Clinical Significance

The hypothalamic-pituitary-thyroid axis controls thyroid hormone synthesis, release, and action. Thyrotropin-releasing hormone (TRH) secreted from the hypothalamus stimulates the synthesis and release of thyrotropin or thyroid-stimulating hormone (TSH). TSH, in turn, stimulates the synthesis, storage, secretion, and metabolism of thyroxine (T4) and triiodothryonine (T3). Both free and bound forms of T4 and T3 are present in the blood. More than 99% of the T4 and T3 circulate in the blood bound to carrier proteins, leaving less than 1% unbound. It is this level of unbound or free hormone that correlates with the functional thyroid state in most individuals.

Free T4 and free T3 regulate normal growth and development by maintaining body temperature and stimulating calorigenesis. In addition, free T4 and free T3 affect all aspects of carbohydrate metabolism as well as certain areas of lipid and vitamin metabolism. Fetal and neonatal development also require thyroid hormones.

Clearly elevated free T4 levels support the clinical findings of a diagnosis of hyperthyroidism while clearly low free T4 levels couples with appropriate clinical findings, can establish a diagnosis of hypothyroidism. Measurement of free T4 levels along with other thyroid tests and clinical findings can establish borderline hyperthyroid and hypothyroid diagnosis.

Equilibrium dialysis RIA is considered the reference method for measuring free T4 becuase it allows for the seperation of free T4 from protein bound T4 before direct measurement of the free T4. However, this method is cumbersome, technically demanding, and not suited to routine clinical laboratory use. More recently, radioimmunoassays and enzyme immunoassays have been developed for measuring free T4. These assays employ various combinations of analog or non-analog tracers and one-step or two-step incubation procedures.

_{Source: Access Free T4 IFU #33880, 12/16/16}