Thyroid Unit, Endocrine Tumor Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Thyroid. 2023 Jun;33(6):666-673. doi: 10.1089/thy.2022.0344.
Before the development of antithyroid drugs in the 1940s, treatment of Graves' hyperthyroidism was primarily surgical. Surgical mortality was quite variable, but a significant minority of patients died during or after surgery. In 1936, Karl Compton, President of the Massachusetts Institute of Technology, in a lecture attended by Massachusetts General Hospital physicians, suggested that artificially radioactive isotopes might be useful for studying metabolism. By 1942, Hertz and Roberts reported on the successful use of radioactive iodine (RAI) to treat Graves' hyperthyroidism. RAI uptake was subsequently demonstrated in well-differentiated thyroid cancer metastases. In 1948, Seidlin demonstrated stimulation of uptake in thyroid cancer metastases by thyrotropin (TSH). By 1990, 69% of endocrinologists in North America recommended RAI for Graves' hyperthyroidism. Currently RAI is less frequently used for Graves' hyperthyroidism, related to concerns about exacerbation of thyroid eye disease, about radiation exposure, and about potential adverse consequences of permanent hypothyroidism. Similarly, RAI was administered to the majority of patients with thyroid cancer for decades, but its use is now more selective. RAI is a remarkable example of interinstitutional cooperation between physicians and scientists to transition from bench to bedside in only three years. It is the model for a theranostic approach to disease (the simultaneous use of a radioactive drug for diagnosis and therapy). The future of RAI is less certain; inhibition of TSH receptor stimulating antibodies in Graves' disease and more precise targeting of genes that drive thyroid oncogenesis may diminish the use of RAI. Alternatively, redifferentiation techniques may improve the efficacy of RAI in RAI-refractory thyroid cancer.
在 20 世纪 40 年代抗甲状腺药物发展之前，Graves 病甲亢的治疗主要是手术。手术死亡率差异很大，但仍有相当一部分患者在手术期间或手术后死亡。1936 年，马萨诸塞州技术研究所所长卡尔·康普顿（Karl Compton）在麻省总医院医生参加的一次演讲中建议，人工放射性同位素可能有助于研究代谢。到 1942 年，赫兹（Hertz）和罗伯茨（Roberts）报告了放射性碘（RAI）成功治疗 Graves 病甲亢。随后，放射性碘在分化良好的甲状腺癌转移灶中被证明可以摄取。1948 年，塞德林（Seidlin）证明促甲状腺激素（TSH）可刺激甲状腺癌转移灶摄取。到 1990 年，北美 69%的内分泌学家建议用放射性碘治疗 Graves 病甲亢。目前，由于担心甲状腺眼病恶化、辐射暴露以及永久性甲状腺功能减退的潜在不良后果，放射性碘治疗 Graves 病甲亢的频率降低。同样，几十年来，RAI 被用于大多数甲状腺癌患者，但现在使用更加有选择性。RAI 是医生和科学家之间机构间合作的一个典范，仅用三年时间就从实验室过渡到临床。它是疾病治疗诊断综合疗法（同时使用放射性药物进行诊断和治疗）的模式。RAI 的未来不太确定；Graves 病中 TSH 受体刺激抗体的抑制以及更精确地针对驱动甲状腺癌发生的基因的靶向治疗可能会减少 RAI 的使用。或者，重新分化技术可能会提高 RAI 在 RAI 难治性甲状腺癌中的疗效。
