What is the recommended management for a patient with hyperthyroidism?

Hyperthyroidism Management

First-Line Medical Treatment

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 should be used. 1

Initial Drug Selection

• Methimazole is recommended as the primary antithyroid medication for most patients with hyperthyroidism 1
• The starting dose should not exceed 15-20 mg/day to minimize the risk of dose-dependent agranulocytosis 2
• Propylthiouracil is reserved for two specific situations only: patients intolerant to methimazole, and women in the first trimester of pregnancy 1
• Propylthiouracil carries significant risk of severe hepatotoxicity, particularly hepatic failure requiring liver transplantation or resulting in death, making it inappropriate as first-line therapy 1, 3, 2

Immediate Symptomatic Management

Beta-blockers provide immediate symptomatic relief and should be initiated alongside antithyroid drugs in all symptomatic patients. 1, 4

• Atenolol 25-50 mg daily or propranolol are the preferred agents for controlling tachycardia, tremor, and anxiety 1
• Titrate beta-blocker dose targeting heart rate <90 bpm if blood pressure allows 1
• If beta-blockers are contraindicated, use non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) as alternatives 4
• Dose reduction of beta-blockers is required once the patient achieves euthyroid state 1

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Monitoring During Initial Treatment

Thyroid Function Testing Schedule

• Monitor free T4 or free T3 index every 2-4 weeks during initial treatment 1
• Target: maintain free T4/T3 in the high-normal range using the lowest effective dose 1
• Do NOT target TSH normalization initially—TSH may remain suppressed for months even after achieving euthyroidism 1

Critical Safety Monitoring

Agranulocytosis typically occurs within the first 3 months of thioamide treatment and requires immediate action. 1

• Instruct patients to report sore throat and fever immediately 1, 5
• Obtain CBC immediately if these symptoms occur and discontinue the drug 1
• Monitor for hepatotoxicity (especially with propylthiouracil): fever, nausea, vomiting, right upper quadrant pain, dark urine, jaundice 1, 3
• Watch for vasculitis: skin changes, hematuria, respiratory symptoms—this can be life-threatening 1, 5, 3

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Definitive Treatment Options

Radioactive Iodine (I-131) Ablation

• Absolutely contraindicated in pregnancy and breastfeeding 1
• Pregnancy must be avoided for 4 months following administration 1, 6
• Potential risk of worsening Graves' ophthalmopathy—consider corticosteroid cover in patients with active eye disease 1, 6
• Treatment of choice for toxic nodular goitre 6, 2, 7

Surgical Thyroidectomy

• Rarely used for Graves' disease unless radioiodine refused or large compressive goitre present 6
• Should be performed as (near) total thyroidectomy 2
• Patient must be rendered euthyroid with antithyroid drugs before surgery 6

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Special Clinical Scenarios

Destructive Thyroiditis (Including Immune Checkpoint Inhibitor-Induced)

Destructive thyroiditis is self-limited and requires different management—antithyroid drugs are NOT indicated. 1, 4

• Use beta-blockers for symptomatic relief only during the hyperthyroid phase 1, 4
• Atenolol 25-50 mg daily, titrate for heart rate <90 if blood pressure allows 4
• Monitor with symptom evaluation and free T4 testing every 2 weeks 1, 4
• Continue immune checkpoint inhibitor therapy in most cases—thyroid dysfunction rarely requires treatment interruption 4
• High-dose corticosteroids are not routinely required 4
• Introduce thyroid hormone replacement if the patient becomes hypothyroid (low free T4/T3, even if TSH not yet elevated) 1, 4

Hyperthyroidism with Atrial Fibrillation

Beta-blockers are recommended for rate control unless contraindicated. 1, 4

• Atrial fibrillation occurs in 5-15% of hyperthyroid patients, more frequently in those over 60 years 1
• When beta-blockers cannot be used, administer diltiazem or verapamil 1, 4
• Anticoagulation should be guided by CHA₂DS₂-VASc risk factors, not solely by presence of hyperthyroidism 1
• Never attempt cardioversion without first achieving euthyroid state—antiarrhythmic drugs and cardioversion are generally unsuccessful while thyrotoxicosis persists 1, 4
• Normalize thyroid function before cardioversion to reduce risk of recurrence 4

Subclinical Hyperthyroidism

For TSH <0.1 mIU/L, treatment should be considered, particularly for patients older than 60 years or those with increased risk for heart disease, osteopenia, or osteoporosis. 1

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

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Drug Interactions Requiring Dose Adjustments

When patients transition from hyperthyroid to euthyroid state, several medications require dose reduction. 1

• Warfarin: increased anticoagulation effect—additional monitoring of PT/INR required 1, 5, 3
• Beta-blockers: may need dose reduction when euthyroid due to decreased clearance 1, 5, 3
• Digoxin: serum levels may increase when euthyroid—reduced dosage may be needed 5, 3
• Theophylline: clearance decreases when euthyroid—reduced dose may be needed 1, 5, 3

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Common Pitfalls to Avoid

• Do not reduce methimazole based solely on suppressed TSH while free T4 remains elevated or high-normal—this leads to inadequate treatment and recurrent hyperthyroidism 1
• Do not use antithyroid drugs for destructive thyroiditis—they are ineffective and expose patients to unnecessary drug risks 1, 4
• Do not overlook the need for beta-blocker dose reduction once euthyroid—this can cause symptomatic bradycardia 1
• Do not forget to counsel patients about pregnancy avoidance for 4 months after radioiodine 1, 6
• Do not miss early signs of agranulocytosis—educate patients to report sore throat and fever immediately 1, 5