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In light of several recent recommendations to use total thyroxine (T4) measurements in the diagnosis of thyroid function in pregnancy (in particular, "Clinical Practice Guidelines for Hypothyroidism in Adults," cosponsored by the American Thyroid Association and the American Association of Clinical Endocrinologists, which promote the use of T4 over free T4 [FT4 ]), we have examined the implications of employing T4 for diagnostic discrimination in both pregnant and nonpregnant patient panels. Use of T4 assays has significant drawbacks in this regard, and we believe that the suggestion is a retrograde step in thyroid function testing. Summary and Analysis of the interplay between the concentrations of T4 and thyroxine-binding globulin (TBG), typifying their respective reference ranges in either the nonpregnant or pregnant euthyroid state, shows that the effective T4 range is widened significantly by the accompanying hidden variation in TBG levels. Accordingly FT4 assays that fully compensate for serum T4-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 T4 levels. Parallel effects on T4 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.


John E M Midgley, Rudolf Hoermann. Measurement of total rather than free thyroxine in pregnancy: the diagnostic implications. Thyroid : official journal of the American Thyroid Association. 2013 Mar;23(3):259-61

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PMID: 23301702

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