What is the appropriate management for a patient with laboratory results indicating hyperthyroidism?

Management of Laboratory-Confirmed Hyperthyroidism

Start beta-blockers immediately for all symptomatic patients with hyperthyroidism to control heart rate, prevent atrial fibrillation, and reduce cardiovascular mortality, using atenolol 25-50 mg daily or metoprolol, titrating to heart rate <90 bpm if blood pressure allows. 1, 2

Immediate Initial Steps

Confirm Diagnosis and Establish Etiology

• Repeat TSH with free T4 and total T3 or free T3 to confirm hyperthyroidism and assess severity 1, 3
• Measure TSH receptor antibodies (TRAb) to diagnose Graves disease, which accounts for 70% of hyperthyroidism cases 3, 4
• Order thyroid ultrasound to identify nodular disease 3, 5
• Obtain radioactive iodine uptake scan if nodules are present, antibodies are negative, or etiology remains unclear to distinguish between Graves disease (diffuse uptake), toxic nodular goiter (focal uptake), and thyroiditis (low uptake) 3, 6, 5

Cardiovascular Protection

• Beta-blockers are mandatory for symptomatic patients to prevent tachycardia-induced cardiomyopathy, atrial fibrillation, and heart failure, which are the chief causes of death in hyperthyroidism, particularly in patients >50 years old 1, 2
• Propranolol is an alternative if atenolol or metoprolol are contraindicated 2
• Monitor for atrial fibrillation with ECG, as hyperthyroidism increases cardiovascular mortality 1

Definitive Treatment Based on Etiology

Graves Disease (70% of cases)

First-line treatment options include antithyroid drugs, radioactive iodine, or thyroidectomy, with the choice depending on patient factors and preferences 3, 4, 6:

Antithyroid Drug Therapy

• Start methimazole as first-line antithyroid drug for most patients 7, 6, 5
• Use propylthiouracil only in first trimester of pregnancy (due to methimazole teratogenicity) or in patients intolerant to methimazole, as propylthiouracil carries risk of severe hepatotoxicity including liver failure 7, 8
• Standard course is 12-18 months, but recurrence occurs in approximately 50% of patients 3
• Consider long-term treatment (5-10 years) as it reduces recurrence to 15% compared to 50% with short-term treatment 3
• High-risk features for recurrence include: age <40 years, free T4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 3
• Monitor thyroid function tests every 4-6 weeks initially, then every 2-3 months once stable 7, 8
• Warn patients to report immediately: sore throat, fever, rash, jaundice, right upper quadrant pain, or general malaise due to risk of agranulocytosis and hepatotoxicity 7, 8
• Check CBC with differential if symptoms of infection develop 7, 8
• Monitor prothrombin time before surgical procedures as antithyroid drugs may cause hypoprothrombinemia 7, 8

Radioactive Iodine (131I)

• Radioactive iodine is the most widely used treatment in the United States and resolves hyperthyroidism in >90% of patients 6, 5
• Hypothyroidism develops in most patients within 1 year after treatment, requiring lifelong levothyroxine replacement 4, 5
• Contraindicated in pregnancy, lactation, and children; avoid pregnancy for 4 months after administration 9, 6
• May worsen Graves ophthalmopathy; consider corticosteroid prophylaxis in patients with active eye disease 9
• Preferred treatment for toxic nodular goiter 3, 9, 5

Thyroidectomy

• Reserved for patients with: large compressive goiter causing dysphagia/orthopnea, refusal of radioactive iodine, or contraindications to medical therapy 9, 6, 5
• Near-total or total thyroidectomy is preferred over subtotal to reduce recurrence risk 9

Toxic Nodular Goiter (16% of cases)

• Radioactive iodine or thyroidectomy are treatments of choice, as antithyroid drugs do not cure toxic nodular disease 3, 9, 5
• Antithyroid drugs may be used temporarily to achieve euthyroid state before definitive therapy 9, 6
• Radiofrequency ablation is an emerging option for select cases 3

Thyroiditis (3% of cases)

• Thyroiditis is self-limiting and requires only supportive care with beta-blockers; high-dose corticosteroids are not routinely required 1, 2
• Monitor free T4 every 2 weeks during hyperthyroid phase 1, 2
• Introduce levothyroxine when patient transitions to hypothyroid phase (low free T4, even if TSH not yet elevated), which typically occurs 1-2 months after onset 1, 2
• Permanent hypothyroidism develops in most patients after thyroiditis 1

Drug-Induced Hyperthyroidism (9% of cases)

• Caused by amiodarone, tyrosine kinase inhibitors, or immune checkpoint inhibitors 3
• For immune checkpoint inhibitor-induced thyrotoxicosis: continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1, 2
• Manage with beta-blockers for symptomatic relief 1, 2
• Monitor TSH every 4-6 weeks for asymptomatic patients on immune checkpoint inhibitors 2
• Hold immunotherapy only for grade 3-4 toxicity (severe symptoms, hospitalization required) 1

Special Populations

Pregnancy

• Use propylthiouracil in first trimester due to methimazole teratogenicity (congenital malformations); switch to methimazole in second and third trimesters to avoid propylthiouracil hepatotoxicity 7, 8
• Untreated hyperthyroidism increases risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal hyperthyroidism 7, 8
• Use lowest effective dose to avoid fetal goiter and cretinism 7, 8
• Many pregnant women experience spontaneous improvement; consider dose reduction or discontinuation in late pregnancy 7, 8
• Radioactive iodine and surgery are contraindicated during pregnancy 9, 6

Subclinical Hyperthyroidism

• Defined as low TSH with normal free T4 and T3 1, 4
• Treat patients at highest risk: age >65 years, TSH <0.1 mIU/L, presence of cardiac disease, atrial fibrillation, or osteoporosis 1, 4
• Repeat TSH in 2 weeks for patients with cardiac disease or atrial fibrillation; otherwise repeat in 3 months 1
• If TSH remains 0.1-0.45 mIU/L with normal free T4 and T3, recheck every 3-12 months until stable or normalized 1

Monitoring and Follow-Up

During Antithyroid Drug Therapy

• Monitor thyroid function tests every 4-6 weeks initially, then every 2-3 months once stable 7, 8
• Rising TSH indicates need for dose reduction 7, 8
• Check prothrombin time before surgical procedures 7, 8
• Adjust doses of beta-blockers, digoxin, and theophylline as patient becomes euthyroid, as clearance of these drugs increases in hyperthyroidism 7, 8

After Radioactive Iodine or Surgery

• Monitor for development of hypothyroidism, which occurs in most patients within 1 year 4, 5
• Check thyroid function tests at 4-6 weeks, then every 3 months for first year 5
• Initiate levothyroxine replacement when hypothyroidism develops 5

Critical Pitfalls to Avoid

• Never start thyroid hormone replacement before corticosteroids in patients with concurrent adrenal insufficiency, as this can precipitate adrenal crisis 1
• Do not use propylthiouracil as first-line therapy except in first trimester pregnancy or methimazole intolerance, due to severe hepatotoxicity risk including liver failure and death 8
• Do not delay beta-blocker initiation in symptomatic patients, as cardiovascular complications are the leading cause of death in hyperthyroidism 1
• Do not assume thyroiditis requires steroids; it is self-limiting and steroids are reserved only for severe cases 1, 2
• Do not discontinue immune checkpoint inhibitors for thyroid dysfunction alone, as it rarely requires treatment interruption 1, 2