The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. [PubChem]
Indication
For use alone or in combination with antithyroid agents to treat hypothyroidism, goiter, chronic lymphocytic thyroiditis, myxedema coma, and stupor.
Pharmacology
Levothyroxine (T4) is a synthetically prepared levo isomer of thyroxine, the major hormone secreted from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine (T3) which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, food metabolism, and body temperature, among other effects. The symptoms of thyroid deficiency relieved by levothyroxine include slow speech, lack of energy, weight gain, hair loss, dry thick skin and unusual sensitivity to cold.
Toxicity
LD50=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.
Affected Organisms
Humans and other mammals
Biotransformation
Approximately 70% of secreted T4 is deiodinated to equal amounts of T3 and reverse triiodothyronine (rT3), which is calorigenically inactive. Elimination of T4 and T3 involves hepatic conjugation to glucuronic and sulfuric acids. The hormones undergo enterohepatic circulation as conjugates are hydrolyzed in the intestine and reabsorbed. Conjugated compounds that reach the colon are hydrolyzed and eliminated as free compounds in the feces. Other minor T4 metabolites have been identified.
Absorption
Bioavailability varies from 48% to 80%. Human studies have confirmed the importance of an intact jejunum and ileum for levothyroxine absorption and have shown some absorption from the duodenum.
Half Life
T4, 6 to 7 days. T3, 1 to 2 days.
Protein Binding
> 99% to serum proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA)
Elimination
Thyroid hormones are primarily eliminated by the kidneys.
Research Area: Endocrinology Biological Activity: L-Thyroxine is a synthetic form of thyroxine and a hormone replacement drug. L-Thyroxine is typically used to treat hypothyroidism. L-Thyroxine may also be used to treat goiter via its ability to lower thyroid-stimulating hormone (TSH), a hormone that is considered goiter-inducing.
Biochem/physiol Actions L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis. Packaging 1, 5 g in glass bottle 100, 500 mg in glass bottle Other Notes Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. T2376.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.
Biochem/physiol Actions L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis. Reconstitution To prepare 20 μg/ml stock solution, dissolve in 50 ml sterile culture medium per mg thyroxine. Physical form powder-0 °C; stock-frozen in working aliquots, avoid repeated freeze/thaw, solution stable 2-8 °C, 30 days
Biochem/physiol Actions L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis. Legal Information BCR is a registered trademark of European Commission
Biochem/physiol Actions L-Thyroxine (T4) and triiodo-L-thyronine (T3) are iodine-containing hormones produced from thyroglobulin in the thyroid follicular cells. The stimulation of metabolic rate and regulation of growth and development by these hormones appear to be due to their effects on DNA transcription and, thus, protein synthesis. Other Notes Review1
One of the thyroid hormones involved in the maintenance of metabolic homeostasis. Synthesized and stored as amino acid residues of thyroglobulin, the major protein component of the thyroid follicular colloid. Synthesis and secretion are regulated by the p
References
PubChem Literature
From Data Sources
• Post, A., et al.: Anal. Profiles Drug Subs., 5, 225 (1976)
• Nelson, J.C., et al.: Clin. Chem., 34, 1737 (1976)
• Cavalieri, R.R., et al.: Thyroid, 7, 177 (1976)
• Fischer, D.A., et al.: Clin. Chem., 42, 135 (1976)
