What are the diagnosis and management options for a patient with Graves' disease?

Diagnosis and Management of Graves' Disease

Diagnosis

Confirm Graves' disease with TSH, free T4, and TSH receptor antibody (TRAb) testing—low TSH, elevated free T4, and positive TRAb establish the diagnosis. 1

Initial Laboratory Evaluation

• Measure TSH and free T4 or free T4 index (FTI) to confirm thyrotoxicosis 2
• Obtain TRAb testing to confirm Graves' disease specifically 1
• These three tests together provide definitive diagnosis without need for additional imaging in most cases 1

Physical Examination Findings

• Assess for thyroid bruit, which is diagnostic of Graves' disease 2
• Examine for ophthalmopathy signs including proptosis (bulging eyes), eyelid retraction, and other ocular symptoms 1
• The presence of ophthalmopathy or thyroid bruit confirms Graves' disease clinically 2

Initial Treatment

Methimazole is the preferred first-line antithyroid drug for most patients with Graves' disease, dosed to maintain free T4 in the high-normal range. 2, 1, 3

Antithyroid Drug Therapy

• Methimazole (MMI) is FDA-approved and preferred over propylthiouracil for initial treatment 3
• Standard treatment duration is 12-18 months 1, 4
• Goal is to maintain free T4 or FTI in the high-normal range using the lowest possible dosage 2
• Methimazole allows once-daily dosing, improving adherence compared to propylthiouracil 5

Monitoring Protocol

• Check free T4 or FTI every 2-4 weeks initially to adjust medication dosage 2
• Once stable, monitor every 4-6 weeks, then extend to every 2-3 months 1
• Critical monitoring window: Watch for adverse effects particularly within the first 90 days of therapy 2, 4

Adverse Effects to Monitor

• Agranulocytosis (rare but serious) 2, 4
• Hepatotoxicity 4
• Vasculitis 2
• Thrombocytopenia 2

Symptomatic Management

Beta-blockers provide immediate symptomatic relief while waiting for antithyroid drugs to reduce thyroid hormone levels. 2, 1

• Use propranolol or atenolol for tachycardia, tremor, and anxiety 2, 1
• Continue until antithyroid therapy reduces thyroid hormone levels 2
• Provide hydration and supportive care for moderate to severe symptoms 2

Treatment Outcomes and Alternatives

Expected Response to Antithyroid Drugs

• Approximately 50% of patients achieve remission after 12-18 months of therapy 4
• Remaining 50% will experience relapse and require alternative therapy 4
• Long-term low-dose methimazole is increasingly considered for patients with recurrent disease 6

Definitive Treatment Options

• Radioactive iodine (RAI) is the preferred treatment for adults in the United States 4, 5
• RAI results in permanent hypothyroidism requiring lifelong levothyroxine replacement 4
• Surgery (near-total thyroidectomy) is preferred when: 4
  • Concomitant suspicious or malignant thyroid nodules present
  • Coexisting hyperparathyroidism
  • Large goiters present
  • Moderate to severe thyroid eye disease and antithyroid drugs contraindicated
  • Patient preference for definitive treatment

Special Populations

Pregnancy

Switch from methimazole to propylthiouracil during the first trimester only, then return to methimazole after the first trimester. 1, 7

• Propylthiouracil has limited placental transfer compared to methimazole 7, 5
• Methimazole has teratogenic effects in first trimester 1
• Monitor maternal heart rate and fetal growth throughout pregnancy 2
• Alert the newborn's physician about maternal Graves' disease due to risk of neonatal thyroid dysfunction 2
• RAI is absolutely contraindicated during pregnancy 1, 4
• Patients should not breastfeed for four months after RAI treatment 2

Thyroid Storm

Thyroid storm requires immediate hospitalization and multi-drug treatment including antithyroid drugs and potassium iodide solutions. 2

• Clinical presentation: fever, tachycardia out of proportion to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia 2
• This is a medical emergency requiring immediate treatment 2

Ophthalmopathy Management

Initial Assessment and Monitoring

• Monitor for optic neuropathy with visual acuity, color vision, visual fields, pupillary exam, and fundus exam 1
• Ocular lubricants are almost always needed to combat exposure from eyelid retraction and proptosis 1
• Selenium supplementation may reduce inflammatory symptoms in milder thyroid eye disease 1

Advanced Treatment

• Teprotumumab (IGF-1R inhibitor) reduces proptosis and clinical activity score in active thyroid eye disease 1
• RAI therapy can worsen ophthalmopathy in 15-20% of patients 4
• Surgery is preferred over RAI in patients with moderate to severe thyroid eye disease 4

Critical Pitfalls to Avoid

• Failing to recognize transition from hyperthyroidism to hypothyroidism during treatment 1
• Using radioactive iodine in pregnant or breastfeeding women 1
• Delaying treatment of severe ophthalmopathy, which can lead to permanent vision loss 1
• Missing adverse drug reactions by inadequate monitoring in the first 90 days 2, 4