Apparent hyperthyroidism caused by biotin-like interference from IgM anti-streptavidin antibodies

Abstract

Background: Exclusion of analytical interference is important when there is discrepancy between clinical and laboratory findings. However, interferences on immunoassays are often mistaken as isolated laboratory artefacts. The mechanism of a rare cause of interference in two patients that caused erroneous thyroid function tests, and also affects many other biotin dependent immunoassays, was characterized and reported. Patient findings: Patient 1 was a 77-year-old female with worsening fatigue while taking carbimazole over several years. Her thyroid function tests, however, were not suggestive of hypothyroidism. Patient 2 was a 25-year-old female also prescribed carbimazole for apparent primary hyperthyroidism. Despite an elevated free thyroxine, the lowest thyrotropin on record was 0.17 mIU/L. In both cases, thyroid function tests performed by an alternative method were markedly different. Further characterization of both patients' serum demonstrated analytical interference on many immunoassays using the biotin-streptavidin interaction. Sandwich assays (e.g., thyrotropin, follicle-stimulating hormone, troponin T, beta-human chorionic gonadotropin) were falsely low, while competitive assays (e.g., free thyroxine, free triiodothyronine, TSH binding inhibitory immunoglobulin) were falsely high. Pre-incubation of serum with streptavidin microparticles removed the analytical interference, initially suggesting the cause of interference was biotin. However, neither patient had been taking biotin. Instead, a ∼100 kDa immunoglobulin M (IgM) immunoglobulin with high affinity to streptavidin was isolated from each patient's serum. The findings confirm IgM anti-streptavidin antibodies as the cause of analytical interference. Summary: Two patients with apparent hyperthyroidism as a result of analytical interference caused by IgM anti-streptavidin antibodies are described. Conclusion: Analytical interference identified on one immunoassay should raise the possibility of other affected results. Characterization of interference may help to identify other potentially affected immunoassays. In the case of anti-streptavidin antibodies, the pattern of interference mimics that due to biotin ingestion. However, the degree of interference varies between individual assays and between patients.