陕西省铜川地区妊娠妇女血清甲状腺激素水平参考范围的建立及临床应用

目的　建立陕西省铜川地区妊娠妇女血清甲状腺激素水平参考范围，为铜川地区临床诊治妊娠妇女甲状腺疾病提供参考依据。方法　①回顾性分析2017 年6 月1 日～ 2020 年10 月31 日在铜川市人民医院进行甲状腺激素水平检查的健康妇女样本，按照标准筛选后纳入9 442 例，其中对照组（T0）3 169 例，早孕组（T1）2 642 例，中孕组（T2）1 895 例和晚孕组（T3）1 736 例。使用西门子ADVIA centaur XP 全自动化学发光免疫分析仪检测受试者血清中的促甲状腺激素（thyroid stimulating hormone，TSH）、总三碘甲状腺原氨酸（total triiodothyronine，TT3）、甲状腺素（total thyroxine hormone，TT4）、游离三碘甲状腺原氨酸（free triiodothyronine，FT3）和游离甲状腺素（free thyroxinehormone，FT4）水平。②使用该研究建立的参考范围和《妊娠及产后甲状腺疾病诊治指南》第二版提供的参考范围，对纳入人群进行筛查，比较不同孕期甲状腺疾病的检出率。结果　①妊娠三期血清甲状腺激素水平不同，早、中、晚期和对照组TSH 参考范围分别为1.64（0.06 ～ 6.74） mIU/L，1.94（0.06 ～ 5.80） mIU/L，2.35（0.74 ～ 4.71 ）mIU/L 和2.42（0.55 ～ 7.59） mIU/L；TT3 分别为2.01（1.30 ～ 3.24） nmol/L，2.51（1.62 ～ 3.71） nmol/L，2.44（1.48 ～ 3.53 ）nmol/L 和1.69（1.16 ～ 2.39） nmol/L；TT4 分别为131.30（77.83 ～ 230.80 ）nmol/L，159.40（96.60 ～ 246.20 ）nmol/L，155.30（92.10 ～ 247.00） nmol/L 和104.40（65.10 ～ 152.70） nmol/L；FT3 分别为4.89（4.00 ～ 6.12 ）pmol/L，4.59（3.65 ～5.79 ）pmol/L，4.02（3.22 ～ 4.96 ）pmol/L 和5.04（3.97 ～ 6.19 ）pmol/L；FT4 分别为14.33（11.16 ～ 19.23 ）pmol/L，13.64（10.22 ～ 18.55） pmol/L，12.84（10.05 ～ 20.09 ）pmol/L 和14.81（11.54 ～ 17.20） pmol/L。TSH 在妊娠期低于非妊娠期，早孕期最低，中晚孕期有逐渐回升趋势；TT3 和TT4 在整个妊娠期高于未妊娠期；FT3 和FT4 在整个妊娠期低于未妊娠期。四组间TSH，TT3，TT4，FT3 和FT4 比较，差异均有统计学意义(Z=457.225 ～ 2 927.436，均P ＜ 0.05)。②相较于《指南》中的通用参考范围，使用新建的参考范围时，妊娠期单纯低甲状腺素血症、妊娠期亚临床甲减和妊娠期临床甲减的检出率低于应用《指南》中通用参考范围的检出率（χ2=9.218 ～ 60.437，均P ＜ 0.01），而妊娠期甲状腺毒症的检出率高于应用《指南》中通用参考范围的检出率（χ2=7.559 ～ 8.199，均P ＜ 0.01），差异均有统计学意义。结论　使用非本地区参考范围可能导致甲状腺疾病的误诊和漏诊，建立区域和方法特异的妊娠妇女血清甲状腺激素水平参考范围很有必要。

Establishment and Clinical Application of Reference Intervals of Serum Thyroid Hormone Level of Pregnant Women in Tongchuan

Objective　To establish the reference intervals of serum thyroid hormone level of pregnant women in Tongchuan,so as to provide reference basis for clinical diagnosis and treatment of thyroid diseases during pregnancy. Methods　① A retrospective analysis was made on the samples of healthy women who underwent thyroid hormone level examination in Tongchuan People’s Hospital from June 1, 2017 to October 31, 2020. 9 442 cases were included after screening according to the standard, of which the control group (T0) 3 169 cases, 2 642 cases in early pregnancy group (T1), 1 895 cases in middle pregnancy group (T2) and 1 736 cases in late pregnancy group (T3). The serum thyroid stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine hormone (TT4), free triiodothyronine (FT3) and free thyroxine hormone (FT4) were detected by ADVIA centaur XP automatic luminescence immune analyzer. ② Using the reference intervals established by this study and the reference intervals provided by the guide(Chinese Medical Association Guideline on diagnosis and management of thyroid diseases during pregnancy and postpartum (2nd edition) to screen and compare the detection rates of thyroid diseases in different pregnancy periods for the included population. Results　① The levels of serum thyroid hormones were different among three periods of pregnancy women. Reference interval of TSH were 1.64（0.06 ～ 6.74） mIU/L，1.94（0.06 ～ 5.80） mIU/L，2.35（0.74 ～ 4.71 ）mIU/L and 2.42（0.55 ～ 7.59） mIU/L respectively in the early pregnancy, middle pregnancy, late pregnancy and control group.TT3 were 2.01（1.30 ～ 3.24） nmol/L，2.51（1.62 ～ 3.71） nmol/L，2.44（1.48 ～ 3.53 ）nmol/L and 1.69 （1.16 ～ 2.39） nmol/L, respectively. TT4 were 131.30（77.83 ～ 230.80 ）nmol/L，159.40（96.60 ～ 246.20 ）nmol/L， 155.30（92.10 ～ 247.00） nmol/L and 104.40（65.10 ～ 152.70） nmol/L, respectively. FT3 were 4.89（4.00 ～ 6.12）pmol/L， 4.59（3.65 ～ 5.79 ）pmol/L，4.02（3.22 ～ 4.96 ）pmol/L and 5.04（3.97 ～ 6.19 ）pmol/L, respectively. FT4 were14.33 （11.16 ～ 19.23 ）pmol/L，13.64（10.22 ～ 18.55 pmol/L，12.84（10.05 ～ 20.09 ）pmol/L and 14.81（11.54 ～ 17.20） pmol/L, respectively.TSH in pregnancy was lower than that in non-pregnancy, the lowest in early pregnancy, and the trend of gradual recovery in middle and late pregnancy. TT3 and TT4 were higher during the whole pregnancy than before pregnancy. FT3 and FT4 were lower in the whole pregnancy than before pregnancy. Comparison of TSH, TT3, TT4, FT3 and FT4 among the four groups showed statistically significant differences(Z=457.225 ～ 2 927.436, all P ＜ 0.05). ② Compared with the general reference intervals in the guide, when using the reference intervals of this region, simple hypothyroxemia, subclinical hypothyroidism, the detection rate of clinical hypothyroidism was lower than that of the general reference intervals in the application of the guide (χ2=9.218 ～ 60.437, all P ＜ 0.01), while the detection rate of thyroid toxin during pregnancy was higher than that of the general reference intervals in the application of the guide (χ2=7.559 ～ 8.199, all P ＜ 0.01), the differences were statistically significant, respectively. Conclusion　The use of non-local reference intervals may lead to misdiagnosis and missed diagnosis of thyroid diseases. It is necessary to establish regional and method-specific reference intervals for serum thyroid hormone levels in pregnant women.