Treatment of Hyperthyroidism in Adults
When to Start Treatment
For overt hyperthyroidism (suppressed TSH with elevated free T4 or T3), treatment should be initiated immediately, while subclinical hyperthyroidism with TSH <0.1 mIU/L warrants treatment particularly in patients over 60 years or those with cardiac disease, osteopenia, or osteoporosis risk. 1
Overt Hyperthyroidism
- Begin treatment immediately upon biochemical confirmation (low TSH with elevated free T4 or free T3) 1, 2
- All patients with symptomatic hyperthyroidism require treatment regardless of age 2
Subclinical Hyperthyroidism Treatment Thresholds
TSH <0.1 mIU/L:
- Treat patients over 60 years due to 3-fold increased risk of atrial fibrillation over 10 years 1
- Treat those with or at increased risk for heart disease, osteopenia, or osteoporosis 3, 1
- Treat estrogen-deficient women due to bone loss risk 3
- Consider treatment in younger patients if TSH remains persistently <0.1 mIU/L for months 3
TSH 0.1-0.45 mIU/L:
- Routine treatment is NOT recommended due to insufficient evidence of adverse outcomes 3, 1
- Consider treatment only in elderly individuals with cardiovascular risk factors 3
Exception: Destructive Thyroiditis
- Do NOT treat with antithyroid drugs as this is self-limited 1, 4
- Provide symptomatic management only with beta-blockers 3, 1
How to Treat Hyperthyroidism
First-Line Pharmacologic Treatment
Methimazole is the preferred first-line antithyroid drug for all patients except during the first trimester of pregnancy, when propylthiouracil must be used. 1
Methimazole Dosing and Monitoring
- Initial dose: Start methimazole at appropriate dose based on severity (typically 10-30 mg daily) 4
- Monitoring schedule: Check free T4 or free T3 index every 2-4 weeks during initial treatment 1
- Treatment goal: Maintain free T4/T3 in the high-normal range using the lowest effective dose 1
- Critical pitfall to avoid: Do NOT reduce methimazole based solely on suppressed TSH while free T4 remains elevated or high-normal, as TSH may remain suppressed for months even after achieving euthyroidism 1
Dose Adjustment Algorithm
- If free T4/T3 is in the high-normal range: maintain current methimazole dose 1
- If free T4/T3 drops below normal: reduce methimazole dose or discontinue temporarily 1
- Base all adjustments on free T4/T3 levels, NOT TSH 1
Treatment Duration
- Standard course: 12-18 months for Graves' disease, with approximately 50% recurrence rate 5, 2
- Long-term treatment: 5-10 years is feasible and associated with only 15% recurrence rate 5
- Predictors of recurrence: Age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 5
Pregnancy-Specific Treatment
- First trimester: Use propylthiouracil exclusively due to methimazole's teratogenic risk 1
- After first trimester: Switch back to methimazole 1
- Goal: Maintain FT4 or free T3 index in the high-normal range using the lowest possible thioamide dosage 1
- Breastfeeding: Both propylthiouracil and methimazole are compatible 1
- Contraindication: Radioactive iodine is absolutely contraindicated in pregnancy and breastfeeding; avoid pregnancy for 4 months following I-131 administration 1, 6
Immediate Symptomatic Management
Beta-blockers provide immediate symptomatic relief and should be started concurrently with antithyroid drugs in all symptomatic patients. 1
- Preferred agents: Atenolol 25-50 mg daily or propranolol 1
- Target: Heart rate <90 bpm if blood pressure allows 1
- Symptoms controlled: Tachycardia, tremor, anxiety 1, 4
- Dose adjustment: Reduce beta-blocker dose once euthyroid state is achieved 1
Definitive Treatment Options
Radioactive Iodine (I-131) Ablation
- Most widely used treatment in the United States 4
- Preferred for: Toxic nodular goiter 6
- Absolute contraindications: Pregnancy and breastfeeding 1, 6
- Risk: May worsen Graves' ophthalmopathy; consider corticosteroid cover to reduce this risk 6
- Long-term sequela: Risk of radioiodine-induced hypothyroidism 6
Surgical Thyroidectomy
- Indications: Large goiter causing compressive symptoms, patient refusal of radioiodine, or specific contraindications to other treatments 6
- Goal: Cure underlying pathology while leaving residual thyroid tissue to maintain postoperative euthyroidism 6
Critical Monitoring for Adverse Effects
Agranulocytosis
- Timing: Typically occurs within first 3 months of thioamide treatment 1
- Presentation: Sore throat and fever 1
- Action: Immediate CBC and drug discontinuation 1
Hepatotoxicity
- Higher risk with: Propylthiouracil 1
- Monitor for: Fever, nausea, vomiting, right upper quadrant pain, dark urine, jaundice 1
- Action: Immediate drug discontinuation if suspected 1
Vasculitis
Special Populations and Comorbidities
Cardiovascular Disease
- Atrial fibrillation: Occurs in 5-15% of hyperthyroid patients, more frequently in those over 60 years 1
- Rate control: Beta-blockers are recommended, with dose reduction once euthyroid 1
- Alternative: Nondihydropyridine calcium channel antagonists when beta-blockers cannot be used 1
- Anticoagulation: Guide by CHA₂DS₂-VASc risk factors, not solely by presence of hyperthyroidism 1
Drug Interactions
- Warfarin: Requires dose adjustment due to increased anticoagulation effect with antithyroid drugs 1
- Theophylline: Clearance decreases when euthyroid 1
Disease-Specific Considerations
Toxic Nodular Goiter
- Antithyroid drugs will NOT cure this condition 6
- Preferred treatment: Radioiodine or thyroidectomy 6
- Alternative: Radiofrequency ablation (rarely used) 5
Destructive Thyroiditis (Subacute, Postpartum)
- Natural course: Self-limited, biphasic (hyperthyroid then hypothyroid) 1
- Treatment: Beta-blockers for symptomatic relief only 3, 1
- Monitoring: Symptom evaluation and free T4 testing every 2 weeks 1
- Hypothyroid phase: Introduce thyroid hormone replacement if patient becomes hypothyroid (low free T4/T3, even if TSH not yet elevated) 1
- Severe cases: Steroids only if severe 5