Plasma immunoreactive TSH: spurious elevation due to antibodies to bovine TSH which cross-react with human TSH

A patient with thyroid carcinoma treated by thyroidectomy who received multiple injections of bovine (bTSH) exhibited elevated and nonsuppressible levels of plasma "immunoreactive TSH." Antibodies to TSH of the IgG class which bound bTSH and human TSH (hTSH) were demonstrated using specific radioimmunoassay and radioimmunoelectrophoretic techniques. Antibodies were present for more than one year and binding of bTSH was greater than that of hTSH throughout this period. Characterization of the antibodies with respect to the binding of human and bovine glycoprotein hormones and subunits revealed two populations of antibodies, one of which bound both bTSH and hTSH and the other which bound only bTSH. Both antibodies appeared to be directed toward antigenic sites on the beta subunit of TSH as both hTSH-beta and bTSH-beta displaced the binding of intact TSH from antibodies whereas the alpha subunits were virtually unreactive. The binding studies suggest that the cross-reactivity of the antibody to hTSH occurred on the basis of common antigenic determinants on the beta subunits of the two species. Documentation of a true elevation of plasma hTSH was achieved by gel filtration of plasma in which a peak of immunoreactivity co-eluting with [125I]-hTSH could be shown. Evidence for suppression of TSH secretion by thyroxine administration in the presence of interfering antibody was obtained by demonstrating that the level of plasma "immunoreactive TSH" did not change in response to TRH administration.