What is the initial management for a patient with Graves' disease in a primary care setting?

Primary Care Management of Graves' Disease

Start methimazole 15 mg daily as first-line therapy for most patients with Graves' disease, add a beta-blocker for symptomatic relief, and refer to endocrinology for co-management. 1, 2

Confirm the Diagnosis

Before initiating treatment, ensure the diagnosis is secure:

• Check TSH (suppressed), free T4 (elevated), and TSH receptor antibodies (positive) to confirm Graves' disease 1
• Examine for diagnostic physical findings: thyroid bruit or ophthalmopathy (proptosis, lid lag, extraocular muscle dysfunction) are pathognomonic for Graves' disease and warrant immediate endocrine referral 3, 1
• Thyroid ultrasound typically shows a hypervascular, hypoechoic, diffusely enlarged gland 4

Initiate Antithyroid Drug Therapy

Methimazole is the preferred antithyroid drug for nearly all patients:

• Start with 15 mg daily rather than higher doses—this significantly reduces the risk of agranulocytosis (0.22% vs 0.81% with 30 mg daily) while maintaining effectiveness 1, 5
• FDA-approved indications include Graves' disease with hyperthyroidism when surgery or radioactive iodine is not appropriate, or to ameliorate symptoms before definitive therapy 2
• For severe hyperthyroidism (very high T3, large goiter, or severe symptoms), consider 10 mg every 8 hours (30 mg total daily) to achieve euthyroidism within 3 months, though this increases agranulocytosis risk 6, 5

Critical exception—use propylthiouracil instead of methimazole in these situations:

• Women planning pregnancy or in the first trimester (methimazole is teratogenic in early pregnancy) 1, 4
• Patients intolerant to methimazole 7
• Propylthiouracil dosing: 100 mg every 8 hours (300 mg total daily) 7, 6

Provide Symptomatic Relief

Add a beta-blocker immediately for symptomatic control while waiting for antithyroid drugs to take effect:

• Atenolol 25-50 mg daily or propranolol (titrate to heart rate <90 bpm if blood pressure allows) 3, 1
• Beta-blockers control tachycardia, tremor, anxiety, and heat intolerance 1

Monitor Thyroid Function Closely

The monitoring schedule is critical to catch transitions and adjust therapy:

• Every 2-3 weeks initially after starting treatment to detect the transition to hypothyroidism (common with thyroiditis) or assess response 3, 1
• Every 4-6 weeks once improving, then every 2-3 months once stable on maintenance therapy 1
• Goal: maintain free T4 in the high-normal range using the lowest effective methimazole dose 1

Refer to Endocrinology

Endocrine consultation is recommended for all Graves' disease patients to establish co-management:

• Immediate referral if: ophthalmopathy present, pregnancy involved, severe symptoms (grade 3-4), or persistent hyperthyroidism beyond 6 weeks 3, 1
• Routine referral: for treatment planning, monitoring guidance, and decisions about duration of therapy 1

Plan Duration of Therapy

Treat with methimazole for 12-18 months, then reassess:

• Measure TSH receptor antibodies at 12-18 months: if persistently elevated, continue methimazole for another 12 months or consider definitive therapy 1, 4
• Approximately 50% of patients achieve remission after 12-18 months of antithyroid drug therapy 4, 8
• If relapse occurs after stopping: offer definitive therapy (radioactive iodine or thyroidectomy) or consider long-term low-dose methimazole 1, 4

Consider Definitive Therapy

Radioactive iodine or thyroidectomy should be discussed as alternatives to prolonged medical management:

• Indications for definitive therapy: patient preference, relapse after antithyroid drugs, intolerance to antithyroid drugs, large goiter, suspicious thyroid nodules, or coexisting hyperparathyroidism 1, 8
• Radioactive iodine is contraindicated in pregnancy, breastfeeding, and active/severe thyroid eye disease (may worsen ophthalmopathy in 15-20% of patients) 1, 4, 8
• Thyroidectomy requires an experienced high-volume thyroid surgeon to minimize complications (hypoparathyroidism, vocal cord paralysis) 1, 4

Manage Thyroid Eye Disease

If ophthalmopathy is present:

• Ocular lubricants are almost always needed for exposure symptoms from lid retraction and proptosis 1
• Selenium supplementation may reduce inflammatory symptoms in mild thyroid eye disease 1
• For moderate-to-severe disease: consider teprotumumab (IGF-1 receptor inhibitor), high-dose steroids, orbital decompression, or radiation—requires ophthalmology referral 1

Critical Pitfalls to Avoid

• Do not miss agranulocytosis: warn patients to stop methimazole immediately and seek urgent care for fever, sore throat, or mouth ulcers (most common in first 90 days of therapy) 8, 5
• Do not use methimazole in early pregnancy: switch to propylthiouracil when planning pregnancy and during first trimester 1, 4
• Do not fail to monitor frequently enough: thyroid function can change rapidly, and missing the transition to hypothyroidism is common 3, 1
• Do not give radioactive iodine to patients with active ophthalmopathy: this can precipitate severe worsening of eye disease 4, 8

Severe Disease/Thyroid Storm

Hospitalize immediately if severe symptoms, altered mental status, or cardiovascular instability:

• High-dose antithyroid drugs, beta-blockers, hydrocortisone, and saturated solution of potassium iodide (SSKI) under endocrine consultation 3, 1
• Urgent endocrine consultation for all grade 3-4 cases 3