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Review |
a Author for correspondence. Fax (819) 564-5445; e-mail agrant01{at}courrier.usherb.ca.
Measurements of thyrotropin and of total and free thyroxine and triiodothyronine are widely used diagnostic methods for thyroid function evaluation. However, some serum samples will demonstrate a nonspecific binding with assay reagents that can interfere with the measurement of these hormones. Several recent case reports have described the presence of such interferences resulting in reported abnormal concentrations of thyroid hormones inconsistent with the patient's thyroid state. Circulating thyroid hormone autoantibodies, described in thyroid and nonthyroid disorders, are an important class of interference factor and can bind to hormone tracers used in various immunoassays. Two additional categories of interfering antibodies may particularly interfere within two-site immunoassays for thyrotropin. These include heterophile antibodies, especially human anti-mouse antibodies, and rheumatoid factors, which can cause interferences by immunoglobulin aggregation and (or) cross-linking of both capture and signal antibodies. Here we review the nature of these disturbances; their occurrence, prevalence, and detection; and the clinical consequences of the failure to recognize such interference.
The following articles in journals at HighWire Press have cited this article:
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  G. van der Watt, D. Haarburger, and P. Berman Euthyroid Patient with Elevated Serum Free Thyroxine Clin. Chem., July 1, 2008; 54(7): 1239 - 1241. [Full Text] [PDF]
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M. D. Kellogg, T. C. Law, S. Huang, and N. Rifai A Girl with Goiter and Inappropriate Thyroid-Stimulating Hormone Secretion Clin. Chem., July 1, 2008; 54(7): 1241 - 1244. [Full Text] [PDF]
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 V R Jahagirdar, P Strouhal, G Holder, R Gama, and B M Singh Thyrotoxicosis factitia masquerading as recurrent Graves' disease: endogenous antibody immunoassay interference, a pitfall for the unwary Ann Clin Biochem, May 1, 2008; 45(3): 325 - 327. [Abstract] [Full Text] [PDF]
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S. A. Zouwail, A. M. O'Toole, P. M. S. Clark, and J. P. Begley Influence of Thyroid Hormone Autoantibodies on 7 Thyroid Hormone Assays Clin. Chem., May 1, 2008; 54(5): 927 - 928. [Full Text] [PDF]
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S. L. La'ulu and W. L. Roberts Second-Trimester Reference Intervals for Thyroid Tests: The Role of Ethnicity Clin. Chem., September 1, 2007; 53(9): 1658 - 1664. [Abstract] [Full Text] [PDF]
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 D. J. Halsall, M. Mangi, M. Soos, M. N. Fahie-Wilson, G. Wark, R. Mainwaring-Burton, and S. O'Rahilly Hypoglycemia due to an Insulin Binding Antibody in a Patient with an IgA-{kappa} Myeloma J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2013 - 2016. [Abstract] [Full Text] [PDF]
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 S G S Krishnan, R Pathalapati, L Kaplan, and R K Cobbs Falsely raised TSH levels due to human anti-mouse antibody interfering with thyrotropin assay Postgrad. Med. J., November 1, 2006; 82(973): e27 - e27. [Abstract] [Full Text] [PDF]
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M. Panteghini Selection of Antibodies and Epitopes for Cardiac Troponin Immunoassays: Should We Revise Our Evidence-Based Beliefs? Clin. Chem., May 1, 2005; 51(5): 803 - 804. [Full Text] [PDF]
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D. J. Warren, J. Bjerner, E. Paus, O. P. Bormer, and K. Nustad Use of an In Vivo Biotinylated Single-Chain Antibody as Capture Reagent in an Immunometric Assay to Decrease the Incidence of Interference from Heterophilic Antibodies Clin. Chem., May 1, 2005; 51(5): 830 - 838. [Abstract] [Full Text] [PDF]
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 Y. D. Dai, P. Eliades, K. A. Carayanniotis, D. J. McCormick, Y.-c. M. Kong, V. Magafa, P. Cordopatis, P. Lymberi, and G. Carayanniotis Thyroxine-Binding Antibodies Inhibit T Cell Recognition of a Pathogenic Thyroglobulin Epitope J. Immunol., March 1, 2005; 174(5): 3105 - 3110. [Abstract] [Full Text] [PDF]
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R. Sapin, A. Agin, and F. Gasser Misleading High Thyrotropin Results Obtained with a Two-Site Immunometric Assay Involving a Chimeric Antibody Clin. Chem., May 1, 2004; 50(5): 946 - 948. [Full Text] [PDF]
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C. M. Preissner, D. J. O'Kane, R. J. Singh, J. C. Morris, and S. K. G. Grebe Phantoms in the Assay Tube: Heterophile Antibody Interferences in Serum Thyroglobulin Assays J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3069 - 3074. [Abstract] [Full Text] [PDF]
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V. I. Luzzi, M. G. Scott, and A. M. Gronowski Negative Thyrotropin Assay Interference Associated with an IgG{kappa} Paraprotein Clin. Chem., April 1, 2003; 49(4): 709 - 710. [Full Text] [PDF]
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 A. D Toft and G. J Beckett Thyroid function tests and hypothyroidism BMJ, February 8, 2003; 326(7384): 295 - 296. [Full Text] [PDF]
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V. Marks False-Positive Immunoassay Results: A Multicenter Survey of Erroneous Immunoassay Results from Assays of 74 Analytes in 10 Donors from 66 Laboratories in Seven Countries Clin. Chem., November 1, 2002; 48(11): 2008 - 2016. [Abstract] [Full Text] [PDF]
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A. A.A. Ismail, P. L. Walker, J. H. Barth, K. C. Lewandowski, R. Jones, and W. A. Burr Wrong Biochemistry Results: Two Case Reports and Observational Study in 5310 Patients on Potentially Misleading Thyroid-stimulating Hormone and Gonadotropin Immunoassay Results Clin. Chem., November 1, 2002; 48(11): 2023 - 2029. [Abstract] [Full Text] [PDF]
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J. Bjerner, K. Nustad, L. F. Norum, K. H. Olsen, and O. P. Bormer Immunometric Assay Interference: Incidence and Prevention Clin. Chem., April 1, 2002; 48(4): 613 - 621. [Abstract] [Full Text] [PDF]
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R. Sapin, M. d'Herbomez, J. L. Schlienger, and J. L. Wemeau Anti-Thyrotropin Antibody Interference in Thyrotropin Assays Clin. Chem., December 1, 1998; 44(12): 2557 - 2559. [Full Text] [PDF]
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