Measurement of Total Rather Than Free Thyroxine in Pregnancy: The Diagnostic Implications

Background: In light of several recent recommendations to use total thyroxine (T-4) measurements in the diagnosis of thyroid function in pregnancy (in particular, Clinical Practice Guidelines for Hypothyroidism in Adults,'' co-sponsored by the American Thyroid Association and the American Association of Clinical Endocrinologists, which promote the use of T-4 over free T-4 [FT4]), we have examined the implications of employing T-4 for diagnostic discrimination in both pregnant and nonpregnant patient panels. Use of T-4 assays has significant drawbacks in this regard, and we believe that the suggestion is a retrograde step in thyroid function testing. Summary and Conclusions: Analysis of the interplay between the concentrations of T-4 and thyroxine-binding globulin (TBG), typifying their respective reference ranges in either the nonpregnant or pregnant euthyroid state, shows that the effective T-4 range is widened significantly by the accompanying hidden variation in TBG levels. Accordingly FT4 assays that fully compensate for serum T-4-binding protein concentrations should discriminate dysfunctionality from normality more efficiently than total hormone measurements, whether in pregnant or nonpregnant states. The euthyroid FT4 reference ranges typical of late pregnancy should also be more compact than those for the total hormone, because of the increased dominance of higher, though equivalently variable TBG concentrations on T-4 levels. Parallel effects on T-4 from similarly variable, though lower concentrations of TBG are indicated in the nonpregnant group. While acknowledging the difficulties in FT4 measurement arising from inconsistent calibration of present-day commercial assays, this finding questions the recommendation that total hormone assays should supersede the former in pregnancy.