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Thyroxine free (FT4)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Biologically Active Fraction of Thyroxine - Most Accurate Reflection of Thyroid Hormone Status)

Synonyms

  • Free T4
  • FT4
  • Unbound thyroxine
  • Free thyroxine index (FTI is older surrogate)
  • Dialyzable T4 (equilibrium dialysis method)

Units of Measurement

  • pmol/L
  • ng/dL
  • ng/100 mL
  • ng%
  • ng/L
  • pg/mL
  • ng/mL

Unit Conversions

Molecular Weight of Thyroxine (T4) = 776.87 g/mol

pmol/L ↔ ng/dL

1 ng/dL=12.87 pmol/L1\ \text{ng/dL} = 12.87\ \text{pmol/L}1 ng/dL=12.87 pmol/L 1 pmol/L=0.0776 ng/dL1\ \text{pmol/L} = 0.0776\ \text{ng/dL}1 pmol/L=0.0776 ng/dL

pmol/L ↔ pg/mL

1 pmol/L=0.7769 pg/mL1\ \text{pmol/L} = 0.7769\ \text{pg/mL}1 pmol/L=0.7769 pg/mL 1 pg/mL=1.287 pmol/L1\ \text{pg/mL} = 1.287\ \text{pmol/L}1 pg/mL=1.287 pmol/L

pg/mL ↔ ng/L

1 pg/mL=1 ng/L1\ \text{pg/mL} = 1\ \text{ng/L}1 pg/mL=1 ng/L

ng/dL = ng/100 mL = ng%

ng/mL ↔ ng/dL

1 ng/mL=100 ng/dL1\ \text{ng/mL} = 100\ \text{ng/dL}1 ng/mL=100 ng/dL

Description

Free thyroxine (FT4) measures the unbound fraction (~0.03%) of circulating T4 that is:

  • Not bound to TBG
  • Not bound to albumin
  • Not bound to transthyretin

This small fraction represents the hormonally active component that enters tissues and exerts physiologic effects.

FT4 is more accurate than total T4, especially when binding proteins are altered.

Physiological Role

FT4 regulates:

  • Basal metabolic rate
  • Oxygen consumption
  • Thermogenesis
  • General metabolic activity
  • Cardiovascular contractility
  • Lipid and carbohydrate metabolism
  • CNS development (critical in infants)
  • Bone turnover

Most FT4 is converted to T3, the active hormone.

Clinical Significance

Elevated FT4

Indicates thyrotoxicosis, especially when TSH is suppressed.

Causes

1. Primary Hyperthyroidism

  • Graves' disease
  • Toxic multinodular goiter
  • Toxic adenoma

2. Thyroiditis

  • Subacute
  • Silent / postpartum
  • Painful thyroiditis

3. Excess Thyroxine Intake

  • Over-replacement
  • Factitious thyrotoxicosis

4. Drugs

  • Amiodarone
  • Heparin (in vitro increase via displacement)
  • High-dose glucocorticoids

5. TSH-secreting pituitary adenoma

FT4 high with high TSH.

6. Thyroid Hormone Resistance

FT4 high with normal / high TSH.

Low FT4

Indicates hypothyroidism degree depends on TSH.

1. Primary Hypothyroidism

  • Hashimoto thyroiditis
  • Post-surgical thyroid removal
  • Post-radioiodine ablation

2. Secondary/tertiary Hypothyroidism

  • Pituitary insufficiency
  • Hypothalamic disease

(FT4 low with low TSH → central hypothyroidism)

3. Severe Non-thyroidal Illness

Low FT4 in critical illness without true hypothyroidism.

4. Drugs lowering FT4

  • Amiodarone
  • Carbamazepine
  • Phenytoin
  • Rifampin
  • Lithium

Reference Intervals

(Tietz 8E + ATA + AACE + Mayo + ARUP)

Free T4 (Adults)

  • 10 – 22 pmol/L
    0.8 – 1.8 ng/dL

Children

  • Slightly higher in early childhood

Pregnancy

Adjusted trimester-specific ranges required due to TBG increase.

Critical Values

  • FT4 > 35 pmol/L → severe thyrotoxicosis
  • FT4 < 5 pmol/L → severe hypothyroidism / myxedema risk

Diagnostic Uses

1. Primary test to assess thyroid hormone levels

Interpreted with TSH.

2. Diagnose Hyperthyroidism

High FT4 + suppressed TSH.

3. Diagnose Hypothyroidism

Low FT4 + high TSH (primary), or low TSH (central).

4. Pregnancy thyroid assessment

FT4 more reliable than total T4.

5. Monitoring Thyroid Hormone Therapy

Levothyroxine dose adjustment.

6. Pituitary Disorders

Central hypothyroidism diagnosis requires FT4.

Analytical Notes

  • FT4 by equilibrium dialysis = gold standard.
  • Immunoassays vary; affected by binding protein abnormalities.
  • Heparin (in vitro) can cause falsely high FT4 due to lipase activation.
  • Biotin supplements may interfere with assays (particularly streptavidin-based).
  • High free fatty acids may displace T4 from binding proteins → false increase.

Clinical Pearls

  • FT4 is more accurate than total T4 when TBG is abnormal (pregnancy, nephrotic syndrome, estrogen therapy).
  • High FT4 + normal TSH → think assay interference or thyroid hormone resistance.
  • Always ask about biotin intake (major cause of false diagnosis).
  • Low FT4 with normal/slightly low TSH strongly suggests central hypothyroidism.
  • FT4 rise after starting heparin infusion is analytical, not clinical.

Interesting Fact

Although free T4 is only 0.03% of circulating T4, it drives nearly all physiologic actions, making FT4 one of the most important endocrine markers in laboratory medicine.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Thyroid Hormones
  2. ATA Guidelines for Thyroid Disease (2016/2022)
  3. AACE/ACE Thyroid Function Guidelines
  4. Mayo Clinic Laboratories - Free T4
  5. ARUP Consult - Thyroid Function Testing
  6. NIH / MedlinePlus - Thyroxine

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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