Unraveling the unexpected: Interference in iron assay leads to diagnosis of multiple myeloma

Background Iron studies are critical for diagnosing iron deficiency and hemochromatosis. We present a case exhibiting macrocytic anemia with perplexingly high plasma iron concentrations. Methods and Results The initial clinical presentation with significantly elevated iron results raised concerns for hemochromatosis. However, inconsistent results in dilution studies suggested the presence of an interfering substance. Inspection of the reaction curves from the instrument revealed very high background absorption in the 800 nm channel. This, coupled with the observation of an insoluble precipitate upon mixing the acid buffer reagent with the patient’s serum, as well as the patient’s high total protein and low albumin levels, suggested immunoglobulin overproduction. Serum protein electrophoresis confirmed a monoclonal gammopathy with a subsequent diagnosis of multiple myeloma. Conclusion Excessive monoclonal immunoglobulins can precipitate in acidic buffers and interfere with spectrophotometric measurements in iron testing. Although challenging, investigating an interference and determining its cause can uncover underlying diseases that have yet to be diagnosed.