Protein interference in thyroid assays: an in vitro study with in vivo consequences

Pathological concentration of plasma proteins may cause problems in immunoanalytics. The low triiodotyronine (T3) and thyroxine (T4) levels, frequently found in seriously ill patients, may be ascribed either to laboratory artifact due to the lower thyroid hormone binding capacity or to a compensatory response of the organism to the disease.

The authors performed an in vitro experiment, in which sera of seriously ill patients with either low immunoglobulin G (IgG), and/or low albumin levels were investigated for free thyroid hormones (fT3, fT4) following stepwise adjustment of the serum IgG and/or albumin. All two hormones were measured with two different automated immunoassays: the microparticle enzyme immunoassay (MEIA) with two steps (AxSym, Abbott, USA) and the electrochemiluminescence immunoassay (ECLIA).

The bias of fT3 and fT4 exhibited positive correlations with serum IgG and albumin. The bias of fT3 was more pronounced than that of fT4 following the addition of albumin (40-150% and 10-40%, respectively) as well as following the addition of IgG (8-30% and 0-8%, respectively). The MEIA method was more sensitively affected in case of fT4, whereas the bias of fT3 was more influenced in the ECLIA assay. In MEIA assay, the influence of albumin on the bias of fT3 and fT4 was stronger if serum IgG levels were low.

The results confirm that pathological thyroid findings in seriously ill patients may largely be ascribed to some laboratory artifacts.