What's the best approach to interpreting thyroid function tests?

Best Approach to Interpreting Thyroid Function Tests

The most effective approach to interpreting thyroid function tests begins with measuring thyroid stimulating hormone (TSH) as the primary screening test, followed by free T4 and possibly free T3 when TSH is abnormal, with careful consideration of clinical context and potential confounding factors.

Initial Testing Strategy

• Start with TSH measurement:

  • High sensitivity (98%) and specificity (92%) when used to confirm suspected thyroid disease 1
  • Most reliable first-line test for detecting both overt and subclinical thyroid dysfunction
  • Normal reference range typically 0.45-4.5 mIU/L 2

• Follow abnormal TSH with free T4 testing:

  • If TSH is elevated: Measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4)
  • If TSH is low: Measure free T4 to distinguish between subclinical hyperthyroidism (normal free T4) and overt hyperthyroidism (elevated free T4) 1, 3

• Add free T3 testing when indicated:

  • Measure free T3 when TSH is suppressed but free T4 is normal to detect T3 thyrotoxicosis 3
  • Not typically needed if TSH and free T4 are normal 2

Interpreting Results

Primary Hypothyroidism

• Overt: Elevated TSH with low free T4
• Subclinical: Elevated TSH (typically 4.5-10 mIU/L) with normal free T4 1
• Values for serum TSH above 6.5 mU/L are generally considered elevated 1

Primary Hyperthyroidism

• Overt: Suppressed TSH with elevated free T4 and/or free T3
• Subclinical: Suppressed TSH with normal free T4 and free T3 1
• Values for serum TSH below 0.1 mU/L are considered low 1

Central (Secondary/Tertiary) Thyroid Dysfunction

• Low/normal TSH with low free T4 suggests central hypothyroidism
• Monitor free T4 levels (not TSH) when managing central hypothyroidism 4

Pitfalls and Special Considerations

Confounding Factors

• Pregnancy: Use trimester-specific reference ranges for TSH 4
• Non-thyroidal illness: Can cause abnormal thyroid function tests without actual thyroid dysfunction 5
• Medications: Consider effects of amiodarone, heparin, glucocorticoids, and levothyroxine 5
• Laboratory artifacts: Heterophile antibodies and other assay interferences can cause misleading results 5

High-Risk Populations

• Pay particular attention to:
  • Elderly patients
  • Postpartum women
  • Patients with radiation exposure (>20 mGy)
  • Patients with Down syndrome
  • Patients with type 1 diabetes (17-30% have autoimmune thyroid disease) 2

Confirmation of Abnormal Results

• Repeat thyroid function tests after 3-6 months to confirm persistent abnormalities before initiating treatment, especially for subclinical dysfunction 1
• Exception: TSH >10 mIU/L or <0.1 mIU/L may warrant more immediate attention 1

Monitoring Considerations

• For patients on levothyroxine treatment:

  • Check TSH 6-8 weeks after any dose change 4
  • Once stable, monitor every 6-12 months 4
  • Target TSH within normal reference range for primary hypothyroidism
  • For central hypothyroidism, monitor free T4 levels, not TSH 4

• For subclinical thyroid dysfunction:

  • Monitor more frequently (every 3-6 months) initially to assess for progression 2
  • Consider thyroid antibody testing (anti-TPO, anti-TG) to identify patients at higher risk for progression 1

By following this structured approach to thyroid function test interpretation, clinicians can accurately diagnose thyroid disorders while avoiding common pitfalls that may lead to misdiagnosis or unnecessary treatment.