Long-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ Disease

Abstract

Clinical ThyroidologyVol. 35, No. 02 HyperthyroidismFree AccessLong-Term, Low-Dose Methimazole Therapy Is Effective in Protecting against Relapses in Graves’ DiseaseGiuseppe BarbesinoGiuseppe BarbesinoThyroid Unit, Division of Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, U.S.A.Search for more papers by this authorPublished Online:8 Feb 2023https://doi.org/10.1089/ct.2023;35.54-56AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Review of: Lertwattanarak R, Kunavisarut T, Sriussadaporn S 2022 Benefits of Long-term continuation of low-dose methimazole therapy in the prevention of recurrent hyperthyroidism in Graves' hyperthyroid patients: A randomized prospective controlled study. Int J Endocrinol 2022:1705740. PMID: 36267362.SUMMARYBackgroundThe management of Graves’ disease (GD) hyperthyroidism has been evolving over the past two decades. The traditional standard of care suggested treatment with methimazole for 12 to18 months followed by radioactive iodine (RAI) treatment or surgery (1) in patients not achieving remission, where remission is defined as the ability to maintain euthyroidism after discontinuation of methimazole. This recommendation is supported by the recognition that longer courses of antithyroid drugs do not increase the rate of lasting remissions after discontinuation (2). This strategy has become less attractive owing to increasing evidence that RAI can cause or worsen thyroid eye disease (3) on the one hand and on the other to concerns about quality of life with hypothyroidism, even when thyroid hormone is optimally replaced (4). This study (5) was conducted to understand whether long-term therapy with low-dose methimazole could protect GD patients from relapses of hyperthyroidism.MethodsThis was a randomized controlled study in adult GD patients who had been euthyroid while taking methimazole for at least 6 months prior to randomization. The patients were randomly assigned to either continue methimazole at low doses (2.5–5 mg daily) or discontinue methimazole. The subjects’ thyroid function was then monitored every 6 months for 36 months. Standard diagnostic criteria for GD were adopted for inclusion. Patients who had already experienced a relapse were excluded. The primary outcome measured was the cumulative incidence of relapsing hyperthyroidism in the two groups.ResultsNinety-two patients were randomly assigned to the discontinuation group and 92 to the low-dose treatment group. Except for minor differences, the two groups were very similar for most epidemiologic parameters (86% female vs. 84% and mean [±SD] age, 39.9±10.9 vs. 42.2±14.9 years), indicating a reliable randomization process. The average duration of methimazole therapy prior to randomization was 37 months in the discontinuation group and 32 months in the low-dose group (not statistically different). In the discontinuation group, the number of relapses increased progressively and uniformly during the study time, reaching 41.2% at 36 months. In the low-dose group, the rate of relapse was 11%, and it was reached 18 months after randomization, with no additional relapses after that time. There were no recorded side effects during the study period.ConclusionsIn patients with GD, long-term treatment with 2.5 to 5 mg of methimazole daily is safe and effective in preventing the relapse of hyperthyroidism. This strategy is a valid alternative to RAI therapy and thyroidectomy in patients who want neither and yet worry about relapses of hyperthyroidism.COMMENTARYGraves’ disease, like many other autoimmune diseases, is often characterized by flares and remissions (6). Patients taking methimazole are typically treated for 12 to 18 months, after which a discontinuation trial is performed, in the hope of a lasting remission. Measuring serum TSH receptor antibodies (TRAbs) before antithyroid drug discontinuation helps to identify patients who are at high risk for early relapses in the 3 to 6 months after discontinuation (7). However, 20 to 30% of patients negative for TRAbs will still relapse months to years after the discontinuation (8,9). This observation, and mounting diffidence towards RAI therapy and surgery, has led to increased interest for long-term methimazole treatment. The data so far available have been mostly retrospective, or have addressed only select patient groups (for example, patients who already have experienced a relapse) (10). Like other endocrinologists, I have been advising some of my patients with GD who appear to be “currently” in remission, to continue methimazole indefinitely at very low doses, typically 2.5 mg daily. This article provides good-quality evidence to support such a practice, which I will continue to apply, especially to older patients and patients who had experienced particularly intense symptoms from the hyperthyroidism at the time of its first presentation.Disclosures: The author has no relevant conflicts of interest to declare.