BACKGROUND
Graves’ disease is the most common cause of hyperthyroidism in the United States. Graves’ disease is caused by the body making an antibody (thyrotropin receptor antibody, TRAb) that attacks and turns on the thyroid gland, causing it to produce too much thyroid hormone. Antithyroid drugs (ATDs), such as methimazole or prophylthioruacil, are the first-line treatment of Graves’ disease to bring thyroid hormone levels back to normal and prevent harmful effects on various organ systems, including heart and bone.

In the 1990s, a treatment strategy using high-dose ATDs to completely shut down the thyroid gland along with levothyroxine to replace the thyroid hormones (known as “block-and-replace” therapy) had gained some popularity. High dose of ATDs used in this regimen was thought to decrease stimulating action of TRAb more rapidly while levothyroxine provides thyroid hormone replacement, compared to using ATDs alone. However, this strategy has not been shown to be quicker in resolving Gaves’ disease than ATDs alone. There were also concerns about increased risks of side effects and overtreatment with high-dose ATDs. Therefore, block-and-replace therapy is currently not routinely used. However, recent studies have suggested that block-and-replace therapy using lower ATD doses (low-dose block and replace) may be able to be effective with less side effects.

This study compared high-dose and low-dose block-andreplace therapy in patients with first episodes of Graves’ disease to determine whether lower ATDs dose would be as effective as higher ATDs dose with possibly less side effects.

THE FULL ARTICLE TITLE
Smolders A et al High-dose versus low-dose block-andreplace treatment for a first episode of Graves’ disease. Eur Thyroid J 2025;14:e250039; doi: 10.1530/ETJ-25-0039. PMID: 40172327.

SUMMARY OF THE STUDY
Records of 120 patients with newly diagnosed Graves’ disease treated between 1990 and 2022 in two hospitals in Belgium were used for this study. A total of 60 patients received high dose regimen, with 30 mg of methimazole and levothyroxine. The other 60 patients received low dose regimen, with methimazole starting at 20-40 mg a day and adjusted to 10-20 mg a day once free thyroxine (FT4) levels became normal. All patients were treated for at least 12 months and monitored for one year afterwards or until recurrence of Graves’ disease off the medications.

The proportion of patients who had recurrence of Graves’ disease after medications are discontinued were similar (63% in the high-dose group and 60% in the low-dose group), with similar time to recurrence (11 months in the high-dose group and 7 months in the low-dose group) between the two groups. TRAb became normal more frequently in the low-dose group than in the high-dose group (86% vs 65%). There were no significant differences in development of thyroid eye disease or frequency of medication side effects between two groups.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors concluded that the low-dose block-and-replace therapy achieved similar results in treatment of Graves’ disease as the high-dose block-and-replace therapy with less medications and better normalization of TRAb levels, which can lead to remission of Graves’ disease. Currently, blockand- replace therapy is rarely used in the United States. Based on findings of this study, block-and-replace therapy with low-dose ATDs may be an option with less concern for potential side effects in select cases, where thyroid function changes significantly on ATDs alone. However, we do not know whether low-dose block-and-replace therapy is more or similarly effective and safe to ATD alone in treating Graves’ disease. Such studies are needed before block-andreplace therapy would be more routinely considered for treatment of Graves’ disease.

— Sun Y. Lee, MD

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