Thyroid Function Tests in N onthyroidal Illness: Correction by Mathematical Method

Diagnostic confusion results when subnormal free T4 values are reported in nonthyroidal illness (NTI) when a variety of free thyroxine index or analogue techniques are used to estimate free thyroxine levels. We tried to correct the changes in free thyroxine assessments by a mathematical method in nonthyroidal illness (NTI). Serum albumin was used to correct the measured hormone concentration by mathematical formulas.
Materials and Methods: The study included 56 patients with acute and chronic systemic illnesses and control groups. Total T4 (1T4), total T3 (TT3), free T4 and free T3 by analogue method (FT4A and FT3A), free T4 by back titration (FT4B), TSH-IRMA, reverse T3, T3 Resin Uptake (T3RU), TBG, albumin and total serum proteins (TSP) were measured. Free T4 index (FT4I) and T4[fBG ratio (T4TBGR) were calculated. Mathematical correction for each hormone was done through equations based on patient's original hormone level and albumin concentration. As an example, the formula for correction of FT4A was: expected FT4A = (patient's FT4A) - X (patient's albumin) + Y;
X = 1.11 x [(mean FT4A in normal subjects) "7- (mean albumin in normal subjects)]; Y = 1.11 x (mean FT4A in normal subjects).
Results: The decrease in albumin and TSP resulted in a decrease in 1T4 and 1T3, FT4A and FT3A in NTI, but it had no significant effect on FT4B. Mathematical correction resulted in an increase in sensitivity of FT4A from 55.4 to 96.4%, FT4B from 94.6 to 100%, T4TBGR from 80.4 to 98.2%, and FT41 from 69.6 to 100%, in differentiating NTI from hypothyroidism. The specificity of tests remained unchanged. The corrections did not affect normal, hypothyroid, and hyperthyroid controls.
Conclusions: Mathematical correction increased sensitivity of tests, which assess free T4 directly or indirectly, in differentiating NTI from hypothyroidism. NTI has been reported as the most common cause of errors reported in thyroid function tests so mathematical correction could significantly increase overall accuracy of free T4 assessments.