**Background**
The thyroid hormone system is critical for regulating metabolism, growth, and development in humans. Thyroxine (T4) serves as a primary prohormone that is converted into the more active triiodothyronine (T3) via deiodination. However, thyroxine can also undergo sulfation to form thyroxine sulfate (T4S), a metabolite that plays a significant role in the peripheral regulation of thyroid hormone levels. Alterations in the concentration of this metabolite are often linked to changes in type I 5-monodeiodinating activity, which can be influenced by fetal development, critical illness, or pharmacological inhibition. Understanding the dynamics of T4S is essential for studying endocrine diseases and metabolic dysfunction. In this context, we will introduce a human endogenous metabolite – Thyroxine.
**Definition**
Thyroxine (specifically thyroxine sulfate) is a thyroid hormone metabolite with the molecular formula C15H11I4NO7S and a molecular weight of 856.93.
**In Vitro and In Vivo Studies**
According to the Thyroxine description, thyroxine sulfate is a normal component of human serum and amniotic fluid. Thyroxine in vitro studies indicate that T4S is primarily derived from thyroxine peripherally and tends to accumulate when type I 5-monodeiodinating activity is low, such as in fetuses or when inhibited by drugs like ipodate. Regarding Thyroxine in vivo activity, significant amounts of T4S have been observed in the meconium, bile, allantoic fluids, and fetal sheep serum. In human pregnancy, T4S concentrations in amniotic fluid increase from 14.3 ng/dL at 14-15 weeks of gestation to 25.5 ng/dL at 18-19 weeks. Furthermore, a significant rise in serum T4S is detected in hyperthyroid patients one day after the ingestion of 1 g of ipodate. In rat models, thyroxine undergoes significant sulfation, and the biliary excretion of T4S is enhanced if type I deiodination is inhibited. Additionally, serum T4S levels are clearly elevated in critically ill patients compared to healthy references, a phenomenon attributed to decreased deiodination by liver D1. In conclusion, Thyroxine (T4S) is a key endogenous metabolite used as a marker for thyroid hormone metabolism and hepatic deiodinase activity.
Keywords
Thyroxine, 77074-49-8, T4Sulfate, Thyroid Hormone Receptor, Drug Metabolite, Endogenous Metabolite, THR, Inhibitor, inhibitor, inhibit
References
[1] Wu SY, et al. Identification of thyroxine-sulfate (T4S) in human serum and amniotic fluid by a novel T4S radioimmunoassay. Thyroid. 1992 Summer;2(2):101-5.
[2] Rutgers M, et al. Effects of propylthiouracil on the biliary clearance of thyroxine (T4) in rats: decreased excretion of 3,5,3′-triiodothyronine glucuronide and increased excretion of 3,3′,5′-triiodothyronine glucuronide and T4 sulfate. Endocrinology. 1989 Oct;125(4):2175-86.
[3] Peeters RP, et al. Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type Ideiodinase activity. J Clin Endocrinol Metab. 2005 Dec;90(12):6460-5.