Large method differences for free thyroid hormone assays in the hyperthyroid range can affect assessment of hyperthyroid status: Comparison of Abbott Alinity to Roche Cobas, Siemens Centaur and equilibrium dialysis LC-MS/MS

Abstract

Background

Free T4 (FT4) determination is one of the most commonly performed biochemical tests in endocrinology. Treatment of thyroid dysfunctions is adjusted based on the severity of symptoms and biochemical test results. For Graves’ hyperthyroidism, clinical guidelines recommend using FT4 as a (rough) guide to dose antithyroid drugs, together with other clinical information. It is well known that different platforms and methods give different FT4 results; however, large non-linear method differences at high FT4 concentrations are less well recognized. Current clinical guidelines do not make it clear that method differences in the hyperthyroid range can affect recommendations.

Method

Serum samples from patients with very low (biochemically hypothyroid) to very high (hyperthyroid) concentrations of FT4 and/or free T3 (FT3) were analyzed using Abbott Alinity and compared to concentrations measured using Roche Cobas, Siemens ADVIA Centaur (FT4 only) and an in-house equilibrium dialysis liquid chromatography tandem mass spectrometry (LC-MS/MS) method.

Results

Alinity measured markedly lower FT4 and FT3 concentrations compared to the other methods, particularly at high FT4 concentrations. Regression analysis indicated that Alinity FT4 had a non-linear (curved) relationship to FT4 measured by the other methods. The method differences affected guideline-recommended treatments for hyperthyroidism.

Conclusion

Measured free thyroid hormone concentrations are highly method-dependent, especially at high FT4 concentrations. Clinicians treating hyperthyroid patients should be aware that patients appear much less hyperthyroid from FT4-measurements performed using Alinity compared to Cobas or Centaur. Guideline-recommended antithyroid drug dosages based on FT4 (including multiples of the upper reference range) have to be adjusted to the FT4 method used. FT4 results from different methods should be clearly distinguished (e.g. separate lines) in medical records.