Sources of variation and establishment of Russian reference intervals for major hormones and tumor markers. Objectives A multicenter study was organized to explore sources of variation (SVs) of reference values (RVs) for 24 major immunochemistry analytes and to determine reference intervals (RIs) for the Russian population. Methods According to IFCC Committee on Reference Intervals and Decision Limits (C-RIDL) protocol, 793 healthy volunteers were recruited in St. Petersburg, Moscow, and Yekaterinburg. Serum samples were tested for five tumor markers, 19 hormones and related tests by Beckman Coulter’s UniCel DxI 800 immunochemistry analyzer. SVs were explored using multiple regression analysis and ANOVA. Standard deviation ratio (SDR) of 0.4 was used as primary guide for partitioning RIs by gender and age. Results SDR for between-city difference was <0.4 for all analytes. Secondary exclusion of individuals was done under the following conditions: for female sex-hormones, those with contraceptives (8%); for CA19-9, those supposed to have negative Lewis blood-group (10.5%); for insulin, those with BMI≥28 kg/m 2 (29.9%); for the thyroid panel, those with anti-thyroid antibodies (10.3% in males; 24.5% in females). Gender-specific RIs were required for all analytes except CA19-9, CA15-3, thyroid-related tests, parathyroid hormone, and insulin. Age-specific RIs were required for α-fetoprotein and all sex-hormones except testosterone. RIs were generally derived by parametric method after Gaussian transformation using modified Box-Cox formula. Exceptions were growth hormone, estradiol, and progesterone, for which nonparametric method was required due to bimodal distribution and/or insufficient detection limit. Conclusion RIs for major hormones and tumor markers specific for the Russian population were derived based on the up-to-date internationally harmonized protocol by careful consideration of analyte-specific SVs.

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主要激素和肿瘤标志物的俄罗斯参考区间的变化和确定来源

主要激素和肿瘤标志物的俄文参考区间的变化和建立的来源。目的开展了一项多中心研究，以探索24种主要免疫化学分析物的参考值（RVs）的变异（SVs）来源，并确定俄罗斯人群的参考区间（RIs）。方法根据IFCC参考区间和决策限度委员会（C-RIDL）协议，在圣彼得堡，莫斯科和叶卡捷琳堡招募了793名健康志愿者。用Beckman Coulter的UniCel DxI 800免疫化学分析仪对血清样品中的5种肿瘤标志物，19种激素进行了相关测试。使用多元回归分析和方差分析探索SV。标准偏差比（SDR）为0.4，用作按性别和年龄划分RI的主要指南。结果所有分析物的城市间差异的SDR <0.4。在以下条件下进行个体的二次排斥：对于女性性激素，那些有避孕药的妇女（8％）；对于CA19-9，那些路易斯血型为阴性的人（10.5％）；对于胰岛素，BMI≥28kg / m 2（29.9％）；对于甲状腺组，那些具有抗甲状腺抗体的人群（男性为10.3％；女性为24.5％）。除CA19-9，CA15-3，甲状腺相关检查，甲状旁腺激素和胰岛素外，所有分析物均需要性别特异性RI。甲胎蛋白和除睾丸激素外的所有性激素都需要有年龄特异性的RIs。RI通常是使用修改后的Box-Cox公式在高斯变换后通过参数方法得出的。生长激素，雌二醇和孕酮除外，由于双峰分布和/或检测限不足，需要使用非参数方法。结论针对俄罗斯人群的主要激素和肿瘤标志物的RIs是根据最新的国际协调方案，通过仔细考虑分析物特异性SV得出的。