Endocrine Abstracts

Objectives: Free thyroxine (fT4) measurements are performed to detect thyroid disorders and monitor treatment. FT4 is measured using automated immunoassays (IAs) which face established analytical challenges due to low serum concentrations in the picomolar range and the precarious equilibrium between free and bound T4 (to thyroid-binding globulin (TBG) and (pre-)albumin). Furthermore, IAs are known to be affected by the composition of the serum sample (matrix-effects), which can lead to falsely high or low results thereby affecting clinical decisions. Isotope-dilution liquid chromatography tandem-mass spectrometry (ID-LC-MS/MS) is not influenced by these matrix effects and considered the gold standard technique. The goal of this study is to unravel the accuracy of a variety of automated fT4 IA methods using samples of pregnant women and hemodialysis patients, conditions characterized by an altered serum matrix.

Methods: FT4 was measured in healthy controls, pregnant women and hemodialysis patients using a method performed following reference method criteria (ID-LC-MS/MS, Radboud Nijmegen) and 5 commercially available automated immunoassays (Alinity (Abbott), Atellica (Siemens), Cobas (Roche), Lumipulse (Fujirebio) and UniCel DXI (Beckman Coulter)). Method comparisons (Bland Altman plots and Passing and Bablok analyses) between ID-LC-MS/MS and IAs were performed for samples of healthy controls, pregnant women and hemodialysis patients.

Results: We collected 30 serum samples from each of the three groups. Mean gestational age in the group with pregnant women was 24.8 weeks. The fT4 IAs deviated +7 to +29% more from the LC-MS/MS method in pregnant women vs healthy controls (false high) and -16 to -27% more from the LC-MS/MS method in hemodialysis patients vs healthy controls (false low).

Conclusion: All tested and frequently used automated IAs are less accurate in measuring fT4 in the altered serum matrix of pregnant women and hemodialysis patients compared to healthy controls. This may lead to an overestimation of fT4 concentrations in pregnant women and to an underestimation of fT4 concentrations in hemodialysis patients when using IAs. Physicians and laboratory specialists should be aware of this phenomenon to avoid drawing wrong conclusions and manufacturers are encouraged to improve their fT4 assays.