Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea.
Department of Preventive Medicine, College of Korean Medicine, Dongguk University, Gyeongju, Korea.
Endocrinol Metab (Seoul). 2024 Apr;39(2):288-299. doi: 10.3803/EnM.2023.1815. Epub 2024 Mar 4.
Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients.
We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy.
A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence.
High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.
目前的研究尚未探讨左旋甲状腺素抑制治疗对甲状腺癌患者继发原发性癌症（SPC）风险的影响。本研究旨在探讨左旋甲状腺素剂量与甲状腺癌患者 SPC 风险之间的关系。
我们进行了一项基于韩国国家健康保险数据库的全国性回顾性队列研究。该队列包括 2004 年至 2018 年间的 342920 例甲状腺癌患者。患者被分为未用左旋甲状腺素组和用左旋甲状腺素组，后者根据四分位法分为四个剂量亚组。通过调整放射性碘（RAI）治疗累积剂量等变量，使用 Cox 比例风险模型评估 SPC 风险。
在中位随访 7.3 年期间，共观察到 17410 例 SPC 病例。与未用左旋甲状腺素组相比，高剂量左旋甲状腺素亚组（Q3 和 Q4）的 SPC 风险更高（校正后的危险比[HR]分别为 1.14 和 1.27；95%置信区间[CI]分别为 1.05-1.24 和 1.17-1.37）。特别是 Q4 亚组中，胃（1.31）、结直肠（1.60）、肝和胆道（1.95）以及胰腺（2.48）癌症的校正 HR 升高。即使在调整了各种混杂变量后，我们仍观察到高剂量左旋甲状腺素剂量与 SPC 风险之间存在正相关。此外，在根据甲状腺切除术类型和 RAI 治疗以及良好依从性患者的亚组分析进行分层分析时，也得到了类似的结果。
无论是否进行 RAI 治疗，甲状腺癌患者使用高剂量左旋甲状腺素与 SPC 风险增加相关。
