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

Treatment of Graves' Disease

Methimazole is the preferred first-line treatment for most patients with Graves' disease, typically given for 12-18 months, with the goal of maintaining free T4 in the high-normal range using the lowest effective dose. 1, 2, 3

Initial Treatment Approach

Antithyroid Drug Selection

• Methimazole is the drug of choice for nearly all patients with Graves' disease, as it is FDA-approved for this indication and recommended by major endocrine societies 1, 4, 2
• Use the lowest dose that maintains euthyroidism (titration method), as higher doses provide no additional benefit for remission rates but increase side effects 1, 5
• The only exception is pregnancy: switch to propylthiouracil when planning pregnancy and during the first trimester due to methimazole's teratogenic potential 6, 1, 3

Symptomatic Management

• Add a beta-blocker (propranolol or atenolol) immediately for symptomatic relief of tachycardia, tremor, and anxiety while waiting for thyroid hormone levels to normalize 6, 1, 4
• Beta-blockers can be discontinued once the patient achieves euthyroidism 6

Monitoring Strategy

Frequency of Testing

• Check free T4 (or FTI) and TSH every 2-4 weeks initially until stable, then every 2-3 months once euthyroid 6, 1, 4
• Critical pitfall: Failing to monitor frequently enough (every 2-3 weeks after diagnosis) can miss the common transition from hyperthyroidism to hypothyroidism 1, 4

Diagnostic Confirmation

• Confirm diagnosis with TSH, free T4, and TSH receptor antibodies if clinical features suggest Graves' disease 1
• Physical findings of ophthalmopathy or thyroid bruit are diagnostic and mandate early endocrine referral 1, 4

Duration and Remission Assessment

Standard Treatment Course

• Continue methimazole for 12-18 months as the standard initial course 1, 3, 7, 8
• Approximately 50% of patients achieve remission after this duration, while 50% will relapse 3, 7, 8

Decision Points at 12-18 Months

• If TSH receptor antibodies remain persistently high: either continue methimazole for another 12 months and recheck antibodies, or proceed to definitive treatment (radioactive iodine or thyroidectomy) 3
• If patient relapses after stopping antithyroid drugs: definitive treatment is recommended, though continued long-term low-dose methimazole is an acceptable alternative 3, 9

Definitive Treatment Options

When to Consider Radioactive Iodine or Surgery

• After 12-18 months of antithyroid drugs without remission 1, 4
• For patients who relapse after completing a course of antithyroid drugs 3
• Radioactive iodine is contraindicated in pregnancy, breastfeeding (avoid for 4 months post-treatment), and patients with active/severe orbitopathy 6, 1, 3

Thyroidectomy Indications

• Concomitant suspicious or malignant thyroid nodules 7
• Coexisting hyperparathyroidism 7
• Large goiters or moderate-to-severe thyroid eye disease in patients who cannot tolerate antithyroid drugs 7
• Must be performed by an experienced high-volume thyroid surgeon 1, 3

Special Populations

Pregnancy Management

• Switch from methimazole to propylthiouracil during pregnancy planning and first trimester 6, 1, 4
• Goal is to maintain free T4 or FTI in the high-normal range using the lowest possible thioamide dose 6
• Monitor free T4 or FTI every 2-4 weeks until stable, then check TSH every trimester 6
• Both propylthiouracil and methimazole are safe during breastfeeding 6
• Radioactive iodine is absolutely contraindicated in pregnancy; if inadvertent exposure occurred after 10 weeks gestation, counsel about risk of congenital hypothyroidism 6

Elderly or Comorbid Patients

• Start with lower doses of thyroid replacement (25-50 mcg levothyroxine) if hypothyroidism develops during treatment 1, 4
• Consider earlier definitive treatment in patients over 70 years 1

Children and Adolescents

• Recommend a 24-36 month course of methimazole rather than the standard 12-18 months 3

Monitoring for Side Effects

Agranulocytosis Warning

• Most serious side effect of thioamides, typically presents with sore throat and fever 6
• Occurs within the first 90 days of therapy 7
• If these symptoms develop: obtain complete blood count immediately and discontinue the thioamide 6
• Other side effects include hepatitis, vasculitis, and thrombocytopenia 6

Management of Thyroid Eye Disease

Adjunctive Therapies

• Ocular lubricants are almost always needed for exposure related to eyelid retraction and proptosis 1
• Selenium supplementation may reduce inflammatory symptoms in milder thyroid eye disease 1
• Teprotumumab (IGF-IR inhibitor) reduces proptosis and clinical activity score in active thyroid eye disease 1

Severe Disease

• For moderate-to-severe thyroid eye disease: consider orbital decompression, high-dose steroids, or radiation treatment 1
• Radioactive iodine can worsen eye disease in 15-20% of patients; steroid prophylaxis is warranted in patients with mild/active orbitopathy receiving radioactive iodine 3, 7

Thyroid Storm Management

Recognition and Treatment

• Extreme hypermetabolic state with fever, tachycardia out of proportion to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia 6
• Immediate hospitalization required with intensive management 1, 4
• Treatment includes: propylthiouracil or methimazole, beta-blockers, saturated solution of potassium iodide (or sodium iodide, Lugol's solution, or lithium), and steroids 6, 1
• Mandatory endocrine consultation for all patients with severe symptoms 1, 4