How do I treat hyperthyroidism, including initial beta‑blocker therapy, choice and dosing of antithyroid drugs (methimazole vs propylthiouracil), monitoring, and definitive options, with special considerations for pregnancy, elderly patients, cardiac disease, and Graves’ ophthalmopathy?

Management of Hyperthyroidism

Initial Symptomatic Control with Beta-Blockers

Start a non-selective beta-blocker immediately at diagnosis to control adrenergic symptoms while awaiting definitive therapy. Propranolol 40–80 mg orally every 6–8 hours is the preferred agent because it also inhibits peripheral T4-to-T3 conversion 1. Continue beta-blockade until the patient achieves euthyroidism, typically 4–8 weeks after starting antithyroid drugs 1.

• Contraindications to beta-blockers include asthma, chronic obstructive pulmonary disease, and decompensated heart failure 1.
• In patients with these contraindications, consider a rate-limiting calcium channel blocker (e.g., diltiazem) as an alternative for heart rate control, though this is not explicitly addressed in the provided evidence.

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Choice and Dosing of Antithyroid Drugs

Methimazole vs. Propylthiouracil: General Population

Methimazole (MMI) is the preferred antithyroid drug for most patients with Graves' disease because it normalizes thyroid function more rapidly and has a lower incidence of hepatotoxicity compared to propylthiouracil (PTU) 2, 3.

• For mild-to-moderate hyperthyroidism (free T4 <7 ng/dL), start MMI 15 mg once daily 3.
• For severe hyperthyroidism (free T4 ≥7 ng/dL), start MMI 30 mg once daily 3.
• MMI 30 mg/d normalized free T4 in 96.5% of patients at 12 weeks, compared to 78.3% with PTU 300 mg/d 3.
• PTU is not recommended for initial therapy due to higher rates of mild hepatotoxicity and inferior efficacy 3.

Special Considerations: Pregnancy

Women planning pregnancy or in the first trimester must switch from MMI to PTU to avoid MMI-associated embryopathy (choanal atresia, aplasia cutis) 2, 4.

• First trimester: Use PTU 100 mg three times daily (total 300 mg/d) 5, 4.
• Second and third trimesters: Switch back to MMI 15–30 mg once daily to minimize the rare but severe risk of PTU-induced hepatotoxicity 4.
• Use the lowest effective dose to maintain maternal free T4 in the upper-normal range, as both antithyroid drugs cross the placenta and can cause fetal hypothyroidism and goiter 5.
• Monitor free T4 and free T3 (not total hormones, which are elevated in pregnancy due to increased thyroxine-binding globulin) every 2–4 weeks 5.

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Monitoring During Antithyroid Drug Therapy

Initial Phase (First 12–18 Months)

• Check free T4, free T3, and TSH every 4–6 weeks during dose titration 2.
• Measure TSH-receptor antibodies (TSH-R-Ab) at diagnosis to confirm Graves' disease and predict relapse risk 2.
• Repeat TSH-R-Ab at 12–18 months before discontinuing therapy: persistently elevated levels predict relapse and warrant either continued MMI or definitive therapy 2.

Monitoring for Adverse Effects

• Obtain baseline complete blood count (CBC) and liver function tests (LFTs) before starting therapy 2.
• Instruct patients to stop the drug immediately and seek urgent evaluation if they develop fever, sore throat (agranulocytosis), or jaundice (hepatotoxicity) 2, 4.
• Routine serial CBC and LFT monitoring is not recommended, as agranulocytosis typically occurs suddenly 2.

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Duration of Antithyroid Drug Therapy

Adults

• Treat for 12–18 months with MMI, then reassess TSH-R-Ab 2.
• If TSH-R-Ab remains elevated at 12–18 months, either continue MMI for another 12 months and recheck antibodies, or proceed to definitive therapy (radioactive iodine or thyroidectomy) 2.
• If the patient relapses after completing a course of ATD, definitive treatment is recommended, though long-term low-dose MMI (5–10 mg/d) is an alternative 2.

Children

• Treat for 24–36 months with MMI before considering definitive therapy, as spontaneous remission rates are lower in children 2.

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Definitive Treatment Options

Radioactive Iodine (RAI)

RAI is the preferred definitive therapy for most adults with Graves' disease who relapse after antithyroid drugs 2.

• Contraindications:
  • Active or severe Graves' orbitopathy (RAI can worsen eye disease) 2.
  • Pregnancy or breastfeeding 2.
• For patients with mild/active orbitopathy, administer steroid prophylaxis (e.g., prednisone 0.3–0.5 mg/kg/d for 6 weeks, tapering over 3 months) to prevent worsening of eye disease 2.
• Pretreatment with MMI is recommended in elderly patients or those with cardiac disease to prevent thyroid storm from RAI-induced thyroiditis 2.

Total Thyroidectomy

Thyroidectomy should be performed by an experienced high-volume thyroid surgeon to minimize complications (hypoparathyroidism, recurrent laryngeal nerve injury) 2.

• Indications for surgery over RAI:
  • Large goiter (>80 g) causing compressive symptoms 2.
  • Coexisting suspicious thyroid nodules requiring histologic evaluation 2.
  • Patient preference or contraindication to RAI 2.
• Preoperative preparation: Achieve euthyroidism with MMI, then add potassium iodide (SSKI) 5 drops twice daily for 7–10 days before surgery to reduce thyroid vascularity 2.

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Special Populations

Elderly Patients

• Start with lower doses of MMI (10–15 mg/d) and titrate cautiously, as elderly patients are more prone to agranulocytosis 2.
• Consider RAI as first-line definitive therapy in elderly patients, especially those with cardiac comorbidities, to avoid prolonged antithyroid drug exposure 2.
• Pretreat with MMI before RAI to prevent thyroid storm in patients with severe hyperthyroidism or atrial fibrillation 2.

Cardiac Disease

• Beta-blockers are essential to control heart rate and prevent atrial fibrillation or heart failure exacerbation 1.
• Achieve euthyroidism rapidly with MMI 30 mg/d (if severe) to reduce cardiac workload 3.
• Avoid PTU due to slower onset of action and higher hepatotoxicity risk 3.
• Definitive therapy (RAI or surgery) is preferred over long-term antithyroid drugs to minimize cardiovascular risk from persistent hyperthyroidism 2.

Graves' Ophthalmopathy

• RAI is contraindicated in active/severe orbitopathy because it can precipitate or worsen eye disease 2.
• If RAI is necessary in mild/active orbitopathy, administer steroid prophylaxis (prednisone 0.3–0.5 mg/kg/d for 6 weeks, tapering over 3 months) 2.
• Thyroidectomy is the preferred definitive therapy in patients with moderate-to-severe orbitopathy 2.

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Common Pitfalls

• Do not use PTU as first-line therapy except in pregnancy (first trimester) or thyroid storm, due to inferior efficacy and higher hepatotoxicity 3, 4.
• Do not stop beta-blockers prematurely—continue until euthyroidism is achieved, as symptoms can persist despite normalizing thyroid hormones 1.
• Do not administer RAI without steroid prophylaxis in patients with mild/active Graves' orbitopathy 2.
• Do not perform thyroidectomy without preoperative iodine preparation (SSKI), as this increases surgical bleeding risk 2.
• Do not rely on total T4/T3 levels in pregnancy—use free T4 and free T3 to avoid misdiagnosis due to elevated thyroxine-binding globulin 5.