What are the treatment guidelines for a patient with hyperthyroidism?

Treatment Guidelines for Hyperthyroidism

First-Line Treatment Selection

For confirmed overt hyperthyroidism (suppressed TSH with elevated T3/T4), initiate antithyroid medication immediately, as untreated disease causes cardiac arrhythmias, heart failure, osteoporosis, and increased mortality. 1

Methimazole as Preferred Agent

• Methimazole is the drug of choice for most patients with hyperthyroidism due to fewer major side effects, once-daily dosing, lower cost, and wider availability compared to propylthiouracil 2, 3
• Start methimazole at 10-30 mg as a single daily dose for initial control 2, 4
• Methimazole can be used as primary treatment for 12-18 months to induce long-term remission in Graves' disease, or as short-term preparative therapy (weeks to months) before radioiodine or surgery 2, 5

When to Use Propylthiouracil Instead

• Propylthiouracil is the preferred agent during the first trimester of pregnancy because methimazole is associated with rare congenital malformations including aplasia cutis and choanal/esophageal atresia 6, 2
• Switch from propylthiouracil to methimazole for the second and third trimesters, as propylthiouracil carries risk of maternal hepatotoxicity 6
• Start propylthiouracil at 100-300 mg every 6 hours (requires multiple daily doses) 2
• Consider propylthiouracil in patients with severe methimazole allergy or intolerance 3

Immediate Rate Control for Cardiac Complications

For patients with atrial fibrillation complicating hyperthyroidism, initiate β-blockers immediately for rate control unless contraindicated. 7, 1

• β-blockers (propranolol, atenolol, or metoprolol) are first-line for controlling ventricular rate in thyrotoxicosis 7, 1
• High doses may be required in thyroid storm 7
• Non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) are alternatives when β-blockers cannot be used 7, 1
• Anticoagulation with heparin or vitamin K antagonist is appropriate when atrial fibrillation persists longer than 48 hours 7
• Normalize thyroid function before attempting cardioversion, as antiarrhythmic drugs and cardioversion are generally unsuccessful while thyrotoxicosis persists 7, 1

Treatment Algorithm for Subclinical Hyperthyroidism

Treat subclinical hyperthyroidism (TSH <0.1 mIU/L with normal free T4) in patients over 60 years or those with cardiovascular risk factors, as this population faces increased cardiovascular mortality and atrial fibrillation risk. 1

• Initiate treatment for all patients with TSH <0.1 mIU/L due to Graves disease or nodular thyroid disease 1
• Treat patients with or at increased risk for heart disease, osteopenia, or osteoporosis (including estrogen-deficient women) when TSH <0.1 mIU/L 1
• For symptomatic patients with TSH 0.1-0.45 mIU/L, interrupt immune checkpoint inhibitors temporarily and start β-blocker therapy; restart when asymptomatic 7

Definitive Treatment Options

Radioactive Iodine Ablation

• Radioactive iodine is the most widely used treatment in the United States and resolves hyperthyroidism in more than 90% of patients with Graves disease and toxic multinodular goiter 4, 8
• It is the treatment of choice for toxic nodular goiter 5
• Hypothyroidism develops in most patients within 1 year after treatment 8
• Avoid in pregnancy, lactation, and children; pregnancy should be avoided for 4 months following administration 5
• May cause deterioration in Graves' ophthalmopathy; corticosteroid cover may reduce this risk 5

Surgical Thyroidectomy

• Thyroidectomy (subtotal or near-total) is the treatment of choice for patients with compressive symptoms from an obstructive goiter 8
• Consider surgery when radioiodine has been refused or there is a large goiter causing neck compression symptoms 5
• The goal is to cure the underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism 5

Critical Monitoring Requirements

Laboratory Surveillance

• Monitor thyroid function tests periodically during antithyroid drug therapy 9, 6
• Once clinical hyperthyroidism resolves, a rising serum TSH indicates that a lower maintenance dose should be employed 9, 6
• Monitor prothrombin time during therapy, especially before surgical procedures, as antithyroid drugs may cause hypoprothrombinemia and bleeding 9, 6

Drug Interactions Requiring Dose Adjustments

• Reduce β-blocker dose when hyperthyroid patients become euthyroid, as hyperthyroidism increases clearance of beta blockers with high extraction ratio 9, 6
• Reduce digitalis glycoside dose when patients on stable regimens become euthyroid, as serum digitalis levels may increase 9, 6
• Reduce theophylline dose when patients on stable regimens become euthyroid, as theophylline clearance may decrease 9, 6
• Monitor PT/INR closely in patients on oral anticoagulants (warfarin), especially before surgical procedures, as antithyroid drugs may increase anticoagulant activity 9, 6

Critical Safety Warnings

Immediate Reporting Requirements

• Instruct patients to report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise, as these may indicate agranulocytosis 9, 6
• Obtain white blood cell and differential counts when these symptoms occur 9, 6
• Patients must promptly report symptoms of vasculitis including new rash, hematuria, decreased urine output, dyspnea, or hemoptysis, as severe complications and death have occurred 9, 6

Hepatotoxicity Monitoring (Propylthiouracil)

• Propylthiouracil carries risk of severe liver injury including hepatic failure requiring liver transplantation or resulting in death, particularly in pediatric patients 6
• Patients should report symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain) particularly in the first 6 months of therapy 6
• Measure liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT/AST) when these symptoms occur 6

Special Populations

Pregnancy Management

• If hyperthyroidism is inadequately treated during pregnancy, there is increased risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal/neonatal hyperthyroidism 9, 6
• Use propylthiouracil in the first trimester, then switch to methimazole for second and third trimesters 6, 2
• Administer sufficient but not excessive doses, as antithyroid drugs cross placental membranes and can induce goiter and cretinism in the developing fetus 9, 6
• Thyroid dysfunction often diminishes as pregnancy proceeds; dose reduction may be possible, and antithyroid therapy can sometimes be discontinued weeks or months before delivery 9, 6

Lactation

• Both methimazole and propylthiouracil are present in breast milk but result in clinically insignificant doses to nursing infants 9, 6, 2
• Long-term studies found no toxicity in infants nursed by mothers receiving methimazole 9
• Monitor infant thyroid function at frequent (weekly or biweekly) intervals 9

Immunotherapy-Related Hyperthyroidism

• For symptomatic hyperthyroidism (usually grade 1 or 2) in patients on immune checkpoint inhibitors, interrupt the immunotherapy and start β-blocker therapy 7
• Restart immunotherapy when asymptomatic 7
• In cases of hypothyroidism following thyroiditis, start prednisone 1 mg/kg orally and taper based on recovery of clinical symptoms 7