What are the treatment options for Graves' disease?

Treatment of Graves' Disease

Methimazole is the preferred first-line antithyroid medication for most patients with Graves' disease, administered for 12-18 months with dose titration to maintain free T4 in the high-normal range using the lowest effective dose. 1, 2, 3

Initial Diagnostic Confirmation

• Confirm diagnosis with TSH (suppressed), free T4 (elevated), and TSH receptor antibodies to distinguish Graves' disease from other causes of thyrotoxicosis 1
• Monitor thyroid function every 4-6 weeks during the initial treatment phase 1

First-Line Medical Therapy: Antithyroid Drugs

Methimazole is superior to propylthiouracil for most patients due to once-daily dosing, better adherence, and a more favorable side-effect profile 2, 3, 4

Dosing Strategy

• Titrate methimazole dose based on thyroid function tests every 4-6 weeks initially, then every 2-3 months once stable 1
• Goal: maintain free T4 in high-normal range with the lowest possible dose 5, 1
• Standard treatment duration: 12-18 months 1, 3, 4
• In children: extend treatment to 24-36 months 3

When to Use Propylthiouracil Instead

Propylthiouracil is reserved for specific situations only: 6

• First trimester of pregnancy (switch from methimazole when planning pregnancy through week 12-13) 5, 1, 3
• Patients intolerant to methimazole 6
• Both agents are safe during breastfeeding 5

Monitoring for Side Effects

Check complete blood count if sore throat or fever develops, as agranulocytosis typically presents within the first 90 days of therapy 5, 4

• Other serious but rare reactions: hepatotoxicity, vasculitis, thrombocytopenia 5, 4
• Discontinue thioamide immediately if agranulocytosis suspected 5

Adjunctive Symptomatic Management

Beta-blockers (propranolol or atenolol) should be initiated for symptomatic relief of tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization 5, 1

Predicting Remission vs. Relapse

Measure TSH receptor antibodies at 12-18 months to guide decision-making: 1, 3

• Persistently high TSH receptor antibodies: either continue methimazole for another 12 months or proceed to definitive therapy 1, 3
• Approximately 50% of patients relapse after completing antithyroid drug course 3, 4, 7
• If relapse occurs after completing therapy, definitive treatment (radioactive iodine or thyroidectomy) is recommended, though long-term low-dose methimazole is an alternative 3

Definitive Therapy Options

Radioactive Iodine (RAI)

RAI is the preferred definitive treatment for most adults in the United States due to ease of administration, safety, effectiveness, and cost 4, 8

Absolute contraindications: 5, 1, 3

• Pregnancy (can cause fetal hypothyroidism if exposed after 10 weeks gestation) 5
• Breastfeeding (must wait 4 months after RAI before resuming) 5, 1
• Active or severe thyroid eye disease 3

Important considerations:

• RAI causes or worsens thyroid eye disease in 15-20% of patients 4
• Steroid prophylaxis warranted in patients with mild/active orbitopathy receiving RAI 3
• Hypothyroidism is an inevitable consequence requiring lifelong levothyroxine 4, 8

Thyroidectomy

Thyroidectomy is preferred when: 1, 4

• Patient does not respond to antithyroid medications 5, 1
• Concomitant suspicious or malignant thyroid nodules present 4
• Coexisting hyperparathyroidism 4
• Large goiters 4
• Moderate to severe thyroid eye disease in patients who cannot use antithyroid drugs 4

Critical caveat: Surgery must be performed by an experienced high-volume thyroid surgeon to minimize risks of hypoparathyroidism and vocal cord paralysis 3, 4

Special Population: Pregnancy

Women with Graves' disease in pregnancy require specific management: 5

• Use propylthiouracil in first trimester, then consider switching to methimazole after week 13 5, 1
• Goal: maintain maternal free T4 in high-normal range with lowest possible thioamide dose 5, 1
• Monitor free T4 or free thyroxine index every 2-4 weeks 5
• Monitor fetal heart rate and growth; ultrasound for fetal goiter only if problems detected 5
• Alert neonatal team about maternal Graves' disease due to risk of neonatal thyroid dysfunction 5
• Thyroidectomy reserved only for women who fail thioamide therapy (preferably second trimester if needed) 5

Thyroid Storm Management

Thyroid storm is a life-threatening emergency requiring immediate hospitalization and intensive management: 5

Diagnostic features: fever, tachycardia disproportionate to fever, altered mental status, vomiting, diarrhea, cardiac arrhythmia 5

Treatment protocol (do not delay for lab confirmation): 5

• High-dose propylthiouracil or methimazole 5
• Saturated solution of potassium iodide (SSKI) or sodium iodide 5
• Beta-blockers for symptom control 5
• Dexamethasone 5
• Supportive care: oxygen, antipyretics, hydration 5
• Treat underlying precipitant (infection, surgery, labor) 5
• Avoid delivery during thyroid storm unless absolutely necessary 5

Critical Pitfalls to Avoid

Watch for transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis—monitor thyroid function every 2-3 weeks after diagnosis 5, 1

Do not overlook ophthalmopathy or thyroid bruit on physical examination, as these findings are diagnostic of Graves' disease and warrant early endocrine referral 5, 1

Elevated TSH during recovery phase of thyroiditis in asymptomatic patients with normal free T4 may not require immediate treatment—consider monitoring for 3-4 weeks to assess for spontaneous recovery 5

Never use radioactive iodine in pregnant or breastfeeding women 5, 1