What laboratory tests are used to diagnose hyperthyroidism?

Laboratory Tests for Diagnosing Hyperthyroidism

The diagnosis of hyperthyroidism requires TSH testing as the initial screening test, followed by free T4 and/or free T3 measurements when TSH is suppressed. 1

Primary Diagnostic Tests

First-Line Testing

• Thyroid Stimulating Hormone (TSH):
  • Most sensitive initial screening test
  • Suppressed (low) in hyperthyroidism
  • Using monoclonal antibodies for accurate measurement 1

Second-Line Testing (when TSH is abnormal)

• Free Thyroxine (Free T4 or FT4):
  • Elevated in overt hyperthyroidism
  • May be normal in subclinical hyperthyroidism or T3 toxicosis 2, 3
• Free Triiodothyronine (Free T3 or FT3):
  • Particularly important when T3 toxicosis is suspected
  • May be elevated when FT4 is normal 4
  • Essential for confirming hyperthyroidism when clinical suspicion is high but FT4 is normal 4

Diagnostic Patterns

Biochemical Patterns in Hyperthyroidism:

• Overt hyperthyroidism: Low/suppressed TSH with elevated FT4 and/or FT3 3
• Subclinical hyperthyroidism: Low/suppressed TSH with normal FT4 and FT3 3
• T3 toxicosis: Low TSH, normal FT4, elevated FT3 4

Additional Tests for Determining Etiology

Once hyperthyroidism is biochemically confirmed, additional tests help determine the underlying cause:

• TSH Receptor Antibodies (TRAb or TSI):

  • Positive in Graves' disease
  • Helps differentiate from other causes of hyperthyroidism 1, 2

• Thyroid Peroxidase Antibodies (TPO):

  • Often positive in autoimmune thyroid disorders
  • May be present in Graves' disease and Hashimoto's thyroiditis 1, 2

• Thyroid Imaging:

  • Thyroid Ultrasonography:

    • Evaluates gland size, nodules, vascularity
    • Helps identify nodular disease 2

  • Radioactive Iodine Uptake Scan (RAIUS) or Technetium-99m scan:

    • Differentiates between causes of hyperthyroidism
    • High uptake: Graves' disease, toxic nodular goiter
    • Low uptake: thyroiditis, exogenous thyroid hormone 1, 5
    • Particularly important when nodules are present or etiology is unclear 3

Special Considerations

• Repeat testing: Thyroid function tests should be repeated to confirm persistent dysfunction before making treatment decisions, unless TSH is <0.1 mIU/L 1

• Pregnancy: TSH and FT4 or FTI (Free Thyroxine Index) should be performed in pregnant women with suspected hyperthyroidism 1

• Medication effects: Consider medication-induced thyroid dysfunction (amiodarone, tyrosine kinase inhibitors, immune checkpoint inhibitors) 2

• Thyroiditis: In suspected thyroiditis, additional tests (TRAb, TPO, imaging) help rule out other causes of thyrotoxicosis 1

Common Pitfalls to Avoid

1. Relying solely on TSH: While TSH is the most sensitive test, both FT4 and FT3 are needed for complete evaluation of thyroid function 4

2. Overlooking T3 toxicosis: Some patients have normal FT4 but elevated FT3 levels 4

3. Not accounting for binding protein abnormalities: Total T4/T3 measurements can be misleading due to variations in binding proteins; free hormone measurements are more reliable 4

4. Missing subclinical hyperthyroidism: Defined as suppressed TSH with normal FT4/FT3, which may still require treatment in high-risk patients 3

5. Single measurement diagnosis: Thyroid function tests should generally be repeated to confirm persistent dysfunction before initiating treatment 1