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

Treatment of Graves' Disease

Methimazole is the recommended first-line treatment for most patients with Graves' disease, typically given for 12-18 months at the lowest effective dose to maintain free T4 in the high-normal range. 1, 2, 3

Initial Management Approach

Confirm the Diagnosis

• Measure TSH (suppressed), free T4 (elevated), and TSH receptor antibodies if clinical features suggest Graves' disease 1, 2
• Physical findings of ophthalmopathy or thyroid bruit are diagnostic and warrant early endocrine referral 1

Start Antithyroid Drug Therapy

Methimazole is the preferred agent for nearly all patients with Graves' hyperthyroidism 1, 2, 3, 4

Dosing strategy:

• Start with 15-20 mg daily (lower doses of 15 mg are as effective as 30 mg and reduce risk of dose-dependent agranulocytosis) 5, 6
• Titrate based on thyroid function tests to maintain free T4 in high-normal range using the lowest possible dose 1, 2
• Continue treatment for 12-18 months as standard protocol 1, 2, 4, 7

Monitoring schedule:

• Every 4-6 weeks during initial treatment phase 1, 2
• Every 2-3 months once stable 1, 2
• Watch for agranulocytosis and hepatotoxicity, which typically occur within the first 90 days 7

Add Symptomatic Relief

Beta-blockers provide immediate symptom control while waiting for antithyroid drugs to take effect 1, 2

• Use atenolol 25-50 mg daily or propranolol, titrating for heart rate <90 bpm if blood pressure allows 8, 1
• Addresses tachycardia, tremor, and anxiety 1, 2

Deciding on Definitive Treatment vs. Continued Medical Therapy

After 12-18 Months of Methimazole

Check TSH receptor antibodies:

• If TSH-R antibodies remain >10 mU/L at 12-18 months, remission is unlikely and definitive treatment (radioactive iodine or thyroidectomy) should be recommended 4, 5
• If antibodies are low, attempt to discontinue methimazole as approximately 50% achieve remission 7
• Alternatively, continue long-term low-dose methimazole if patient prefers to avoid definitive treatment 4

If Disease Relapses After Stopping Methimazole

Definitive treatment is recommended (radioactive iodine or thyroidectomy), though continued long-term low-dose methimazole can be considered 4

Definitive Treatment Options

Radioactive Iodine (RAI)

• Appropriate for patients who relapse after antithyroid drugs or prefer definitive treatment 1, 2, 7
• Stop methimazole at least one week before RAI to reduce risk of treatment failure 5
• Results in permanent hypothyroidism requiring lifelong levothyroxine 7

Contraindications to RAI:

• Pregnancy and breastfeeding (absolute contraindication) 2, 4, 7
• Active or severe thyroid eye disease 4
• Patients should not breastfeed for 4 months after RAI treatment 2

Important caveat: RAI can worsen or trigger thyroid eye disease in 15-20% of patients 7. Use steroid prophylaxis in patients with mild/active orbitopathy receiving RAI 4

Thyroidectomy

• Preferred for patients with very large goiters, suspicious/malignant thyroid nodules, coexisting hyperparathyroidism, or moderate-to-severe thyroid eye disease 1, 7
• Must be performed by an experienced high-volume thyroid surgeon to minimize complications 1, 4
• Perform near-total or total thyroidectomy 4, 5
• Results in permanent hypothyroidism requiring lifelong levothyroxine 7

Special Populations

Pregnant Women

Switch from methimazole to propylthiouracil (PTU) when planning pregnancy and during the first trimester due to teratogenic risk of methimazole 1, 4

• Can switch back to methimazole after first trimester 2
• Maintain maternal free T4 in high-normal range using lowest possible dose 2
• Some women opt for definitive treatment (RAI or surgery) before pregnancy to avoid antithyroid drug exposure 7

Elderly Patients or Those with Cardiovascular Disease

• If hypothyroidism develops after treatment, start with reduced thyroid hormone replacement doses (25-50 mcg) rather than full dose 8, 1

Children

• Use methimazole for 24-36 months (longer than adults) 4

Management of Thyroid Eye Disease

Mild Disease

• Ocular lubricants are almost always needed for exposure symptoms from eyelid retraction and proptosis 1
• Selenium supplementation may reduce inflammatory symptoms 1

Moderate-to-Severe Disease

• Consider orbital decompression, high-dose intravenous glucocorticoids, or radiation treatment 1, 9
• Teprotumumab (IGF-1R inhibitor) reduces proptosis and clinical activity scores in active thyroid eye disease 1, 9
• If orbital decompression is indicated, delay strabismus repair until after decompression 1
• Fresnel or ground-in prisms provide temporary diplopia relief 1

Thyroid Storm/Severe Disease

Hospitalize immediately for intensive management 1, 2

• High-dose antithyroid drugs 1, 2
• Beta-blockers for symptomatic control 1, 2
• Consider additional therapies: corticosteroids and saturated solution of potassium iodide (SSKI) 1, 2
• Obtain endocrine consultation 1

Critical Pitfalls to Avoid

Monitor closely for transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis 1, 2

• Check thyroid function every 2-3 weeks initially to catch this transition 1
• Introduce thyroid hormone replacement if patient becomes hypothyroid (low free T4/T3, even if TSH not yet elevated) 8

Never use propylthiouracil as first-line except in first trimester pregnancy, as it can cause severe liver failure requiring transplantation 5

Do not use RAI in pregnant or breastfeeding women 2, 4, 7

Do not start thyroid hormone before corticosteroids in patients with both adrenal insufficiency and hypothyroidism 1

Do not overlook ophthalmopathy or thyroid bruit on physical exam, as these findings are diagnostic of Graves' disease and should prompt early endocrine referral 1, 2