What is the management of hyperthyroidism, particularly in cases of Graves' disease, according to Harrison?

Management of Hyperthyroidism According to Harrison

Methimazole is the preferred first-line antithyroid drug for most patients with Graves' disease, administered at 10-30 mg daily as a single dose for 12-18 months, with propylthiouracil reserved only for first-trimester pregnancy or methimazole intolerance. 1, 2, 3

Initial Diagnostic Confirmation

• Confirm diagnosis with TSH and Free T4 testing 1
• Consider TSH receptor antibody testing if clinical features suggest Graves' disease (ophthalmopathy, thyroid bruit) 4
• Monitor thyroid function every 4-6 weeks during initial treatment phase 1

First-Line Medical Therapy: Antithyroid Drugs

Methimazole (Preferred Agent)

• Start methimazole 10-30 mg once daily as the drug of choice for most patients 1, 2, 5
• Methimazole has fewer major side effects, allows single daily dosing, and is more cost-effective than propylthiouracil 5
• Continue therapy for 12-18 months using titration method 1, 6
• Titrate to the lowest dose that maintains Free T4 in the high-normal range 1, 4

Propylthiouracil (Limited Indications)

• Reserve propylthiouracil (100-300 mg every 6 hours) only for patients intolerant to methimazole or during first trimester of pregnancy 3, 7
• Propylthiouracil carries risk of severe liver failure requiring transplantation or causing death 7
• Starting dose should not exceed 15-20 mg/day for methimazole due to dose-dependent agranulocytosis risk 7

Symptomatic Management

• Initiate beta-blockers (atenolol 25-50 mg daily or propranolol) for symptomatic relief of tachycardia, tremor, and anxiety 4, 1
• Beta-blockers provide immediate symptom control while awaiting antithyroid drug effect 4

Monitoring Protocol

• Check thyroid function every 2-3 weeks initially after diagnosis 4, 1
• Once stable, extend monitoring to every 4-6 weeks, then every 2-3 months 1
• Watch for agranulocytosis (presents with sore throat and fever) - obtain complete blood count immediately and discontinue thioamide if suspected 4
• Monitor for other side effects including hepatitis, vasculitis, and thrombocytopenia 4

Definitive Treatment Options

Radioactive Iodine (RAI)

• Consider RAI for patients with persistent disease after 12-18 months of medical therapy 1
• Stop antithyroid drugs at least one week before radioiodine to reduce treatment failure risk 7
• Radioactive iodine is absolutely contraindicated in pregnancy and breastfeeding 4, 1
• Patients must not breastfeed for four months after RAI treatment 4, 1

Thyroidectomy

• Recommend thyroidectomy for patients who fail medical therapy, have very large goiters, or have contraindications to both antithyroid drugs and RAI 1
• Perform as near-total or total thyroidectomy 7
• Use antithyroid drugs to achieve euthyroid state before surgery 2

Special Population: Pregnancy

• Propylthiouracil is the drug of choice during first trimester due to methimazole's association with aplasia cutis and choanal/esophageal atresia 4, 5
• Consider switching to methimazole after first trimester 1
• Maintain maternal Free T4 in high-normal range using lowest possible thioamide dose 4, 1
• Both drugs allow safe breastfeeding despite presence in breast milk 4, 5
• Monitor fetal growth and maternal heart rate; ultrasound for fetal goiter only if problems detected 4

Thyroid Storm (Life-Threatening Emergency)

• Hospitalize immediately for intensive management 1
• Administer high-dose antithyroid drugs (propylthiouracil or methimazole) 4
• Add saturated solution of potassium iodide (SSKI) or sodium iodide after antithyroid drug administration 4
• Give dexamethasone to block peripheral T4 to T3 conversion 4
• Provide beta-blockers for symptomatic control 4, 1
• Consider additional therapies: phenobarbital, and in severe cases with bronchospasm, reserpine, guanethidine, or diltiazem 4
• Implement supportive measures: oxygen, antipyretics, hydration, appropriate monitoring 4
• Avoid delivery during thyroid storm unless absolutely necessary 4

Critical Pitfalls to Avoid

• Do not miss the transition from hyperthyroidism to hypothyroidism, which commonly occurs with thyroiditis - this requires close monitoring every 2-3 weeks 4, 1
• Do not overlook ophthalmopathy or thyroid bruit on physical examination, as these are diagnostic of Graves' disease and warrant early endocrine referral 4, 1
• Do not continue methimazole if patient develops sore throat and fever without checking complete blood count for agranulocytosis 4
• Do not use radioactive iodine in women who are pregnant, planning pregnancy, or breastfeeding 4, 1

Predicting Treatment Success

• If TSH receptor antibodies remain above 10 mU/L after 6 months of antithyroid treatment, remission is unlikely and definitive therapy (RAI or thyroidectomy) should be recommended 7
• Approximately 50% of patients relapse after completing 12-18 months of medical therapy and should be offered ablative treatment 6