Total Thyroxine (TT4) and Total Triiodothyronine (TT3) Methods

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Diagnostic Accuracy of Total Hormone Measurements

The diagnostic accuracy of total thyroid hormone measurements would equal that of free hormone if all patients had identical levels of binding proteins (TBG, TTR/TBPA and albumin) with similar affinities for thyroid hormones. Unfortunately, abnormal serum TT4 and TT3 concentrations are more commonly encountered as a result of binding protein abnormalities than result from true thyroid dysfunction. Patients with serum TBG abnormalities secondary to pregnancy or estrogen therapy, as well as genetic abnormalities in binding proteins, are frequently encountered in clinical practice.[141] Abnormal TBG concentrations and/or affinity for thyroid hormone can distort the relationship between total and free hormone measurements.[142] Additionally, some patient sera contain other abnormal binding proteins such as autoantibodies to thyroid hormones that render total hormone measurements diagnostically unreliable.[143,144,145] These binding protein abnormalities compromise the use of TT4 and TT3 measurements as stand-alone thyroid tests. Instead, serum TT4 and TT3 measurements are typically made as part of a two-test panel that includes an assessment of binding protein status, made either directly by TBG immunoassay or by an "uptake" test [Section-3 B2(b)]. Specifically, a mathematical relationship between the total hormone concentration and the "uptake" result is used as a free hormone "index".[146] Free hormone indices (FT4I and FT3I) have been used as free hormone estimate tests for three decades but are rapidly being replaced by one-test free hormone estimate immunoassays [Section-3 B3].