What is the recommended treatment for a patient diagnosed with Graves' disease?

Graves' Disease: Diagnosis and Treatment

Diagnostic Confirmation

Diagnose Graves' disease with TSH (suppressed), free T4 (elevated), and TSH receptor antibodies (TRAb or TSI), while examining for ophthalmopathy or thyroid bruit which are pathognomonic findings. 1, 2

• Measure free T3 if the patient is highly symptomatic to assess biological severity 1
• The presence of ophthalmopathy or thyroid bruit on physical examination is diagnostic and mandates early endocrinology referral 1, 2
• TSH receptor antibody testing provides etiological confirmation and should be obtained 1, 3

First-Line Medical Treatment

Initiate methimazole as the preferred antithyroid drug for all patients except those who are pregnant, planning pregnancy, or intolerant to methimazole. 1, 2, 4, 3

Methimazole Dosing Strategy

• Start methimazole 10 mg every 8 hours (or 30 mg daily) for most patients to achieve euthyroidism within 3 months 5
• Titrate to the lowest dose that maintains free T4 in the high-normal range 6, 2
• Continue treatment for 12-18 months before considering discontinuation 1, 3, 7

Monitoring Protocol

• Check thyroid function every 2-3 weeks initially to detect the transition from hyperthyroidism to hypothyroidism 6, 1
• Once stable, monitor every 4-6 weeks during initial treatment, then every 2-3 months 2
• Measure TSH receptor antibodies at 12-18 months before stopping treatment 3

Adjunctive Symptomatic Management

Add a non-selective beta-blocker (propranolol or atenolol) immediately for symptomatic relief of tachycardia, tremor, and anxiety while awaiting thyroid hormone normalization. 6, 1, 2

• Beta-blockers can be discontinued once euthyroidism is achieved 6
• Propranolol is preferred due to its additional alpha-receptor blocking capacity 6

Special Population Considerations

Pregnancy and Lactation

Switch from methimazole to propylthiouracil when planning pregnancy and throughout the first trimester due to methimazole's teratogenic risk. 6, 1, 2, 8, 3

• Propylthiouracil can be safely used during breastfeeding 6
• Monitor free T4 or free thyroxine index every 2-4 weeks during pregnancy 6
• Maintain free T4 in the high-normal range using the lowest possible dose 6
• Critical: Always start corticosteroids before thyroid hormone replacement if both adrenal insufficiency and hypothyroidism are present to avoid precipitating adrenal crisis 6

Elderly Patients

• Start with lower thyroid replacement doses (25-50 mcg levothyroxine) if hypothyroidism develops during treatment 1, 2

Management Based on Disease Severity

Mild Symptoms

• Initiate methimazole and beta-blocker as outlined above 1
• Outpatient management is appropriate 1

Moderate Symptoms

• Consider holding immune checkpoint inhibitors (if applicable) until symptoms resolve 1, 2
• Obtain endocrinology consultation 1

Severe Symptoms/Thyroid Storm

Hospitalize immediately for intensive management with propylthiouracil or methimazole, saturated solution of potassium iodide (or Lugol's solution), beta-blockers, and consider corticosteroids. 6, 2

• Mandatory endocrinology consultation 1, 2
• Do not delay treatment while awaiting confirmatory laboratory results 6

Definitive Treatment Options

Consider radioactive iodine therapy or thyroidectomy after 12-18 months of antithyroid drugs if remission is not achieved or TSH receptor antibodies remain persistently elevated. 1, 2, 3

Radioactive Iodine (RAI)

• RAI is contraindicated in pregnancy, breastfeeding (avoid for 4 months post-treatment), and patients with active/severe orbitopathy 6, 2, 3
• Steroid prophylaxis is warranted in patients with mild/active orbitopathy receiving RAI 3
• Hypothyroidism is an inevitable consequence requiring lifelong levothyroxine replacement 9

Thyroidectomy

• Should be performed by an experienced high-volume thyroid surgeon 2, 3
• Reserved for patients who do not respond to medical therapy or have contraindications to RAI 6

Critical Monitoring Points and Pitfalls

The most common error is failing to recognize the transition from hyperthyroidism to hypothyroidism, which requires checking thyroid function every 2-3 weeks after diagnosis. 1, 2

Additional Pitfalls to Avoid

• Never use radioactive iodine in pregnant or breastfeeding women 6, 2
• Never initiate thyroid hormone before corticosteroids in patients with concurrent adrenal insufficiency 6
• Watch for agranulocytosis with thioamides—if sore throat and fever develop, obtain complete blood count immediately and discontinue the drug 6
• Other thioamide side effects include hepatitis, vasculitis, and thrombocytopenia 6

Relapse Management

If hyperthyroidism relapses after completing a 12-18 month course of antithyroid drugs (occurs in approximately 50% of patients), offer definitive treatment with RAI or thyroidectomy; alternatively, consider long-term low-dose methimazole. 1, 3, 7