What are the medications used to treat hyperthyroidism?

Medications for Hyperthyroidism

The primary medications for treating hyperthyroidism are thionamides—specifically methimazole and propylthiouracil (PTU)—with methimazole being the preferred first-line agent in most clinical situations, except during the first trimester of pregnancy when PTU is favored. 1, 2, 3

Antithyroid Drug Selection

Methimazole (Preferred Agent)

• Methimazole is the drug of choice for most patients because it has fewer major side effects, can be administered as a single daily dose, is less expensive, and is more widely available 4, 5
• Starting dose: 10-30 mg daily as a single dose 4
• The starting dose should not exceed 15-20 mg/day to minimize the risk of dose-dependent agranulocytosis 5
• Methimazole inhibits thyroid hormone synthesis but does not inactivate existing circulating thyroid hormones 3

Propylthiouracil (PTU)

• PTU should be reserved for specific situations: first trimester of pregnancy or when patients have experienced adverse reactions to methimazole 5
• Starting dose: 100-300 mg every 6 hours (requires multiple daily doses) 4
• PTU has the additional benefit of inhibiting peripheral conversion of T4 to T3, making it potentially useful in thyroid storm 2
• Critical warning: PTU can cause severe hepatotoxicity leading to liver transplantation or death, which is why it should not be used as a first-line agent 5

Special Population Considerations

Pregnancy

• During the first trimester, PTU is preferred because methimazole has been associated with rare congenital anomalies including aplasia cutis and choanal/esophageal atresia 1, 4
• After the first trimester, switching from PTU to methimazole is preferable given the maternal hepatotoxicity risk with PTU 2
• Both drugs have similar therapeutic efficacy and placental transfer kinetics 4
• Goal: maintain free T4 in the high-normal range using the lowest possible dose 1
• Monitor free T4 or free thyroxine index every 2-4 weeks 1
• Both thionamides are safe during breastfeeding 1, 4

Symptomatic Management

• Beta-blockers (atenolol 25-50 mg daily or propranolol) should be used for symptomatic relief while waiting for thionamides to reduce thyroid hormone levels 1
• Beta-blockers are particularly useful for controlling heart rate and reducing symptoms like tremor, palpitations, and anxiety 1
• Short-acting beta-blockers like esmolol are especially useful when hemodynamic instability is a concern 1

Treatment Duration and Monitoring

Standard Course

• Typical treatment duration: 12-18 months (titration method) 6, 7
• Long-term treatment (5-10 years) is associated with fewer recurrences (15%) compared to short-term treatment (50% recurrence rate) 7
• Monitor thyroid function tests periodically; an elevated TSH indicates the need for dose reduction 2

Recurrence Risk Factors

Patients at higher risk for recurrence after stopping antithyroid drugs include those who are: 7

• Younger than 40 years
• Have free T4 concentrations ≥40 pmol/L
• Have TSH-binding inhibitory immunoglobulins >6 U/L
• Have goiter size equivalent to or larger than WHO grade 2

Critical Safety Monitoring

Agranulocytosis

• Patients must immediately report sore throat, fever, or signs of infection 1, 2
• Obtain complete blood count with differential if these symptoms develop and discontinue the thionamide 1
• Risk is dose-dependent, emphasizing the importance of not exceeding recommended starting doses 5

Hepatotoxicity (Especially with PTU)

• Patients should report symptoms of liver dysfunction: anorexia, pruritus, jaundice, light-colored stools, dark urine, or right upper quadrant pain 2
• Monitor liver function tests (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT/AST), particularly in the first 6 months 2

Vasculitis (PTU)

• Patients on PTU must promptly report symptoms of vasculitis: new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 2
• Cases of vasculitis resulting in severe complications and death have occurred with PTU 2

Other Side Effects

• Hepatitis, thrombocytopenia, and vasculitis can occur with both agents 1
• Monitor prothrombin time before surgical procedures as thionamides may cause hypoprothrombinemia 2

Alternative and Adjunctive Therapies

Severe or Refractory Cases

• For severe hyperthyroidism (Grade 3-4), consider hospitalization with endocrine consultation to guide use of: 1
  • Corticosteroids
  • Saturated solution of potassium iodide (SSKI)
  • Thionamides (methimazole or PTU)
  • Possible surgery

Definitive Treatment

• Graves' disease that persists or recurs after medical therapy should be treated with radioactive iodine or thyroidectomy 1, 6
• Radioactive iodine (I-131) is absolutely contraindicated in pregnancy 1
• Thyroidectomy should be reserved for patients who do not respond to thionamide therapy 1
• For toxic nodular goiter, radioiodine or thyroidectomy is preferred over long-term medical management 7

Drug Interactions

• Anticoagulants: Thionamides may increase warfarin activity; monitor PT/INR closely 2
• Beta-blockers: Clearance increases in hyperthyroidism; dose reduction may be needed when euthyroid 2
• Digoxin: Serum levels may increase as patients become euthyroid; dose reduction may be needed 2
• Theophylline: Clearance decreases when patients become euthyroid; dose reduction may be needed 2