Can medication be stopped in Graves' disease when Thyroid-Stimulating Hormone (TSH) levels are within the normal range?

Management of Graves' Disease: When to Stop Medication with Normal TSH

In Graves' disease, medication should not be stopped when TSH normalizes alone; instead, antithyroid drugs (ATDs) should be continued for 12-18 months minimum before considering discontinuation, even with normal TSH values. 1

Antithyroid Drug Treatment Duration and Monitoring

• The European Thyroid Association recommends treating newly diagnosed Graves' hyperthyroidism with methimazole (MMI) for 12-18 months as the standard approach 1
• Children with Graves' disease require longer treatment courses (24-36 months) 1
• During treatment, thyroid function tests should be monitored periodically:
  • TSH and free T4 should be checked every 4-6 weeks during dose adjustments
  • Once stable, monitoring can be reduced to every 6-12 months 2

Criteria for Medication Discontinuation

• Normal TSH alone is insufficient for stopping medication
• Key factors to consider before discontinuation:
  • Completion of 12-18 months of therapy
  • TSH receptor antibody (TRAb) status - negative or significantly decreased levels
  • Stable euthyroid state for at least 6 months on minimum maintenance dose 3

Predictors of Remission

• Development of elevated TSH (>10 μIU/mL) during methimazole treatment is a favorable prognostic indicator for long-term remission 4
• Patients who develop ATD-associated hypothyroidism during treatment have significantly higher remission rates (85% vs 54.1% at 24 months) compared to those who maintain normal TSH throughout treatment 4
• Negative TSH receptor antibodies at the end of treatment period significantly improve remission chances 5

Relapse Risk Assessment

• High-risk factors for relapse include:

  • Persistently elevated TSH receptor antibodies at the end of treatment 1, 6
  • Large goiter size
  • Severe hyperthyroidism at diagnosis
  • Failure to achieve hypothyroidism during treatment 4

• Patients with TRAb-CT values ≥30% inhibition or TRAb-Dyno values ≥3.0 U/L at the time of medication discontinuation have very high relapse rates 5

Management Options After 12-18 Months

1. For patients with negative or low TSH-R-Ab after 12-18 months:

   • Consider discontinuing methimazole
   • Monitor closely for relapse every 1-2 months initially, then every 3-4 months 3

2. For patients with persistently high TSH-R-Ab at 12-18 months:

   • Continue methimazole treatment
   • Reassess TSH-R-Ab after an additional 12 months
   • Consider definitive therapy (radioactive iodine or thyroidectomy) 1

3. For patients who relapse after completing ATD course:

   • Definitive treatment is recommended (radioactive iodine or thyroidectomy)
   • Alternative: continued long-term low-dose methimazole 1

Special Considerations

• Pregnancy planning: Switch from methimazole to propylthiouracil when planning pregnancy and during the first trimester 7, 1
• Thyroid function may improve during pregnancy, allowing dose reduction or even discontinuation 7
• Patients on methimazole should be monitored for potential side effects including agranulocytosis and vasculitis 7

Key Pitfall to Avoid

The most common mistake is stopping medication prematurely based solely on normalized TSH values. This significantly increases relapse risk. Complete the full 12-18 month course of therapy and assess TSH receptor antibody status before discontinuation for best long-term outcomes.