Do Not Discontinue Methimazole in Euthyroid Patients with Graves' Disease
Continue low-dose methimazole (2.5-5 mg daily) indefinitely in patients who have achieved euthyroid status, as this approach significantly reduces recurrence rates compared to discontinuation after the standard 12-18 month course. 1
Evidence for Long-Term Continuation
The highest quality and most recent evidence demonstrates that continuing low-dose methimazole beyond the conventional treatment period provides substantial benefits:
Long-term continuation of low-dose methimazole (2.5-5 mg daily) reduces recurrent hyperthyroidism by 3.8-fold compared to discontinuation (11% vs 41% recurrence at 36 months). 1
The protective effect becomes apparent early, with significantly lower recurrence rates at every time point: 1.2% vs 11.2% at 6 months, 6.8% vs 18.4% at 12 months, and 11% vs 35% at 24 months in continuation versus discontinuation groups. 1
This approach is safe with no major or minor adverse effects observed during long-term low-dose therapy. 1
Why Standard Discontinuation Fails
The conventional approach of stopping methimazole after 12-18 months has poor outcomes:
Approximately 50% of patients relapse after discontinuing antithyroid drugs following the standard treatment duration. 2
Even short-term therapy (4.8 months) results in only 23% sustained remission rates, and extending to 1 year improves this to merely 12%. 3
Recurrence typically occurs within 7-21 months after methimazole withdrawal, even in patients with normal TSH receptor antibody levels. 4
Optimal Management Strategy
For patients who have achieved stable euthyroidism on low-dose methimazole (2.5-5 mg daily) for at least 6 months:
Continue the low-dose methimazole indefinitely rather than discontinuing after 12-18 months. 1
Monitor thyroid function at 3-month intervals initially, then extend to 6-month intervals once stability is confirmed. 1
Ensure patients have no history of adverse effects from methimazole before committing to long-term therapy. 1
Risk Factors Requiring Continued Therapy
Age under 40 years at onset increases recurrence risk by 2.9-fold, making long-term continuation particularly important in younger patients. 1
Patients with larger goiters historically have higher relapse rates, though this is mitigated by continued low-dose therapy. 3
Safety Profile of Long-Term Low-Dose Therapy
Serious reactions to thionamides (agranulocytosis, hepatitis, vasculitis) occur in less than 5% of cases overall, with agranulocytosis affecting only 3 per 10,000 patients. 5
Long-term therapy with doses of 1.25-2.5 mg daily has been documented as safe for up to 31 years without adverse events. 4
The low doses used for maintenance (2.5-5 mg daily) carry substantially lower risk than the higher doses used during initial treatment. 1
Critical Pitfall to Avoid
Do not discontinue methimazole simply because the patient has achieved euthyroid status. The euthyroid state is maintained by the medication, not evidence of disease remission. Discontinuation leads to recurrence in the majority of patients, necessitating either reinitiation of medical therapy or progression to definitive treatment with radioiodine or surgery. 1, 2
When Discontinuation May Be Considered
Discontinuation should only be attempted if the patient:
- Develops adverse effects requiring cessation. 1
- Chooses definitive therapy (radioiodine or thyroidectomy) instead. 2
- Has completed at least 12-18 months of therapy AND accepts the 50% risk of recurrence. 2
For patients tolerating low-dose methimazole without side effects, continuation provides superior outcomes to discontinuation and represents the evidence-based approach to maintaining long-term euthyroidism. 1