What are the recommended antithyroid drugs (ATDs) for managing hyperthyroidism?

Antithyroid Drugs for Hyperthyroidism Management

Methimazole is the recommended first-line antithyroid drug for treating hyperthyroidism in most patients, with propylthiouracil (PTU) reserved specifically for the first trimester of pregnancy and patients who cannot tolerate methimazole. 1

Primary Drug Selection

Methimazole should be your default choice because it offers superior clinical advantages over PTU in the general population 1:

• Single daily dosing improves adherence compared to PTU's multiple daily doses 1, 2
• Fewer major adverse effects, particularly less hepatotoxicity 1, 3
• Lower cost and wider availability 1
• Better efficacy profile with acceptable safety in both children and adults 2

Starting Dosage

• Methimazole: 10-30 mg once daily 4
• PTU: 100-300 mg every 6 hours (if used) 4

When to Use Propylthiouracil Instead

PTU has three specific indications where it becomes the preferred agent 1, 5:

1. First trimester of pregnancy (weeks 0-16): Methimazole is associated with rare but serious congenital anomalies including aplasia cutis and choanal/esophageal atresia 1, 6
2. Adverse reactions to methimazole: When patients develop intolerance 1
3. Thyroid storm: PTU inhibits peripheral conversion of T4 to T3, providing additional benefit 5

Pregnancy-Specific Algorithm

• Weeks 0-16: Use PTU exclusively 1, 6, 3
• After week 16: Switch from PTU to methimazole due to maternal hepatotoxicity risk with PTU 1, 5
• Goal: Maintain free T4 in high-normal range with lowest possible dose 1
• Monitoring: Check free T4 or free thyroxine index every 2-4 weeks 1

Critical evidence: A 2023 meta-analysis confirmed PTU has 20% lower odds of congenital anomalies compared to methimazole (OR 0.80,95% CI 0.69-0.92) 6, while a 2020 meta-analysis showed PTU carries 2.4-fold higher odds of liver injury (OR 2.40,95% CI 1.16-4.96) 3.

Mechanism of Action

Both drugs inhibit thyroid hormone synthesis but do not inactivate existing circulating thyroid hormones 7, 5:

• Methimazole: Blocks thyroid peroxidase, preventing iodine incorporation into thyroglobulin 7
• PTU: Additionally inhibits peripheral T4 to T3 conversion, making it useful in thyroid storm 5

Essential Safety Monitoring

Immediate Reporting Requirements

Patients must report these symptoms immediately and discontinue the drug 1, 5:

• Sore throat, fever, or signs of infection (agranulocytosis warning) 1, 5
• Hepatic symptoms: Anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain 5
• Vasculitis symptoms: New rash, hematuria, decreased urine output, dyspnea, hemoptysis 5

Laboratory Monitoring

• Complete blood count with differential if infection symptoms develop 5
• Liver function tests (bilirubin, alkaline phosphatase, ALT/AST), particularly in first 6 months 5
• Prothrombin time before surgical procedures (both drugs can cause hypoprothrombinemia) 5

Adjunctive Symptomatic Management

Beta-blockers are essential for immediate symptom control while waiting for antithyroid drugs to reduce thyroid hormone levels 1, 8:

• Atenolol 25-50 mg daily or propranolol 1
• Controls heart rate, tremor, palpitations, and anxiety 1
• Particularly important in thyroid storm where high doses may be required 9

Alternative if beta-blockers contraindicated: Non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) 9

Treatment Duration and Long-Term Considerations

• Standard course: 1-2 years for Graves' disease 4
• Long-term low-dose therapy: Methimazole 2.5-5 mg daily may prevent relapse, particularly in patients >35 years old 10
• Evidence: A retrospective study showed continuous low-dose methimazole significantly reduced relapse risk in older patients compared to drug discontinuation 10

Critical Pitfalls to Avoid

1. Never use methimazole in first trimester pregnancy - teratogenic risk outweighs benefits 1, 6
2. Never delay switching from PTU to methimazole after first trimester - maternal hepatotoxicity risk increases with continued PTU use 1, 5
3. Never ignore hepatic symptoms - both drugs can cause severe liver injury, but PTU carries 4-fold higher risk of elevated transaminases 3
4. Never attempt cardioversion before achieving euthyroid state in hyperthyroid patients with atrial fibrillation - antiarrhythmic drugs generally fail while thyrotoxicosis persists 9
5. Radioactive iodine is absolutely contraindicated in pregnancy 1

Alternative Definitive Therapies

Consider radioactive iodine or thyroidectomy for 1:

• Graves' disease persisting or recurring after medical therapy
• Patient preference for definitive treatment
• Severe hyperthyroidism requiring hospitalization with endocrine consultation