A caution regarding high-dose biotin therapy: misdiagnosis of hyperthyroidism in euthyroid patients

High-dose biotin therapy is finding favour as a promising novel agent in the treatment of multiple sclerosis.1 We feel compelled to alert clinicians to an easily overlooked aspect of biotin therapy that has the potential to cause significant harm: it causes profound interference with immunoassays that are based on streptavidin–biotin technology.2,3 Such assays are widely used in routine laboratories. Depending on the method principle, biotin interference may cause falsely high results (typically in competitive immunoassays) or falsely low results (typically in sandwich immunoassays).4 This interference may produce a pattern of results that closely resembles disease, leading to false diagnoses, inappropriate treatment and risk of complications.

Thyroid function tests are particularly misleading under the influence of high-dose biotin when measured using assays applying streptavidin–biotin technology. Biotin interference convincingly mimics hyperthyroidism, causing suppressed thyroid-stimulating hormone (TSH; < 0.01 mIU/L) and markedly elevated free thyroid hormones (free thyroxine > 100 pmol/L, free triiodothyronine 13–20 pmol/L) in euthyroid patients. Antithyroid antibodies, including anti-TSH-receptor antibodies, may also be grossly elevated, providing false evidence of underlying autoimmunity. When such biochemically compelling results of thyroid disease occur in a clinical setting, where intercurrent illness or advanced age may confound clinical signs, the impetus to treat is strong. Indeed, we have witnessed several cases of biotin interference masquerading as hyperthyroidism, triggering unnecessary commencement of antithyroid medication.

Communication between clinicians and laboratories is vital to minimise the risk of misdiagnosis and mismanagement. Indication on request slips of high-dose biotin use will assist laboratories in identifying erroneous results. We advise withholding biotin for 72 hours before blood tests to minimise interference.5 Standard multivitamin formulations and normal dietary intake of biotin are not problematic, but doses exceeding 5 mg can cause interference. Such formulations are available over the counter in skin and hair supplements, extending the risk of biotin interference beyond patients with multiple sclerosis and into the general community. In addition, we must emphasise that an extensive list of tests, such as human chorionic gonadotropin, tumour markers and troponin, and therapeutic drugs can be affected by biotin interference. We therefore urge clinicians to discuss with pathologists when the laboratory results and clinical findings are discordant.