How is Graves' disease managed?

Management of Graves' Disease

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

Initial Diagnosis and Workup

• Confirm thyrotoxicosis with TSH and free T4 or free T4 index (FTI) testing 1
• Examine for thyroid bruit or ophthalmopathy, which are diagnostic of Graves' disease and should not be overlooked 1, 2
• Consider TSH receptor antibody (TSH-R-Ab) testing for accurate diagnosis and differential diagnosis 2, 4

First-Line Treatment: Antithyroid Drug Therapy

Methimazole Protocol

• Methimazole (MMI) is the preferred antithyroid drug for initial treatment in most patients 1, 2, 3
• Standard treatment duration is 12-18 months (24-36 months in children) 1, 4
• Titrate dose to maintain free T4 or FTI in the high-normal range using the lowest possible dosage 1, 2
• Monitor free T4 or FTI every 2-4 weeks initially to adjust medication, then every 4-6 weeks once stable, then every 2-3 months 1, 2

Propylthiouracil (PTU) - Limited Use

• PTU is indicated only for patients intolerant of methimazole 5
• Switch to PTU when planning pregnancy and during the first trimester, then consider switching back to methimazole after first trimester 2, 4

Monitoring for Adverse Effects

• Monitor particularly within the first 90 days for agranulocytosis, hepatitis, vasculitis, and thrombocytopenia 1, 6
• Adverse reactions typically occur early in therapy and are the main limitation of ATD treatment 6

Adjunctive Symptomatic Management

• Use beta-blockers (propranolol or atenolol) for symptomatic relief of tachycardia, tremor, and anxiety until antithyroid therapy reduces thyroid hormone levels 1, 2
• Provide hydration and supportive care for patients with moderate to severe symptoms 1

Predicting Remission and Duration of Therapy

• Measure TSH-R-Ab at 12-18 months to guide decision-making 4
• If TSH-R-Ab remains persistently high at 12-18 months, either continue MMI for another 12 months or proceed to definitive therapy 4
• Approximately 50% of patients achieve remission after a 12-18 month course of ATD 6, 7
• Long-term low-dose MMI can be considered for patients who relapse after completing a course of ATD 4

Definitive Treatment Options

Radioactive Iodine (RAI)

• RAI is absolutely contraindicated in pregnancy and breastfeeding; patients should not breastfeed for four months after RAI treatment 1, 2
• RAI is contraindicated in patients with active/severe orbitopathy 4
• Consider steroid prophylaxis in patients with mild/active orbitopathy receiving RAI 4
• RAI is associated with development or worsening of thyroid eye disease in 15-20% of patients 6
• Results in permanent hypothyroidism requiring lifelong levothyroxine replacement 6

Thyroidectomy

• Thyroidectomy is favored for patients with concomitant suspicious or malignant thyroid nodules, coexisting hyperparathyroidism, very large goiters, or moderate to severe thyroid eye disease who cannot be treated with antithyroid drugs 2, 6
• Must be performed by an experienced high-volume thyroid surgeon 4
• Associated with potential complications including hypoparathyroidism and vocal cord paralysis in a small proportion of patients 6
• Results in permanent hypothyroidism requiring lifelong levothyroxine replacement 6

Special Clinical Situations

Pregnancy

• Women with Graves' disease should be monitored during pregnancy for normal heart rate and appropriate fetal growth 1
• The newborn's physician must be aware of maternal Graves' disease due to risk of neonatal thyroid dysfunction 1
• Some women opt for definitive therapy with RAI or surgery prior to becoming pregnant to avoid potential teratogenic effects of antithyroid drugs 6

Thyroid Storm

• Presents with fever, tachycardia out of proportion to fever, altered mental status, vomiting, diarrhea, and cardiac arrhythmia 1
• Requires immediate hospitalization for intensive management 1, 2
• Treatment includes high-dose antithyroid drugs, beta-blockers, and consideration of additional therapies such as steroids and saturated solution of potassium iodide (SSKI) 1, 2

Critical Pitfall to Avoid

• Do not fail to recognize the transition from hyperthyroidism to hypothyroidism, which is common with thyroiditis and requires close monitoring of thyroid function every 2-3 weeks after diagnosis 2