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Biotin Interference in Clinical Immunoassays: A Cause for Concern

2017; American Medical Association; Volume: 141; Issue: 11 Linguagem: Inglês

10.5858/arpa.2017-0107-le

1543-2165

E W Holmes, Shanika Samarasinghe, Mary Ann Emanuele, Farah Meah,

Advanced biosensing and bioanalysis techniques

An increase in the use of biotin supplements by the general public is producing an increase in the number of reports of analytic interference in biotin-based immunoassays (BBAs) used to evaluate endocrine function.1,2 The fact that BBAs of similar design are currently used to diagnose and manage a wide range of other medical conditions, including anemias, malignancies, autoimmune and infectious diseases, and cardiac damage, raises the concern that the accuracy of results for other routine tests are compromised as well.3 Methods that use immunometric ("sandwich") or competitive formats are at the greatest risk for producing falsely decreased or falsely increased results, respectively, when biotin is present in the sample.In June of 2016, we reviewed the current manufacturers' instructions for use for 374 methods performed by 8 of the most popular immunoassay analyzers used in the United States. Two hundred twenty-one of the methods were BBAs. Eighty-two of these were immunometric or competitive methods that had manufacturer-reported interference thresholds (IFTs) (ie, the concentrations above which exogenous biotin in the sample caused a difference of greater than ±10% in the test result) of less than 51 ng/mL. Another 15 of the methods neither reported an IFT nor identified biotin as a potential interfering substance (Table).Healthy subjects who take a single 1-mg or 100-mg oral dose of biotin have mean peak serum biotin concentrations of 8.64 and 4955 ng/mL, respectively, occurring between 1 and 3 hours post dose and declining with half-lives of 8 to 19 hours. The peak serum biotin concentration following a 1-mg oral dose would, therefore, be expected to increase the risk of an erroneous test result measured by a vulnerable method with an interference threshold of less than 8.6 ng/mL. While peak serum biotin concentrations after oral doses of 5 and 10 mg—the doses most frequently used by the public—have yet to be reported, the 100% bioavailability of such doses5 predicts that they would be even more likely to affect the accuracy of immunoassays with low interference thresholds. And certainly, the peak biotin concentration following a single 100-mg dose would be likely to decrease the analytic accuracy of all 82 of the methods that have thresholds of less than 51 ng/mL. In this case, the risk of an erroneous test result could persist for up to 8 elimination half-lives (>6 days) for a method with an IFT of 2.4 ng/mL. Therefore, it might be necessary to avoid the use of some BBAs altogether when testing subjects who are using the 100-mg biotin supplements that are now available over-the-counter.2,5The confluence of increased biotin supplement use by patients and the design limitations of many of the BBAs have already led to the misdiagnosis and mismanagement of patients.1–3 We are convinced that the risk of analytic interference by biotin supplements is a serious problem that needs to be more widely recognized and promptly addressed by health care providers, directors of clinical laboratories, and decision makers in the clinical diagnostics industry.