基于生物学变异数据建立血清甲状腺激素的个性化参考区间  

Establish Serum Thyroid Hormones Based on Biological Variation Data Personalized Reference Intervals

作　　者：孔丽蕊 周朝琼 何大海 黄英 谢叶红 徐晓华 刘辉 吴风 张艳 KONG Lirui;ZHOU Chaoqiong;HE Dahai;HUANG Ying;XIE Yehong;XU Xiaohua;LIU Hui;WU Feng;ZHANG Yan(Department of Clinical Laboratory,Traditional Chinese Medicine Hospital of Pidu District,Chengdu 611730,China)

机构地区：[1]成都市郫都区中医医院检验科,成都611730

出　　处：《现代检验医学杂志》2023年第5期148-154,共7页Journal of Modern Laboratory Medicine

基　　金：成都市医学科研课题(2021192):基于生物学变异建立临床检测项目个性化参考区间模型研究及临床验证应用;(2022376):运用大数据间接建立成都市郫都区人群参考区间及个性化参考区间的研究;成都中医药大学“杏林学者”医院专项课题(YYZX2021136):基于生物学变异建立郫都区医养中心老年人检测项目个性化参考区间的研究及应用。

摘　　要：目的基于生物学变异(biological variation,BV)估计值和受试者稳态设定点(homeostatic set point,HSP)的不确定度,建立血清促甲状腺激素(thyroid-stimulating hormone,TSH)、三碘甲状腺原氨酸(triiodothyronine,T3)、甲状腺素(thyroxine,T4)、血清游离三碘甲状腺原氨酸(free T3,FT3)和血清游离甲状腺素(free T4,FT4)的个性化参考区间(personalized reference interval,prRI)。方法24h内6个时间点(00:00,04:00,08:00,12:00,16:00,20:00)采集31例健康受试者血样。雅培i2000SR分析仪上重复测定血清TSH,T3,T4,FT3和FT4浓度水平,进行离群值和方差同质性分析,然后对趋势校正的数据(如果相关)进行CV-ANOVA分析。计算血清甲状腺激素的BV可信区间(95%Cl)及参考变化值(reference change value,RCV)、个体指数(individuality index,II)和prRI,并与基于人群的参考区间(population-based reference interval,popRI)进行比较,验证prRI的应用价值。结果血清甲状腺激素水平男性均高于女性,差异具有统计学意义(t=3.081~7.549,均P<0.01)。TSH CV_I较高,RCV较大,II=1.0,其prRI范围很宽。T3,T4,FT3和FT4的RCV相对较小,IIs测量值均≤0.6,大多数被测物的prRI分布范围仅占popRI的一部分。T3,T4,FT3和FT4的参考区间指数(reference interval index,Rii)分别为0.80,0.61,1.10和0.47,与II值相当。prRI落在popRI之内的比例分别为98.92%,90.54%,98.92%和95.41%,符合卫生部行业验证标准。结论除TSH外,T3,T4,FT3和FT4基于短期BV的prRI可以提供准确的实验室结果评价,有效支持有关甲状腺疾病的临床决策,对于健康评估中的“个性化”诊断很有价值。在实验室报告中同时包括popRIs和prRIs,可帮助临床医生评估实验室检测结果,并为健康评估提供个性化参考区间。Objective To establish personalized reference interval(prRI)of the serum thyroid-stimulating hormone(TSH),triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3)and free thyroxine(FT4),based on the biological variation(BV)estimate and the uncertainty of subject homeostatic set point(HSP).Methods Blood samples were collected from 31 healthy subjects at 6 time points(00:00,04:00,08:00,12:00,16:00,20:00).The serum levels of TSH,T3,T4,FT3 and FT4 concentrations were determined in duplicate on an Abbott i2000SR analyzer,outliers and homogeneity of variance analysis,followed by CV-ANOVA analysis of the trend-corrected data(if related).The BV confidence interval(95%CI)and reference change values(RCV),individual index(II)and prRI were calculated for serum thyroid hormones,and compared with the population-based reference interval(popRI)to verify the utility of prRI.Results Serum thyroid hormone levels were higher and in men than women,statistically significant(t=3.081~7.549,all P<0.01).The TSH had a high CVI,relatively large of RCV and II=1.0,for a wide prRI range.The RCV of T3,T4,FT3 and FT4 were relatively small,IIs measurements were all≤0.6,and the prRI distribution range of most subjects tested was only a part of the popRI.The reference interval index(Rii)for T3,T4,FT3 and FT4 were 0.80,0.61,1.10 and 0.47,respectively,comparable to II values.The proportion of prRI falling within popRI was 98.92%,90.54%,98.92%and 95.41%,recpecitiverly.Accorded with the industry verification standards of the Ministry of Health.Conclusion In addition to TSH,T3,T4,FT3 and FT4 prRI based on short-term BV can provide accurate evaluation of laboratory results that can effectively support clinical decisions regarding thyroid disease and be valuable for“personalized”diagnosis in health assessment.Including both popRIs and prRIs in laboratory reports can help clinicians evaluate laboratory test results and provide personalized reference intervals for health assessments.

关 键 词：甲状腺激素 生物学变异(BV) 参考变化值(RCV) 个体指数(II) 个性化参考区间(prRI) 人群参考区间(popRI) 参考区间指数(Rii) 

分 类 号：R446.11[医药卫生—诊断学]