High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference

Clin Chem Lab Med. 2017 May 1;55(6):817-825. doi: 10.1515/cclm-2016-1183.

Abstract

Background: High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various endocrine disorders. We aimed at exploring this interference, to be able to remove biotin and avoid misleading results.

Methods: We measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), parathyroid homrone (PTH), 25-hydroxyvitamin D (25OHD), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, C-peptide, cortisol (Roche Diagnostics assays), biotin and its main metabolites (liquid chromatography tandem mass spectrometry) in 23 plasmas from MS patients and healthy volunteers receiving high-dose biotin, and in 39 biotin-unsupplemented patients, before and after a simple procedure (designated N5) designed to remove biotin by means of streptavidin-coated microparticles. We also assayed fT4, TSH and PTH in the 23 high-biotin plasmas using assays not employing streptavidin-biotin binding.

Results: The biotin concentration ranged from 31.7 to 1160 µg/L in the 23 high-biotin plasmas samples. After the N5 protocol, the biotin concentration was below the detection limit in all but two samples (8.3 and 27.6 μg/L). Most hormones results were abnormal, but normalized after N5. All results with the alternative methods were normal except two slight PTH elevations. In the 39 biotin-unsupplemented patients, the N5 protocol did not affect the results for any of the hormones, apart from an 8.4% decrease in PTH.

Conclusions: We confirm that most streptavidin-biotin hormone immunoassays are affected by high biotin concentrations, leading to a risk of misdiagnosis. Our simple neutralization method efficiently suppresses biotin interference.

Keywords: biotin; hyperthyroidism; immunoassay; interference; multiple sclerosis.

Publication types

  • Validation Study

MeSH terms

  • Artifacts*
  • Biotin / isolation & purification
  • Biotin / metabolism
  • Biotin / therapeutic use*
  • Blood Chemical Analysis / methods*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Endocrine System / metabolism*
  • Female
  • Hormones / blood
  • Humans
  • Immunoassay / methods*
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy
  • Streptavidin / metabolism

Substances

  • Hormones
  • Biotin
  • Streptavidin