成都地区妊娠期特异性甲状腺激素水平参考值范围的探讨及临床分析

Establishing the reference range of pregnancy-specific thyroid hormone levels in chengdu area

目的：建立成都地区妊娠不同时期特异性甲状腺激素水平参考值范围。方法：经过筛选成都市妇女儿童中心医院的各孕期孕妇600例,作为＂标准人群＂。采用化学发光法测定促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）。分析其在孕期的变化特点,制定特异性甲状腺激素水平各项指标参考值范围。并再次收集各孕期孕妇3249例,验证该参考值范围对于诊断妊娠期亚临床甲状腺功能减退（亚甲减）的符合性。结果：（1）妊娠早期血清TSH的中位数及95%参考范围为1.29m IU/L（0.27～3.87m IU/L）,FT3为4.98pg/ml（4.5～5.58pg/ml）,FT4为1.22ng/dl（1～1.45ng/dl）;妊娠中期血清TSH为1.86m IU/L（0.13～4.19m IU/L）,FT3为4.94 pg/ml（4.37～5.6pg/ml）,FT4为1.16ng/dl（0.97～1.42ng/dl）;妊娠晚期血清TSH为2.24m IU/L（0.36～4.63m IU/L）,FT3为4.61pg/ml（4.08～5.21pg/ml）,FT4为1.01ng/dl（0.84～1.54ng/dl）;（2）分别按照20l1年美国甲状腺学会（ATA）指南提出的妊娠三期特异的甲状腺激素水平参考值范围、本次制定的参考值范围及本院非妊娠妇女参考值范围进行诊断,三种诊断标准的亚甲减总患病率分别为21.2%（688/3249）、6.5%（210/3249）、2.5%（82/3249）。结论：（1）妊娠期甲状腺功能指标随着怀孕的时限的增加波动,TSH值在早孕期最低,随着孕周的增加,TSH水平逐渐回升,至晚孕期达到最高。FT4、FT3值早孕期最高,随着孕周的增加逐渐降低,至晚孕期达到最低;（2）本研究制定的参考值范围对于诊断妊娠期亚甲减的患病率与国内其他报道基本一致。但ATA指南的参考值范围并不适合本地区孕妇的亚甲减的诊断;（3）使用非妊娠期甲状腺功能参考值水平可能导致妊娠合并甲状腺疾病的误诊和漏诊,制定本地区妊娠特异参考值范围非常重要。

Objective：To establish the reference range of values of trimester-specific thyroid functions in Chengdu area. Method：After screening pregnant women in different trimesters of pregnancy who visit Chengdu Women and Children＇s Central Hospital, 600 cases were selected as the ＂standard group＂. The chemiluminescence method was used to measure values of thyroid stimulating hormone （ TSH）, free thyroxine （FT4） and free triiodothyronine （ FT3 ）. Characteristics of how these values change during each trimester were analyzed, and the refer- ence range of each trimester-specific thyroid function parameter was established. Subsequently,3,249 cases of pregnant women in different trimesters were collected to validate whether the reference range complies with the standard of diagnosing subclinical hyperthyroidism （SHT）. Results：（ 1 ）The median value of serum TSH as well as the 95% reference range during the 1 st trimester were 1.29 mIU/L（0.27 -3.87 mIU/L）, with FT3 being 4.98pg/ml （4.5 - 5.58pg/ ml） and FT4 being 1.22 ng/dl （1-1.45ng/dl） ;the serum TSH during the 2nd trimester was 1.86mIU/L （0.13 -4.19mIU/L）,with FF3 being 4.94pg/ml （4.37 -5.6pg/ml） and FT4 being 1.16ng/dl （0.97 -1.42ng/dl） ;the serum TSH during the 3rd trimester was 2.24mIU/ L （0.36 -4.63mIU/L） ,with FT3 being 4.61 pg/ml （4.08 -5.21pg/ml） and FT4 being 1.0lng/dl （0.84 -1.54ng/dl）. （2）Diagnoses were made according to the trimester-specific reference range of values as proposed by guidelines of American Thyroid Association （ATA） in 2011 ,the criteria of reference values established in this study,and the standard applicable to non-gestation as made by our hospital respectively. The overall prevalence of SHT was 21.2% （688/3249）, 6.5 % （ 210/3249 ） and 2.5 % （ 82/3249 ）. Conclusion： （ 1 ） Levels of thyroid functions parameters in pregnancy fluctuate as the gestation age increases. The TSH value was lowest during the 1 st trimester, gradually rising as pregnancy progresses and reaching the high-est level during the 3rd trimester. Values of FF4 and FT3 were highest during the 1st trimester, gradually falling as pregnancy progresses and reaching the lowest level during the 3rd trimester. （2） Accuracy of the reference range established in this study in diagnosing SHT in pregnancy and figuring out the prevalence was basically as high as that presented in other domestic case reports. However, the prevalence of SHT as diagnosed based on the ATA standard was apparent- ly higher than that based on the reference range established in this study, and the difference was statistically significant,which shows the ATA standard of diagnosis was unsuitable for acting as the basis of diagnosing SHT pregnant women in our area develop. （ 3 ） The prevalence of SHT as diagnosed based on the trimester-specific reference range established in this study was apparently higher than that diagnosed using non-gestation standards, and the difference was statistically significant. Therefore, using the reference level of thyroid functions during non-gestational periods may lead to misdiagnosis and missed diagnosis of pregnancy associated with thyroid diseases, and it is of vital importance to work out the reference range of pregnancy-specific values applicable to our area.