What does Thyroid Function Test (TFT) comprise of?

Thyroid Function Test (TFT) Components

Primary Components of TFT

Thyroid Function Tests comprise TSH (thyroid-stimulating hormone) as the primary screening test, with free T4 (FT4) and free T3 (FT3) measured as confirmatory tests when TSH is abnormal. 1

Core Testing Panel

• TSH is the most sensitive initial screening test for thyroid dysfunction, with sensitivity above 98% and specificity greater than 92% 2
• Free T4 (FT4) measurement is used to distinguish between subclinical thyroid dysfunction (normal FT4) and overt dysfunction (abnormal FT4) when TSH is persistently abnormal 1
• Free T3 (FT3) measurement may be added when hyperthyroidism is suspected but FT4 is normal, as T3 toxicosis can occur with normal T4 levels 3, 4

Why Free Hormones Are Measured

• Free thyroid hormones (FT4 and FT3) represent a more useful index of thyroid status than total thyroid hormones because total hormones are influenced by variations in thyroid hormone-binding proteins, especially T4-binding globulin (TBG) 3
• Only 0.02% of T4 and 0.3% of T3 circulates in free (unbound) form, but these free fractions are the biologically active components 4
• Free hormone measurements correctly establish euthyroidism in patients with TBG excess, familial dysalbuminemic hyperthyroxinemia, or TBG deficiency, where total hormone levels would be misleading 3

Testing Algorithm Based on Clinical Scenario

For Suspected Hypothyroidism

• Measure TSH first, then add FT4 if TSH is elevated to distinguish subclinical (normal FT4) from overt (low FT4) hypothyroidism 1, 2
• FT3 is typically not needed for hypothyroidism diagnosis, as it may remain normal even in subclinical or mild thyroid failure 3
• Multiple tests should be done over a 3- to 6-month interval to confirm persistently abnormal findings before initiating treatment 1

For Suspected Hyperthyroidism

• Measure TSH and FT3 as the diagnostic strategy, since FT4 may occasionally be elevated in euthyroid subjects (e.g., patients on chronic amiodarone or levothyroxine treatment) 3
• If TSH is suppressed and FT3 is elevated, this confirms hyperthyroidism 3
• FT4 measurement helps assess severity and guide treatment decisions 1

For Monitoring Thyroid Hormone Replacement

• TSH and FT4 should both be measured during dose titration every 6-8 weeks, as FT4 can help interpret ongoing abnormal TSH levels during therapy since TSH may take longer to normalize 2
• Once stable, TSH alone may be sufficient for routine monitoring every 6-12 months 2

Common Pitfalls in TFT Interpretation

Timing and Confirmation Issues

• Never treat based on a single abnormal TSH value, as 30-60% of elevated TSH levels normalize spontaneously on repeat testing 2
• TSH secretion is highly variable and sensitive to acute illness, medications, and physiological factors 5
• Confirm abnormal results with repeat testing after 3-6 weeks before making treatment decisions 2

Clinical Context Matters

• In patients with suspected central hypothyroidism (pituitary or hypothalamic dysfunction), TSH cannot be used as a reliable screening test—both TSH and FT4 must be measured together 4
• During unstable thyroidal status (first months of treatment, altered levothyroxine dose, subacute thyroiditis), TSH determination is diagnostically misleading and only free hormone measurements are reliable 4
• In severe non-thyroidal illness, free hormone measurements remain technically challenging and may not accurately reflect thyroid status 4, 6

Assay Interference and Limitations

• Laboratory artifacts in TSH or thyroid hormone immunoassays can cause discordant results (e.g., raised thyroid hormones with non-suppressed TSH, or raised TSH with normal thyroid hormones) 5
• Different immunoassay methods show moderate to very good agreement but can have quantitative differences, particularly in patients with thyroid diseases 6
• Interference from anti-thyroid hormone antibodies and familial dysalbuminemic hyperthyroxinemia depends on the assay method used 4

Inappropriate Testing Patterns to Avoid

• Ordering FT4 and FT3 routinely with every TSH is inappropriate and contributes to unnecessary healthcare costs 7
• Current guidelines recommend TSH alone as the best initial test to detect and monitor thyroid dysfunction in most clinical scenarios 7
• Free thyroid hormone testing should be reserved for specific clinical indications: confirming abnormal TSH results, suspected hyperthyroidism with normal FT4, or monitoring unstable thyroid conditions 7