Apparent Hyperthyroidism Caused by Biotin-Like Interference from IgM Anti-Streptavidin Antibodies.

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.

METHODS

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.

CONCLUSIONS

Two patients with apparent hyperthyroidism as a result of analytical interference caused by IgM anti-streptavidin antibodies are described.

CONCLUSIONS

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.