Characteristics of patients with Graves' disease who developed drug resistance and required surgery

Although antithyroid drugs (ATDs) are the first-line treatment for patients with Graves' disease (GD) in Japan and other countries, some patients do not achieve remission due to drug resistance, leading to surgery. Even if ATD doses are increased, they often have uncontrolled thyroid function and enlarged goiters, necessitating high-risk emergency surgical treatment. In this study, we aimed to identify the characteristics of patients resistant to ATDs who underwent thyroidectomy and those who achieved remission. We retrospectively analyzed 45 patients with GD who underwent thyroidectomy and 73 patients who achieved remission with ATDs at Shinshu University Hospital between April 1, 2015 and September 30, 2023. In patients who underwent surgery, the drug-resistant patients (DR group; n = 15) had longer disease durations (8.0 vs. 3.0 years, respectively; p = 0.013), higher free triiodothyronine (FT3) / free thyroxine (FT4) ratios (5.54 vs. 3.52, respectively; p = 0.005), higher anti-TSH receptor antibody (TRAb) levels (39.16 vs. 13.31 IU/L, respectively; p = 0.002), and larger thyroid glands (251.00 vs. 54.80 g, respectively; p < 0.001) than non-drug-resistant patients (NDR group; n = 30). Compared with patients who achieved remission with ATDs (Remission group; n = 73), the DR group had higher FT3/FT4 ratios (5.54 vs. 2.99, respectively; p < 0.001) and higher TRAb levels (39.16 vs. 5.9 IU/L, respectively; p < 0.001). Notably, most of the patients in the DR group had a combination of these factors. This suggests that in patients with large thyroid, high FT3/FT4 ratios, and high TRAb levels, early consideration of definitive-curative treatment such as surgery or RI therapy may be warranted instead of continuing prolonged ineffective ATDs treatment.