Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
Front Endocrinol (Lausanne). 2021 Oct 19;12:743057. doi: 10.3389/fendo.2021.743057. eCollection 2021.
The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact.
To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2).
2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies.
Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8. Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3.
Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible.
在妊娠早期，甲状腺激素（TH）的最佳母体水平尚未确定，也未确定开始左甲状腺素治疗（LT）以改善妊娠和胎儿发育的理想时机。推荐促甲状腺激素（TSH）<2.5μIU/mL和游离甲状腺素（FT4）>7.5pg/mL的切点。关于 LT 是否可以在妊娠 9 周前开始（GW）具有积极影响，目前尚无数据。
在 GW8 时确定与 TSH 分别为 2.5μIU/mL 和 FT4 为 7.5pg/mL 对应的 TSH/FT4 百分位数（研究 1），并评估 GW9 前基于方案的 LT 对 TSH≥2.5μIU/mL 和/或 FT4≤7.5pg/mL 的孕妇妊娠进展的影响（研究 2）。
2013-2014 年首次就诊的 2768 例连续妊娠妇女和 2015-2016 年的 3026 例符合研究 1 和 2 的条件。分别有 2043 名（研究 1）和 2069 名（研究 2）女性在这些研究中进行了评估。
研究 1：FT4 水平为 7.5pg/mL 对应的百分位数为 17.9，TSH 水平为 2.5μIU/mL 对应的百分位数为 75.8。TSH≥2.5μIU/mL 的孕妇比 TSH<2.5μIU/mL 的孕妇更频繁地有胎儿丢失史（OR 2.33（95%CI）：1.58-3.12），FT4≤7.5pg/ml 的孕妇比 FT4>7.5pg/ml 的孕妇更频繁地有胎儿丢失史（OR 4.81；3.25-8.89）。研究 2：共有 1259 名孕妇 TSH/FT4 水平最佳（组 1），672 名（32.4%，组 2）TSH 或 T4l 不理想，138 名（6.7%，组 3）两者均不理想。组 2 中有 393 名（58.5%）和组 3 中有 88 名（63.8%）在 GW9 前开始 LT。GW24 时的平均（SD）TSH 水平为 1.96±1.22μIU/mL，FT4 水平为 7.07±1.25pg/mL。FT4 的最高值为 12.84pg/mL。如果 LT 早期开始，组 2 的不良事件风险调整后为 0.71（0.43-0.91），组 3 的不良事件风险调整后为 0.80（0.66-0.94）。
在 GW9 或之前，对 TSH/FT4（≥2.5μIU/mL/≤7.5pg/ml）水平不理想的孕妇进行 LT 是安全的，可改善妊娠进展。这些数据支持采用这些 LT 起始切点的建议，LT 应尽早开始。
