Qiang Judy K, Sutradhar Rinku, Everett Karl, Eskander Antoine, Lega Iliana C, Zahedi Afshan, Lipscombe Lorraine
Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
Thyroid. 2025 Feb;35(2):208-215. doi: 10.1089/thy.2024.0330. Epub 2024 Dec 26.
Levothyroxine to suppress thyrotropin (TSH) to <0.5 mIU/L following thyroidectomy in differentiated thyroid cancer (DTC) may reduce recurrence in higher-risk DTC. However, there is limited evidence to support guideline recommendations to maintain TSH in the low-normal range of 0.5-2 mIU/L to reduce recurrence in patients with lower risk DTC. The primary objective was to assess the association between exposure to high normal serum TSH (2-4 mIU/L) as compared with low normal TSH (0.5-2 mIU/L) target ranges and cancer recurrence in patients with DTC after thyroidectomy. This population-based retrospective cohort study used linked, administrative health care databases from Ontario, Canada, to follow patients with DTC post-thyroidectomy from 2007 to 2018. The exposure was time updated, serum TSH, treated as a cumulative and instantaneous exposure. Multivariable cause-specific proportional hazard regression analyses were performed to determine time to DTC recurrence from index date, defined as a composite of repeat neck surgery, radioactive iodine (RAI) treatment, and/or DTC-specific death. Results were also stratified by initial treatment as a marker of baseline recurrence risk in a sensitivity analysis. This cohort of 26,336 individuals (78% female) with DTC and a median age of 50 years were followed for a median of 5.9 (interquartile range 3.6-8.6) years; 40.9% were initially treated with a hemi-thyroidectomy only and 38.2% received a total thyroidectomy and RAI. Compared with exposure to TSH 0.5 to ≤2 mIU/L, DTC recurrence rate was similar for each additional 3 months of exposure to TSH >2 to ≤4 mIU/L (adjusted cause specific [cs] hazard ratio [HR] 0.99 [confidence interval or CI 0.97-1.02]) but was significantly increased with each additional 3 months of exposure to TSH >4 mIU/L (adjusted csHR 1.07 [CI 1.04-1.09]). Results were similar across baseline treatment groups. There was no difference in clinically significant recurrence in those with low-risk DTC maintained with a TSH of 0.5-2 mIU/L compared with 2-4 mIU/L. Guidelines should consider liberalizing target TSH level post thyroidectomy in low-risk cohorts. These results cannot be applied to patients with high-risk DTC.
在分化型甲状腺癌（DTC）甲状腺切除术后，将左甲状腺素用于抑制促甲状腺激素（TSH）至<0.5 mIU/L可能会降低高危DTC的复发率。然而，支持指南建议将TSH维持在0.5 - 2 mIU/L的低正常范围内以降低低危DTC患者复发率的证据有限。主要目的是评估甲状腺切除术后DTC患者中，高正常血清TSH（2 - 4 mIU/L）与低正常TSH（0.5 - 2 mIU/L）目标范围暴露与癌症复发之间的关联。这项基于人群的回顾性队列研究使用了加拿大安大略省相关的行政医疗保健数据库，对2007年至2018年甲状腺切除术后的DTC患者进行随访。暴露因素是随时间更新的血清TSH，被视为累积和即时暴露。进行多变量特定病因比例风险回归分析，以确定从索引日期到DTC复发的时间，索引日期定义为重复颈部手术、放射性碘（RAI）治疗和/或DTC特异性死亡的综合情况。在敏感性分析中，结果也按初始治疗进行分层，作为基线复发风险的一个指标。该队列包括26336名DTC患者（78%为女性），中位年龄为50岁，中位随访时间为5.9年（四分位间距3.6 - 8.6年）；40.9%的患者最初仅接受了甲状腺半切除术，38.2%的患者接受了全甲状腺切除术和RAI。与TSH暴露于0.5至≤2 mIU/L相比，TSH暴露每增加3个月，TSH>2至≤4 mIU/L时DTC复发率相似（调整后的特定病因[cs]风险比[HR]为0.99[置信区间或CI为0.97 - 1.02]），但TSH暴露每增加3个月，TSH>4 mIU/L时复发率显著增加（调整后的csHR为1.07[CI为1.04 - 1.09]）。各基线治疗组的结果相似。TSH维持在0.5 - 2 mIU/L的低危DTC患者与TSH维持在2 - 4 mIU/L的患者相比，临床显著复发率没有差异。指南应考虑放宽低危队列甲状腺切除术后的目标TSH水平。这些结果不适用于高危DTC患者。
