Graves’ disease, the most common type of hyperthyroidism, is an autoimmune disease associated with autoantibodies (TRAb), the exact mechanism of which is not well understood, and is traditionally treated with antithyroid drugs (ATD), radioactive iodine (RAI) and surgery. Only ATD treatment targets immune factors and ultimately cures hyperthyroidism by converting TRAb to negative. ATD therapy has been repeatedly emphasized in Chinese and foreign literature as the basic treatment for all Graves’ hyperthyroidism and the first choice for hyperthyroidism worldwide (except in the U.S.), as it does not destroy the thyroid follicular structure, is safe and effective, is reversible, and does not cause permanent hypothyroidism. The treatment pathway for Graves’ hyperthyroidism proposed by Prof. Cooper (NEJM, 2005), president of ATA, can give us some clinical guidance. Graves’ disease accounts for approximately 90% of all hyperthyroidism cases and is the most common type of hyperthyroidism. It is an organ-specific autoimmune disease characterized by the presence of autoantibodies (TRAb) in the serum that react with thyroid tissue and excite the thyroid tissue when the antibodies bind to TSH receptors, leading to hyperplasia and hyperfunction of the thyroid tissue. The pathogenic mechanism of Graves’ hyperthyroidism is not well understood and involves a variety of immune molecules, cytokines and chemokines, just like a network. According to the findings of the Thyroid Unit of Ruijin Hospital, Graves’ hyperthyroidism is partly caused by antigenic (viral or bacterial) stimulation, which leads to an increase in the number of peripheral blood dendritic cells (DCs), especially an increase in the percentage of subpopulations of pDCs, and a significant increase in interferon alpha (IFNa) secreted by pDCs in the serum of hyperthyroid patients, leading to transdifferentiation of thyroid follicular cells in hyperthyroid patients. An increase in MHC-II molecules specific to antigen-presenting cells occurs, which transmits the same increased TSH receptor (TSHR) to T and B cells, eventually producing antibodies to the TSH receptor (TRAb). At the same time, interferon alpha also acts as a suppressor of regulatory T cells, promoting the value-added of T cells and accelerating antibody production. There are three traditional treatments for Graves’ hyperthyroidism: antithyroid drug (ATD) therapy, radioactive iodine (RAI) and surgery. Only ATD treatment targets immune factors and ultimately cures hyperthyroidism by converting TRAb to negative. ATD antithyroid drugs are mainly thiourea derivatives, drug molecules containing sulfur or sulfhydryl groups that coalesce in the thyroid gland and inhibit thyroxine synthesis by preventing the tyrosine residues in thyroglobulin from being iodinated mediated by thyroid peroxidase. In addition to this primary effect, ATD therapy also has the following effects: blocking T4-T3 conversion; immunosuppressive effects; and induction of apoptosis of lymphocytes in the thyroid gland. The characteristics of ATD therapy: (1) It is the basic treatment for all Graves’ hyperthyroidism, which has been repeatedly emphasized in Chinese and foreign literature. (2) It is the treatment of choice for hyperthyroidism worldwide (except in the U.S.). 2008 ATA meeting in the U.S. reported that Graves’ hyperthyroidism was treated with ATD in Europe: 80% in the UK, >90% in Spain, and 77% in the rest of Europe (ETA). Asia: 80% in China, 88% in Japan, >80% in South Korea. Australia >80%. Only the United States 31%. (3) ATD treatment is safe and effective, the drug effect is reversible and does not cause permanent hypothyroidism. (4) ATD treatment is the only treatment that does not destroy the follicular structure of the thyroid gland. ATD therapy can be preferred not only as a single option, but also as a superior option before surgery and isotope therapy. Walter MA concluded with Mata analysis2 that the use of ATD before RAI significantly reduces complications such as new-onset atrial fibrillation or death. Another Andrade et al. concluded that the use of ATD before RAI significantly reduced the chance of developing hyperthyroid crisis due to radioinflammation. ATD is indicated for all patients with hyperthyroidism, especially mild, mild to moderately enlarged Graves’ disease, who are under 20 years of age, or who have hyperthyroidism in pregnancy, or who are elderly and frail. Hypothyroidism can occur in children after radioactive iodine (RAI) therapy for hyperthyroidism, and hypothyroidism can have a significant impact on growth and development in children. Anti-thyroid medication is the preferred treatment for hyperthyroidism in children because it is easy to use, has less impact on learning, and avoids permanent and irreversible damage to the child. Absolute contraindications to RAI treatment include: pregnancy and lactation; caution or non-use of RAI in the following cases: those under 20 years of age; severe cardiac, hepatic or renal insufficiency or active tuberculosis; moderate to severe (active) infiltrative proptosis; peripheral blood leukocytes below 3000/mm or neutrophils below 1500/mm; and thyroid crisis. Disadvantages of isotope (RAI) therapy: isotope (RAI) therapy is always destructive and can lead to permanent hypothyroidism, requiring lifelong medication; can lead to radiation thyroiditis, especially 10 days after isotope administration; may induce thyroid crisis if isotope therapy is not preceded by an ATD-optimal regimen; aggravates infiltrative proptosis: Bartelena L et al. 1998) that 14% of hyperthyroidism combined with proptosis was aggravated by treatment with isotopes (RAI), 86% was unchanged, and there was no improvement. In the group treated with ATD, there was a 3.6% improvement rate, 3.6% worsening rate, and no change in the rest. It can be seen that treatment with ATD is superior to RAI treatment for eye disease. A questionnaire survey of 698 UK endocrine endocrinologists (Clin Endocrinol, 2008) found that, in general, respondents preferred to use isotope therapy for patients with recurrent hyperthyroidism, elderly patients, comorbid cardiac disease, and poor compliance with long-term medication. They were less likely to administer isotope therapy to patients with thyroid-related eye disease and to children. The majority of respondents (46%) avoided isotope therapy for patients with comorbid active eye disease and administered it under glucocorticoid protection for those with inactive disease, but 26% avoided isotope therapy for patients with comorbid active eye disease and administered it without glucocorticoid protection for those with inactive disease. Comparing the cost of ATD therapy with RAI therapy: ATD therapy is not expensive in terms of medication, but mainly slightly more expensive in terms of labs; the later is the maintenance amount of ATD and the lab interval is long. In addition to the one-time cost of isotope, RAI treatment causes hypothyroidism and requires lifelong replacement of lifelong laboratory tests, which is not less expensive than ATD treatment, or even more expensive. Due to the uneven medical conditions in China, indicators such as TRAb (thyrotropic receptor antibodies) are often not detected (hyperthyroidism in Hashimoto’s thyroiditis) and misdiagnosis directly leads to permanent hypothyroidism, and more complications after RAI treatment usually increase the psychological stress of patients and the cost of treatment, leading to a waste of medical resources. In the United States, the appointment system is not conducive to the adjustment of medications for hyperthyroidism ATD treatment, so RAI treatment is chosen more often. However, Tominiga et al. (Thyroid, 1997) found that the majority of young patients with hyperthyroidism are still treated with ATD, regardless of whether they are in Asia, Europe, or the United States. Therefore, Professor Cooper (NEJM, 2005), president of ATA, proposed a treatment pathway for Graves’ hyperthyroidism: ATD therapy is preferred for mild to moderate hyperthyroidism, mild to moderate goiter, childhood hyperthyroidism or pregnant/lactating women with severe ophthalmopathy, with thyroid function testing to adjust medication and discontinuation after 12-18 months, followed by testing every 2 months for 6 months. The frequency can be reduced thereafter. After remission, the test should be performed once a year. In case of relapse, a second course of ATD is used for children and adolescents, and ATD treatment can be repeated or RAI treatment can be used for adults. In adults with severe biochemical changes (e.g., serum T3 >700ng/dl, very large goiter, >4 times normal), RAI therapy is considered the first choice. However, even then, in elderly people or those with cardiac disease, RAI treatment should be preceded by ATD treatment to bring the thyroid function to normal levels. In summary, ATD therapy has been used in clinical practice for 60 years. Among the major treatments for Graves’ hyperthyroidism, only ATD can achieve satisfactory results without damaging the thyroid gland and can restore normal thyroid function after cure without the need for lifelong replacement with thyroid preparations. Although the cure rate of antithyroid drugs has been reported to be inconsistent, there is still a considerable cure rate as long as sufficient courses of treatment are used and appropriate discontinuation indications are chosen. Therefore, ATD therapy should remain the first choice for Graves’ hyperthyroidism. Of course, for patients with markedly enlarged thyroid, drug allergy or severe complications, radionuclide RAI therapy and surgery are necessary additions to the treatment of hyperthyroidism.