What are the treatment options for hyperthyroidism?

Hyperthyroidism Treatment

For hyperthyroidism, the three definitive treatment options are antithyroid drugs (methimazole preferred over propylthiouracil), radioactive iodine ablation (most widely used in the United States), or thyroidectomy, with the choice depending on the underlying etiology, patient factors, and contraindications. 1, 2

Initial Diagnostic Workup

Before initiating treatment, confirm the diagnosis and establish the underlying cause:

• Biochemical confirmation: Low TSH with elevated free T4 and/or T3 2
• Etiologic diagnosis: Check TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy if the diagnosis is unclear or nodules are present 3, 2
• Common causes: Graves' disease (70%), toxic multinodular goiter (16%), subacute thyroiditis (3%), and drug-induced (9%) 3

Treatment by Etiology

Graves' Disease

Antithyroid drugs are the preferred initial treatment 3:

• Methimazole is the first-line agent at a starting dose of 15-20 mg/day (do not exceed this dose to minimize agranulocytosis risk) 4, 5
• Propylthiouracil should NOT be used as first-line due to risk of severe liver failure, liver transplantation, or death 6, 4. It is reserved only for: first trimester pregnancy or patients intolerant to methimazole 6, 4
• Treatment duration: Standard course is 12-18 months, but recurrence occurs in approximately 50% of patients 3

Predictors of recurrence after antithyroid drugs 3:

• Age younger than 40 years
• Free T4 ≥40 pmol/L at diagnosis
• TSH-binding inhibitory immunoglobulins >6 U/L
• Goiter size ≥WHO grade 2

Long-term antithyroid drug therapy (5-10 years) reduces recurrence to 15% compared to 50% with short-term treatment 3

Definitive therapy indications: If TSH-receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely and radioiodine or thyroidectomy should be recommended 4

Toxic Nodular Goiter (Toxic Adenoma or Multinodular Goiter)

Radioactive iodine ablation is the preferred treatment 4, 3:

• Stop antithyroid drugs at least one week before radioiodine to reduce treatment failure risk 4
• Alternative options: thyroidectomy or rarely radiofrequency ablation 3

Thyroiditis (Destructive Thyrotoxicosis)

Supportive care is the mainstay 3:

• Beta-blockers (atenolol 25-50 mg daily or propranolol) for symptomatic relief 7
• Monitor thyroid function every 2-3 weeks as patients typically transition to hypothyroidism 7
• Steroids only for severe cases 3
• Thyroiditis is self-limited and resolves in weeks 7

Symptomatic Management by Severity

Mild Symptoms (Grade 1)

• Continue monitoring 7
• Beta-blocker for symptomatic relief if needed 7

Moderate Symptoms (Grade 2)

• Consider holding treatment temporarily 7
• Beta-blocker for symptom control 7
• Hydration and supportive care 7
• Endocrine consultation if symptoms persist >6 weeks 7

Severe/Life-Threatening Symptoms (Grade 3-4)

• Hospitalize immediately 7
• Mandatory endocrine consultation 7
• Beta-blocker therapy 7
• Consider additional therapies: steroids, SSKI (saturated solution of potassium iodide), or thionamides (methimazole or propylthiouracil) 7
• Surgery may be necessary in severe cases 7

Special Populations

Pregnancy

• First trimester: Propylthiouracil is preferred over methimazole 7, 6
• Second/third trimester: Can switch to methimazole 7
• Goal: Maintain free T4 in high-normal range with lowest possible thioamide dose 7
• Monitor fetal growth and heart rate 7
• Radioactive iodine is absolutely contraindicated 7

Immune Checkpoint Inhibitor-Related Thyrotoxicosis

• Most cases are transient thyroiditis requiring only supportive care 7
• Beta-blockers for symptomatic management 7
• Monitor for transition to hypothyroidism (most common outcome) 7
• If Graves' disease is suspected (ophthalmopathy, thyroid bruit), obtain TSH-receptor antibodies and refer to endocrinology early 7

Critical Safety Considerations

Propylthiouracil black box warnings 6:

• Severe liver failure requiring transplantation or causing death
• Increased risk during pregnancy
• Monitor for fever, loss of appetite, nausea, vomiting, right upper quadrant pain, dark urine, pale stools, or jaundice
• Stop immediately if liver toxicity suspected

Methimazole monitoring 4:

• Agranulocytosis risk (dose-dependent, usually within first 3 months)
• Monitor for fever, chills, or sore throat
• Check complete blood count if infection symptoms develop

Radioactive iodine considerations 4:

• Most widely used definitive treatment in the United States 1
• Stop antithyroid drugs ≥1 week prior to maximize efficacy 4
• Contraindicated in pregnancy and breastfeeding 7

Thyroidectomy approach 4:

• Should be performed as (near) total thyroidectomy 4
• Reserved for patients with contraindications to other therapies or patient preference 1, 2