What are the functions of Triiodothyronine (T3) and Thyroxine (T4)?

Functions of Triiodothyronine (T3) and Thyroxine (T4)

T3 and T4 are essential thyroid hormones that regulate metabolism, cardiovascular function, and tissue development throughout the body, with T3 being the more biologically active form that controls most physiological actions.

Metabolic Functions

• T3 regulates daily rhythms in glucose metabolism, with faster glucose clearance occurring during the early active phase 1
• T3 controls lipolysis and fatty acid oxidation during fasting states, influencing serum triglyceride levels and overall lipid metabolism 1
• Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis, with T3 and T4 diffusing into cell nuclei to bind to thyroid receptor proteins attached to DNA 2
• The hormone-nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins 2
• The majority of T3 (approximately 80%) is derived from peripheral conversion of T4 by deiodination in peripheral tissues 2, 3

Cardiovascular Functions

• T3 increases the force and speed of systolic contraction and the speed of diastolic relaxation in cardiac tissue 4, 1
• T3 decreases systemic vascular resistance, including coronary vascular tone 4, 1
• T3 increases resting heart rate and left ventricular contractility 4, 1
• T3 enhances isovolumic ventricular relaxation, improving cardiac function 1
• T3 increases coronary arteriolar angiogenesis 4
• The hemodynamic effects of thyroid hormones include decreased systemic vascular resistance, increased resting heart rate, increased LV contractility, and enhanced isovolumic ventricular relaxation 4

Regulation and Production

• T3 and T4 production is primarily regulated by thyroid-stimulating hormone (TSH) from the pituitary gland 1, 5
• TSH controls multiple aspects of thyroid hormone synthesis, including stimulation of iodide uptake, activation of thyroid peroxidase enzyme, and regulation of T4 and T3 secretion 5
• T3 participates in TSH secretion regulation through negative feedback 1
• T4 is the primary hormone secreted by the thyroid gland, while T3 is also generated from peripheral metabolism of T4 3, 6
• The T3/T4 ratio is inversely correlated with free T4 index, reflecting a compensatory mechanism to maintain euthyroidism 7

Tissue-Specific Functions

• T3 is crucial for bone health, influencing the production of collagen type I through hydroxylases 1
• T3 affects bone mineral density and overall bone health 1
• T3 promotes both physiological and pathological myocardial hypertrophy 4
• T3 can decrease pulmonary vascular resistance 4
• T3 shows distinct daily rhythmic patterns that differ between diurnal humans and nocturnal rodents 1

Clinical Implications

• Abnormal T3 and T4 levels can lead to thyroid dysfunction, manifesting as either hypothyroidism (insufficient thyroid hormones) or hyperthyroidism (excess thyroid hormones) 4, 1
• T3 deficiency can result in decreased metabolic rate, while excess T3 increases metabolic rate 1, 5
• Iron deficiency can impair the conversion of T4 to T3, affecting thyroid function 1, 5
• Selenium is required for the deiodination of T4 to T3 via the selenoenzyme Type 1 5'-deiodinase 1, 5
• Hypothyroidism promotes myocardial fibrosis by stimulating fibroblasts, whereas hyperthyroidism has the opposite effect 4

Pharmacological Considerations

• Levothyroxine (synthetic T4) is used as replacement therapy for hypothyroidism, exerting the same physiologic effects as endogenous T4 2
• The physiological actions of thyroid hormones are produced predominantly by T3, making the conversion of T4 to T3 crucial for proper thyroid function 2
• Several conditions like stress, diseases, and physical exercise can promote changes in local thyroid hormone metabolism 8