What is the initial management approach for hyperthyroidism?

Management of Hyperthyroidism

Initial Diagnostic Confirmation and Workup

For suspected hyperthyroidism, confirm biochemically with TSH (suppressed) and free T4 levels, and check T3 in highly symptomatic patients with minimal FT4 elevations to establish the diagnosis. 1

• Obtain TSH-receptor antibodies to diagnose Graves' disease, which is the most common cause of hyperthyroidism (70% of cases) 1, 2
• Perform physical examination assessing for diffuse goiter, thyroid bruit, or ophthalmopathy—these findings are diagnostic of Graves' disease and warrant early endocrine referral 1
• If thyroid nodules are present or the etiology remains unclear, thyroid scintigraphy is recommended to distinguish between Graves' disease, toxic nodular goiter, and thyroiditis 3
• Thyroid ultrasonography can help identify nodular disease versus diffuse enlargement 2

First-Line Pharmacologic Treatment

Initiate methimazole as the first-line antithyroid drug for most patients with hyperthyroidism, starting at 15-20 mg/day maximum to minimize the dose-dependent risk of agranulocytosis. 1, 4

Antithyroid Drug Selection

• Methimazole is preferred over propylthiouracil in all patients except during the first trimester of pregnancy, as propylthiouracil can cause severe liver failure requiring transplantation or death 1, 5, 4
• For pregnant patients in the first trimester, use propylthiouracil due to methimazole's association with aplasia cutis and choanal/esophageal atresia 1, 5
• Consider switching from propylthiouracil to methimazole for the second and third trimesters given propylthiouracil's hepatotoxicity risk 1, 5
• Methimazole inhibits thyroid hormone synthesis but does not inactivate existing circulating hormones, so clinical improvement takes time 5

Symptomatic Control with Beta-Blockers

• Start atenolol 25-50 mg daily or propranolol to control symptoms while waiting for antithyroid drugs to take effect 1
• Titrate beta-blocker to achieve heart rate <90 bpm if blood pressure allows 1
• Beta-blockers are particularly important in elderly patients, as cardiovascular complications are the chief cause of death in older patients with hyperthyroidism 1
• Note that hyperthyroidism increases clearance of beta-blockers with high extraction ratios, and dose reduction may be needed when the patient becomes euthyroid 5

Monitoring Strategy During Treatment

Monitor free T4 every 2-4 weeks initially to adjust dosing, with the goal of maintaining FT4 in the high-normal range using the lowest possible thioamide dose. 1

• Once on stable dosing, check TSH and free T4 after 6-8 weeks 1
• Monitor for transition to hypothyroidism every 2-3 weeks after diagnosis 1
• A rising serum TSH indicates that a lower maintenance dose should be employed 6
• Monitor prothrombin time during therapy, especially before surgical procedures, as methimazole may cause hypoprothrombinemia and bleeding 5

Critical Safety Monitoring

Counsel patients to report immediately any sore throat, fever, skin eruptions, or general malaise, as these are warning signs of agranulocytosis—a potentially life-threatening complication. 1, 5

• Obtain white blood cell and differential counts if any signs of illness develop 5
• Other serious side effects include hepatitis and thrombocytopenia 1
• Inform patients about vasculitis risk and to promptly report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 5
• The risk of agranulocytosis is dose-dependent, which is why starting doses should not exceed 15-20 mg/day 4

Treatment Duration and Definitive Therapy Options

For Graves' disease, prescribe antithyroid drugs for 12-18 months with a view to inducing long-term remission, but recognize that recurrence occurs in approximately 50% of patients. 7, 2

Predicting Recurrence Risk

• Age younger than 40 years increases recurrence risk 2
• FT4 concentrations ≥40 pmol/L at presentation increase recurrence risk 2
• TSH-binding inhibitory immunoglobulins >6 U/L increase recurrence risk 2
• Goiter size equivalent to or larger than WHO grade 2 increases recurrence risk 2
• If TSH-receptor antibodies remain above 10 mU/L after 6 months of antithyroid treatment, remission is unlikely and radioiodine or thyroidectomy should be recommended 4

Long-Term Antithyroid Drug Therapy

• Long-term treatment with antithyroid drugs (5-10 years) is feasible and associated with fewer recurrences (15%) than short-term treatment (12-18 months) 2
• However, antithyroid drugs will not cure hyperthyroidism associated with toxic nodular goiter 7

Radioactive Iodine Therapy

• Radioiodine is the most widely used treatment in the United States and is growing as first-line therapy 7, 8
• It is well tolerated, with the only long-term sequela being radioiodine-induced hypothyroidism 7
• Radioiodine is absolutely contraindicated in pregnant women and should be avoided during lactation 1
• Pregnancy should be avoided for 4 months following radioiodine administration 7
• For toxic nodular goiter, radioiodine is the treatment of choice 7, 2
• Stop antithyroid drugs at least one week prior to radioiodine to reduce the risk of treatment failure 4
• Radioiodine may cause deterioration in Graves' ophthalmopathy; corticosteroid cover may reduce this risk 7

Surgical Thyroidectomy

• Surgery has limited but specific roles: when radioiodine has been refused or there is a large goiter causing compressive symptoms (dysphagia, orthopnea, voice changes) 7, 3
• Thyroidectomy should be performed as (near) total thyroidectomy 4
• The goal is to cure the underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism 7

Special Populations

Pregnant Patients

• Use propylthiouracil in the first trimester due to methimazole's teratogenic risks 1, 5
• Consider switching to methimazole for second and third trimesters given propylthiouracil's hepatotoxicity risk 1, 5
• Untreated or inadequately treated Graves' disease increases risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal/neonatal hyperthyroidism 5
• Monitor closely and adjust treatment such that a sufficient, but not excessive, dose is given during pregnancy 5
• In many pregnant women, thyroid dysfunction diminishes as pregnancy proceeds, allowing dose reduction or discontinuation several weeks or months before delivery 5

Elderly Patients

• Start with lower doses of thyroid replacement if hypothyroidism develops in elderly patients with cardiovascular disease 1
• Beta-blockers are particularly important as cardiovascular complications are the chief cause of death in older patients with hyperthyroidism 1
• Treatment for subclinical hyperthyroidism is recommended for patients older than 65 years or with persistent serum thyrotropin <0.1 mIU/L due to increased risk of osteoporosis and cardiovascular disease 3

Thyroiditis-Induced Thyrotoxicosis

• Destructive thyrotoxicosis (painless/silent thyroiditis) is usually mild and transient 2
• This condition is self-limited and typically requires only supportive care with beta-blockers, not antithyroid drugs 1, 2
• Steroids are required only in severe cases 2

Drug Interactions and Dose Adjustments

• Oral anticoagulants (warfarin): Methimazole may increase anticoagulant activity; additional monitoring of PT/INR is needed, especially before surgical procedures 5
• Beta-blockers: Dose reduction may be needed when a hyperthyroid patient becomes euthyroid due to decreased clearance 5
• Digitalis glycosides: Serum digitalis levels may increase when hyperthyroid patients become euthyroid; reduced dosage may be needed 5
• Theophylline: Clearance may decrease when hyperthyroid patients become euthyroid; reduced dose may be needed 5

Common Pitfalls to Avoid

• Do not use radioactive iodine in pregnant women—it is absolutely contraindicated 1
• Do not assume all hyperthyroidism requires antithyroid drugs; thyroiditis-induced thyrotoxicosis is self-limited and requires only supportive care 1
• Do not start propylthiouracil as first-line agent except in first trimester pregnancy or in individuals who have experienced adverse responses to methimazole 4
• Do not exceed starting doses of 15-20 mg/day methimazole due to dose-dependent agranulocytosis risk 4
• Do not continue antithyroid drugs up to the time of radioiodine therapy; stop at least one week prior to reduce treatment failure risk 4