Signs and Symptoms of Agranulocytosis in Patients Taking Methimazole
Fever and sore throat are the hallmark early warning signs of agranulocytosis in patients taking methimazole and require immediate discontinuation of the drug and urgent complete blood count. 1, 2
Cardinal Presenting Symptoms
The most common initial manifestations include:
- Fever occurs in 75-83% of cases as the earliest sign of agranulocytosis 3
- Sore throat presents in 75% of patients and should trigger immediate evaluation 1, 3
- Flu-like symptoms including generalized weakness and malaise 1, 4
These symptoms typically develop within 15-57 days of starting methimazole therapy, with a median onset at 30 days of treatment 5, 3
Oral and Pharyngeal Manifestations
Specific oral cavity findings that may be present include:
- Generalized gingival necrosis with tissue breakdown 6
- Mucosa ulceration throughout the oral cavity 6
- Odontogenic abscess formation, which can complicate the clinical picture and mimic other conditions 7
Systemic Signs of Infection
Due to the profound neutropenia, patients are at high risk for severe infections:
- Sepsis can develop rapidly and may initially be mistaken for thyroid storm, as both conditions present with fever, tachycardia, and systemic symptoms 7
- Profound leukopenia with neutrophil counts often dropping to 0.01-0.14 × 10⁹/L 3
Critical Diagnostic Pitfall
The similarity between early sepsis symptoms and thyroid storm can lead to dangerous diagnostic delays 7. When a patient on methimazole presents with fever and tachycardia, agranulocytosis with secondary infection must be ruled out immediately before attributing symptoms solely to worsening hyperthyroidism 7.
Laboratory Findings
- Absolute neutrophil count falls below 0.5 × 10⁹/L, defining agranulocytosis 1
- Methimazole tends to cause more severe neutropenia (median 0.01 × 10⁹/L) compared to propylthiouracil (median 0.14 × 10⁹/L) 3
- Complete blood cell count should be obtained immediately when symptoms develop 1
Timing and Patient Education
Patients must be instructed before starting methimazole to immediately report fever or sore throat 2. The median interval between first symptoms and drug withdrawal should be minimized, ideally 0-1 day, as delays worsen outcomes 3. While agranulocytosis can occur as early as 15 days or as late as 1,344 days after starting therapy, most cases develop within the first 30-40 days 5, 3.
Associated Hematologic Abnormalities
Beyond agranulocytosis, methimazole can cause: