Division of Internal Medicine and Cardiovascular Endocrinology, Department of Clinical Medicine and Surgery, University Federico II of Naples, 80131 Naples, Italy.
Division of Endocrinology and Metabolism, Department of Medicine UConn Health, Farmington, CT 06030-8075, USA.
J Clin Endocrinol Metab. 2023 Sep 18;108(10):2708-2716. doi: 10.1210/clinem/dgad224.
Hypothyroidism is a common condition, and numerous studies have been published over the last decade to assess the potential risks associated with this disorder when inappropriately treated. The standard of care for treatment of hypothyroidism remains levothyroxine (LT4) at doses to achieve biochemical and clinical euthyroidism. However, about 15% of hypothyroid patients experience residual hypothyroid symptoms. Some population-based studies and international population-based surveys have confirmed dissatisfaction with LT4 treatment in some hypothyroid patients. It is well established that hypothyroid patients treated with LT4 exhibit higher serum thyroxine:triiodothyronine ratios and can have a persistent increase in cardiovascular risk factors. Moreover, variants in deiodinases and thyroid hormone transporter genes have been associated with subnormal T3 concentrations, persistent symptoms in LT4-treated patients, and improvement in response to the addition of liothyronine to LT4 therapy. The American (ATA) and European Thyroid Association (ETA) guidelines have recently evolved in their recognition of the potential limitations of LT4. This shift is reflected in prescribing patterns: Physicians' use of combination therapy is prevalent and possibly increasing. Randomized clinical trials have recently been published and, while they have found no improvement in treating hypothyroid patients, a number of important limitations did not allow generalizability. Meta-analyses have reported a preference rate for combination therapy in 46.2% hypothyroid patients treated with LT4. To promote discussions about an optimal study design, the ATA, ETA, and British Thyroid Association have recently published a consensus document. Our study provides a useful counterpoint on the controversial benefits of treating hypothyroid patients with combination therapy.
甲状腺功能减退症是一种常见疾病，在过去十年中，已经发表了许多研究来评估在治疗不当的情况下与这种疾病相关的潜在风险。甲状腺功能减退症的治疗标准仍然是左甲状腺素 (LT4)，剂量要达到生化和临床甲状腺功能正常。然而，大约 15%的甲状腺功能减退症患者仍存在甲状腺功能减退症状。一些基于人群的研究和国际基于人群的调查证实，一些甲状腺功能减退症患者对 LT4 治疗不满意。已经证实，接受 LT4 治疗的甲状腺功能减退症患者血清甲状腺素：三碘甲状腺原氨酸比值较高，心血管危险因素持续增加。此外，脱碘酶和甲状腺激素转运蛋白基因的变异与 T3 浓度降低、LT4 治疗患者持续存在症状以及添加三碘甲状腺原氨酸至 LT4 治疗后反应改善有关。美国甲状腺协会 (ATA) 和欧洲甲状腺协会 (ETA) 指南最近在认识到 LT4 的潜在局限性方面发生了变化。这种转变反映在处方模式上：医生联合治疗的使用很普遍，而且可能在增加。最近发表了随机临床试验，尽管它们没有发现治疗甲状腺功能减退症患者的改善，但许多重要的局限性不允许推广。荟萃分析报告称，在接受 LT4 治疗的 46.2%甲状腺功能减退症患者中，联合治疗的偏好率更高。为了促进关于最佳研究设计的讨论，ATA、ETA 和英国甲状腺协会最近发表了一份共识文件。我们的研究为用联合疗法治疗甲状腺功能减退症患者的有争议的益处提供了一个有用的对比。
