建立并验证贝克曼库尔特Unicel DxI800免疫分析平台促甲状腺激素（TSH）新一代试剂（TSH 3rd）检测方法的生物参考区间，并评估TSH受年龄、季节和气温变化的影响情况。

参照美国临床和实验室标准化协会EP28-A3c指南文件，利用大数据筛选2020年4月1日至2021年3月31日深圳市中医院计算机中心数据库的TSH检验结果共47 502例为研究总体，患者平均年龄（42±15）岁；剔除缺失值1834例和离群值1568例，再剔除甲状腺过氧化物酶抗体和甲状腺球蛋白抗体阳性1960例；最后符合纳入标准的普通人群样本42 140例（A组）。将A组人群分为男性、女性、成人、未成人组，再次进行数据转换后，按上述方法再分别剔除离群值，最后完全符合纳入标准的男性14 566例（B组），女性27 394例（C组）；成年41 375例（D组），未成年571例（E组）。再将普通人群中31~96岁患者分成6小组，分析TSH值与年龄变量的相关性。此外，将普通人群数据分为4季，评估不同季节TSH值差异。利用SPSS 22.0和Minitab 18.0统计软件对TSH数据进行统计学分析，确定生物参考区间，多组间比较采用单因素方差分析，2组间比较采用Mann-Whitney U检验，相关性分析采用Pearson相关性检验。

TSH生物参考区间：A组为0.40~6.29 mIU/L，B组为0.45~5.80 mIU/L，C组为0.43~6.52 mIU/L，D组为0.40~6.28 mIU/L，E组为0.46~6.65 mIU/L；Mann-Whitney U检验显示，B组与C组（P＜0.001）、D组与E组（P＜0.05）比较，差异均有统计学意义。不同年龄组及不同季节TSH值差异有统计学意义（F=9.26，P＜0.01；F=4.10，P＜0.01）。TSH值与年龄变量呈正相关（r=0.740，P＜0.01），与气温呈负相关（r=-0.658，P＜0.05）。

TSH的生物参考区间具有性别和年龄差异性，适时建立性别和年龄专属的生物参考区间有利于甲状腺功能紊乱的临床诊断和治疗，同时将季节和气温变化纳入考虑。

To establish and verify the biological reference intervals for third generation thyroid stimulating hormone (TSH) assay using the Beckman Coulter Unicel DxI800 immunoassay platform, and assesse the effects of age, seasonal climate, and temperature variation on TSH.

Referring to the Clinical and Laboratory Standards Institute (CLSI) EP 28-A3c guidelines, 47 502 subjects with test results of TSH were initially obtained from the database of Computer Center of Shenzhen Traditional Chinese Medicine Hospital using big data technology from April 1, 2020 to March 31, 2021. The subjects had an average age of (42±15) years old. In total, 1834 cases with missing values, 1568 with outliers, and 1960 with positive thyroid peroxidase antibody and/or thyroglobulin antibody were excluded. Finally, 42 140 cases meeting the inclusion criteria were considered as the overall population (group A). Group A was divided into male, female, adult and non-adult groups. After data conversion again, outliers were removed according to the above methods. Finally, patients who fully met the inclusion criteria, 14 566 were male (group B) and 27 394 were female (group C); 41 575 were adults (group D) and 571 were juvenile (group E). Furthermore, the individuals aged 31-96 years old in the overall population were divided by age into six groups to analyze the correlation between TSH and age. In addition, the data of the overall population were divided into by season to evaluate the difference of TSH values in different seasons. The biological reference intervals for TSH were determined statistically using SPSS 22.0 and Minitab 18.0 statistical software. One-way ANOVA was used for comparison among groups, and Mann-Whitney U test was used for pairwise comparison. Pearson correlation test was used for correlation analysis.

The biological reference intervals for TSH of group A-E were 0.40-6.29 mIU/L, 0.45-5.80 mIU/L, 0.43-6.52mIU/L, 0.40-6.28 mIU/L, and 0.46-6.65 mIU/L, respectively. Mann-Whitney U test showed that there were significant differences between group B and C (P＜0.001), and between group D and E (P＜0.05). There were significant differences in TSH in different age groups and among different seasons (F=9.26, P＜0.01; F=4.10, P＜0.01). There was a positive correlation between TSH and age (r=0.740, P＜0.01). Conversely, there was a negative correlation between TSH and temperature variation (r=-0.658, P＜0.05).

There are differences in biological reference intervals for TSH with regard to gender and age. Establishment of gender- and age-specific reference intervals properly will be helpful to clinical diagnosis and treatment of thyroid dysfunction. Seasonal and temperature variations should also be taken into account.