Endocrine and Diabetes Department, Prince Charles Hospital, Cwm Taf University Health Board, Merthyr Tydfil, CF47 9DT, UK.
Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK.
Expert Rev Endocrinol Metab. 2023 Jan;18(1):67-79. doi: 10.1080/17446651.2023.2167709. Epub 2023 Feb 5.
The thionamide anti-thyroid drugs namely carbimazole, methimazole, and propylthiouracil, have been the predominant therapy modality for Graves' hyperthyroidism for over 60 years. Although these agents have proven efficacy and favorable side-effect profiles, non-thionamide alternatives are occasionally indicated in patients who are intolerant or unresponsive to thionamides alone. This review examines the available non-thionamide drug options for the control of Graves' hyperthyroidism and summarizes their clinical utility, efficacy, and limitations.
We reviewed existing literature on mechanisms, therapeutic utility, and side-effect profiles of non-thionamide anti-thyroid drugs. Established non-thionamide agents act on various phases of the synthesis, release, and metabolism of thyroid hormones and comprise historical agents such as iodine compounds and potassium perchlorate as well as drug repurposing candidates like lithium, glucocorticoids, beta-blockers, and cholestyramine. Novel experimental agents in development target key players in Graves' disease pathogenesis including B-cell depletors (Rituximab), CD40 blockers (Iscalimab), TSH-receptor antagonists, blocking antibodies, and immune-modifying peptides.
Non-thionamide anti-thyroid drugs are useful alternatives in Graves' hyperthyroidism and more clinical trials are needed to establish their safety and long-term efficacy in hyperthyroidism control. Ultimately, the promise for a cure will lie in novel approaches that target the well-established immunopathogenesis of Graves' disease.
硫脲类抗甲状腺药物,即卡比马唑、甲巯咪唑和丙基硫氧嘧啶,已成为 Graves 甲亢 60 多年的主要治疗方法。尽管这些药物已被证明具有疗效且副作用小,但在对硫脲类药物不耐受或无反应的患者中,偶尔需要使用非硫脲类药物。本文回顾了 Graves 甲亢控制中可用的非硫脲类药物选择,并总结了它们的临床实用性、疗效和局限性。
我们回顾了非硫脲类抗甲状腺药物的作用机制、治疗效用和副作用特征的现有文献。已确立的非硫脲类药物作用于甲状腺激素合成、释放和代谢的各个阶段,包括碘化合物和高氯酸钾等历史药物以及锂、糖皮质激素、β受体阻滞剂和考来烯胺等药物再利用候选药物。正在开发中的新型实验性药物针对 Graves 病发病机制中的关键参与者,包括 B 细胞耗竭剂(利妥昔单抗)、CD40 阻滞剂(Iscalimab)、TSH 受体拮抗剂、阻断抗体和免疫调节肽。
非硫脲类抗甲状腺药物是 Graves 甲亢的有用替代药物,需要更多的临床试验来确定它们在控制甲状腺功能亢进症中的安全性和长期疗效。最终,治愈的希望将在于针对 Graves 病明确确立的免疫发病机制的新方法。