09 December 2008
Free thyroid hormones (free thyroxine, FT<sub>4</sub>, and free triiodothyronine, FT<sub>3</sub>) represent a more useful index of thyroid status than total thyroid hormones, because the latter are influenced by variations of thyroid hormone-binding proteins, especially T<sub>4</sub>-binding globulin (TBG). Thus, increased serum total T<sub>4</sub> (TT<sub>4</sub>) and, in many instances, T<sub>3</sub> (TT<sub>3</sub>) concentrations are encountered in euthyroid subjects with TBG excess, familial dysalbuminemic hyperthyroxinemia and transthyretin-associated hyperthyroxinemia, while decreased serum TT<sub>4</sub> and TT<sub>3</sub> levels are associated with TBG deficiency: under these circumstances, measurement of serum FT<sub>4</sub> and FT<sub>3</sub> levels correctly establishes the diagnosis of euthyroidism. In cases of suspected hyperthyroidism, a diagnostic strategy can be suggested based on serum FT<sub>3</sub> (and TSH) measurement, since FT<sub>4</sub> may occasionally be elevated, also in euthyroid subjects, e.g., in patients under chronic amiodarone or L-T<sub>4</sub> treatment. When hypothyroidism is suspected, the most reliable test appears to be FT<sub>4</sub> (together with TSH), because FT<sub>3</sub> may still be normal in patients with subclinical or mild thyroid failure. In any case, it is essential that reliable free thyroid hormone assays be used, which are devoid of methodological limitations responsible for artifactual results under particular circumstances, such as thyroid hormone-binding protein abnormalities, pregnancy and nonthyroidal illness.