What are the appropriate labs and treatment for a patient with suspected agranulocytosis (low white blood cell count) due to methimazole (antithyroid medication) treatment for hyperthyroidism?

Methimazole-Induced Agranulocytosis: Laboratory Evaluation and Management

If a patient on methimazole develops fever or sore throat, immediately obtain a complete blood count with differential and discontinue methimazole—agranulocytosis is a potentially life-threatening complication that requires urgent intervention. 1

Immediate Laboratory Workup

When methimazole-induced agranulocytosis is suspected, obtain the following labs urgently:

• Complete blood count (CBC) with differential and peripheral smear to confirm absolute neutrophil count (ANC) and assess for agranulocytosis (ANC <500/μL) 1
• Reticulocyte count to evaluate bone marrow response 2
• Prothrombin time (PT/INR) as methimazole may cause hypoprothrombinemia and bleeding risk 1
• Liver function tests including bilirubin, alkaline phosphatase, ALT, and AST to assess for concurrent hepatotoxicity 1
• Renal function tests (serum creatinine, BUN) 2
• Blood cultures and infectious workup including viral studies (CMV, EBV, parvovirus) if febrile 2

Diagnostic Criteria and Severity Grading

Agranulocytosis is defined as ANC <500/μL and occurs in approximately 0.1-1% of patients, typically within the first three months of methimazole therapy. 1, 3

The severity determines management intensity:

• Mild neutropenia: ANC 1,000-1,500/μL 1
• Severe agranulocytosis: ANC <500/μL 1

Immediate Management Steps

Drug Discontinuation

• Permanently discontinue methimazole immediately upon confirmation of agranulocytosis 1
• Do NOT substitute propylthiouracil (PTU) as cross-reactivity occurs and PTU is contraindicated 4

Supportive Care and Monitoring

• Hospitalize the patient with reverse isolation precautions to prevent infection 5, 6
• Initiate broad-spectrum intravenous antibiotics empirically if fever is present, even before culture results 6, 3
• Monitor CBC daily until neutrophil recovery is documented 1, 6
• Consult hematology for severe cases (ANC <500/μL) 2

Growth Factor Support

• Consider granulocyte colony-stimulating factor (G-CSF/filgrastim) to accelerate neutrophil recovery, particularly in severe cases with infection 4, 6
• Recovery typically occurs within 7-10 days after drug cessation, with complete resolution in 2-3 weeks 3

Alternative Hyperthyroidism Management During Agranulocytosis

Since antithyroid drugs are contraindicated, use the following bridge therapies to definitive treatment:

• Beta-adrenergic blockers (e.g., propranolol) for symptom control 2, 4
• Saturated solution of potassium iodide (SSKI) for short-term thyroid hormone suppression (typically <4 weeks to avoid escape phenomenon) 4
• Cholestyramine to reduce thyroid hormone levels by interrupting enterohepatic circulation 4
• Corticosteroids in severe thyrotoxicosis 4
• Definitive therapy with radioactive iodine (RAI) once infection is controlled and patient is stable 3
• Thyroidectomy as alternative definitive therapy if RAI contraindicated 2

Critical Pitfalls to Avoid

• Never continue methimazole once agranulocytosis is confirmed—this is potentially fatal 1, 5
• Do not switch to PTU as it carries the same risk of agranulocytosis 4
• Do not delay antibiotic therapy while awaiting culture results in febrile patients 6, 3
• Monitor for agranulocytosis even after drug discontinuation—rare cases have developed symptoms 3 weeks after stopping methimazole 7
• Avoid routine prophylactic CBC monitoring in asymptomatic patients, as agranulocytosis typically develops suddenly; instead, educate patients to report fever or sore throat immediately 1, 5

Patient Education

Instruct all patients starting methimazole to immediately report fever, sore throat, mouth sores, or signs of infection and seek urgent medical evaluation with CBC testing 1