What are the criteria for starting antithyroid medication in a hyperthyroid patient with symptoms and abnormal thyroid function tests?

Criteria for Starting Antithyroid Drugs in Hyperthyroid Patients

Start antithyroid drugs when biochemical hyperthyroidism is confirmed (low TSH with elevated free T4 or free T3) AND a nosological diagnosis identifies Graves' disease or toxic nodular goiter as the underlying cause. 1

Initial Diagnostic Confirmation Required

Before initiating antithyroid medication, you must establish two things:

• Biochemical confirmation: Document suppressed TSH with elevated free T4 (FT4) and/or free T3 (FT3) levels 1
• Nosological diagnosis: Identify the specific cause of hyperthyroidism using TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and scintigraphy 1

The most common causes requiring antithyroid drugs are Graves' disease (70% of cases) and toxic nodular goiter (16% of cases) 1. Importantly, destructive thyrotoxicosis from subacute thyroiditis does not require antithyroid drugs since the hyperthyroidism is transient and self-limited 2, 1.

Disease-Specific Treatment Indications

Graves' Disease

Antithyroid drugs are the preferred first-line treatment for Graves' hyperthyroidism 1. Start treatment when:

• TSH is suppressed with elevated FT4 and/or FT3 1
• TSH-receptor antibodies are positive, confirming Graves' disease 1
• Patient has symptoms of hyperthyroidism (heat intolerance, tachycardia, anxiety, weight loss) or the condition is detected biochemically 3

The standard approach is a 12-18 month course of antithyroid drugs to induce remission 4, 1. However, long-term treatment (5-10 years) is associated with fewer recurrences (15%) compared to short-term treatment (50% recurrence rate) 1.

Toxic Nodular Goiter

Antithyroid drugs will not cure toxic nodular goiter 4. They should only be used:

• As a short-term measure to render the patient euthyroid before definitive therapy with radioiodine or thyroidectomy 4
• Stop antithyroid drugs at least one week prior to radioiodine administration to reduce the risk of treatment failure 5

The definitive treatment of choice for toxic nodular goiter is radioiodine, not antithyroid drugs 5, 4.

Drug Selection and Dosing

Methimazole (First-Line Choice)

Methimazole is the preferred antithyroid drug except in specific contraindicated situations 5.

• Starting dose: 15-20 mg daily maximum - do not exceed this dose as agranulocytosis risk is dose-dependent 5
• Single daily dosing is effective and superior to propylthiouracil 6
• A single daily dose of 15 mg methimazole is significantly more effective than 150 mg propylthiouracil in inducing euthyroidism 6

Propylthiouracil (Limited Indications Only)

Propylthiouracil should NOT be used as first-line therapy due to risk of severe liver failure requiring transplantation or causing death 5. Use propylthiouracil ONLY when:

• Antithyroid drug is needed during the first trimester of pregnancy 5
• Patient has experienced adverse responses to methimazole 5

Adult dosing (when propylthiouracil is indicated): Initial dose 300 mg daily in 3 divided doses; may increase to 400 mg daily for severe hyperthyroidism or very large goiters; occasional patients require 600-900 mg daily initially 7. Usual maintenance dose is 100-150 mg daily 7.

Pediatric dosing: Propylthiouracil is generally not recommended in pediatric patients except in rare instances where alternative therapies are inappropriate 7. Most severe liver injury cases were associated with doses of 300 mg/day and higher 7.

Special Populations and Contraindications

Pregnancy and Breastfeeding

• First trimester: Use propylthiouracil if antithyroid drug is necessary 5
• Second and third trimesters: Switch to methimazole if possible
• Avoid radioiodine during pregnancy and lactation 4
• Avoid pregnancy for 4 months following radioiodine administration 4

Graves' Ophthalmopathy

• Radioiodine may cause deterioration in Graves' ophthalmopathy 4
• Corticosteroid cover may reduce this complication risk 4

Monitoring and Treatment Duration

• Monitor thyroid function and dose adjustment is essential during treatment 2
• Standard treatment course is 12-18 months 4, 1
• Consider long-term treatment (5-10 years) for better remission rates 1

Predictors of Recurrence After Antithyroid Drugs

Consider definitive therapy (radioiodine or thyroidectomy) rather than continuing antithyroid drugs when:

• Age younger than 40 years 1
• FT4 concentrations ≥40 pmol/L before treatment 1
• TSH-binding inhibitory immunoglobulins >6 U/L 1
• Goiter size equivalent to or larger than WHO grade 2 1
• TSH-receptor antibodies remain above 10 mU/L after 6 months of treatment - remission is unlikely and radioiodine or thyroidectomy should be recommended 5

Common Pitfalls to Avoid

• Do not start antithyroid drugs for destructive thyrotoxicosis (subacute thyroiditis) - symptomatic treatment is sufficient as hyperthyroidism is transient 2
• Do not exceed 15-20 mg daily starting dose of methimazole - higher doses increase agranulocytosis risk 5
• Do not use propylthiouracil as first-line therapy - reserve for first trimester pregnancy or methimazole intolerance only 5
• Do not continue antithyroid drugs within one week of planned radioiodine therapy - this increases treatment failure risk 5
• Do not assume antithyroid drugs will cure toxic nodular goiter - they are only temporizing measures before definitive therapy 4