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Functional Blood Chemistry Manual

T3 Free

Marker Name: Free T3


Laboratory reference range: 2.0–4.4 pg/mL

Functional reference range: 2.5–4.0 pg/mL


Triiodothyronine (T3) is the most biologically active thyroid hormone in humans.1 T3 modifies gene transcription in virtually every cell, which alters the rate of protein synthesis and substrate turnover.2 Thyroid hormone is critical for the development of brain and other tissues in fetuses and infants and sets the “metabolic tone” of cells in adults. As such, the synthesis and secretion of thyroid hormone is tightly regulated through several feedback mechanisms.3

The synthesis and secretion of T4 and T3 by the thyroid gland is under direct control of thyroid-stimulating hormone (TSH, also called thyrotropin). Thyroid-stimulating hormone is produced by the pituitary gland in response to elevations in thyrotropin-releasing hormone (TRH) produced in the hypothalamus.3 As levels of T4 and T3 increase in the blood, they exert negative feedback signals on both the hypothalamus and the pituitary gland to reduce secretion of TRH and TSH, respectively.



While T4 production takes place solely within the thyroid gland, approximately 80 percent of T3 is produced from T4 in peripheral tissues by deiodinase enzymes.3 The remaining 20 percent is synthesized and secreted by the thyroid gland.3 Two major forms of thyroxine-5′-deiodinase enzymes (type I and type II) are responsible for converting free T4 into the more active thyroid hormone, T3.3 Type I thyroxine-5′-deiodinase is a plasma membrane-bound enzyme present mostly in liver, kidney, and thyroid tissue. Type II thyroxine-5′-deiodinase is a microsomal enzyme found in muscle, brain, pituitary, skin, and placental tissue.

The action of type I thyroxine-5′-deiodinase is increased during hyperthyroidism, but decreased in hypothyroidism, starvation, diabetes mellitus, uremia, or treatment with propylthiouracil, amiodarone, or propranolol.3 Type II thyroxine-5′-deiodinase is increased in hypothyroidism and decreased in hyperthyroidism. Amiodarone also decreases the action of type II thyroxine-5′-deiodinase.3

Elevated free T3 levels may indicate hyperthyroidism, thyroid hormone resistance syndrome, or T3 toxicosis.4,5 Serum T3 levels can be expected to increase during normal pregnancy.6 Free T3 is generally more accurate in cases of hyperthyroidism than it is for diagnosing hypothyroidism.

Decreased free T3 levels in the serum usually indicate hypothyroidism or chronic or subacute thyroiditis. Drugs that interfere with the conversion of T4 to T3 will decrease free T3 levels, with a reflexive increase in T4 levels. Amiodarone, for example, can inhibit the conversion of T4 to T3.7 Free T3 is actually less useful as an indicator of thyroid function than T4.1,8 Free T3 may be normal in hypothyroidism, when TSH levels are high and free T4 levels are low. Furthermore, any serious illness can interfere with the activity of type I thyroxine-5′-deiodinase and lower free T3 levels.9

Clinical laboratories do not directly measure free T3.10,11 Free T3 is estimated from Total T3 and thyroid hormone-binding index.10 Thus, free T3 is not measured without total T3. Free T3 is usually also measured with serum TSH, total T4, and free T4. An abnormal free T3 may be followed by tests to identify autoimmune causes of thyroid disease including thyroid peroxidase (TPO), thyroglobulin (Tg), and the TSH receptor antibody studies.10


High in:6,7,10,12

  • Pregnancy
  • Hyperthyroidism (e.g., Graves’ disease)
  • Acute thyroiditis (e.g., postpartum thyroiditis)
  • T3 toxicosis
  • Thyroid hormone resistance syndrome

Low in:9,10,12

  • Hypothyroidism
  • Chronic thyroiditis
  • Subacute thyroiditis
  • Critical, non-thyroidal illness
  • Drugs that impair deiodination (i.e., conversion from T4 to T3)
    • Amiodarone
    • Glucocorticoids
    • Contrast agents
    • Propylthiouracil
    • Propranolol
    • Nadolol


High in:

  • Hyperthyroidism
  • Facetious hyperthyroidism

Low in:

  • Hypothyroidism
  • Inflammation


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