Hou Xin, Guan Haixia, Sun Shuang, Shi Yang, Li Chenyan, Liu Aihua, Li Yongze, Gao Xiaotong, Hou Yuanyuan, Yang Yang, Li Yushu, Shan Zhongyan, Teng Weiping
Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Department of Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
Thyroid. 2022 Aug;32(8):983-989. doi: 10.1089/thy.2022.0088. Epub 2022 Jul 18.
The use of antithyroid drugs (ATDs) carries potential risk for teratogenic effects. For women with well-controlled hyperthyroidism on a low dose of ATDs, drug withdrawal upon pregnancy is recommended by international medical guidelines. Therefore, it is necessary to determine the characteristics of patients suitable for ATD withdrawal, subsequent changes in thyroid function after ATD discontinuation, and its impact on pregnancy and offspring outcomes. This prospective study recruited 63 pregnant women with well-controlled Graves' hyperthyroidism who had stopped ATDs during early pregnancy. Patients were followed up until the end of pregnancy and data on pregnancy outcomes were collected. Overall, 20 patients (31.7%) had rebound of hyperthyroidism. Patients with either subnormal thyrotropin (TSH) levels (TSH <0.35 mIU/L, odds ratio [OR] = 5.12, confidence interval [CI = 1.29-20.34], = 0.03) or positive thyrotropin receptor antibody (TRAb) (TRAb >1.75 IU/L, OR = 3.79, [CI = 1.17-12.30], = 0.02) at the time of ATDs withdrawal presented a higher risk of rebound than those with either normal TSH levels or negative TRAb. Patients with both subnormal TSH and positive TRAb at the time of ATD withdrawal were more likely to experience rebound (83.3%, 5/6) than those with both normal TSH and negative TRAb (13%, 3/23, OR = 33.33, [CI = 2.83-392.60], = 0.003). The prevalence of adverse pregnancy outcomes was significantly higher in patients who experienced rebound compared with those who did not (55.0% vs. 9.3%, OR = 11.92, [CI = 3.08-46.18], = 0.0002). Subnormal TSH levels and TRAb positivity at the time of ATD withdrawal in early pregnancy may be associated with rebound of Graves' hyperthyroidism. Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.
使用抗甲状腺药物（ATD）存在致畸作用的潜在风险。对于使用低剂量ATD且甲状腺功能亢进得到良好控制的女性，国际医学指南建议在怀孕时停药。因此，有必要确定适合停药的患者特征、停药后甲状腺功能的后续变化及其对妊娠和后代结局的影响。这项前瞻性研究招募了63名在妊娠早期停用ATD且甲状腺功能亢进得到良好控制的孕妇。对患者进行随访直至妊娠结束，并收集妊娠结局数据。总体而言，20名患者（31.7%）出现甲状腺功能亢进复发。在停用ATD时促甲状腺激素（TSH）水平低于正常（TSH<0.35 mIU/L，比值比[OR]=5.12，置信区间[CI=1.29 - 20.34]，P=0.03）或促甲状腺激素受体抗体（TRAb）呈阳性（TRAb>1.75 IU/L，OR=3.79，[CI=1.17 - 12.30]，P=0.02）的患者比TSH水平正常或TRAb呈阴性的患者复发风险更高。在停用ATD时TSH低于正常且TRAb呈阳性的患者比TSH正常且TRAb呈阴性的患者更易复发（83.3%，5/6比13%，3/23，OR=33.33，[CI=2.83 - 392.60]，P=0.003）。与未复发的患者相比，复发患者的不良妊娠结局发生率显著更高（55.0%对9.3%，OR=11.92，[CI=3.08 - 46.18]，P=0.0002）。妊娠早期停用ATD时TSH水平低于正常和TRAb阳性可能与格雷夫斯甲状腺功能亢进复发有关。妊娠期间甲状腺功能亢进复发可能增加不良妊娠结局的风险。需要更大规模的前瞻性研究来证实这些发现。
