Sustained Euthyroidism during Thionamide Antithyroid Drug Treatment: Comparison of Short- and Long-term Methimazole Therapy

Background: Extended low serum thyrotropin (TSH) levels may increase the risk of cardiovascular events in patients with hyperthyroidism. Objectives: This study aimed to compare the time spent with sustained normal TSH concentration following short- and long-term methimazole treatment. Methods: A total of 258 patients with Graves’ hyperthyroidism completed 18 - 24 months of methimazole therapy and were randomized to discontinue treatment (n = 128, short-term group) or continue an additional 36 - 102 months of methimazole therapy (n = 130, long-term group). Clinical and laboratory evaluations were performed every 6 months for 132 months after randomization. Results: There was no difference in serum-free thyroxine, triiodothyronine, and TSH concentrations between the 2 groups at the time of randomization. Of 128 patients in the short-term group, 5 left in follow-up, 2 became hypothyroid, 67 (54%) had a relapse of hyperthyroidism, and only 54 (44%) were euthyroid at the end of the study. Among 130 patients on the long-term methimazole therapy, 4 were left in follow-up, 24 developed hyperthyroidism, 4 developed hypothyroidism, and 98 (78%) were euthyroid 132 months post-randomization. Total time spent on euthyroidism was 90.4% ± 8.1% of the study period in the short-term and 95.8% ± 7.0% in the long-term treatment groups (P < 0.001). The lowest time spent in euthyroidism (74.6% ± 6.4% of the study period) belonged to 29 (24%) patients in the short-term group under levothyroxine therapy because of fluctuation in serum TSH. Patients in both groups with hyperthyroidism relapse who chose methimazole therapy spent >90% of the study time in euthyroidism. Conclusions: In patients with Graves' hyperthyroidism, sustained normal serum TSH levels were more common in the long term as compared to the short-term methimazole treatment.