The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.
Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm
Open accessAbstract
Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“interference from heterophilic antibodies can result in both low and high measures, with elevated values being more common.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [81]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Rarely, more extreme analytical errors are present137 (Table 5).”
In the citing paper
“A number of medications can affect the thyroid function tests not only by interfering with the synthesis, transport, and metabolism of TSH and thyroid hormones but also by interfering with thyroid function immunoassays (30, 37–40) ( Table 1 ).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [38]
In the citing paper
“Furthermore, assay variability, potential interference with rheumatoid factors or heterophilic antibodies, occasional cases of macro-TSH, the observed age related shift towards higher TSH concentrations in older iodine sufficient patients, and obesity may affect this population based sample to an extent.45 46 47 48”
From Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study (2019) · cites this paper as [45]
In the citing paper
“It is worth highlighting that whilst immunoassay platforms are currently the method of choice for the measurement of thyroid function tests [116], there are limitations; as well as macro-TSH, interference from biotin, thyroid hormone autoantibodies, heterophilic antibodies, antistreptavidin antibodies, anti-ruthenium antibodies, and heterophilic antibodies can occur [116].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [116]
In the citing paper
“It is worth highlighting that whilst immunoassay platforms are currently the method of choice for the measurement of thyroid function tests [116], there are limitations; as well as macro-TSH, interference from biotin, thyroid hormone autoantibodies, heterophilic antibodies, antistreptavidin antibodies, anti-ruthenium antibodies, and heterophilic antibodies can occur [116].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [116]
In the citing paper
“Low free T4 combined with inappropriately low or normal TSH is also frequent in several other situations where treatment is not required, e.g.due to heterophilic antibodies or other interfering factors in the serum of the patient/person under study (Favresse et al., 2018).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Favresse et al., 2018
In the citing paper
“Biotin, antistreptavidin antibodies, antiruthenium antibodies, and thyroid hormone autoantibodies provide other sources of interference with the TSH test that may lead to an aberrant result [36].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [36]
In the citing paper
“Immunoassay platforms can be susceptible to interferences, potentially leading to incorrect clinical decisions.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [81]
In the citing paper
“Suspecting macro-TSH interference is advised with isolated TSH elevation (typically higher than 10 mUI/L) and thyroid hormones within the upper normal range, without clinical evidence of thyroid dysfunction.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [81]
In the citing paper
“Anti-T4 and anti-T3 autoantibodies, found in 40% of autoimmune thyroid disease cases, can lead to false hormone elevations”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [81]
In the citing paper
“Biotin (in doses higher than 1.5 mg/d) can cause falsely low TSH levels and elevated fT4 and fT3, with its impact depending on the platform used, and being avoided with a washout period.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [81]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fundamentals of Clinical Chemistry.
(1977) · Annals of Internal Medicine · doi:10.7326/0003-4819-87-1-142_1 · Cited by 2,624
The Clinical Significance of Subclinical Thyroid Dysfunction
Biondi, B., & Cooper, D. S. (2008) · Endocrine Reviews · doi:10.1210/er.2006-0043 · Cited by 1,418
Tietz Fundamentals of Clinical Chemistry
Burtis, E. B. C. A., & Ashwood, E. R. (1996) · Cited by 919
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
Human Anti-Animal Antibody Interferences in Immunological Assays
Kricka, L. J. (1999) · Clinical Chemistry · doi:10.1093/clinchem/45.7.942 · Cited by 581
Tate, J. R., & Ward, G. (2004) · PubMed · Cited by 426
Park, J. Y., & Kricka, L. J. (2013) · Elsevier eBooks · doi:10.1016/b978-0-08-097037-0.00027-0 · Cited by 372
The thyroxine-binding proteins
Schussler, G. C. (2000) · Thyroid · doi:10.1089/thy.2000.10.141 · Cited by 329
Evidence‐based (S3) guideline for the treatment of androgenetic alopecia in women and in men
Blumeyer, A., Tosti, A., Messenger, A. G., Reygagne, P., del Mármol, V., Spuls, P. I., Trakatelli, M. G., Finner, A. M., Kiesewetter, F., Trüeb, R. M., et al. (2011) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/j.1610-0379.2011.07802.x · Cited by 304
Central Hypothyroidism: Pathogenic, Diagnostic, and Therapeutic Challenges
Persani, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1616 · Cited by 295
Cited by
Sorted by citations
Items 201–258 of 258
Peverelli, E., Giardino, E., Treppiedi, D., Catalano, R., Mangili, F., & Mantovani, G. (2022) · Springer eBooks · doi:10.1007/978-3-030-90475-3_8
Frequenti interferenze di laboratorio negli esami di funzione tiroidea: presentazione di due casi
Carducci, S., & Mian, C. (2022) · L Endocrinologo · doi:10.1007/s40619-022-01058-9
Reply: Subacute thyroiditis after anti-SARS-CoV-2 (Ad5-nCoV) vaccine
Flores-Rebollar, A. (2022) · Enfermedades infecciosas y microbiologia clinica (English ed ) · doi:10.1016/j.eimce.2022.03.005
Évaluation biologique de la fonction thyroïdienne
Raverot, V., & d’Herbomez, M. (2022) · Elsevier eBooks · doi:10.1016/b978-2-294-77583-3.00003-4
Troubles de la sensibilité aux hormones thyroïdiennes
Espiard, S. (2022) · Elsevier eBooks · doi:10.1016/b978-2-294-77583-3.00017-4
Démarche diagnostique et prise en charge thérapeutique de l’hyperthyroïdie
Morcel, P., Hadjadj, S., Ansquer, C., Lun, A. Y., Cariou, B., Chesneau, A.-S. D., Bras, M. L., Langlois, E., & Drui, D. (2022) · La Revue de Médecine Interne · doi:10.1016/j.revmed.2021.12.009
Dasgupta, A., & Wahed, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-815960-6.00003-0
Sensor Systems for Drug Analysis Their Interferences
Rezaei, B., & Mandani, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-8333-6_11
Spuriously Low Thyroid-Stimulating Hormone? A Laboratory Phenomenon
Danalakshmi, S., & Soni, M. (2022) · Apollo Medicine · doi:10.4103/am.am_81_22
Cause meno frequenti di aumento del TSH
Dell’Acqua, M., & Persani, L. (2023) · L Endocrinologo · doi:10.1007/s40619-023-01203-y
Cruz‐Bautista, I., Almeda‐Valdés, P., López-Carrasco, G., Antonio‐Villa, N. E., Núñez‐Álvarez, C. A., Aguilar-Salinas, C. A., & Hernández‐Molina, G. (2022) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/f6k1d6
O′Connor, K., & Goldberg, L. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-82921-2.00013-5
Un caso di ipertireotropinemia familiare non autoimmune
Piva, I. R., Manso, J., & Mian, C. (2023) · L Endocrinologo · doi:10.1007/s40619-023-01331-5
Biochemical Diagnosis of Thyroid Dysfunctions
Giovanella, L., D’Aurizio, F., & Ovčariček, P. P. (2023) · Springer eBooks · doi:10.1007/978-3-031-35213-3_3
Falsely Elevated Thyroid Stimulating Hormone in Two Cases Requiring Special Follow-up
Colak, S., Özgün, E., Andaç, B., Okur, M., Bülbül, B. Y., & Çelik, M. (2023) · Namık Kemal Tıp Dergisi · doi:10.4274/nkmj.galenos.2023.19870
Discordant TFT in Lupus Nephritis Patients: A Case Report and Comprehensive Literature Review
(2023) · Journal of Surgical Academia · doi:10.17576/jsa.2019.0901.05
Marković, B., Petrović-Mucok, A., Klet, S., Janić, T., Babić, J., Stojković, M., Nedeljković-Beleslin, B., Ćirić, J., & Žarković, M. (2023) · Medicinski glasnik Specijalne bolnice za bolesti štitaste žlezde i bolesti metabolizma · doi:10.5937/mgiszm2391068m
Ocampo, P. J. F., Benavent, A. T., Lara, E. J., & Ruiz, F. A. (2024) · Atención Primaria Práctica · doi:10.1016/j.appr.2024.100199
Sabolić, L. L. G. (2023) · Acta Clinica Croatica · doi:10.20471/acc.2023.62.03.17
Immunoassays for newborn screening
Luong, J. H. T., & Vashist, S. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95509-6.00020-3
Guglielmi, R., Mian, C., Andreoli, C., Bagnasco, M., Boniardi, M., Menis, E. D., Rimini, M. L. D., Tina, D., Fiorentini, G., Locantore, P., et al. (2025) · L Endocrinologo · doi:10.1007/s40619-025-01601-4
Diagnostic Challenges: A Review of Non Classic Thyroid Function Test Patterns
Varadaraj, P., & Panchagnula, R. (2025) · National Journal of Laboratory Medicine · doi:10.7860/njlm/2025/73696.2899
Lin, S., Wang, Q., Yu, X., Yajun, T., Yao, Y., Mao, W., & Ma, G. (2025) · Scientific Reports · doi:10.1038/s41598-025-07065-8
Correlation of Homocysteine and Biochemical Markers in Pregnancy Loss: A Molecular‐Level Study
Talal, N., & Asi, W. N. (2025) · Macromolecular Symposia · doi:10.1002/masy.70158
Bokulić, A., Zec, I., Stanišić, L., Šupe-Domić, D., Pezo, A., Kocijančić, M., Marijančević, D., Kuprešanin, M. S., Goreta, S., Đuras, A., et al. (2025) · Biochemia Medica · doi:10.11613/bm.2025.030505
Refractory Hypothyroidism: Unexpected Outcome During Treatment of Giant Cell Arteritis
Deprince, E., Grunenwald, S., Mouly, C., Benoit, J., & Caron, P. J. (2025) · Clinical Case Reports · doi:10.1002/ccr3.71289
Variation in Thyroid Function Tests in Acute Scrub Typhus Infection
Gogineni, S. N., Asirvatham, A. R., Vasireddy, N. T., Ramadesikan, V. K., Ranjan, A., & Mahadevan, S. (2025) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_28_25
Liu, J., Chen, Q., Zhao, G., Fan, X., & Wang, W. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1671397
Daquilema, K. D. A., & Tenempaguay, R. E. C. (2025) · Esprint Investigación · doi:10.61347/ei.v4i3.218
Zhan, M., Zhang, Q., Ma, Z., Han, L., Yan, J., Zheng, G., Zhou, W., Zhou, W., & Huang, X. (2025) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2025-0874
Refractory hypothyroidism: Diagnostic evaluation and management strategies
Mavromati, M., Jarlborg, P., Demarchi, M. S., & Leboulleux, S. (2026) · Annales d Endocrinologie · doi:10.1016/j.ando.2026.102489 · Cited by 1
Analytical measurement of thyroid-related hormones, proteins, and autoantibodies in serum
Feldt‐Rasmussen, U. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00386-1
Xia, C.-S., Zhou, L., Jing, C., Fan, C., Hong, Y., Yue, Z.-H., Gao, L., & Ren, F. (2026) · Case Reports in Immunology · doi:10.1155/crii/8400162
Diagnostic Utility of Genetic Testing in Hyperthyroxinemia With Non‐Suppressed TSH
Sekizkardes, H., Eltan, M., Demir, Ş., Giray, D., Abalı, Z. Y., & Abalı, S. (2026) · Clinical Endocrinology · doi:10.1111/cen.70126
Lefèvre, C. R., Vaduva, P., Kvasnička, A., Lenski, M., Senarathne, U. D., Taie, S. F., Zibar, K., & Rolić, T. (2026) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2026-0101
Shelly, M., Miller, L., Graver, K., & Arastu, M. I. (2026) · JCEM Case Reports · doi:10.1210/jcemcr/luag034
Wang, J., Fu, F., Chen, Y., Fu, K., Luo, H., Yang, J., & Ruan, H. (2026) · Annals of Medicine · doi:10.1080/07853890.2026.2643496
Real or Not Real? An Elevated TSH
Sevilla, M., Carcoana, A. O. D., Yang, J. Y., McPhaul, M. J., Islam, M. S., & Weiss, R. E. (2026) · Journal of Investigative Medicine High Impact Case Reports · doi:10.1177/23247096261430087
Wood, C. S., Abele, S., Alsbach, J., Gervalla, A., Meinel, D. M., & Cuny, A. P. (2026) · medRxiv · doi:10.64898/2026.03.26.26348440
Mohammed, H. O., Mekkawy, L. H., Ali, R. K., & Shourbagy, O. E. S. O. E. (2026) · BMC Pediatrics · doi:10.1186/s12887-026-06635-7
Li, Y., Zhang, K., Chai, X., Liu, H., Cheng, X., Wang, X., Chi, Y., Li, N., & Lian, X. (2026) · Endocrine · doi:10.1007/s12020-026-04579-7
Agrawal, P. K., Dev, S., & Garg, R. (2026) · Journal of Mid-life Health · doi:10.4103/jmh.jmh_32_26
Thyroid Hormone Excess in Sudden Death: A Clinicopathological Spectrum in an Autopsy Study
Hata, Y., Saito, Y., Hirono, K., Ichimata, S., & Nishida, N. (2026) · Hormone and Metabolic Research · doi:10.1055/a-2851-8963
Vera-Ponce, V. J., Ballena-Caicedo, J., Valladolid-Sandoval, L. A. M., Zuzunaga-Montoya, F. E., Mestanza, R. L. P., & Castillo, M. F. G. (2026) · Health Sciences Review · doi:10.1016/j.hsr.2026.100268
Ismaili, H. A., & Kiyumi, M. H. A. (2026) · Cureus · doi:10.7759/cureus.108937
Lu, J., Tang, C.-M., Ge, G. M., Cheng, K. K., Lee, K. Y., Tan, K. C. B., Lam, S. K. K., Cheung, E. Y., Cheung, C., & Li, G. H. (2026) · BMC Medicine · doi:10.1186/s12916-026-04942-5
Duloxetine-Induced Reversible Central Hypothyroidism: A Case Report
Villanova, M., Capellini, M., Giorgi‐Pierfranceschi, M., & Maninetti, L. (2026) · Cureus · doi:10.7759/cureus.109903
Prevalence and Clinical Characteristics of Macro-TSH in Patients with Subclinical Hypothyroidism
Nishihara, E., Fukata, S., Imamura, C., Ito, M., Nishikawa, M., Miyauchi, A., & Akamizu, T. (2026) · Thyroid · doi:10.1177/10507256261456988
Thyroid and Nutrition: Interplay, Clinical Implications, and Public Health Perspectives
Selim, S., Lona, H., Rana, M. M., & Mahmood, S. A. (2026) · Bangladesh Journal of Endocrinology and Metabolism · doi:10.4103/bjem.bjem_25_26
Lum, C. L. T., Tay, W. L., Chiang, B., Lim, M. H., & Ho, C. K. M. (2026) · Journal of Clinical Pathology · doi:10.1136/jcp-2026-210787
Bornikowska, K., Król, A., Ostrowska, M., Kowalski, K., Zgliczyński, W., & Glinicki, P. (2026) · Practical Laboratory Medicine · doi:10.1016/j.plabm.2026.e00549
Yu, L., Ma, Y., Pang, Y., & Shen, X. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c02273
Elhassan, A., Mahgoub, A., & Ali, I. (2026) · Cureus · doi:10.7759/cureus.116246
BIOTIN INTERFERENCE IN THYROID FUNCTION AND CARDIAC TROPONIN ASSAYS
Beppler, B. R., do Nascimento, F. C., de Lima, T. P., Salle, T. R., Fernandes, M. A. D. E., da Silva, J. B. U., & Tokuno, A. J. Y. (2026) · Revista de Geopolítica · doi:10.56238/revgeov17n10-038
Isolated Elevation of Free Triiodothyronine in Euthyroid Patients: A Diagnostic Pitfall
Nasrallah, Z., & Morkos, M. (2026) · AACE Endocrinology and Diabetes · doi:10.1016/j.aed.2026.09.023
Macro TSH and the Misdiagnosis of Hypothyroidism: Evidence from a Cross-Sectional StudyPreprint
Amirkashani, D., Sarvi, M. A., Masoumi, M., & Nourbakhash, M. (2026) · Research Square · doi:10.21203/rs.3.rs-11058799/v1
Ebanoidze, L., Koval, A. A., Pigarova, E. A., Dzeranova, L. K., Starostina, E. A., Орлова, К. В., Nikankina, L. V., Kolesnikova, G. S., & Platonova, N. M. (2026) · Clinical and experimental thyroidology · doi:10.14341/ket12852
Metadata
- Authors
- Favresse, J., Burlacu, M.-C., Maiter, D., & Gruson, D.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- Corresponding author
- Gruson, Damien
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2018-07-04
- Volume
- 39
- Issue
- 5
- Pages
- 830-850
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2894797166
- Cited by
- 258
- References
- 158
- Citations by year
- 2026: 33 · 2025: 27 · 2024: 20 · 2023: 47 · 2022: 35 · 2021: 36 · 2020: 37 · 2019: 21 · 2018: 2
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- Funders
- Université Catholique de Louvain
- Topics
- Health Sciences › Health Professions › Medical Laboratory Technology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- thyroid function tests, immunoassay interference, thyroid-stimulating hormone, free thyroxine, free triiodothyronine, biotin interference, heterophile antibodies, detection algorithm, misdiagnosis, inappropriate treatment
- MeSH terms
- Algorithms, Humans, Immunoassay, Sensitivity and Specificity, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine
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
