DataSheet_1_The reference intervals for thyroid hormones: A four year investigation in Chinese population.pdf

IntroductionThe reference intervals (RIs) are of great importance for physicans to determine whether or not an individual is healthy. However, many clinical laboratories in China still adopted the default RI provided by the manufacturers; and these “uncalibrated” RIs might lead to the misdiagnosis of diseases. In the present study, we enroll reference people with the purpose of determining the RIs of serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in Chinese population, and explore the possible roles of age and sex on the levels of biomarkers.
MethodsSerum samples from 66,609 individuals who met the inclusion criteria were analyzed using an Roche Cobas E 601 hormone analyzer. The dynamic trends of biomarker were visually assessed by their concentrations over age and sex. Specific partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated for each reference partition using a non-parametric rank approach.
ResultsThe serum level of T3, T4, FT4 or TSH showed a right-skewed distribution in both males and females while FT3 presented an approximate normal distribution. Females had a higher mode value of serum T3 or T4, but a lower mode value of serum TSH, FT3 or FT4. All five biomarkers did not need age partitioning according to the approach of harris and boyd, while T3 and FT3 need sex partitioning.
ConclusionsThe present study not only determined the age- and sex-specific trends of the five thyroid hormones, but provided sex-stratified RIs for T3 and FT3, valuably contributing to the current literature and timely evaluation of thyroid health and disease.

引言
参考区间（reference intervals, RIs）是临床医师判断个体健康状态的核心依据之一。然而国内多数临床实验室仍直接沿用厂商提供的默认参考区间，这类未经过本土化校准的参考区间可能引发疾病误诊。本研究招募符合标准的健康参考人群，旨在建立中国人群血清三碘甲状腺原氨酸（triiodothyronine, T3）、甲状腺素（thyroxine, T4）、游离三碘甲状腺原氨酸（free triiodothyronine, FT3）、游离甲状腺素（free thyroxine, FT4）及促甲状腺激素（thyroid-stimulating hormone, TSH）的参考区间，并探究年龄与性别对上述生物标志物水平的潜在影响。

方法
本研究采用罗氏（Roche）Cobas E 601激素分析仪，对66609名符合纳入标准的个体的血清样本开展检测。通过不同年龄、性别亚组的生物标志物浓度分布，直观评估其动态变化趋势；采用Harris-Boyd法确定分组依据。针对每个参考亚组，采用非参数秩和法计算对应2.5th与97.5th百分位数的参考区间，同时同步给出0.5th、25th、50th、75th及99.5th百分位数的统计结果。

结果
男性与女性的血清T3、T4、FT4及TSH水平均呈右偏态分布，而FT3则近似服从正态分布。女性血清T3、T4的众数水平高于男性，而TSH、FT3及FT4的众数水平则低于男性。依据Harris-Boyd法，五种生物标志物均无需按年龄进行分组，但T3与FT3需按性别分层。

结论
本研究不仅明确了五种甲状腺激素随年龄与性别的变化趋势，还为T3与FT3建立了按性别分层的参考区间，可为当前甲状腺相关研究提供重要学术补充，同时助力甲状腺健康状态与疾病的及时评估。