Background
There is no international reference standard for fT4 measurement. Recent attempts to re-standardise fT4 methods to bring them into better alignment have not been able to overcome the variability between current assays.
Method
Fifty-two fT4>30pmol/L samples were compared using 5 commercially available assays – Axsym (Ax), Architect (A), Beckman Coulter (BC) , Immulite2000 (IM) and Roche Modular (R) analysers. In addition, 380 samples with fT4<30pmol/L were tested on the A and R analysers.
Results
For fT4>30pmol/L, the mean±SD and median varied widely between methods. The Ax and A were closest to each other with mean of 41.8±15.6 and 40±14.7, and median of 41.7 and 42.1 respectively. BC mean was 46.99 ±15.5 and median was 46.7. Mean of IM was 53.6±19.4 and median was 54.3, while R mean was 64.3±28.1 and median was 67.1. Figure 1 shows the comparison between the individual values for each patient in each assay. Two step assays A and BC gave lower values for fT4 than single step assays.
For fT4<30pmol/L samples tested on A vs R, mean±SD was 22.1±3.2 vs 26.1±4.5 and median was 21.7 vs 25.3. This showed that fT4 levels are much higher on the R assay. Despite the increased harmonisation of fT4 at levels <30pmol/L, 16 more patients would be classified as hyperthyroidism based on higher levels on the R assay (Fig 2).
Conclusion
Standardisation of assays and harmonisation of reference ranges are crucial in the diagnosis of thyroid dysfunction. Non-linearity of fT4 values >30pmol/L in certain assays may influence anti-thyroid medication doses with possible risk to patients. In addition, the difference as to whether a patient is hyperthyroid or not may vary depending on the assay used for fT4.
Figure1 Figure 2