Antithyroid and Adjunctive Medications for Hyperthyroidism
Comparative Table of Mechanisms, Dosages, and Side Effects
| Medication | Mechanism of Action | Dosage | Side Effects |
|---|---|---|---|
| Propylthiouracil (PTU) | Inhibits thyroid hormone synthesis; blocks peripheral conversion of T4 to T3 [1] | Initial: 300 mg/day divided every 8 hours [2,3] | Common: Nausea, vomiting, upper abdominal pain, joint pain, itching, headache, altered taste, hair loss [1] Serious: Hepatotoxicity (higher than methimazole), agranulocytosis (0.1-0.5%), vasculitis, severe bleeding risk, Stevens-Johnson syndrome [1,2,4] |
| Methimazole (MMI) | Inhibits thyroid hormone synthesis [5] | Mild-moderate hyperthyroidism: 15 mg once daily [2,3] Severe hyperthyroidism (FT4 ≥7 ng/dL): 30 mg once daily [2] |
Common: Skin rash, itching, mild leukopenia (3-5% of patients) [4] Serious: Agranulocytosis (0.1-0.5%), hepatotoxicity (lower than PTU), aplastic anemia, thrombocytopenia, lupus-like syndrome, vasculitis [4] |
| Carbimazole (CBZ) | Prodrug converted to methimazole; inhibits thyroid hormone synthesis [6] | Rarely used; consider when anti-TSH receptor antibodies positive [6] | Similar to methimazole: skin rash, agranulocytosis (0.1-0.5%), hepatotoxicity, vasculitis [4] |
| Propranolol | Beta-adrenergic blockade; provides symptomatic relief of hyperthyroid symptoms (tachycardia, tremor, anxiety); does not affect thyroid hormone synthesis [6,7] | Symptomatic relief dosing (specific dose not provided in guidelines but used for palpitations, tremors, anxiety) [6,7] | Common: Dizziness, drowsiness, fatigue [1] Serious: Bradycardia, hypotension, bronchospasm (avoid in asthma), heart block, worsening heart failure [8] |
Key Clinical Considerations
Drug Selection Algorithm
For initial treatment of Graves' disease hyperthyroidism:
Methimazole 15 mg once daily is the first-line choice for mild-to-moderate hyperthyroidism (FT4 <7 ng/dL) due to superior efficacy, once-daily dosing, and lower hepatotoxicity compared to PTU 2, 3, 9
Methimazole 30 mg once daily should be used for severe hyperthyroidism (FT4 ≥7 ng/dL), as it normalizes FT4 more effectively than PTU 300 mg/day or lower-dose methimazole 2
Propylthiouracil is NOT recommended for initial use due to higher hepatotoxicity and less effective normalization of thyroid hormones 2, 9
Carbimazole is rarely required but may be considered when anti-TSH receptor antibodies are positive in the context of immune-mediated hyperthyroidism 6
Adjunctive Beta-Blocker Therapy
Propranolol (or atenolol) should be initiated immediately for symptomatic relief in all patients with hyperthyroid symptoms including tachycardia, tremor, anxiety, palpitations, or heat intolerance, regardless of severity grade 6, 7
Beta-blockers provide rapid symptomatic control while awaiting thyroid hormone normalization with thionamides 6
Continue beta-blocker therapy until thyroid function normalizes, then taper as symptoms resolve 6, 7
Critical Safety Monitoring
Agranulocytosis risk (0.1-0.5% with all thionamides):
Occurs most commonly within the first 3 months of treatment 1, 4
Instruct patients to immediately report fever, chills, or sore throat and obtain urgent complete blood count 1
Treat with granulocyte colony-stimulating factor if agranulocytosis develops 4
Hepatotoxicity:
PTU carries significantly higher risk of severe hepatotoxicity compared to methimazole 2, 4
Monitor liver function tests at baseline and with any symptoms of hepatic dysfunction 1
Vasculitis:
Can involve skin, kidneys, or lungs and may be life-threatening 1
Patients must report immediately: skin color changes (red/purple), rash, foamy or dark urine, decreased urine output, shortness of breath, or hemoptysis 1
Treatment Duration and Monitoring
Monitor thyroid function (TSH, free T4) every 2-3 weeks initially to detect transition from hyperthyroidism to hypothyroidism, especially in thyroiditis cases 6, 7
For persistent hyperthyroidism beyond 6 weeks, refer to endocrinology for additional workup to exclude Graves' disease 6, 7
Methimazole achieves euthyroidism approximately 4 times more effectively than PTU at equivalent doses when using once-daily regimens 3