Long-Term Antithyroid Drug Treatment: Trends in Serum TSH and TSH Receptor Antibody Changes in Patients with Graves’ Disease

Objectives: Trends in serum thyroid-stimulating hormone (TSH) and TSH receptor antibody (TRAb) changes during antithyroid drug treatment, and long-term prognosis were evaluated in Graves’ hyperthyroidism (GD). Methods: In 609 GD patients initially treated with 15 mg of methyl-mercapto imidazole (MMI), the changes in serum TRAb and long-term prognosis were compared in the TSH-normalized group (A) and the TSH-suppressed group (B and C) during the initial 180 days of treatment. Results: Early responses to MMI during 180 days of treatment were as follows: 48 cases (7.9%) became hypothyroid with elevated TSH (A1), and 188 cases (30.9%) became euthyroid with normal TSH (A2). Among patients with continuously suppressed TSH, the free T4 (fT4) level was low in 31 cases (5.1%) (B1-inappropriately suppressed TSH), fT4 and fT3 were normal in 185 cases (30.4%) (B2), fT4 was normal, but fT3 remained high in 84 cases (13.8%) (B3), and fT4 remained high in 73 cases (12.0%) (C-refractory). Serum TRAb became negative after < 5 years then remained negative in 25% - 51% of the cases (smooth type), became negative after < 5 years then became positive again in 30% - 43% of the cases (fluctuating type), and remained positive after > 5 years in 10% - 42% of the cases (smoldering type). In total, remission occurred after 6.2 (3.0 - 10.4) years of treatment in 42%, possible remission on a small maintenance dosage of antithyroid drug occurred in 13%, and spontaneous hypothyroidism occurred in 4.4% of the cases. The smoldering type was more frequent in the B1 and C groups than in others, and remission was less frequent. The difference in the long-term prognosis depending on the early response to MMI disappeared after excluding the ablated patients. Without ablation, remission or spontaneous hypothyroidism could be expected in 60% - 75% of patients after tenacious treatment for > 10 years. Conclusions: Prolonged suppression of serum TSH may suggest active TRAb activity during treatment, and continuous TRAb positivity for more than 5 years suggests persistent GD activity.