Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
Department of Biostatistics, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
Thyroid. 2022 Jul;32(7):764-771. doi: 10.1089/thy.2021.0634. Epub 2022 Jun 7.
Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM). We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder. We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002-2.764, = 0.049) and stroke (IRR = 1.757, CI 1.073-2.877, = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy. The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations.
联合使用左甲状腺素（LT3）和左甲状腺素钠（LT4）治疗持续存在症状的患者，尽管给予了足够剂量的 LT4。LT3 也可用于一些准备接受放射性碘治疗的甲状腺癌患者。然而，LT3 使用的安全性存在争议，并且在亚洲人群中，LT3 治疗的长期安全性尚无明确证据。本研究旨在使用通用数据模型（CDM）检查 LT3 治疗的长期安全性。我们在四个编码为观察性医疗结果合作研究组织（OMOP）CDM 的医院数据库中进行了回顾性多中心研究。LT3 使用者被定义为至少接受 LT3 处方 90 天（无论是否使用 LT4）的患者，在 1:4 倾向评分匹配后，将他们的安全性结果与仅使用 LT4 的患者进行比较。安全性结果包括骨质疏松症、心血管疾病、癌症、焦虑症和情绪障碍的发生率。我们确定了 1434 名 LT3 使用者和 3908 名仅使用 LT4 的患者。LT3 使用者和仅使用 LT4 的使用者之间的安全性结果发生率存在统计学差异。心力衰竭（发病率比 [IRR] = 1.664，95%置信区间 [95%CI] 1.002-2.764，= 0.049）和中风（IRR = 1.757，CI 1.073-2.877，= 0.025）的风险更高。在根据是否存在甲状腺癌病史和甲状腺激素替代治疗的持续时间进行亚组分析时，有甲状腺癌病史和接受≥52 周 LT3 治疗的 LT3 使用者心力衰竭风险更高。此外，无甲状腺癌病史和接受≥52 周 LT3 治疗的 LT3 使用者中风风险更高。LT3 的使用与 LT3 使用时间较长和有甲状腺癌病史的患者心力衰竭和中风发生率增加相关。因此，临床医生应考虑长期使用 LT3 的甲状腺癌患者发生心力衰竭和中风的风险。这些发现需要在其他人群中得到证实。
