Objectives
Several international guidelines concerning subclinical hyperthyroidism and thyroid cancer advice absolute cut-off values for aiding clinical decisions in the low range of thyroid-stimulating hormone (TSH) concentrations. However, TSH assays are poorly standardized. Therefore, we performed a TSH assay method comparisons with a focus on this low range. We aimed to estimate the clinical impact of the use of absolute TSH cut-offs considering possible standardization differences.

Methods

Three TSH immunoassays, i.e. Cobas® (Roche Diagnostics), Alinity® (Abbott Laboratories) and Atellica® (Siemens Healthcare Diagnostics) were compared using Passing-Bablok regressions and Bland-Altman plots. Sixty samples, selected to cover a wide range of TSH concentrations (< 0.01 to 120 mU/L) with oversampling in the lower range (< 0.4 mU/L), were used for the method comparison and twenty samples were used to assess the coefficient of variation from duplicate measurements.

Results

The studied TSH immunoassays showed standardization differences with a bias for the total range between 7% and 16% and for the low range between 1% and 14%. The imprecision differed from 1.6% to 5.5% and was higher in the lower range of the assay. Considering the greatest bias and translated into the number of samples which would theoretically cross the clinically important value of TSH = 0.1 mU/L, this would be 1.5% of all measured TSH values below <0.40 mU/L and 0.2% of all TSH measurements measured in our laboratory over the last six months (n = 9316).  

Conclusions

We established the standardization differences of the most frequently used TSH assays for the total and low concentration range. As guidelines use absolute TSH values to guide clinical decision making, caution must be applied with TSH concentrations close to these cut-offs, although we established that the effect of standardization differences seems limited for the cut-off of 0.1 mU/L.