What is the treatment for Graves' disease (Diffuse Toxic Goiter)?

Treatment of Graves' Disease (Diffuse Toxic Goiter)

Methimazole is the preferred first-line treatment for most patients with Graves' disease, with treatment typically continued for 12-18 months to induce remission. 1, 2

Initial Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with:

• TSH (suppressed), Free T4 (elevated), and TSH receptor antibody testing to distinguish Graves' disease from other causes of thyrotoxicosis 1
• Physical examination for ophthalmopathy or thyroid bruit, which are diagnostic of Graves' disease and warrant early endocrine referral 1
• Radioiodine uptake scan if the diagnosis remains unclear, showing diffusely increased uptake in Graves' disease 3, 4

First-Line Treatment: Antithyroid Medications

Methimazole (Preferred Agent)

• Start methimazole as the first-line agent for most patients with Graves' disease 1, 2
• Titrate dose based on thyroid function tests every 4-6 weeks initially, aiming to maintain FT4 in the high-normal range using the lowest effective dose 1
• Once stable, monitor thyroid function every 2-3 months 1
• Continue treatment for 12-18 months with the goal of inducing long-term remission 1, 4
• Remission occurs in approximately 55-61% of patients after this treatment course 5, 6

Propylthiouracil (Alternative Agent)

• Reserve propylthiouracil for patients intolerant of methimazole 7
• Use propylthiouracil during pregnancy planning and first trimester instead of methimazole due to teratogenicity concerns 1

Treatment Monitoring

• For persistent hyperthyroidism beyond 6 weeks, refer to endocrinology for additional workup and possible adjustment of medical therapy 1
• Monitor closely for transition to hypothyroidism, which can occur during treatment and requires prompt initiation of thyroid hormone replacement 3, 1

Symptomatic Management

Beta-Blockers

• Prescribe beta-blockers (atenolol or propranolol) for symptomatic relief of tachycardia, tremor, anxiety, and heat intolerance 3, 1
• Non-selective beta-blockers with alpha-receptor blocking capacity are preferred for more comprehensive symptom control 3

Second-Line Definitive Therapies

When to Consider Radioactive Iodine or Surgery

• After 12-18 months of antithyroid drug therapy without remission 1, 8
• For patients who refuse or cannot tolerate antithyroid drugs 2, 8
• For large goiters causing compressive symptoms 8

Radioactive Iodine Therapy

• Radioactive iodine is increasingly used as first-line therapy, particularly in older patients 8, 4
• Contraindicated in pregnancy, breastfeeding, and active/severe thyroid eye disease 1, 8
• Pregnancy must be avoided for 4 months following administration 8
• May worsen Graves' ophthalmopathy; consider corticosteroid prophylaxis in patients with eye disease 8
• Hypothyroidism is the expected long-term outcome, requiring lifelong thyroid hormone replacement 8

Thyroidectomy

• Perform subtotal or near-total thyroidectomy by an experienced high-volume thyroid surgeon 1, 8
• Consider for large goiters, failed medical therapy, or patient preference 8
• Permanent hypothyroidism occurs in approximately 65% of patients 5

Management of Thyroid Eye Disease

If ophthalmopathy is present:

• Use ocular lubricants for exposure symptoms from eyelid retraction and proptosis 1
• Consider selenium supplementation for mild thyroid eye disease to reduce inflammatory symptoms 1
• For moderate-to-severe disease, consider teprotumumab (IGF-IR inhibitor), orbital decompression, high-dose steroids, or radiation 1
• Delay strabismus repair until after orbital decompression if both are indicated 1

Severe Disease/Thyroid Storm

For patients with severe symptoms or thyroid storm:

• Hospitalize immediately for intensive management 1
• Use combination therapy: beta-blockers, high-dose antithyroid drugs, and consider steroids and saturated solution of potassium iodide (SSKI) 1
• Obtain urgent endocrine consultation 3, 1

Critical Pitfalls to Avoid

• Never start thyroid hormone replacement before corticosteroids in patients with concurrent adrenal insufficiency, as this can precipitate adrenal crisis 3, 1
• Do not use radioactive iodine in pregnant or breastfeeding women 1, 8
• Monitor thyroid function every 2-3 weeks after diagnosis to catch the transition to hypothyroidism, which is commonly missed 3, 1
• Do not assume antithyroid drugs will cure toxic nodular goiter; these patients require definitive therapy with radioiodine or surgery 8