Free
thyroid hormones (free
thyroxine, FT4, and free
triiodothyronine, FT3) 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 T4-binding
globulin (TBG). Thus, increased serum total T4 (TT4) and, in many instances, T3 (TT3) concentrations are encountered in euthyroid subjects with TBG excess,
familial dysalbuminemic hyperthyroxinemia and
transthyretin-associated
hyperthyroxinemia, while decreased serum TT4 and TT3 levels are associated with
TBG deficiency: under these circumstances, measurement of serum FT4 and FT3 levels correctly establishes the diagnosis of euthyroidism. In cases of suspected
hyperthyroidism, a diagnostic strategy can be suggested based on serum FT3 (and TSH) measurement, since FT4 may occasionally be elevated, also in euthyroid subjects, e.g., in patients under chronic
amiodarone or L-T4 treatment. When
hypothyroidism is suspected, the most reliable test appears to be FT4 (together with TSH), because FT3 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.