What is FT4 (free thyroxine) and is it connected to the thyroid?

What is FT4 and Its Connection to the Thyroid

FT4 (free thyroxine) is a thyroid hormone test that measures the unbound (free) form of thyroxine in the blood and is directly produced by the thyroid gland, making it an essential marker for diagnosing and monitoring thyroid function.

Understanding FT4

FT4 represents the biologically active portion of thyroxine (T4) that is not bound to proteins in the blood. While most thyroid hormone (about 99.98%) circulates bound to proteins, only the free portion (0.02% of T4) is available to act on target tissues 1.

Key characteristics of FT4:

• Produced directly by the thyroid gland (accounts for 80% of thyroid hormone production)
• Measures the active, unbound form of T4
• More clinically relevant than total T4 measurements
• Not affected by variations in thyroid hormone-binding proteins 2

Relationship to Thyroid Function

FT4 is intimately connected to the thyroid gland in several ways:

1. Production: The thyroid gland directly produces T4 (thyroxine), which is released into circulation
2. Regulation: FT4 levels are regulated by TSH (thyroid-stimulating hormone) from the pituitary gland
3. Diagnostic value: FT4 helps differentiate between various thyroid disorders:
   • Low FT4 with high TSH: Primary hypothyroidism
   • Low FT4 with low/normal TSH: Central (secondary) hypothyroidism
   • High FT4 with low TSH: Hyperthyroidism
   • Normal FT4 with abnormal TSH: Subclinical thyroid disease 3

Clinical Significance

FT4 measurement is crucial in thyroid function assessment for several reasons:

• Diagnostic accuracy: FT4 provides a more reliable assessment of thyroid status than total T4, especially when binding protein abnormalities exist 2
• Treatment monitoring: Used to monitor response to thyroid medication
• Differential diagnosis: Helps distinguish between primary and central thyroid disorders 3

When to measure FT4:

• When TSH is abnormal
• When evaluating suspected thyroid dysfunction despite normal TSH
• In patients with pituitary disorders
• When monitoring thyroid hormone replacement therapy
• In critically ill patients where TSH may be unreliable 3

Interpretation Considerations

Several factors can affect FT4 interpretation:

1. Method variability: Different laboratory methods can yield significantly different results, especially in the hyperthyroid range 4
2. Non-thyroidal illness: Severe illness can alter FT4 levels without true thyroid dysfunction
3. Medications: Many drugs can affect FT4 levels, including:
   • Amiodarone
   • Glucocorticoids
   • Estrogens
   • Beta-blockers
   • Salicylates 5

Clinical Pitfalls to Avoid

• Relying on TSH alone: Some laboratories only measure TSH initially and reflex to FT4 if abnormal. This approach can miss central hypothyroidism where TSH may be normal but FT4 is low 6
• Ignoring method differences: Be aware that FT4 reference ranges and results vary significantly between different laboratory methods 4
• Misinterpreting results in pregnancy: Pregnancy alters thyroid physiology and binding proteins, affecting interpretation 3
• Overlooking medication effects: Many medications can alter FT4 levels without affecting actual thyroid function 5

In clinical practice, both TSH and FT4 should be measured together when evaluating thyroid function, especially when patients are symptomatic, as this provides a more complete picture of thyroid status 3.