What is the difference between T3 (triiodothyronine) and T4 (thyroxine)?

Differences Between T3 and T4 Thyroid Hormones

T3 (triiodothyronine) and T4 (thyroxine) are distinct thyroid hormones that differ in their structure, potency, metabolism, and physiological roles, with T3 being the more biologically active form that contains three iodine atoms, while T4 contains four iodine atoms and primarily serves as a prohormone that gets converted to T3 in peripheral tissues.

Chemical Structure and Production

• T4 (Thyroxine):

  • Contains four iodine atoms in its molecular structure 1
  • Formed by coupling two molecules of diiodotyrosine (DIT) 2
  • Primary hormone secreted by the thyroid gland (80% of thyroid output) 3
  • Has a longer half-life of 6-7 days 1
  • 99.96% bound to plasma proteins 1

• T3 (Triiodothyronine):

  • Contains three iodine atoms in its molecular structure 2
  • Formed by coupling one molecule of diiodotyrosine (DIT) with one molecule of monoiodotyrosine (MIT) 2
  • Only 20% is directly secreted by the thyroid gland 3
  • 80% is produced peripherally through deiodination of T4 1, 4
  • Has a shorter half-life of ≤2 days 1
  • 99.5% bound to plasma proteins 1

Biological Activity and Function

• T3 (Triiodothyronine):

  • Approximately 4 times more potent than T4 1
  • Primary active hormone at the cellular level 1
  • Responsible for most physiological actions of thyroid hormones 4
  • Diffuses into cell nuclei and binds to thyroid receptor proteins attached to DNA 1
  • More rapidly increases oxygen consumption compared to T4 4
  • Controls DNA transcription and protein synthesis 1

• T4 (Thyroxine):

  • Primarily serves as a prohormone or reservoir for T3 1
  • Less biologically active than T3 1
  • Slower onset of action due to need for conversion to T3 4
  • Provides more stable serum levels due to longer half-life 5

Metabolism and Regulation

• T4 to T3 Conversion:

  • Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination 1
  • Conversion occurs primarily in the liver, kidneys, and other peripheral tissues 1
  • Conversion can be affected by various conditions including illness, stress, and physical exercise 4
  • When T4 conversion to T3 is impaired, serum T3 concentrations decline and inactive reverse T3 (rT3) increases 6

• T3/T4 Ratio:

  • Inversely correlates with free T4 levels in healthy individuals 7
  • Serves as a regulatory mechanism to maintain euthyroidism despite variations in T4 levels 7
  • Increases progressively as T4 levels fall 7

Clinical Implications

• Diagnostic Value:

  • Free T4 measurement is more reliable for assessing thyroid function than T3 3
  • T3 levels may remain normal even in cases of T4 over-replacement 8
  • T3 testing has limited value in assessing levothyroxine over-replacement 8

• Treatment Considerations:

  • Levothyroxine (synthetic T4) is the standard treatment for hypothyroidism 5
  • Provides more consistent and stable hormone levels compared to liothyronine (synthetic T3) 5
  • T3 levels are not a reliable indicator of thyroid status in patients on levothyroxine replacement 8

Physiological Effects

• Thyroid Function:

  • Iron is crucial for thyroid function, particularly for the heme-containing enzyme thyroid peroxidase (TPO) 9
  • TPO is involved in the conversion of T4 to T3 9
  • Both hormones are essential for normal growth and development 9

• Metabolic Effects:

  • T3 increases oxygen consumption more rapidly than T4 4
  • T3 has stronger effects on regulating mitochondrial function and thermogenesis 4
  • T3 plays a critical role in cardiac function, increasing heart rate and contractility 4

Understanding the differences between T3 and T4 is crucial for proper diagnosis and management of thyroid disorders, with recognition that T3 is the more biologically active form while T4 serves primarily as a prohormone that gets converted to T3 in peripheral tissues.