Treatment of Graves' Disease
Methimazole is the preferred first-line antithyroid drug for most patients with Graves' disease, dosed at 15-30 mg daily with the goal of maintaining free T4 in the high-normal range using the lowest effective dose. 1, 2, 3
Initial Medical Management
Antithyroid Drug Selection
- Methimazole is the preferred agent for routine management because it allows once-daily dosing, is less expensive, and has lower rates of major toxicity compared to propylthiouracil 1, 3, 4
- Methimazole is FDA-approved for Graves' disease when surgery or radioactive iodine is not appropriate, and for symptom amelioration before definitive therapy 2
- Starting doses of 15 mg daily are as effective as 30 mg daily for rapid control of thyroid hormone overproduction 5
- Propylthiouracil should be reserved for patients intolerant to methimazole, those in thyroid storm, and pregnant/lactating women 6, 4
Treatment Duration and Monitoring
- Treat for 12-18 months initially in adults, with 24-36 months recommended for children 1, 3
- Monitor thyroid function (TSH and free T4) every 4-6 weeks during initial treatment, then every 2-3 months once stable 1
- Measure TSH receptor antibodies at 12-18 months to guide decision-making 1, 3
- If TSH receptor antibodies remain persistently elevated at 12-18 months, either continue methimazole for another 12 months or proceed to definitive therapy 1, 3
Symptomatic Management
- Beta-blockers (atenolol 25-50 mg daily or propranolol) provide immediate symptomatic relief of tachycardia, tremor, and anxiety while awaiting antithyroid drug effect 7, 1
- Titrate beta-blocker dose to maintain heart rate <90 bpm if blood pressure tolerates 7
Special Population Considerations
Pregnancy and Lactation
- Switch from methimazole to propylthiouracil when planning pregnancy and during the first trimester due to methimazole's teratogenic risk 7, 1, 3
- Maintain free T4 or free thyroxine index in the high-normal range using the lowest possible thioamide dose 7
- Check free T4 or free thyroxine index every 2-4 weeks during pregnancy 7
- Both propylthiouracil and methimazole are safe during breastfeeding 7
- Radioactive iodine is absolutely contraindicated in pregnancy; if inadvertent exposure occurs after 10 weeks gestation, counsel regarding risk of congenital hypothyroidism 7
Elderly and Comorbid Patients
- For patients >70 years old or those with cardiac disease and multiple comorbidities, use caution with antithyroid drugs and consider earlier definitive therapy 7
- Beta-blockers are particularly important in elderly patients to prevent cardiac complications 7
Definitive Treatment Options
When to Consider Definitive Therapy
- After relapse following a complete course of antithyroid drugs, definitive treatment with radioactive iodine or thyroidectomy is recommended 1, 3
- Patients who fail to achieve remission after 12-18 months of therapy should consider radioactive iodine or surgery 1, 8
- Long-term low-dose methimazole is an alternative for patients who decline or cannot receive definitive therapy 3
Radioactive Iodine Therapy
- Radioactive iodine results in permanent hypothyroidism requiring lifelong levothyroxine replacement 8
- Contraindicated in patients with active/severe thyroid eye disease, pregnancy, breastfeeding, and large goiters 3, 8
- Associated with development or worsening of thyroid eye disease in 15-20% of patients 8
- Steroid prophylaxis is warranted in patients with mild/active orbitopathy receiving radioactive iodine 3
- Women should not breastfeed for 4 months after radioactive iodine treatment 7
Thyroidectomy
- Thyroidectomy should be performed by an experienced high-volume thyroid surgeon to minimize complications 1, 3
- Preferred for patients with concomitant suspicious thyroid nodules, coexisting hyperparathyroidism, large goiters, or moderate-to-severe thyroid eye disease 1, 8
- Risks include hypoparathyroidism and vocal cord paralysis in a small proportion of patients 8
- Reserved for patients who do not respond to thioamide therapy 7
Management of Severe Disease (Thyroid Storm)
- Hospitalize immediately for patients with severe symptoms including fever, tachycardia out of proportion to fever, altered mental status, vomiting, diarrhea, or cardiac arrhythmia 7, 1
- Use combination therapy: propylthiouracil or methimazole PLUS saturated solution of potassium iodide (or sodium iodide, Lugol's solution, or lithium as alternatives) 7
- Add beta-blockers for symptom control 7
- Endocrine consultation is mandatory for all patients with severe symptoms 7, 1
- Do not delay treatment while awaiting confirmatory lab results 7
Critical Monitoring and Safety Considerations
Antithyroid Drug Toxicity
- Agranulocytosis typically presents with sore throat and fever within the first 90 days of therapy 7, 8
- If these symptoms develop, obtain complete blood count immediately and discontinue the thioamide 7
- Other serious adverse effects include hepatotoxicity, vasculitis, and thrombocytopenia 7, 8
Transition to Hypothyroidism
- Monitor closely for transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis 7, 1
- Check thyroid function every 2-3 weeks after diagnosis to catch this transition 7, 1
- Elevated TSH during recovery phase may be transient; in asymptomatic patients with normal free T4, monitor for 3-4 weeks before treating 7