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In China the therapeutic options to treat hyperthyroidism comprise antithyroid drugs (ATDs), radioiodine (131I) therapy and surgery. Physicians in China avoid the risk of hypothyroidism as a consequence of either treatment because patients from rural districts cannot easily comply with long-term medication. Therefore, we prospectively assessed the efficacy and safety of 131I versus ATDs.Of 2021 hyperthyroid patients 460 without any previous treatment were enrolled in a 9-year prospective, randomized, open-label blinded endpoint study and randomly assigned to receive either 131I or ATD. Follow-up was 98.4±5.5 months. The primary outcome was euthyroidism, persistent hyperthyroidism, recurrence, and hypothyroidism.Euthyroidism was achieved in 69.9 and 41.2% using either 131I or ATD, 2.4 and 19.2% remained hyperthyroid, hypothyroidism occurred in 21.5 and 9.0%, recurrence in 6.2 and 30.5%, respectively. Time to cure was shorter with 131I (44.8 vs. 74.8 months, P<0.01). Goiter size extended time to cure. Hard goiter, complications, or ophthalmopathy were protective against hypothyroidism after 131I therapy. Large goiters or long courses of hyperthyroidism predicted failure of ATD treatment.This study showed a shorter cure time using 131I. Time to remission in ATD patients was shorter during the first 9 months. Thereafter, the 131I group showed a higher remission rate. Low long-term hypothyroidism and low recurrence or persistent hyperthyroidism rates were achieved with our 131I dose regimen, regardless of the underlying disease. Lesser 131I activity was used as compared with current guidelines. Within limitations, our concept may simplify procedures in other geographical regions.