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Continuous Methimazole Therapy and Its Effect on the Cure Rate of Hyperthyroidism Using Radioactive Iodine: An Evaluation by a Randomized Trial

Departments of Endocrinology and Metabolism (S.J.B., F.N.B., L.H.) and Nuclear Medicine (A.V., J.M.), Odense University Hospital, DK-5000 Odense C, Denmark

Address all correspondence and requests for reprints to: Steen J. Bonnema, M.D., Ph.D., Department of Endocrinology and Metabolism, Odense University Hospital, DK-5000 Odense C, Denmark. E-mail: steen.bonnema{at}dadlnet.dk.

Background: A randomized clinical trial was performed to clarify whether continuous use of methimazole (MTZ) during radioiodine (¹³¹I) therapy influences the final outcome of this therapy.

Design: Consecutive patients with Graves’ disease (n = 30) or a toxic nodular goiter (n = 45) were rendered euthyroid by MTZ and randomized to stop MTZ 8 d before ¹³¹I (–MTZ; n = 36) or to continue MTZ until 4 wk after ¹³¹I (+MTZ; n = 39). Calculation of the ¹³¹I activity included an assessment of the ¹³¹I half-life and the thyroid volume.

Results: The 24-h thyroid ¹³¹I uptake was lower in the +MTZ group than in the –MTZ group (44.8 ± 15.6% vs. 62.1 ± 9.9%, respectively; P < 0.001). At 3 wk after therapy, no significant change in serum free T₄ index was observed in the +MTZ group (109 ± 106 vs. 83 ± 28 nmol/liter at baseline; P = 0.26), contrasting an increase in the –MTZ group (180 ± 110 vs. 82 ± 26 nmol/liter; P < 0.001). The number of cured patients was 17 (44%) and 22 (61%) in the +MTZ and –MTZ groups, respectively (P = 0.17). Cured patients tended to have a lower 24-h thyroid ¹³¹I uptake (50.1 ± 13.8% vs. 56.4 ± 17.1%; P = 0.09). By adjusting for a possible interfactorial relationship through a regression analysis (variables: randomization, 24- and 96-h thyroid ¹³¹I uptake, type and duration of disease, age, gender, presence of antithyroid peroxidase antibodies, thyroid volume, dose of MTZ), only the continuous use of MTZ correlated with treatment failure (P = 0.006), whereas a low 24-h thyroid ¹³¹I uptake predicted a better outcome (P = 0.006).

Conclusion: Continuous use of MTZ hinders an excessive increase of the thyroid hormones during ¹³¹I therapy of hyperthyroid diseases. However, such a strategy seems to reduce the final cure rate, although this adverse effect paradoxically is attenuated by the concomitant reduction of the thyroid ¹³¹I uptake.