BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. Graves’ disease is an autoimmune disease where the body makes an antibody directed against the TSH receptor that attacks and turns on the thyroid. This antibody is called thyroid stimulating immunoglobulin (TSI). Antithyroid medications (methimazole/MMI or PTU) are used to control the hyperthyroidism before definitive therapy or to treat until a remission occurs (ie when the TSI goes away). The definitive options that destroy the thyroid include radioactive iodine therapy and surgery. In the past, radioactive iodine therapy was the most common treatment for Graves’ disease in the United States. Recently, more and more physicians have been preferring treating patients with anti-thyroid medications instead of with radioactive iodine ablation, with MMI the most common antithyroid medication used. The goal is to treat until a remission occurs.

Remission of Graves’ disease with MMI has been reported anywhere from 3 – 48 months. However, recent studies have shown that patients are more likely to have a remission from Graves’ disease if they were on methimazole for a total of 60 months (long term) as compared to only 12-18 months (short term). While factors that predict recurrence in short term MMI therapy have been previously reported, these may differ when considering long term MMI therapy. This study was performed to assess predictors of relapse and to determine the rate of relapse of patients after short and long-term MMI therapy.

THE FULL ARTICLE TITLE
Azizi F et al. Risk of recurrence at the time of withdrawal of short- or long-term methimazole therapy in patients with Graves’ hyperthyroidism: a randomized trial and a risk-scoring model. Endocrine 2024;84(2):577-588; doi: 10.1007/s12020-023-03656-5. PMID: 38165576.

SUMMARY OF THE STUDY
A total of 302 patients with Graves’ disease were treated for 18-24 months with MMI. Of these patients, 128 were monitored off medication after completing short-term treatment, and 130 patients were continued on MMI longer for a total treatment duration of 60-120 months. The primary end point was relapse into overt hyperthyroidism, and the secondary end points were hypothyroidism and subclinical hyperthyroidism.

Overt hyperthyroidism occurred in 56% (67 patients) of the short term MMI group and only 17% (20 patients) of the long term MMI group. Overall, 44% of the short term MMI group (53 patients) and 83% (98 patients) of the long term MMI group were still successfully in remission after 84 months. Even after adjusting for other factors that might affect the results, the short term MMI group was 16.2 x more likely than the long term MMI group have a Graves’ recurrence after treatment. The patient’s free T4 hormone level was a risk factor for recurrence in the short term MMI group, but not the long term MMI group. In both the short term and the long term MMI groups, the following factors were clinically significant for increasing chances of recurrence: male sex, T3 level, TSI level, and size of the goiter.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
In patients experiencing their first Graves’ disease episode, this data shows that long term MMI treatment of >60 months is more likely to ensure a remission than the short term MMI treatment of 18 months. This is important since the current 2016 American Thyroid Association guidelines recommend stopping methimazole after 12-18 months. To help determine the likelihood of remission, the authors are proposing a scoring system that will divide patients into risks of recurrence of 20% or 60%. This scoring system will need to be tested in larger studies but holds a lot of promise in helping to determine the best option for treatment of Graves’ disease.

— Pinar Smith, MD

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