Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial

Abstract

Objective: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ( 131 I) therapy. Design: A randomized clinical trial was performed to clarify whether resumption of methimazole after 131 I influences the final outcome of this treatment. Methods: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (þATD) or not to resume (2ATD) methimazole 7 days after 131 I. Before 131I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the 131 I therapy. Results: During the follow-up period of 12 months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the þATD group; the respective numbers in the 2ATD group were 16, 42 and 18 (P ¼ 0.88). At 3 weeks after 131 I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) 215.5 to 5.4%) in the þ ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the 2ATD group (P , 0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid volume reduction, assessed by ultrasonography, was smaller in the þATD group [38.7% (95% CI 33.3to 44.1%)] than in the 2ATD group [48.6% (95% CI: 41.5 -55.6%)] (P , 0.05). Conclusion:No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after 131 I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by 131 I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

Glucocorticoids do not influence the effect of radioiodine therapy in Graves’ disease

“…We did not find an adverse influence of either PTU or methimazole use. Although some retrospective studies (19 -21) have indicated that ATDs reduce the cure rate following 131 I therapy, our present results are in line with the findings in randomized studies by us and others on the use of methimazole (22)(23)(24). The fact that we were unable to demonstrate any radioprotective property of PTU is in contrast to that which has been shown by two recent prospective trials (25,26), and may be due to the relatively few patients receiving this drug.…”

Radioiodine treatment for benign thyroid diseases

“…If a patient requires antithyroid drug treatment with propylthiouracil prior to radioiodine treatment, this protective effect can be overcome by stopping drug treatment 2 months beforehand or by giving a higher dose of radioiodine. Patients should avoid antithyroid drug treatment for at least 7 days after radioiodine treatment, as this is known to be without detriment to outcome, but it is not yet known if a shorter period before starting treatment is also without effect on outcome 30 . Whether propylthiouracil has any greater potential to have an adverse effect on outcome compared to carbimazole or methimazole when given after radioiodine administration is also not clear.…”

Antithyroid Drug Therapy in Patients with Graves’ Disease

“…There is some evidence to support restarting ATDs 7 days after radioiodine administration in patients considered to be at risk for cardiovascular complications, owing to the fact that thyroid hormone levels may be more stable with ATD treatment both before and after radioiodine administration [ 64 ]. Since ATDs interfere with iodine utilization by the thyroid gland, the drug must be stopped for about 3 days prior to radioiodine administration; stopping it for longer than 3 days is not necessary [ 65 ].…”