What is the best course of treatment for a 44-year-old female patient with hyperthyroidism, presenting with a suppressed Thyroid-Stimulating Hormone (TSH) level and elevated Thyroxine (T4) level of 2.2?

Hyperthyroidism Management

Immediate Diagnostic Confirmation Required

This patient has overt hyperthyroidism requiring urgent evaluation to determine the underlying cause before initiating treatment. 1, 2

The laboratory findings of TSH 0.01 mIU/L (suppressed) with elevated T4 2.2 definitively confirm biochemical hyperthyroidism. 2, 3 However, the critical next step is determining the etiology, as this fundamentally changes management—you cannot simply start treatment without knowing whether this is Graves' disease, toxic nodular goiter, thyroiditis, or another cause. 1, 2

Essential Diagnostic Workup

Before any treatment decisions, obtain:

• TSH-receptor antibodies (TRAb) - If positive, this confirms Graves' disease (the most common cause, affecting 2% of women). 1, 2
• Thyroid ultrasound - Evaluates for nodules, diffuse enlargement, or signs of thyroiditis. 3
• Thyroid scintigraphy - Mandatory if nodules are present or if the etiology remains unclear after antibody testing. 2, 3 Increased uptake indicates Graves' disease or toxic nodular goiter; decreased/absent uptake suggests thyroiditis. 1

Additional helpful tests include thyroid peroxidase (TPO) antibodies, though TRAb is more specific for Graves' disease. 1

Treatment Algorithm Based on Etiology

If Graves' Disease (Most Likely - 70% of Cases)

Antithyroid drugs are the preferred first-line treatment. 4, 1, 2

• Methimazole is the drug of choice for non-pregnant patients, given once daily with better tolerability than propylthiouracil. 5, 1
• Start methimazole 10-30 mg daily depending on severity (T4 of 2.2 suggests moderate-severe disease). 1
• Propylthiouracil should be avoided except in first trimester pregnancy or methimazole intolerance, due to severe hepatotoxicity risk including liver failure and death. 6, 1

Treatment duration: 12-18 months is standard, though approximately 50% of patients will relapse after stopping. 1, 2 Risk factors for relapse include age <40 years, FT4 ≥40 pmol/L, TRAb >6 U/L, and large goiter (≥WHO grade 2). 1 Consider long-term treatment (5-10 years) which reduces recurrence to 15%. 1

Definitive therapy options if antithyroid drugs fail or patient prefers:

• Radioactive iodine (RAI) - Growing as first-line therapy, well-tolerated, main risk is hypothyroidism. 4, 2 Avoid in pregnancy/lactation; delay pregnancy 4 months post-treatment. 4 May worsen Graves' ophthalmopathy—consider corticosteroid prophylaxis if eye disease present. 4
• Thyroidectomy - Reserved for large compressive goiters, RAI refusal, or specific patient preference. 4, 2

If Toxic Nodular Goiter (16% of Cases)

Antithyroid drugs will NOT cure this condition. 4 They may be used temporarily for symptom control, but definitive treatment is required:

• Radioactive iodine is the treatment of choice for toxic nodular goiter. 4, 1
• Surgery is an alternative, particularly if large compressive symptoms exist. 4
• Radiofrequency ablation is emerging but rarely used. 1

If Thyroiditis (3% of Cases)

Observation or supportive care only. 2 This is typically self-limited—the thyrotoxic phase resolves spontaneously within weeks to months. 1 Steroids are reserved only for severe cases. 1

Critical Monitoring During Antithyroid Drug Therapy

• Thyroid function tests every 4-6 weeks until euthyroid, then every 6-12 months. 5, 6
• Complete blood count with differential - Watch for agranulocytosis (sore throat, fever, infection). 5, 6
• Liver function tests - Particularly with propylthiouracil, which carries severe hepatotoxicity risk. 6
• Prothrombin time before surgery - Both drugs can cause hypoprothrombinemia. 5, 6

Patients must immediately report: sore throat, fever, rash, jaundice, right upper quadrant pain, or any signs of illness. 5, 6

Special Considerations for This 44-Year-Old Female

• Pregnancy planning: If she desires pregnancy, this is urgent—untreated hyperthyroidism causes spontaneous abortion, preterm birth, stillbirth, and fetal hyperthyroidism. 5, 6 Methimazole is contraindicated in first trimester due to congenital malformations; propylthiouracil is preferred despite hepatotoxicity risk, then switch to methimazole for second/third trimesters. 5, 6
• Cardiovascular risk: Untreated hyperthyroidism causes atrial fibrillation, heart failure, and increased mortality. 2 Consider beta-blocker for symptom control while awaiting definitive diagnosis. 2
• Bone health: Hyperthyroidism accelerates bone loss and fracture risk, particularly concerning in a perimenopausal woman. 2

Common Pitfalls to Avoid

• Never start treatment without determining etiology - Thyroiditis requires no treatment; toxic nodular goiter won't respond to antithyroid drugs long-term. 4, 1
• Don't use propylthiouracil as first-line except in first trimester pregnancy—hepatotoxicity risk is too high, including fatal liver failure. 6, 1
• Don't assume this is Graves' disease without confirming TRAb positivity—10-30% of hyperthyroidism has other causes. 1, 2
• Don't delay treatment - Untreated hyperthyroidism increases mortality and causes irreversible complications. 2