What is the treatment for a severe disease (grave disease)?

Treatment of Graves' Disease

Methimazole is the preferred first-line treatment for most patients with Graves' disease, with beta-blockers added for symptomatic relief of tachycardia, tremor, and anxiety. 1

Initial Management

Diagnostic Confirmation

• Confirm diagnosis with TSH (suppressed), Free T4 (elevated), and TSH receptor antibodies (TRAb) 1, 2
• Physical findings of ophthalmopathy or thyroid bruit are diagnostic and warrant early endocrine referral 1
• Thyroid ultrasonography shows diffuse enlargement with increased vascularity 2

First-Line Antithyroid Drug Therapy

Methimazole is the preferred agent for most patients due to superior efficacy and tolerability compared to propylthiouracil 1.

• Dosing strategy: Titrate based on thyroid function tests, maintaining Free T4 in the high-normal range using the lowest effective dose 1
• Monitoring frequency: Check thyroid function every 4-6 weeks during initial treatment, then every 2-3 months once stable 1
• Duration: Typically 12-18 months of therapy is attempted before considering alternative treatments 1

Important exception: Switch to propylthiouracil during pregnancy planning and first trimester due to methimazole's teratogenic risk 1

Symptomatic Management

Beta-blockers provide immediate symptomatic relief while awaiting antithyroid drug effect 1:

• Atenolol or propranolol for tachycardia, tremor, and anxiety 1
• Start immediately at diagnosis alongside antithyroid drugs 1

Severe Disease/Thyroid Storm

Hospitalize patients with severe symptoms for intensive management 1:

• High-dose antithyroid drugs (methimazole 60-80 mg daily or propylthiouracil 600-1000 mg daily) 1
• Beta-blockers (propranolol preferred for additional peripheral T4 to T3 conversion blockade) 1
• Saturated solution of potassium iodide (SSKI) to block thyroid hormone release (given 1 hour after antithyroid drug) 1
• Corticosteroids to block peripheral conversion and treat potential adrenal insufficiency 1
• Mandatory endocrine consultation 1

Second-Line Definitive Treatments

For patients not achieving remission after 12-18 months of antithyroid drugs (occurs in 60-70% of patients), consider definitive therapy 1, 3:

Radioactive Iodine (RAI)

• Effective in 67-75% of patients with single dose 4
• Contraindications: Pregnancy, breastfeeding, active/severe ophthalmopathy 1
• Results in hypothyroidism in 70-100% of patients at 10 years 4

Thyroidectomy

• Highest cure rate (95-100%) in shortest time 4
• Must be performed by high-volume thyroid surgeon 1
• Complications in experienced hands: recurrent nerve palsy (0-4.5%), permanent hypocalcemia (0-0.6%), reoperation for hemorrhage (0-1.3%) 4
• Greater than 90% remain euthyroid at 2 years 4

Management of Thyroid Eye Disease

Mild Disease

• Ocular lubricants for exposure symptoms from eyelid retraction and proptosis 1
• Selenium supplementation (200 mcg daily) reduces inflammatory symptoms 1

Moderate-to-Severe Disease

• Teprotumumab (IGF-1R inhibitor) is highly effective for reducing proptosis and clinical activity score 1
• High-dose corticosteroids for active inflammation 1
• Orbital decompression surgery for severe cases 1
• Timing consideration: Delay strabismus repair until after orbital decompression if both are needed 1
• Fresnel or ground-in prisms provide temporary diplopia relief 1

Special Populations

Pregnant Women

• Switch from methimazole to propylthiouracil before conception and during first trimester 1
• Metyrapone may be considered with precautions in selected pregnant women, targeting cortisol <1.5× upper limit of normal 5
• RAI is absolutely contraindicated 1

Elderly Patients (>70 years)

• Start with lower doses if hypothyroidism develops post-treatment 1
• Consider earlier definitive therapy given lower remission rates with antithyroid drugs 1

Critical Pitfalls to Avoid

• Failing to recognize transition from hyperthyroidism to hypothyroidism during thyroiditis or overtreatment 1
• Inadequate monitoring frequency (must check every 2-3 weeks initially after diagnosis) 1
• Using RAI in pregnant/breastfeeding women 1
• Initiating thyroid hormone before corticosteroids in patients with concurrent adrenal insufficiency 1
• Delaying endocrine referral when ophthalmopathy or persistent hyperthyroidism (>6 weeks) is present 1