What are the treatment options for hyperthyroidism?

Treatment Options for Hyperthyroidism

First-Line Antithyroid Drug Therapy

Methimazole is the preferred first-line antithyroid drug for hyperthyroidism due to superior efficacy and safety profile, except during the first trimester of pregnancy when propylthiouracil is preferred. 1

Methimazole Dosing Strategy

• Start with 15-20 mg daily for mild to moderate hyperthyroidism 2
• Use 30 mg daily for severe hyperthyroidism (free T4 ≥7 ng/dL), which normalizes thyroid function more effectively than lower doses 3
• Monitor free T4 or free T3 every 2-4 weeks initially, maintaining levels in the high-normal range using the lowest effective dose 1
• Treatment duration is typically 12-18 months, though long-term therapy (5-10 years) reduces recurrence rates from 50% to 15% 4

Propylthiouracil: Limited Indications Only

Propylthiouracil should be reserved exclusively for patients intolerant to methimazole and for first trimester pregnancy due to severe hepatotoxicity risk. 1, 5

• Propylthiouracil can cause severe liver failure requiring transplantation or death, particularly in pregnant women, infants, and pediatric patients 5
• After the first trimester, switch back to methimazole 1
• Both drugs are compatible with breastfeeding 1
• Starting dose should not exceed 300 mg daily 2, 3

Immediate Symptomatic Management

Beta-blockers provide immediate symptomatic relief and should be initiated promptly while awaiting thyroid hormone normalization. 1

• Atenolol 25-50 mg daily or propranolol are preferred agents 1
• Target heart rate <90 bpm if blood pressure tolerates 1
• Reduce dose once euthyroid state is achieved to avoid excessive beta-blockade 1, 5
• Particularly important for controlling tachycardia, tremor, and anxiety 1

Definitive Treatment Options

Radioactive Iodine (I-131) Ablation

• Preferred definitive treatment for toxic nodular goiter 6, 4
• Growing use as first-line therapy for Graves' disease 6
• Absolutely contraindicated in pregnancy and breastfeeding 1
• Avoid pregnancy for 4 months following administration 1, 6
• Stop antithyroid drugs at least one week prior to radioiodine to reduce treatment failure risk 2
• May worsen Graves' ophthalmopathy; consider corticosteroid prophylaxis 1, 6

Thyroidectomy

• Indicated when radioiodine is refused or large goiter causes compressive symptoms 6
• Should be performed as near-total or total thyroidectomy 2
• Limited role in Graves' disease management 6

Treatment Selection Algorithm by Etiology

Graves' Disease

• Start methimazole (15-30 mg daily based on severity) plus beta-blocker 1, 3
• If TSH-receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely—consider radioiodine or thyroidectomy 1
• Predictors of recurrence after 12-18 months of antithyroid drugs: age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, goiter ≥WHO grade 2 4

Toxic Nodular Goiter

• Radioiodine is the treatment of choice 2, 6
• Antithyroid drugs do not cure toxic nodular goiter 6
• Surgery is alternative for large compressive goiters 6

Destructive Thyroiditis

• Beta-blockers for symptomatic relief only—antithyroid drugs are NOT indicated 1
• Self-limited biphasic course requiring different management than Graves' disease 1
• Monitor symptoms and free T4 every 2 weeks 1
• Introduce thyroid hormone replacement if hypothyroidism develops (low free T4/T3, even before TSH elevation) 1

Subclinical Hyperthyroidism Treatment Thresholds

Treat subclinical hyperthyroidism when TSH <0.1 mIU/L, particularly in patients >60 years or those with cardiovascular disease, osteopenia, or osteoporosis. 1

• TSH <0.1 mIU/L carries 3-fold increased risk of atrial fibrillation over 10 years in patients >60 years 1
• Associated with up to 3-fold increased cardiovascular mortality in individuals >60 years 1
• For TSH 0.1-0.45 mIU/L, routine treatment is not recommended due to insufficient evidence of adverse outcomes 1

Critical Safety Monitoring

Agranulocytosis (Life-Threatening)

• Occurs within first 3 months of thioamide therapy 1
• Presents with sore throat and fever 1
• Requires immediate CBC and drug discontinuation 1
• Instruct patients to report any illness, particularly sore throat, fever, or general malaise immediately 5

Hepatotoxicity (Especially with Propylthiouracil)

• Monitor for fever, nausea, vomiting, right upper quadrant pain, dark urine, jaundice 1, 5
• Discontinue drug immediately if suspected 1
• Particularly dangerous in first 6 months of therapy 5

Vasculitis (Life-Threatening)

• Watch for new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 1, 5
• Can involve skin, kidneys, or lungs 5
• Requires immediate drug discontinuation 1

Special Populations

Pregnancy

• First trimester: Use propylthiouracil (despite hepatotoxicity risk, methimazole may cause fetal abnormalities) 1, 5
• Second and third trimesters: Switch to methimazole to reduce maternal hepatotoxicity risk 1, 5
• Maintain FT4 or free T3 in high-normal range using lowest possible dose 1

Cardiovascular Comorbidities

• Beta-blockers for rate control in hyperthyroid patients with cardiac disease 1
• Atrial fibrillation occurs in 5-15% of hyperthyroid patients, more frequently in those >60 years 1
• Anticoagulation should be guided by CHA₂DS₂-VASc risk factors, not solely by hyperthyroidism presence 1
• Intravenous beta-blockers indicated for acute rate control in acute coronary syndrome with new-onset AF 1
• Use nondihydropyridine calcium channel antagonists when beta-blockers contraindicated 1

Important Drug Interactions

• Warfarin: Increased anticoagulation effect requires dose adjustment and additional PT/INR monitoring 1, 5
• Beta-blockers: Reduced dose needed when euthyroid (hyperthyroidism increases clearance) 1, 5
• Digoxin: Reduced dose needed when euthyroid (serum levels increase) 5
• Theophylline: Reduced dose needed when euthyroid (clearance decreases) 1, 5