What is the incidence of agranulocytosis (a potentially life-threatening reduction in white blood cells) in patients taking methimazole (a medication used to treat hyperthyroidism)?

Incidence of Agranulocytosis with Methimazole

Agranulocytosis is a rare but potentially life-threatening adverse effect of methimazole that occurs in approximately 1% of patients taking this medication for hyperthyroidism. 1, 2

Epidemiology and Risk Factors

• The incidence of agranulocytosis with methimazole is estimated at 0.1-1% of treated patients
• Risk factors include:
  • Higher doses of methimazole (dose-dependent relationship)
  • First 3-6 months of therapy (highest risk period)
  • However, cases can occur at any time during treatment

Timing of Onset

While agranulocytosis typically develops within the first 3-6 months of methimazole treatment, several important exceptions exist:

• Cases have been documented after 18 months of stable therapy 3
• Atypically, agranulocytosis can develop even after discontinuation of methimazole 4
• This highlights the importance of monitoring throughout treatment and even after discontinuation

Clinical Presentation

Agranulocytosis from methimazole typically presents with:

• Sore throat and fever (cardinal symptoms) 1
• Signs of infection (often upper respiratory or odontogenic) 5
• Symptoms may mimic thyroid storm, potentially causing diagnostic confusion 5

Monitoring and Management

When agranulocytosis is suspected:

1. Immediately discontinue methimazole 1
2. Obtain a complete blood count
3. If confirmed, consider:
   • Hospitalization with reverse isolation
   • Broad-spectrum antibiotics
   • Granulocyte colony-stimulating factor (rhG-CSF) which can significantly shorten recovery time 6

Recovery Timeline

• Without specific treatment: 10-12 days average recovery time 6
• With rhG-CSF treatment: approximately 6-7 days average recovery time 6
• Recovery is faster when residual granulocyte counts are higher (>0.1 x 10^9/L) 6

Prevention and Vigilance

• Regular monitoring of complete blood counts is essential during methimazole therapy
• Patient education about warning signs (sore throat, fever) is crucial
• Immediate medical attention should be sought if symptoms develop
• Consider alternative treatments for hyperthyroidism in patients with history of agranulocytosis

Other Medications Associated with Agranulocytosis

It's worth noting that other medications can also cause agranulocytosis:

• Clozapine (approximately 1% risk) 2
• Deferiprone (used in iron overload conditions) 1
• TMP/SMX (trimethoprim/sulfamethoxazole) 1
• Fluconazole 1

The risk of agranulocytosis with methimazole underscores the importance of appropriate patient selection, monitoring, and prompt recognition of this serious adverse effect.