What are the initial steps in a hyperthyroid (thyroid disorder characterized by excessive production of thyroid hormones) work-up?

Initial Steps in Hyperthyroid Work-up

The initial steps in hyperthyroid work-up should include measuring TSH and free T4, followed by determining the etiology through TSH-receptor antibodies, thyroid peroxidase antibodies, thyroid ultrasonography, and possibly scintigraphy. 1, 2

Diagnostic Algorithm for Hyperthyroidism

Step 1: Biochemical Confirmation

• Measure TSH and free T4 to confirm hyperthyroidism 1
• Low TSH with elevated free T4 and/or free T3 confirms overt hyperthyroidism 2, 3
• Low TSH with normal free T4 and T3 indicates subclinical hyperthyroidism 3

Step 2: Etiological Diagnosis

Once hyperthyroidism is biochemically confirmed, determine the underlying cause:

1. Measure TSH-receptor antibodies - Positive results strongly suggest Graves' disease (accounts for approximately 70% of hyperthyroidism cases) 2
2. Thyroid peroxidase antibodies - May be present in autoimmune thyroid disorders 1, 2
3. Thyroid ultrasonography - To evaluate thyroid morphology and identify nodules 2
4. Thyroid scintigraphy - Recommended if thyroid nodules are present or etiology remains unclear after initial testing 3

Common Etiologies to Consider

• Graves' disease (70% of cases) - Diffusely enlarged thyroid, positive TSH-receptor antibodies, may have ophthalmopathy 2, 3
• Toxic nodular goiter (16% of cases) - Single or multiple hyperfunctioning nodules 2, 4
• Subacute thyroiditis (3% of cases) - Often following viral infection, with neck pain 2
• Drug-induced hyperthyroidism (9% of cases) - Consider medications like amiodarone, tyrosine kinase inhibitors, and immune checkpoint inhibitors 2

Risk Assessment

During the initial work-up, assess for complications and risk factors:

• Cardiovascular assessment - Hyperthyroidism significantly affects the cardiovascular system with increased risk of atrial fibrillation (3-fold increased risk in adults ≥60 years with TSH ≤0.1 mIU/L) 1, 5
• Bone health evaluation - Increased risk of osteoporosis, especially with prolonged hyperthyroidism 3
• Pregnancy status - Requires special management considerations 1, 6
• Age and comorbidities - Elderly patients and those with cardiac conditions require careful management 1, 5

Special Considerations and Pitfalls

• Do not rely on TSH alone - Always measure both TSH and free T4 to properly classify thyroid dysfunction 1
• Consider subclinical hyperthyroidism - Treatment is recommended for patients >65 years or with persistent serum TSH <0.1 mIU/L due to increased cardiovascular and bone risks 3
• Beware of thyroid storm - A life-threatening emergency requiring immediate treatment with antithyroid drugs, beta-blockers, iodine, and supportive care 1, 5
• Multiple tests may be needed - Confirm abnormal findings with repeat testing over a 3-6 month interval 1
• Look for other autoimmune conditions - Especially in patients with autoimmune thyroid disease 1

By following this systematic approach to hyperthyroid work-up, clinicians can efficiently diagnose the condition, determine its etiology, and assess for complications that will guide treatment decisions.