T3 T4 Free refers to the unbound, biologically active concentrations of the two primary thyroid hormones circulating in the bloodstream: triiodothyronine (T3) and thyroxine (T4). Since over 99% of these hormones are bound to carrier proteins like Thyroxine-Binding Globulin (TBG), only the small, free fraction is able to enter cells and bind to nuclear receptors to exert metabolic effects. Clinically, the measurement of Free T3 and Free T4 provides the most accurate assessment of the body’s true thyroid status and metabolic drive. This is the crucial indicator for diagnosing and managing thyroid dysfunction.
Origin
Thyroid hormones themselves are ancient tyrosine-based hormones, but the distinction between bound and “free” hormone levels arose with the advent of specific radioimmunoassay techniques in the mid-20th century. Before this, only total hormone levels were measured, which were often misleading due to variations in binding protein concentration. The realization that only the unbound hormone fraction is physiologically active cemented the clinical necessity of measuring the free concentrations for precise endocrinology.
Mechanism
Free T4 is considered the prohormone, which enters target cells and is converted by deiodinase enzymes into the highly potent Free T3, the active form. Free T3 then translocates to the cell nucleus, where it binds to the Thyroid Hormone Receptor (TR), a member of the steroid nuclear receptor superfamily. This binding event modulates gene transcription, resulting in increased expression of genes that control basal metabolic rate, oxygen consumption, and protein synthesis across virtually every tissue in the body.
We use cookies to personalize content and marketing, and to analyze our traffic. This helps us maintain the quality of our free resources. manage your preferences below.
Detailed Cookie Preferences
This helps support our free resources through personalized marketing efforts and promotions.
Analytics cookies help us understand how visitors interact with our website, improving user experience and website performance.
Personalization cookies enable us to customize the content and features of our site based on your interactions, offering a more tailored experience.