol Metab,2005,18:443-452.

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