What lab workup is indicated for hyperthyroidism (elevated T4 levels)?

Laboratory Workup for Elevated T4 (Hyperthyroidism)

The essential laboratory workup for elevated T4 levels (hyperthyroidism) should include TSH, free T4, and free T3 measurements, with thyroid autoantibody testing (TSI, TPOAb, TgAb) to determine the underlying etiology.

Initial Laboratory Assessment

When evaluating a patient with elevated T4 levels, a systematic approach to laboratory testing is crucial:

1. First-line tests:

   • Thyroid Stimulating Hormone (TSH)
   • Free T4 (FT4)
   • Free T3 (FT3)

2. Second-line tests to determine etiology:

   • Thyroid autoantibodies:
     • Thyroid Stimulating Immunoglobulin (TSI)
     • Thyroid Peroxidase Antibodies (TPOAb)
     • Thyroglobulin Antibodies (TgAb)

The inverse log-linear relationship between TSH and free T4 is crucial for diagnosis - an increased free T4 with suppressed TSH (<0.01 mU/L) is consistent with hyperthyroidism 1.

Interpretation of Results

• Overt hyperthyroidism: Elevated free T4 with suppressed TSH
• Subclinical hyperthyroidism: Normal free T4 with suppressed TSH
• T3 toxicosis: Normal free T4, elevated free T3, suppressed TSH
• TSH-secreting pituitary tumor: Elevated free T4 with normal or elevated TSH

Special Considerations

Aberrant Results

In approximately 3.3% of patients, an elevated free T4 may be found with a normal TSH 2. This pattern requires careful evaluation as it may indicate:

• Laboratory interference
• Thyroid hormone resistance
• TSH-secreting pituitary adenoma
• Recent treatment for hyperthyroidism
• Non-thyroidal illness

Testing Methods

Direct equilibrium dialysis for free T4 measurement is recommended for patients with significant alterations in serum T4 binding proteins, as other methods may yield false-positive results 1.

Additional Testing Based on Clinical Suspicion

• Complete Blood Count (CBC): To assess for anemia or infection
• Liver Function Tests: Hyperthyroidism can affect liver enzymes
• Calcium levels: To check for hypercalcemia (can occur in hyperthyroidism)
• Glucose levels: Hyperthyroidism can affect glucose metabolism
• Radioactive Iodine Uptake (RAIU): To differentiate between Graves' disease and thyroiditis
• Thyroid Ultrasound: If a palpable thyroid nodule or goiter is detected

Common Pitfalls to Avoid

1. Relying solely on TSH: While TSH is highly sensitive, both free T4 and free T3 should be measured to accurately assess thyroid function 1.

2. Overlooking potential causes of aberrant results: When encountering unusual combinations (like elevated T4 with normal TSH), thorough investigation of underlying causes is essential 2.

3. Using inappropriate free T4 testing methods: In patients with significant alterations of serum T4 binding, only direct equilibrium dialysis or ultrafiltration provides reliable results 1.

4. Failing to consider T3 toxicosis: Some patients may have normal T4 but elevated T3 levels, which can be missed if T3 is not measured.

5. Not considering medication effects: Many medications can affect thyroid function tests.

By following this systematic approach to laboratory evaluation of elevated T4 levels, clinicians can accurately diagnose hyperthyroidism and determine its underlying cause, leading to appropriate treatment decisions.