What are the pharmacologic and non-pharmacologic management options for hyperthyroidism?

Management of Hyperthyroidism

Pharmacologic Management

Beta-blockers (propranolol or atenolol) should be initiated immediately for symptomatic relief in all patients with hyperthyroidism, regardless of severity, while definitive treatment is being arranged. 1

Antithyroid Drugs (Thionamides)

Methimazole and propylthiouracil are the two FDA-approved antithyroid medications that inhibit thyroid hormone synthesis. 2, 3

Mechanism and Pharmacology

• Methimazole and propylthiouracil both inhibit thyroid hormone synthesis but do not inactivate existing circulating thyroid hormones. 2, 3
• Propylthiouracil has the additional benefit of inhibiting peripheral conversion of T4 to T3, making it particularly useful in thyroid storm. 2
• Both drugs are readily absorbed, with propylthiouracil being extensively metabolized and approximately 35% excreted in urine within 24 hours. 2

Drug Selection

• Propylthiouracil is preferred during the first trimester of pregnancy due to rare fetal abnormalities associated with methimazole. 2
• Switching from propylthiouracil to methimazole for the second and third trimesters may be preferable given the risk of maternal hepatotoxicity with propylthiouracil. 2
• Methimazole is generally preferred outside of pregnancy due to better safety profile, particularly regarding hepatotoxicity. 2

Treatment Duration and Efficacy

• Standard antithyroid drug therapy for Graves' disease should be given for 12-18 months with the goal of inducing long-term remission. 4, 5
• Approximately 50% of patients will experience recurrence of hyperthyroidism after a 12-18 month course. 5
• Long-term treatment with antithyroid drugs (5-10 years) is associated with fewer recurrences (15%) compared to short-term treatment (12-18 months). 5

Risk Factors for Recurrence

• Age younger than 40 years increases risk of recurrence. 5
• Free T4 concentrations of 40 pmol/L or higher at presentation increase recurrence risk. 5
• TSH-binding inhibitory immunoglobulins higher than 6 U/L predict higher recurrence rates. 5
• Goiter size equivalent to or larger than WHO grade 2 before treatment increases recurrence risk. 5

Critical Safety Monitoring

• Patients must report immediately any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain), particularly in the first six months. 2
• White blood cell and differential counts should be obtained immediately if patients develop sore throat, skin eruptions, fever, headache, or general malaise to assess for agranulocytosis. 2
• Prothrombin time monitoring should be considered during therapy, especially before surgical procedures, as propylthiouracil may cause hypoprothrombinemia. 2
• Postmarketing reports of severe liver injury including hepatic failure requiring transplantation or resulting in death have been reported in pediatric patients with propylthiouracil. 2

Beta-Adrenergic Blocking Agents

Beta-blockers are recommended to control ventricular rate in patients with hyperthyroidism, particularly those with atrial fibrillation complicating thyrotoxicosis. 1

Specific Indications

• In hyperthyroidism with atrial fibrillation, beta-blocker administration is a Class I recommendation unless contraindicated. 1
• Short-acting beta-blockers (esmolol) are particularly useful when hemodynamic instability is a concern. 1
• High doses of intravenous beta-blockers may be required in thyroid storm. 1
• For immune checkpoint inhibitor-induced thyrotoxicosis, beta-blockers (atenolol or propranolol) should be used for symptomatic relief across all severity grades. 1

Alternative Rate Control

• When beta-blockers cannot be used, non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) are recommended as alternatives. 1
• Digoxin is less effective when adrenergic tone is high, limiting its utility in acute hyperthyroidism. 1

Supportive Care for Thyroiditis-Induced Thyrotoxicosis

Thyroiditis is self-limited and the initial hyperthyroidism generally resolves in weeks with supportive care, most often progressing to primary hypothyroidism. 1

• For mild to moderate symptoms (Grade 1-2), beta-blockers and hydration provide adequate symptomatic relief. 1
• Close monitoring of thyroid function every 2-3 weeks is essential to catch the transition to hypothyroidism. 1
• For persistent thyrotoxicosis lasting more than 6 weeks, endocrine consultation should be obtained for additional workup. 1

Severe Hyperthyroidism (Grade 3-4)

In severe or life-threatening hyperthyroidism, hospitalization with endocrine consultation is mandatory, and additional medical therapies including steroids, SSKI (saturated solution of potassium iodide), or thionamides should be considered. 1

Non-Pharmacologic Management

Radioactive Iodine Ablation

Radioactive iodine ablation is the most widely used treatment for hyperthyroidism in the United States and is the preferred treatment for toxic nodular goiter. 6, 4, 5

Indications and Efficacy

• Radioiodine is well tolerated with the only long-term sequela being the risk of developing radioiodine-induced hypothyroidism. 4
• Radioiodine can be used in all age groups except children, and should be avoided in pregnancy and during lactation. 4
• Pregnancy should be avoided for 4 months following radioiodine administration. 4

Special Considerations

• Radioiodine may cause deterioration in Graves' ophthalmopathy, and corticosteroid cover may reduce this risk. 4
• For toxic nodular goiter, radioiodine is the treatment of choice. 4, 5

Surgical Thyroidectomy

Surgery (subtotal or near-total thyroidectomy) has limited but specific roles in hyperthyroidism treatment. 4

Specific Indications for Surgery

• Surgery is indicated when radioiodine has been refused or contraindicated. 4
• Large goiters causing compressive symptoms in the neck (dysphagia, orthopnea, voice changes) are best managed surgically. 7, 4
• The goal of surgery is to cure the underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism. 4
• Radiofrequency ablation is rarely used for toxic nodular goiter but represents an emerging alternative. 5

Pre-Treatment Optimization

Patients should be rendered euthyroid with antithyroid drugs before definitive therapy with radioiodine or thyroidectomy. 4

If a rhythm control strategy is desirable for atrial fibrillation, thyroid function must be normalized prior to cardioversion, as the risk of relapse remains high otherwise. 1

Antiarrhythmic drugs and direct current cardioversion are generally unsuccessful while thyrotoxicosis persists. 1

Treatment Selection Algorithm

For Graves' Disease

1. First-line: Antithyroid drugs for 12-18 months (or longer-term 5-10 years for reduced recurrence). 4, 5
2. Radioiodine ablation is increasingly used as first-line therapy and is growing in acceptance. 4
3. Surgery is reserved for specific situations: refusal of radioiodine, large compressive goiters, or patient preference. 4

For Toxic Nodular Goiter

1. Radioiodine is the treatment of choice. 4, 5
2. Surgery is an alternative for large compressive goiters. 4
3. Antithyroid drugs will not cure toxic nodular goiter but may be used for symptom control. 4

For Destructive Thyroiditis

1. Observation with supportive care (beta-blockers, hydration) for mild cases. 5
2. Steroids only in severe cases. 5
3. Monitor for transition to hypothyroidism. 1

Critical Pitfalls to Avoid

• Never delay beta-blocker therapy while awaiting definitive treatment, as symptomatic relief is immediate and prevents cardiovascular complications. 1
• Do not use antithyroid drugs as definitive therapy for toxic nodular goiter—they will not cure the condition. 4
• Avoid cardioversion attempts in atrial fibrillation until euthyroid state is achieved. 1
• Do not overlook hepatotoxicity monitoring with propylthiouracil, especially in pediatric patients where it can be fatal. 2
• Ensure pregnancy testing before radioiodine and counsel on 4-month contraception requirement post-treatment. 4
• Consider corticosteroid prophylaxis before radioiodine in patients with Graves' ophthalmopathy. 4