What is the recommended first‑line treatment and overall management plan for hyperthyroidism, including antithyroid drug selection and dosing, beta‑blocker use, and indications for definitive therapy such as radioactive iodine or thyroidectomy?

Management of Hyperthyroidism

First-Line Treatment Selection

Beta-blockers should be initiated immediately in all patients with symptomatic hyperthyroidism to control heart rate and reduce cardiovascular complications, regardless of the underlying etiology. 1

• Intravenous beta-blockers are indicated for rate control in patients with hyperthyroidism to reduce myocardial oxygen demands, particularly in those with atrial fibrillation or acute coronary syndrome 1
• Beta-blockers are effective in controlling ventricular rate and are particularly important in cases of thyroid storm 1
• When beta-blockers cannot be used, nondihydropyridine calcium channel antagonists (diltiazem or verapamil) are the recommended alternative for rate control 1

Antithyroid Drug Therapy

Methimazole is the preferred antithyroid drug for most patients with Graves' disease due to its superior safety profile, once-daily dosing, lower cost, and greater availability. 2

Methimazole Dosing

• Starting dose: 10-30 mg once daily for most patients with Graves' disease 2
• The single daily dosing improves adherence compared to propylthiouracil 2
• Major side effects are less common with methimazole than propylthiouracil 2

Propylthiouracil (PTU) Dosing and Indications

• Starting dose: 100-300 mg every 6 hours (requires multiple daily doses) 2
• PTU is the drug of choice during pregnancy because methimazole is associated with aplasia cutis and choanal/esophageal atresia, while no such congenital anomalies are linked to PTU 2
• Both drugs are safe during lactation despite presence in breast milk 2

Duration of Antithyroid Drug Therapy

• Antithyroid drugs should be prescribed for 12-18 months in Graves' disease with the goal of inducing long-term remission 3
• Long-term remission can be expected in 20-50% of adults and 20-30% of children 4
• Antithyroid drugs will not cure hyperthyroidism associated with toxic nodular goiter—definitive therapy is required 3

Definitive Therapy: Radioactive Iodine vs. Surgery

Radioactive Iodine (RAI) - Preferred Definitive Treatment

Radioactive iodine is the treatment of choice for toxic nodular goiter and is increasingly used as first-line therapy for Graves' disease in adults. 3, 4

Indications for RAI

• Preferred in most adult patients with Graves' disease, especially those over 30 years of age 3, 5
• Treatment of choice for elderly patients and those with cardiac disease—RAI should be given immediately after achieving euthyroidism with antithyroid drugs in these high-risk groups 4
• First-line therapy for autonomous thyroid adenoma in patients who are not surgical candidates 5
• Simple, safe, effective, and economical procedure administered on an outpatient basis 4

Contraindications to RAI

• Pregnancy and lactation (absolute contraindications) 3
• Pregnancy must be avoided for 4 months following RAI administration 3
• Children (relative contraindication) 3
• Active Graves' ophthalmopathy—RAI may cause deterioration; corticosteroid cover may reduce this risk 3

Expected Outcome

• Radioiodine-induced hypothyroidism is the expected long-term outcome and should not be considered a complication but rather the therapeutic endpoint 4

Surgical Thyroidectomy - Limited but Specific Indications

Surgery (total or near-total thyroidectomy) is reserved for specific clinical scenarios where RAI is contraindicated or inappropriate. 4

Clear Indications for Surgery

• Suspected or confirmed thyroid malignancy 4
• Pregnancy and breastfeeding (when RAI is contraindicated) 4
• Large goiter (>80 grams) or goiter causing compressive symptoms (dysphagia, orthopnea, voice changes) 4, 6
• Severe toxic side effects of antithyroid medications 4
• Requirement for immediate disease control 4
• Age younger than 5 years 4
• Active ophthalmopathy (relative indication) 4
• Patient preference or refusal of radioiodine 3

Surgical Approach

• Total or near-total thyroidectomy is the preferred surgical approach over subtotal thyroidectomy 4
• The risk of surgical complications is negatively correlated with surgeon experience—referral to high-volume thyroid surgeons is critical 4
• Postoperative hypothyroidism is the expected outcome and should be managed with thyroid hormone replacement 4

Treatment Algorithm by Etiology

Graves' Disease

1. Initiate beta-blocker immediately for symptom control 1
2. Start methimazole 10-30 mg once daily (or PTU if pregnant) 2
3. Continue antithyroid drugs for 12-18 months to attempt remission 3
4. If relapse occurs or patient prefers definitive therapy:
   • RAI is preferred in most adults, especially those >30 years or with cardiac disease 3, 4
   • Surgery if large goiter, compressive symptoms, pregnancy, or patient preference 4

Toxic Nodular Goiter

1. Initiate beta-blocker for symptom control 1
2. Short-term antithyroid drugs to achieve euthyroidism (weeks to months) 3
3. Radioactive iodine is the definitive treatment of choice—antithyroid drugs will not cure this condition 3, 4

Thyroiditis (Subacute, Postpartum, or Drug-Induced)

1. Beta-blockers for symptomatic relief during the thyrotoxic phase 1
2. Observation or supportive care—thyrotoxicosis is self-limited 6
3. Antithyroid drugs are NOT indicated because the thyroid is not overproducing hormone 6

Special Populations

Hyperthyroidism with Atrial Fibrillation

• Beta-blockers are the first-line agents for rate control 1
• Intravenous amiodarone is an appropriate alternative for rate control and may facilitate conversion to sinus rhythm 1
• Digoxin may be considered in those with severe left ventricular dysfunction and heart failure 1
• Anticoagulation should be guided by CHA₂DS₂-VASc risk factors, not solely by the presence of hyperthyroidism 1
• Cardioversion often fails to achieve sustained sinus rhythm while thyrotoxicosis persists—efforts to restore normal sinus rhythm should be deferred until the patient is euthyroid 1

Hyperthyroidism in Pregnancy

• PTU is the drug of choice due to lower risk of congenital anomalies 2
• Surgery (thyroidectomy) is preferred over RAI if definitive therapy is required 4
• RAI is absolutely contraindicated during pregnancy and lactation 3

Elderly Patients and Those with Cardiac Disease

• RAI should be administered immediately after achieving euthyroidism with antithyroid drugs 4
• Beta-blockers are particularly important in this population 1
• Surgery carries higher perioperative risk and should be avoided unless specific indications exist 4

Common Pitfalls to Avoid

• Do not delay beta-blocker initiation—cardiovascular complications (atrial fibrillation, heart failure) are the chief cause of death in hyperthyroidism, especially in patients >50 years 1
• Do not use antithyroid drugs as sole long-term therapy for toxic nodular goiter—they will not cure the condition 3
• Do not attempt cardioversion in atrial fibrillation before achieving euthyroidism—it will likely fail 1
• Do not use methimazole in pregnancy—switch to PTU to avoid congenital anomalies 2
• Do not overlook the need for corticosteroid cover when using RAI in patients with Graves' ophthalmopathy—this may prevent deterioration 3
• Recognize that hypothyroidism after RAI or surgery is the expected therapeutic endpoint, not a complication—lifelong thyroid hormone replacement is required 4