What is the recommended management for a patient with hyperthyroidism?

Hyperthyroidism Management

Initial Diagnostic Confirmation and Rate Control

For patients with suspected hyperthyroidism, immediately initiate beta-blocker therapy to control ventricular rate while confirming the diagnosis and determining the underlying etiology. 1

• Beta-blockers are the first-line agents for symptomatic control, particularly in patients with tachycardia, tremor, anxiety, or heat intolerance 1, 2
• Short-acting beta-blockers like esmolol are particularly useful when hemodynamic instability is a concern 1
• High doses may be required in severe cases such as thyroid storm 1
• If beta-blockers are contraindicated, use non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) as alternatives 1
• Digoxin is less effective when adrenergic tone is high and should be avoided as monotherapy 1

Establishing the Etiology

Determine whether hyperthyroidism is due to overproduction (Graves' disease, toxic nodular goiter) or destructive release (thyroiditis) before selecting definitive treatment. 2, 3

• Graves' disease accounts for 70% of hyperthyroidism cases, toxic nodular goiter for 16%, and thyroiditis for 3% 4
• Measure TSH-receptor antibodies to diagnose Graves' disease 3, 4
• Obtain thyroid ultrasonography to identify nodules 4
• Perform thyroid scintigraphy if nodules are present or the etiology is unclear 3
• Thyroiditis typically presents with a thyrotoxic phase followed by hypothyroidism and requires only supportive care 3, 4

Treatment Selection Based on Etiology

For Graves' Disease

Antithyroid drugs (methimazole preferred) are the first-line treatment in Europe and many parts of the world, while radioactive iodine ablation is most commonly used in the United States. 5, 2, 4

Antithyroid Drug Therapy

• Methimazole is the preferred antithyroid drug except during the first trimester of pregnancy 6, 7, 4
• Start methimazole at 15-20 mg/day maximum to minimize the risk of dose-dependent agranulocytosis 7
• Propylthiouracil should only be used during the first trimester of pregnancy due to risk of severe hepatotoxicity requiring liver transplantation or causing death 8, 7
• Continue antithyroid drugs for 12-18 months with the goal of inducing remission 5, 4
• Recurrence after short-term treatment (12-18 months) occurs in approximately 50% of patients 4
• Long-term treatment (5-10 years) reduces recurrence rates to 15% 4

Predictors of recurrence after antithyroid drug therapy include: 4

• Age younger than 40 years

• FT4 concentrations ≥40 pmol/L at diagnosis

• TSH-receptor antibodies >6 U/L after 6 months of treatment

• Goiter size ≥WHO grade 2

• If TSH-receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely and radioiodine or thyroidectomy should be recommended 7

Radioactive Iodine Ablation

• Radioactive iodine is well tolerated and can be used in all age groups except children, pregnant women, and lactating women 5
• Pregnancy should be avoided for 4 months following radioiodine administration 5
• Stop antithyroid drugs at least one week prior to radioiodine to reduce the risk of treatment failure 7
• The only long-term sequela is radioiodine-induced hypothyroidism 5
• Radioiodine may worsen Graves' ophthalmopathy; corticosteroid cover may reduce this risk 5

Surgical Thyroidectomy

• Surgery should be performed as near-total or total thyroidectomy 7
• Surgery is indicated when radioiodine has been refused or there is a large goiter causing compressive symptoms (dysphagia, orthopnea, voice changes) 5, 3
• Render the patient euthyroid with antithyroid drugs before surgery 5

For Toxic Nodular Goiter (Toxic Adenoma or Multinodular Goiter)

Radioactive iodine is the treatment of choice for toxic nodular goiter. 5, 7

• Antithyroid drugs will not cure toxic nodular goiter but can be used for short-term control before definitive therapy 5
• Stop antithyroid drugs at least one week before radioiodine treatment 7
• Surgery (total thyroidectomy) is an alternative if radioiodine is contraindicated 4
• Radiofrequency ablation is rarely used 4

For Destructive Thyroiditis

Thyrotoxicosis from thyroiditis is usually mild and transient, requiring only supportive care with beta-blockers. 3, 4

• Steroids are reserved for severe cases 4
• The condition is self-limiting and typically resolves spontaneously 3

Special Populations and Situations

Pregnancy

• Propylthiouracil is preferred during the first trimester due to rare fetal abnormalities associated with methimazole 8, 6
• Switch to methimazole for the second and third trimesters to avoid maternal hepatotoxicity from propylthiouracil 8, 6
• Untreated or inadequately treated hyperthyroidism increases risk of maternal heart failure, spontaneous abortion, preterm birth, stillbirth, and fetal/neonatal hyperthyroidism 8, 6
• Use the lowest effective dose to avoid fetal goiter and cretinism 8, 6
• Thyroid dysfunction often diminishes as pregnancy progresses, allowing dose reduction or discontinuation 8, 6

Atrial Fibrillation Complicating Hyperthyroidism

Antithrombotic therapy is recommended based on the presence of other stroke risk factors, not hyperthyroidism alone. 1

• Beta-blockers are recommended to control ventricular rate unless contraindicated 1
• If beta-blockers cannot be used, administer diltiazem or verapamil 1
• Normalize thyroid function before cardioversion, as the risk of relapse remains high otherwise 1
• Antiarrhythmic drugs and direct current cardioversion are generally unsuccessful while thyrotoxicosis persists 1
• Once euthyroid, antithrombotic prophylaxis recommendations are the same as for patients without hyperthyroidism 1

Subclinical Hyperthyroidism

Treatment is recommended for patients at highest risk of osteoporosis and cardiovascular disease. 3

• Treat patients older than 65 years 3
• Treat patients with persistent serum TSH <0.1 mIU/L 3
• Subclinical hyperthyroidism affects 0.7-1.4% of people worldwide 3

Immune Checkpoint Inhibitor-Induced Thyroiditis

Continue immune checkpoint inhibitor therapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 1

• Thyroiditis is self-limiting with two phases: hyperthyroid followed by hypothyroid 1
• During the hyperthyroid phase, use beta-blockers if symptomatic (atenolol 25-50 mg daily, titrate for heart rate <90 if blood pressure allows) 1
• Monitor closely with symptom evaluation and free T4 testing every 2 weeks 1
• High-dose corticosteroids are not routinely required 1
• Introduce thyroid hormone replacement if the patient becomes hypothyroid 1

Monitoring and Safety Considerations

For Antithyroid Drug Therapy

Patients must be counseled to immediately report symptoms of agranulocytosis or hepatotoxicity. 8, 6

• Agranulocytosis symptoms: sore throat, fever, skin eruptions, general malaise 8, 6
• Hepatotoxicity symptoms: anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain 8
• Obtain white blood cell and differential counts if illness develops 8, 6
• Monitor prothrombin time before surgical procedures due to potential hypoprothrombinemia 8, 6
• Monitor thyroid function tests periodically; rising TSH indicates need for lower maintenance dose 8, 6
• Promptly report symptoms of vasculitis: new rash, hematuria, decreased urine output, dyspnea, hemoptysis 8, 6

Drug Interactions

Antithyroid drugs inhibit vitamin K activity, increasing oral anticoagulant effects. 8, 6

• Monitor PT/INR more frequently, especially before surgical procedures 8, 6
• Beta-blocker clearance increases in hyperthyroidism; reduce dose when patient becomes euthyroid 8, 6
• Digitalis levels may increase when hyperthyroid patients become euthyroid; reduce digitalis dose 8, 6
• Theophylline clearance decreases when patients become euthyroid; reduce theophylline dose 8, 6

Prognosis and Long-Term Considerations

Hyperthyroidism is associated with increased mortality, cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes if untreated. 3, 4

• Rapid and sustained control of hyperthyroidism may improve prognosis 4
• No single treatment modality offers an absolute cure 5
• Treatment choices should be individualized based on underlying diagnosis, contraindications, severity, and patient preference 2