What is the initial treatment for hyperthyroidism?

Initial Treatment for Hyperthyroidism

The initial treatment for hyperthyroidism is antithyroid medication, specifically methimazole, which should be started at 15-20 mg/day (not exceeding this dose to minimize agranulocytosis risk), with propylthiouracil reserved only for first-trimester pregnancy or methimazole intolerance. 1, 2, 3

Treatment Selection Algorithm

First-Line Pharmacologic Therapy

• Methimazole is the preferred antithyroid drug for initial management, as it inhibits thyroid hormone synthesis without inactivating existing circulating hormones 2, 3
• The starting dose should be 15-20 mg/day maximum to reduce the dose-dependent risk of agranulocytosis 3
• For moderate to severe hyperthyroidism (free T4 ≥5 ng/dL), combining methimazole 15 mg/day with inorganic iodine 38 mg/day achieves faster normalization of thyroid function (73.9% euthyroid by 60 days) compared to methimazole 30 mg/day alone (63.1% by 60 days), while causing fewer adverse effects requiring drug discontinuation (7.5% vs 14.8%) 4

When to Avoid Methimazole

• Propylthiouracil should replace methimazole only during the first trimester of pregnancy due to methimazole's association with congenital malformations during organogenesis 2
• Switch back to methimazole for the second and third trimesters, as propylthiouracil carries risk of severe hepatotoxicity leading to liver transplantation or death 2, 3
• Propylthiouracil is also acceptable for patients who have experienced adverse reactions to methimazole 3

Essential Pre-Treatment Workup

• Confirm diagnosis with TSH (suppressed) and free T4 or free T3 (elevated) before initiating therapy 5, 6
• Add T3 measurement if symptoms are severe despite minimal free T4 elevation, as isolated T3 toxicosis can occur 5
• Measure TSH receptor antibodies if Graves' disease is suspected based on clinical features (diffuse goiter, ophthalmopathy, thyroid bruit) 5
• Obtain baseline prothrombin time before starting methimazole, as it may cause hypoprothrombinemia and bleeding 2
• Perform baseline cardiovascular assessment, as hyperthyroidism increases cardiac workload and can precipitate heart failure in patients with underlying cardiac disease 5

Critical Monitoring Requirements

• Monitor thyroid function tests every 2-3 weeks initially to detect transition from hyperthyroidism to hypothyroidism, which commonly occurs with transient thyroiditis 5
• For patients on antithyroid drugs, repeat TSH and free T4 after 6-8 weeks to adjust dosing 5
• Once clinical hyperthyroidism resolves, a rising TSH indicates the need for a lower maintenance dose 2
• Instruct patients to report immediately: sore throat, skin eruptions, fever, headache, or general malaise, as these may indicate agranulocytosis requiring white blood cell count assessment 2
• Monitor for vasculitis symptoms: new rash, hematuria, decreased urine output, dyspnea, or hemoptysis 2

Common Pitfalls to Avoid

• Do not start methimazole at doses exceeding 20 mg/day, as agranulocytosis risk is dose-dependent 3
• Do not use propylthiouracil as first-line therapy except in specific circumstances (first trimester pregnancy, methimazole intolerance), given its hepatotoxicity risk 2, 3
• Be aware that hyperthyroid patients may require dose adjustments of concurrent medications: beta-blockers, digoxin, theophylline, and warfarin all have altered pharmacokinetics as patients transition to euthyroid status 2
• Stop antithyroid drugs at least one week before radioiodine therapy if definitive treatment is planned, to reduce risk of treatment failure 3

Duration and Definitive Treatment Considerations

• Standard antithyroid drug courses last 12-18 months for Graves' disease, with approximately 50% recurrence rate 6, 7
• Predictors of recurrence after antithyroid drug therapy include: age <40 years, free T4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 6
• If TSH receptor antibodies remain >10 mU/L after 6 months of treatment, remission is unlikely and radioiodine or thyroidectomy should be recommended 3
• Long-term antithyroid drug therapy (5-10 years) is associated with lower recurrence rates (15%) compared to standard 12-18 month courses 6