A specialized diagnostic methodology used in clinical endocrinology to accurately estimate or directly measure the concentration of biologically active, unbound hormones circulating in the plasma. The free hormone fraction, unlike the total hormone level which includes protein-bound components, is the physiologically relevant portion capable of interacting with target cell receptors to elicit a biological response. This indexing provides a superior clinical assessment of true hormonal status.
Origin
The practice developed from the recognition in the mid-20th century that most steroid and thyroid hormones circulate bound to transport proteins, such as sex hormone-binding globulin (SHBG) and albumin. Indexing methods were created to account for these binding dynamics and provide a more accurate functional measure.
Mechanism
The index is often calculated using a mathematical model that incorporates the total hormone concentration and the concentration of its primary binding protein, such as SHBG, or is determined directly via equilibrium dialysis or ultrafiltration techniques. By quantifying the free, unbound hormone, clinicians gain insight into the actual bioavailability and functional signaling capacity, allowing for more precise diagnosis and titration of hormonal therapies.
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