False serum calcitonin high levels using a non-competitive two-site IRMA

Dual site antibody-base immunoassays are commonly used in clinical laborato ries to quantify the CT serum concentrations as a specific and sensitive ma rker of medullary thyroid carcinoma (MTC). Heterophile antibodies can inter fere with these assays, however, and cause erroneous results. In order to a void this interference, immobilized and conjugated antibodies from two diff erent animal species or immunoreactive antibody fragments, as well as the a ddition of non-immune globulins, are generally included among the assay rea gents. We describe the case of a 73-year-old man affected by a multinodular goiter, who showed high basal CT plasma levels as measured by a monoclonal antibody based IRMA. The finding of negative results for the presence of M TC at fine needle aspiration (FNA) and the mild increase observed in plasma CT during a pentagastrin (Pg) stimulation test, suggested that the high CT levels might depend on a cross-reaction with heterophilic antibodies. In f act, after the addition of the heterophilic blocking tube (HBT) to each spe cimen, the CT levels markedly decreased by more than 80% (average decrease +/- SE= 87.6 +/-2.668%). Such a decrease strongly suggests that in our case the routinely used F(ab ')(2) fragments were unable to eliminate all of th e interference and that the elevated serum CT levels might have been caused by human heterophilic antibodies. In conclusion, these results indicate a novel cause of CT false positivity, suggesting that high serum CT levels, w hen combined with a slight increase during Pg stimulation, should be critic ally interpreted in view of the possible presence of heterophilic antibodie s in the specimens.