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

Marie-Liesse Piketty 1 , Dominique Prie 2 , Frederic Sedel 3 , Delphine Bernard 3 , Claude Hercend 2 , Philippe Chanson 4 , 5 ,  and Jean-Claude Souberbielle 2
  • 1 Service des explorations fonctionnelles, G.H. Necker Enfants Malades, 149 rue de Sèvres, 75743 Paris cedex 15, France
  • 2 Service des explorations fonctionnelles, G.H. Necker Enfants Malades, Paris, France
  • 3 MedDAY Pharmaceuticals, Paris, France
  • 4 Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France
  • 5 INSERM 1185, Univ Paris-Sud, Université Paris-Saclay, Fac Med Paris Sud, Le Kremlin Bicêtre, France
Marie-Liesse Piketty, Dominique Prie, Frederic Sedel, Delphine Bernard, Claude Hercend, Philippe Chanson and Jean-Claude Souberbielle

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.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.

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