What is the drug of choice for a patient with hyperthyroidism?

Drug of Choice for Hyperthyroidism

Methimazole is the drug of choice for treating hyperthyroidism in most patients, with the critical exception of the first trimester of pregnancy when propylthiouracil (PTU) is preferred. 1, 2

Primary Antithyroid Drug Selection

• Methimazole is superior to PTU because it has fewer major side effects, can be administered as a single daily dose, is less expensive, and is more widely available 2, 3
• The typical starting dose of methimazole is 10-30 mg daily as a single dose, while PTU requires 100-300 mg divided every 6 hours 4, 3
• PTU should be reserved exclusively for: patients intolerant to methimazole, and the first trimester of pregnancy due to its potential to cause severe liver failure requiring transplantation or resulting in death 1, 5, 6

Critical Safety Distinction

• The FDA has issued a black box warning for PTU regarding severe liver injury and acute liver failure, some fatal, requiring liver transplantation in both adult and pediatric patients 5
• Methimazole during first trimester pregnancy has been associated with rare congenital anomalies including aplasia cutis and choanal/esophageal atresia, making PTU the safer choice during this specific period 2, 4
• After the first trimester, switching from PTU back to methimazole is recommended given the maternal hepatotoxicity risk with PTU 1, 2

Treatment Monitoring Algorithm

• Monitor free T4 or free T3 index every 2-4 weeks during initial treatment, not TSH, which may remain suppressed for months even after achieving euthyroidism 1, 2
• The goal is to maintain free T4 in the high-normal range using the lowest effective dose, not to normalize TSH 1, 2
• Common pitfall to avoid: Do not reduce methimazole based solely on suppressed TSH while free T4 remains elevated or high-normal, as this leads to inadequate treatment and recurrent hyperthyroidism 1

Essential Adjunctive Therapy

• Beta-blockers (atenolol 25-50 mg daily or propranolol) should be initiated immediately for symptomatic relief of tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization 1, 2
• Beta-blocker dose reduction is required once the patient achieves euthyroid state 1
• For patients with atrial fibrillation from hyperthyroidism, beta-blockers are recommended for rate control unless contraindicated 1

Critical Adverse Effect Monitoring

• Agranulocytosis typically occurs within the first 3 months and presents with sore throat and fever—patients must immediately report these symptoms, obtain CBC, and discontinue the drug 1, 2
• Hepatotoxicity (especially with PTU) requires monitoring for: fever, nausea, vomiting, right upper quadrant pain, dark urine, and jaundice, with immediate drug discontinuation if suspected 1, 5
• The starting dose of methimazole should not exceed 15-20 mg/day to reduce the dose-dependent risk of agranulocytosis 6

Special Clinical Scenarios

• For destructive thyroiditis: antithyroid drugs are NOT indicated; use beta-blockers for symptomatic relief only, as this condition is self-limited 1, 2
• For subclinical hyperthyroidism with TSH <0.1 mIU/L: consider treatment in patients over 60 years or those with cardiac disease, osteopenia, or osteoporosis due to 3-fold increased risk of atrial fibrillation 1
• Radioactive iodine or surgery should be considered for Graves' disease that persists or recurs after 12-18 months of medical therapy 2, 7