Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient Taking Biotin Megadoses
Abstract
Background: Accurate immunoassays measuring minute quantities of hormones are the cornerstone of the practice of endocrinology. Despite tremendous advances in this field, novel pitfalls in these tests emerge from time to time. Oral biotin can interfere with immunoassays of several hormones. The purpose of this report is to relate an extreme case of such interference. Patient findings: A patient with progressive multiple sclerosis was found to have extremely elevated free thyroxine, triiodothyronine, and suppressed thyrotropin (TSH) levels. His TSH receptor binding inhibiting antibody level was also elevated. This constellation of laboratory findings suggested a diagnosis of severe Graves' disease. All of the assays yielding abnormal results employed the biotin–streptavidin affinity in their design. The patient had no symptoms of hyperthyroidism, and detailed review of his medications revealed intake of megadoses of biotin. Temporary discontinuation of biotin treatment resulted in complete resolution of the biochemical abnormalities. Conclusions: Non-physiologic biotin supplementation may interfere with several immunoassays, including thyroid hormones, TSH, thyroglobulin, and TSH receptor binding inhibiting antibody, leading to erroneous diagnoses. Questioning for biotin intake should be part of the evaluation for patients undergoing endocrine tests. Interruption of biotin supplementation for at least two days prior to biotin-sensitive tests should be sufficient to avoid major misdiagnoses.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ingestion of high doses of biotin may cause spurious results in assays that utilize a streptavidin-biotin separation technique.
“Ingestion of high doses of biotin may cause spurious results in assays that utilize a streptavidin-biotin separation technique (41,42).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [42]
Cites
Institute of Medicine (1998) · National Academies Press eBooks · doi:10.17226/6015 · Cited by 2,464 · see citing works
The biotin-(strept)avidin system: principles and applications in biotechnology
Diamandis, E. P., & Christopoulos, T. K. (1991) · Clinical Chemistry · doi:10.1093/clinchem/37.5.625 · Cited by 748 · see citing works
Clinical Utility of TSH Receptor Antibodies
Barbesino, G., & Tomer, Y. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4309 · Cited by 237 · see citing works
Self-citationHigh doses of biotin in chronic progressive multiple sclerosis: A pilot study
Sedel, F., Papeix, C., Bellanger, A., Touitou, V., Lebrun‐Frénay, C., Damien Galanaud, E., Gout, O., Lyon‐Caen, O., & Tourbah, A. (2015) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2015.01.005 · Cited by 230 · see citing works
B IOTIN IN M ETABOLISM AND M OLECULAR B IOLOGY
McMahon, R. J. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.121101.112819 · Cited by 183 · see citing works
Wijeratne, N. G., Doery, J. C. G., & Lu, Z. X. (2012) · Pathology · doi:10.1097/pat.0b013e32835a3c17 · Cited by 84 · see citing works
Biotin interference on TSH and free thyroid hormone measurement
Kwok, J. S.-S., Chan, I. H.-S., & Chan, M. H.-M. (2012) · Pathology · doi:10.1097/pat.0b013e3283514002 · Cited by 74 · see citing works
Falsely Low Parathyroid Hormone Secondary to Biotin Interference: A Case Series
Waghray, A., Milas, M., Nyalakonda, K., et al. (2013) · Endocrine Practice · doi:10.4158/ep12158.or · Cited by 50 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“Ingestion of high doses of biotin may cause spurious results in assays that utilize a streptavidin–biotin separation technique (41,42).”
BackgroundInterferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm
Favresse, J., Burlacu, M.-C., Maiter, D., & Gruson, D. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00119 · Cited by 258 · see citing works
Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Ettleson, M. D., & Bianco, A. C. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa430 · Cited by 75 · see citing works
Biochemical Testing in Thyroid Disorders
Esfandiari, N. H., & Papaleontiou, M. (2017) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2017.04.002 · Cited by 50 · see citing works
Biotin interference in assays for thyroid hormones, thyrotropin and thyroglobulin
Ylli, D., Soldin, S. J., Stolze, B., Wei, B., Nigussie, G., Nguyen, H., Mendu, D. R., Mete, M., Wu, D., Gomes-Lima, C. J., et al. (2021) · Thyroid · doi:10.1089/thy.2020.0866 · Cited by 44 · see citing works
Diagnostic procedure in suspected Graves’ disease
Goichot, B., Leenhardt, L., Massart, C., Raverot, V., Tramalloni, J., & Iraqi, H. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.08.002 · Cited by 32 · see citing works
Drugs and Other Substances Interfering with Thyroid Function
Montanelli, L., Benvenga, S., Hegedüs, L., Vitti, P., Latrofa, F., & Duntas, L. H. (2018) · Endocrinology · doi:10.1007/978-3-319-45013-1_27 · Cited by 18 · see citing works
- Authors
- Barbesino, G.
- Affiliations
- Harvard University (US)
- Corresponding author
- Barbesino, Giuseppe
- ORCID
- Barbesino, Giuseppe
- Venue
- Thyroid®
- Publisher
- SAGE Publications
- Published
- 2016-06
- Volume
- 26
- Issue
- 6
- Pages
- 860-863
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2396241021
- Cited by
- 105
- References
- 8
- Citations by year
- 2026: 6 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 13 · 2020: 13 · 2019: 13 · 2018: 19 · 2017: 16 · 2016: 11 · 2015: 1
- FWCI
- 19.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- Graves' disease, biotin interference, immunoassay interference, free thyroxine, triiodothyronine, TSH suppression, thyroglobulin, multiple sclerosis, biotin supplementation, laboratory test interference
- MeSH terms
- Biotin, Diagnostic Errors, Graves Disease, Humans, Hyperthyroidism, Male, Middle Aged, Thyrotropin, Thyroxine, Triiodothyronine, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
