What is the recommended treatment approach for a patient with hyperthyroidism?

Treatment Approach for Hyperthyroidism

Initial Diagnostic Confirmation and Etiology

The recommended treatment approach for hyperthyroidism depends critically on establishing the underlying cause through biochemical confirmation (suppressed TSH with elevated free T4 and/or T3) followed by etiology-specific therapy using antithyroid drugs, radioactive iodine, or surgery. 1, 2, 3

Confirm Hyperthyroidism Biochemically

• Measure TSH, free T4, and free T3 to confirm thyrotoxicosis—low TSH with elevated thyroid hormones establishes the diagnosis 1, 2, 3
• A suppressed TSH (<0.1 mIU/L) with elevated free T4 or T3 indicates overt hyperthyroidism requiring treatment 1, 2
• Subclinical hyperthyroidism (TSH <0.1 mIU/L with normal T4/T3) requires treatment in patients >65 years or those with cardiovascular disease or osteoporosis risk 1, 4

Establish the Underlying Cause

• Graves disease (70% of cases): Check TSH-receptor antibodies (TRAb) or look for pathognomonic thyroid eye disease (exophthalmos, stare, lid lag) 1, 2, 3
• Toxic nodular goiter (16% of cases): Perform thyroid ultrasound to identify nodules; patients may have compressive symptoms like dysphagia or orthopnea 1, 2, 3
• Thyroiditis (3% of cases): Typically presents with transient thyrotoxicosis, tender thyroid, and elevated inflammatory markers 2, 3
• Drug-induced (9% of cases): Review medication history for amiodarone, tyrosine kinase inhibitors, or immune checkpoint inhibitors 2
• Obtain radioactive iodine uptake scan if the etiology remains unclear after antibody testing—high uptake indicates Graves disease or toxic nodular goiter, while low uptake suggests thyroiditis 2, 3

Treatment Selection Based on Etiology

Graves Disease Treatment Options

For Graves disease, three equally effective treatment modalities exist: antithyroid drugs (methimazole preferred), radioactive iodine ablation, or thyroidectomy—selection depends on patient age, pregnancy status, goiter size, and patient preference. 1, 5, 2, 3

Antithyroid Drug Therapy (First-Line for Most Patients)

• Methimazole is the preferred antithyroid drug except during the first trimester of pregnancy due to rare teratogenic effects 6, 2, 3
• Start methimazole 10-30 mg daily depending on severity (higher doses for FT4 >40 pmol/L above normal) 2, 3
• Continue treatment for 12-18 months to induce remission, though approximately 50% of patients experience recurrence after discontinuation 5, 2, 3
• Propylthiouracil should only be used in the first trimester of pregnancy or in patients with severe methimazole allergy, due to risk of severe hepatotoxicity including liver failure and death 7, 6, 2
• Monitor complete blood count and liver function tests before starting therapy and if symptoms of agranulocytosis (sore throat, fever) or hepatotoxicity (jaundice, right upper quadrant pain, dark urine) develop 7, 6
• Long-term antithyroid drug therapy (5-10 years) reduces recurrence rates to 15% compared to 50% with short-term therapy 2

Predictors of Recurrence After Antithyroid Drugs

• Age <40 years increases recurrence risk 2
• FT4 ≥40 pmol/L above normal at diagnosis predicts higher recurrence 2
• TSH-binding inhibitory immunoglobulins >6 U/L indicate higher recurrence risk 2
• Goiter size ≥WHO grade 2 before treatment increases recurrence likelihood 2

Radioactive Iodine Ablation

• Radioactive iodine (¹³¹I) resolves hyperthyroidism in >90% of patients with Graves disease and is increasingly used as first-line therapy 5, 2, 3
• Avoid radioactive iodine during pregnancy, lactation, and in children; pregnancy must be avoided for 4 months after administration 5, 2
• Hypothyroidism develops in most patients within 1 year after radioactive iodine treatment, requiring lifelong levothyroxine replacement 5, 3
• Radioactive iodine may worsen Graves' ophthalmopathy—consider corticosteroid prophylaxis in patients with active eye disease 5, 2
• Render patients euthyroid with antithyroid drugs before radioactive iodine to prevent thyroid storm 5, 2

Thyroidectomy

• Surgery (subtotal or near-total thyroidectomy) is indicated for patients with large compressive goiters causing dysphagia, orthopnea, or voice changes 5, 2, 3
• Thyroidectomy is the treatment of choice for patients with obstructive goiter symptoms 3
• Surgery is appropriate when radioactive iodine is refused or contraindicated and antithyroid drugs have failed 5, 2
• Render patients euthyroid with antithyroid drugs before surgery to prevent thyroid storm 5, 2

Toxic Nodular Goiter Treatment

• Radioactive iodine is the treatment of choice for toxic multinodular goiter and toxic adenoma, resolving hyperthyroidism in >90% of patients 5, 2, 3
• Antithyroid drugs do not cure toxic nodular goiter but can control hyperthyroidism temporarily or as preparation for definitive therapy 5, 2, 3
• Thyroidectomy is indicated for toxic nodular goiter with compressive symptoms 2, 3
• Radiofrequency ablation is an emerging option for toxic adenomas but is rarely used 2

Thyroiditis Management

• Thyroiditis-induced thyrotoxicosis is typically mild and transient, requiring only supportive care with beta-blockers for symptomatic relief 1, 2, 3
• Antithyroid drugs are ineffective for thyroiditis because the thyroid is not overproducing hormone—it is releasing preformed hormone from damaged follicles 2, 3
• Corticosteroids are reserved for severe cases of subacute granulomatous thyroiditis with significant pain or systemic symptoms 2
• Monitor thyroid function as patients often develop transient hypothyroidism following the thyrotoxic phase 2, 3

Subclinical Hyperthyroidism Treatment Criteria

• Treat subclinical hyperthyroidism (TSH <0.1 mIU/L with normal T4/T3) in patients >65 years due to increased risk of atrial fibrillation, osteoporosis, and cardiovascular mortality 1, 4
• Treatment is mandatory in patients with persistent TSH <0.1 mIU/L and comorbidities such as atrial fibrillation, osteoporosis, or heart disease 1, 4
• For patients with TSH 0.1-0.45 mIU/L, monitor every 3-12 months unless high-risk features are present 8, 4
• Mild subclinical hyperthyroidism (TSH 0.1-0.45 mIU/L) in younger patients without comorbidities can be monitored without immediate treatment 4

Special Populations and Situations

Pregnancy

• Propylthiouracil is preferred during the first trimester of pregnancy due to rare teratogenic effects of methimazole (aplasia cutis, choanal atresia) 7, 6, 2
• Switch from propylthiouracil to methimazole for the second and third trimesters to reduce maternal hepatotoxicity risk 7, 6, 2
• Avoid radioactive iodine during pregnancy and for 4 months before conception 5, 2
• Untreated hyperthyroidism in pregnancy increases risk of maternal heart failure, preterm birth, stillbirth, and fetal hyperthyroidism 7, 6, 2

Thyroid Storm

• Thyroid storm is a life-threatening complication requiring immediate hospitalization, high-dose antithyroid drugs, beta-blockers, corticosteroids, and supportive care 2
• Render patients euthyroid before elective surgery or radioactive iodine to prevent thyroid storm 5, 2

Atrial Fibrillation

• Hyperthyroidism-induced atrial fibrillation often resolves with treatment of the underlying thyroid disorder 1, 2
• Beta-blockers control heart rate while awaiting definitive thyroid treatment 2, 3
• Anticoagulation should be considered based on CHA₂DS₂-VASc score 2

Critical Monitoring and Safety Considerations

Antithyroid Drug Monitoring

• Patients must report immediately any sore throat, fever, rash, or jaundice—these may indicate life-threatening agranulocytosis or hepatotoxicity 7, 6
• Check complete blood count and liver function tests if symptoms of infection or liver dysfunction develop 7, 6
• Monitor prothrombin time before surgery in patients on antithyroid drugs due to potential vitamin K inhibition 7, 6
• Adjust doses of beta-blockers, digoxin, theophylline, and warfarin as patients become euthyroid—clearance of these drugs increases in hyperthyroidism 7, 6

Vasculitis Risk

• Both propylthiouracil and methimazole can cause ANCA-positive vasculitis affecting skin, kidneys, or lungs 7, 6
• Instruct patients to report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis immediately 7, 6

Common Pitfalls to Avoid

• Never use antithyroid drugs to treat thyroiditis—they are ineffective because the thyroid is not actively producing excess hormone 2, 3
• Do not use propylthiouracil as first-line therapy except in first trimester pregnancy due to severe hepatotoxicity risk including liver failure and death 7, 2
• Avoid radioactive iodine in patients with active Graves' ophthalmopathy without corticosteroid prophylaxis 5, 2
• Do not perform thyroidectomy or administer radioactive iodine in thyrotoxic patients—render euthyroid first with antithyroid drugs to prevent thyroid storm 5, 2
• Failing to monitor for agranulocytosis (occurs in first 3 months) can result in life-threatening infections 7, 6