What is the primary class of drugs for treating hyperthyroidism?

Thionamides: The Primary Drug Class for Hyperthyroidism

The primary class of drugs for treating hyperthyroidism is thionamides (also called antithyroid drugs), which includes methimazole, carbimazole (a prodrug of methimazole), and propylthiouracil (PTU). 1, 2, 3

Mechanism of Action

Thionamides work by inhibiting thyroid hormone synthesis within the thyroid gland. 2, 3 Specifically:

• Both methimazole and PTU block the synthesis of new thyroid hormones but do not inactivate existing thyroxine (T4) and triiodothyronine (T3) already stored in the thyroid or circulating in the blood. 2, 3
• PTU has an additional peripheral effect: it inhibits the conversion of T4 to T3 in peripheral tissues, which may make it particularly effective for thyroid storm. 2
• Neither drug interferes with the effectiveness of exogenous thyroid hormones given orally or by injection. 2, 3

Drug Selection: Methimazole vs. Propylthiouracil

Methimazole is the preferred first-line thionamide for most patients with hyperthyroidism. 1 The American Academy of Family Physicians recommends methimazole as primary therapy because it offers several advantages:

• Fewer major side effects compared to PTU 1
• Once-daily dosing (versus PTU requiring dosing every 6-8 hours) 1, 4
• Lower cost and wider availability 1
• Better pharmacokinetic profile 5

When to Use PTU Instead

PTU should be reserved for two specific situations: 1

1. First trimester of pregnancy (weeks 0-13): Methimazole has been associated with rare but serious congenital anomalies including aplasia cutis (scalp defects) and choanal/esophageal atresia. 1, 4
2. Patients who have experienced adverse reactions to methimazole 1

After the first trimester, switching from PTU to methimazole is preferable due to the risk of maternal hepatotoxicity with PTU. 1, 2

Dosing and Monitoring

Starting doses: 4

• Methimazole: 10-30 mg as a single daily dose
• PTU: 100-300 mg every 6 hours

The treatment goal is to maintain free T4 in the high-normal range using the lowest possible thionamide dose. 1 Monitor free T4 or free thyroxine index every 2-4 weeks during initial therapy. 1

Adjunctive Symptomatic Management

Beta-blockers should be used for symptomatic relief while waiting for thionamides to reduce thyroid hormone levels. 1 Common options include:

• Atenolol 25-50 mg daily 1
• Propranolol (dose varies) 6, 1

Beta-blockers are particularly effective for controlling heart rate, tremor, palpitations, and anxiety associated with hyperthyroidism. 6, 1 They are especially important in thyroid storm, where high doses may be required. 6

Critical Safety Monitoring

Agranulocytosis is the most serious acute side effect of thionamides. 6, 2 It typically presents with:

• Sore throat
• Fever
• Signs of infection

Patients must immediately report these symptoms, obtain a complete blood count with differential, and discontinue the thionamide. 1, 2 This complication usually occurs within the first few months of therapy. 2

Other important adverse effects to monitor: 6, 1, 2

• Hepatotoxicity (particularly with PTU): Monitor for anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain
• Vasculitis (can be severe and life-threatening with PTU): Monitor for new rash, hematuria, decreased urine output, dyspnea, hemoptysis
• Thrombocytopenia
• Hypoprothrombinemia: Consider monitoring prothrombin time, especially before surgical procedures

Duration and Efficacy

Typical treatment duration is 12-18 months when using thionamides as primary therapy for Graves' disease. 7, 8 However:

• Hyperthyroidism relapses in approximately 50% of patients after discontinuation of antithyroid drugs. 7
• Long-term low-dose methimazole therapy is an effective and safe option for Graves' disease and toxic multinodular goiter. 9
• Thionamides will not cure hyperthyroidism associated with toxic nodular goiter, which typically requires definitive therapy with radioiodine or surgery. 8

Special Populations

Pregnancy and lactation: 6, 2, 4

• Both methimazole and PTU cross the placenta and can induce fetal goiter and cretinism if doses are excessive
• PTU is present in breast milk in small amounts but results in clinically insignificant doses to nursing infants
• Women treated with either agent can breastfeed safely

Radioiodine (I-131) is absolutely contraindicated in pregnancy. 6, 1