How to interpret thyroid function tests?

How to Interpret Thyroid Function Tests

The most effective approach to interpreting thyroid function tests is to begin with TSH measurement, followed by free T4 if TSH is abnormal, as this provides the most accurate diagnostic information for thyroid disorders. 1

Initial Testing Strategy

• First-line test: Measure serum TSH

  • High sensitivity (98%) and specificity (92%) when used to confirm suspected thyroid disease 2
  • Most sensitive indicator of primary hypothyroidism 1
  • Normal TSH indicates euthyroidism with >99% accuracy 3

• Second-line test: Free T4 (if TSH is abnormal)

  • Helps distinguish between subclinical and overt thyroid dysfunction 1
  • Essential for diagnosing central hypothyroidism (which may be missed by TSH alone) 3

• Third-line test: T3 measurement (only in specific situations)

  • Obtain when TSH is undetectable and free T4 is normal to identify T3-toxicosis 4, 5

Interpreting Results

Condition	TSH	Free T4	Diagnosis
Subclinical Hypothyroidism	Elevated	Normal	Mild hypothyroidism
Overt Hypothyroidism	Elevated	Low	Severe hypothyroidism
Subclinical Hyperthyroidism	Low	Normal	Mild hyperthyroidism
Overt Hyperthyroidism	Low	Elevated	Severe hyperthyroidism
Central Hypothyroidism	Low/Normal	Low	Pituitary/hypothalamic failure

Important Clinical Considerations

• Serial measurements are crucial:

  • A single abnormal TSH value is insufficient for diagnosis 1
  • TSH can vary by up to 50% day-to-day 1
  • Repeat testing in 2 weeks to 3 months to confirm diagnosis 1

• Reference ranges:

  • Normal TSH: 0.45-4.12 mU/L (slightly broader above age 60) 3
  • TSH values below 0.1 mU/L are considered low 2
  • TSH values above 6.5 mU/L are considered elevated 2

• Monitoring treatment:

  • For primary hypothyroidism: Monitor TSH every 6-8 weeks during dose adjustments 1, 6
  • Target TSH for treated hypothyroidism: 0.25-2.0 mU/L 3
  • For central hypothyroidism: Monitor free T4 levels (not TSH) 4
  • For thyroid cancer patients: Target TSH ≤0.10 mU/L 3

Common Pitfalls and Challenges

• Laboratory interference:

  • Heterophilic antibodies may cause falsely elevated TSH values 3
  • Non-thyroidal illness can affect test results 7
  • Medications (amiodarone, heparin, biotin) can interfere with assays 7

• Special populations:

  • Pregnancy: TSH reference ranges are trimester-specific 6
  • Elderly: May have slightly higher TSH reference range (0.4-5.9 mU/L for 70-79 years) 3
  • Down syndrome: Evaluating hypothyroidism is difficult as some symptoms overlap with typical findings 2

• Discordant results:

  • When TSH and free T4 results seem incongruent, consider:
    1. Medication effects
    2. Laboratory assay interference
    3. Recent treatment changes
    4. Rare disorders (resistance to thyroid hormone, TSH-secreting pituitary adenoma) 7

• Subclinical disease:

  • Subclinical hypothyroidism may progress to overt hypothyroidism at 2.6-4.3% per year 1
  • Treatment generally recommended when TSH exceeds 10 mIU/L 1
  • Subclinical hyperthyroidism associated with atrial fibrillation, dementia, and osteoporosis 2

Monitoring Approach

• For newly diagnosed hypothyroidism:

  • Check TSH and free T4 at 6-8 weeks after starting treatment or dose change 1, 6
  • Once stable, monitor every 6-12 months 6

• For pediatric patients:

  • Monitor TSH and free T4 at 2 and 4 weeks after treatment initiation
  • 2 weeks after any dosage change
  • Every 3-12 months after dosage stabilization 6

By following this structured approach to thyroid function testing, clinicians can accurately diagnose and monitor thyroid disorders while avoiding unnecessary testing and treatment.