High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference
-
Marie-Liesse Piketty
, Dominique Prie
, Frederic Sedel , Delphine Bernard , Claude Hercend , Philippe Chanson und 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.
Acknowledgments
We are grateful to Marie-Helene Novotny for excellent technical assistance, and to Yohann Hervy (Laboratoire Atlanbio) for measurements of biotin and biotin metabolites concentrations.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: FS and DB are employed by MedDAY Pharmaceuticals.
Honorarium: JCS reports lecture fees and/or travel/hotel expenses from DiaSorin, Roche Diagnostics, Abbott, Amgen, Shire, MSD, Lilly, Rottapharm, Meda.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Zempleni J, Wijeratne SS, Hassan YI. Biotin. Biofactors 2009;35:36–46.10.1002/biof.8Suche in Google Scholar PubMed PubMed Central
2. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord 2015;4:159–69.10.1016/j.msard.2015.01.005Suche in Google Scholar PubMed
3. Tourbah A, Lebrun-Frenay C, Edan G, Clanet M, Papeix C, Vukusic S, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: a randomised, double-blind, placebo-controlled study. Mult Scler 2016;22:1719–31.10.1177/1352458516667568Suche in Google Scholar PubMed PubMed Central
4. Minkowsky A, Lee MN, Dowlatshahi M, Angell T, Mahrokhian L, Petrides AK, et al. High-dose biotin treatment for secondary progressive multiple sclerosis may interfere with thyroid assays. AACE Clin Case Rep 2016;2:e370–3.10.4158/EP161261.CRSuche in Google Scholar PubMed PubMed Central
5. Piketty M-L, Polak M, Flechtner I, Gonzales-Briceño L, Souberbielle J-C. False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences. Clin Chem Lab Med 2017;55:780–8.10.1515/cclm-2016-0606Suche in Google Scholar PubMed
6. Barbesino G. Misdiagnosis of Graves’ disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26:860–3.10.1089/thy.2015.0664Suche in Google Scholar PubMed
7. Elston MS, Sehgal S, Du Toit S, Yarndley T, Conaglen JV. Facticious Graves’ disease due to biotin immunoassay interference – A case and review of the literature. J Clin Endocrinol Metab 2016;101:3251–5.10.1210/jc.2016-1971Suche in Google Scholar PubMed
8. Simó-Guerrero O, Giménez-Pérez G, Recsens-Garci A, Villà-Blasco C, Castells-Fusté I. False overt hyperthyroidism by interference in immunoassays. Endocrinol Nutr 2016;63:431–2.10.1016/j.endoen.2016.09.010Suche in Google Scholar
9. Batista MC, Ferreira CE, Fauhaber AC, Hidal JT, Lottenberg SA, Mangueira CL. Biotin interference in immunoassays mimicking subclinical Graves’disease and hyperestrogenism: a case series. Clin Chem Lab Med 2017;55:e99–103.10.1515/cclm-2016-0628Suche in Google Scholar PubMed
10. Kummer S, Hermsen D, Distelmaier F. Biotin treatment mimicking Graves’ disease. N Engl J Med 2016;375:704–6.10.1056/NEJMc1602096Suche in Google Scholar PubMed
11. Bülow Pedersen I, Laurberg P. Biochemical hyperthyroidism in a newborn baby caused by assay interaction from biotin intake. Eur thyroid J 2016;5:212–5.10.1159/000448034Suche in Google Scholar
12. Peyro Saint Paul L, Debruyne D, Bernard D, Mock DM, Defer GL. Pharmacokinetics and pharmacodynamics of MD1003 (high dose biotin) in the treatment of progressive multiple sclerosis. Expert Opin Drug Metab Toxicol 2016;12:327–44.10.1517/17425255.2016.1136288Suche in Google Scholar
13. Meany DL, Jan De Beur SM, Bill MJ, Sokoll LJ. A case of renal osteodystrophy with unexpected serum intact parathyroid hormone concentrations. Clin Chem 2009;55: 1737–41.10.1373/clinchem.2008.121921Suche in Google Scholar
14. Holmøy T, Torkildsen Ø. Can vitamin D reduce inflammation in relapsing-remitting multiple sclerosis? Expert Rev Neurother 2016;16:233–5.10.1586/14737175.2016.1146134Suche in Google Scholar
15. Sundström P, Salzer J. Vitamin D and multiple sclerosis – from epidemiology to prevention. Acta Neurol Scand 2015;132:56–61.10.1111/ane.12432Suche in Google Scholar
16. Burfeind K, Yadav V, Marks D. Hypothalamic dysfunction and multiple sclerosis: implication for fatigue and weight dysregulation. Curr Neurol Neurosci Rep 2016;16:98.10.1007/s11910-016-0700-3Suche in Google Scholar
17. Powell D, Moss-Morris R, Liossi C, Schlotz W. Circadian cortisol and fatigue severity in relapsing-remitting multiple sclerosis. Psychoneuroendocrinology 2015;56:120–31.10.1016/j.psyneuen.2015.03.010Suche in Google Scholar
18. Bove R, Musallam A, Healy BC, Raghavan K, Glantz BI, Bakshi R, et al. Low testosterone is associated with disability in men with multiple sclerosis. Mult Scler 2014;20:1584–92.10.1177/1352458514527864Suche in Google Scholar
19. Foroughipour A, Norbakhsh V, Najafabadi SH, Meamar R. Evaluating sex hormone levels in reproductive age women with multiple sclerosis and their relationship with disease severity. J Res Med Sci 2012;17:882–5.Suche in Google Scholar
20. Gold S, Voskhul R. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res 2009;175:239–51.10.1016/S0079-6123(09)17516-7Suche in Google Scholar
21. Wijeratne NG, Doery JC, Lu ZX. Positive and negative interference in immunoassays following biotin ingestion: a pharmacokinetic study. Pathology 2012;44:674–5.10.1097/PAT.0b013e32835a3c17Suche in Google Scholar PubMed
22. Joly D, Drueke TB, Alberti C, Houillier P, Lawson-Body E, Martin KJ, et al. Variation in serum and plasma PTH levels in second-generation assays in hemodialysis patients: a cross-sectional study. Am J Kidney Dis 2008;51:987–95.10.1053/j.ajkd.2008.01.017Suche in Google Scholar PubMed
23. Henry JG, Sobki S, Arafat N. Interference by biotin therapy on measurement of TSH and FT4 by enzymeimmunoassay on Boehringer Mannheim ES700 analyser. Ann Clin Biochem 1996;33:162–3.10.1177/000456329603300214Suche in Google Scholar PubMed
24. Trambas CM, Sikaris KA, Lu ZX. More on biotin treatment mimicking Graves’ disease. N Engl J Med 2016;375:1698–9.10.1056/NEJMc1611875Suche in Google Scholar PubMed
25. Mock DM, Nyalala JO, Raguseo RM. A direct streptavidin-binding assay does not accurately quantitate biotin in human urine. J Nutr 2001;131:2208–14.10.1093/jn/131.8.2208Suche in Google Scholar PubMed
26. Seaborg E. Thyroid month January 2016: beware of biotin. In endocrine news. Washington, USA: Endocrine society, 2016:42. Available at: http://endocrinenews.endocrine.org/January-2016-thyroid-month-beware-of-biotin. Accessed: January 2016.Suche in Google Scholar
Supplemental Material:
The online version of this article (DOI: 10.1515/cclm-2016-1183) offers supplementary material, available to authorized users.
©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Biotin interference on immunoassay methods: sporadic cases or hidden epidemic?
- Reviews
- False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences
- Vitamin K plasma levels determination in human health
- Mini Review
- Point-of-care testing INR: an overview
- Opinion Paper
- Could accreditation bodies facilitate the implementation of medical guidelines in laboratories?
- Genetics and Molecular Diagnostics
- QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions
- General Clinical Chemistry and Laboratory Medicine
- High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference
- Multicenter performance evaluation of a second generation cortisol assay
- A rapid UPLC-MS/MS assay for the simultaneous measurement of fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations in serum
- A microplate assay to measure classical and alternative complement activity
- Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2
- Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience
- Infrared analysis of lipoproteins in the detection of alcohol biomarkers
- Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk
- Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome
- Cardiovascular Diseases
- The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis
- Letters to the Editor
- Biotin interference in immunoassays mimicking subclinical Graves’ disease and hyperestrogenism: a case series
- A simple method to detect biotin interference on immunoassays
- Proposed classification for a variant of Kounis syndrome
- Lyophilized hemoglobin E control material for the dichlorophenol-indophenol (DCIP) test
- Procalcitonin variation before and after 100-km ultramarathon
- Preliminary study in specific activity of molecular components in allergy: implications for diagnostics and relationship with disease severity
- A 2-min at 4500 g rather than a 15-min at 2200 g centrifugation does not impact the reliability of 10 critical coagulation assays
- Immunoassay interference caused by heterophilic antibodies interacting with biotin
- Red blood cell distribution width and mean platelet volume are potential prognostic indices for patients with primary biliary cirrhosis
- Neutrophil CD64 molecule expression can predict bloodstream infection in septic shock patients
Artikel in diesem Heft
- Frontmatter
- Editorial
- Biotin interference on immunoassay methods: sporadic cases or hidden epidemic?
- Reviews
- False biochemical diagnosis of hyperthyroidism in streptavidin-biotin-based immunoassays: the problem of biotin intake and related interferences
- Vitamin K plasma levels determination in human health
- Mini Review
- Point-of-care testing INR: an overview
- Opinion Paper
- Could accreditation bodies facilitate the implementation of medical guidelines in laboratories?
- Genetics and Molecular Diagnostics
- QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions
- General Clinical Chemistry and Laboratory Medicine
- High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference
- Multicenter performance evaluation of a second generation cortisol assay
- A rapid UPLC-MS/MS assay for the simultaneous measurement of fluconazole, voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations in serum
- A microplate assay to measure classical and alternative complement activity
- Serological diagnosis and prognosis of severe acute pancreatitis by analysis of serum glycoprotein 2
- Retrospective evaluation of the clinical utility of serological biomarkers in Chinese patients with inflammatory bowel disease: 2-year clinical experience
- Infrared analysis of lipoproteins in the detection of alcohol biomarkers
- Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk
- Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome
- Cardiovascular Diseases
- The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis
- Letters to the Editor
- Biotin interference in immunoassays mimicking subclinical Graves’ disease and hyperestrogenism: a case series
- A simple method to detect biotin interference on immunoassays
- Proposed classification for a variant of Kounis syndrome
- Lyophilized hemoglobin E control material for the dichlorophenol-indophenol (DCIP) test
- Procalcitonin variation before and after 100-km ultramarathon
- Preliminary study in specific activity of molecular components in allergy: implications for diagnostics and relationship with disease severity
- A 2-min at 4500 g rather than a 15-min at 2200 g centrifugation does not impact the reliability of 10 critical coagulation assays
- Immunoassay interference caused by heterophilic antibodies interacting with biotin
- Red blood cell distribution width and mean platelet volume are potential prognostic indices for patients with primary biliary cirrhosis
- Neutrophil CD64 molecule expression can predict bloodstream infection in septic shock patients