What labs should be ordered besides TSH (Thyroid-Stimulating Hormone) to diagnose hyperthyroidism?

Laboratory Tests for Diagnosing Hyperthyroidism

Free T4 (FT4) and Free T3 (FT3) should be ordered alongside TSH to properly diagnose hyperthyroidism. 1

Diagnostic Algorithm for Hyperthyroidism

Initial Testing

• TSH: Always the first-line test
• Free T4 (FT4): Should be ordered when TSH is abnormal
• Free T3 (FT3): Should be ordered when TSH is suppressed but FT4 is normal (to detect T3 thyrotoxicosis)

Interpretation of Results

1. Overt hyperthyroidism: Low/suppressed TSH with elevated FT4 and/or FT3
2. Subclinical hyperthyroidism: Low TSH with normal FT4 and FT3
3. T3 thyrotoxicosis: Low TSH, normal FT4, elevated FT3

Evidence-Based Rationale

When evaluating for hyperthyroidism, TSH alone is insufficient for complete diagnosis. According to JAMA guidelines, when TSH is suppressed (<0.1 mIU/L), both FT4 and FT3 (or total T3) should be measured to confirm the diagnosis and determine the severity of thyrotoxicosis 1.

The Journal for ImmunoTherapy of Cancer guidelines specifically state that "thyrotoxicosis (high free T4 or total T3 with low or normal TSH) may occur secondary to thyroiditis or Graves' disease" 1. This underscores the importance of measuring both thyroid hormones alongside TSH.

Free hormone measurements are superior to total hormone measurements because they are not affected by changes in thyroid hormone-binding proteins 2, 3. This is particularly important in conditions like pregnancy, acute illness, or when patients are taking certain medications.

Clinical Applications

When to Order FT3

• FT3 testing is most useful when TSH is suppressed and FT4 is normal or decreased 4
• The likelihood of detecting T3 thyrotoxicosis increases with lower TSH values (27.6% when TSH <0.01 μIU/L) 4
• T3 thyrotoxicosis is more commonly diagnosed in outpatient settings (34%) than inpatient settings (14%) 4

Monitoring Treatment

• For patients on antithyroid medications (methimazole or propylthiouracil), thyroid function tests should be monitored periodically 5, 6
• Once clinical evidence of hyperthyroidism has resolved, an elevated serum TSH indicates that a lower maintenance dose of antithyroid medication should be employed 5, 6

Common Pitfalls to Avoid

1. Overreliance on TSH alone: While TSH is the most sensitive test for thyroid dysfunction, it cannot distinguish between different causes of hyperthyroidism or determine severity without FT4/FT3 1

2. Unnecessary testing: Ordering FT3 for all patients with abnormal TSH leads to excessive costs. FT3 should be reserved for cases where TSH is suppressed and FT4 is normal or low 4, 7

3. Misinterpretation in special populations:

   • In pregnancy, trimester-specific reference ranges should be used
   • In severe non-thyroidal illness, free hormone measurements may be technically challenging 2
   • In patients on amiodarone, FT4 may be elevated in euthyroid individuals 3

4. Single measurement reliance: Due to day-to-day variations in thyroid hormone levels, diagnosis should not rely on a single abnormal result 1

By following this evidence-based approach to laboratory testing for hyperthyroidism, clinicians can ensure accurate diagnosis while avoiding unnecessary tests, ultimately improving patient outcomes related to morbidity, mortality, and quality of life.