Anti-ruthenium antibodies mimic macro-TSH in electrochemiluminescent immunoassay

Macro-hormones are circulating conjugates of hormones with immunoglobulins, which often artefactually elevate biochemical test results. Particularly when causing only moderate elevation no suspicion will be raised. By far the most frequently encountered macro-hormone is macro-prolactin. Here we report a female patient with rheumatoid arthritis who had persistently and grossly elevated thyroid stimulating hormone (TSH) but normal free thyroxine in electrochemiluminescent assays. Although clinically euthyroid, she was put on thyroxine therapy which caused hyperthyroid symptoms. An analytic interference by macro-TSH was assumed by dilution experiments, polyethylene-glycol-precipitation, the addition of a heterophilic antibody blocking reagent and size exclusion chromatography. Further workup, however, revealed the presence of anti-ruthenium antibodies. To our knowledge this is the first report of anti-ruthenium antibodies selectively interfering with a TSH assay and causing erratic gross elevation of TSH mimicking macro-TSH.