Variability in the detection of macro TSH in different immunoassay systems
Abstract
Design: Macro TSH is a large molecular-sized TSH that is mostly a complex of TSH and IgG. Patients with macro TSH have elevated serum TSH and normal free thyroxine levels, mimicking subclinical hypothyroidism. The aim of this study was to clarify the degree of cross-reactivity of macro TSH to different commercial immunoassay systems. Methods: Screening for macro TSH was done using a polyethylene glycol (PEG) method and confirmed with gel filtration chromatography in serum samples from 1901 patients with subclinical hypothyroidism. Interference due to human anti-mouse antibodies (HAMA) was examined using HAMA blockers. TSH was measured with an enzyme immunoassay for the analysis of macro TSH. Serum TSH values in patients with macro TSH were also determined with the widely used commercial immunoassay platforms Elecsys, Centaur and Architect, and the detectability of macro TSH was compared among them. Results: Gel filtration chromatography was performed with 174 serum samples with PEG-precipitable TSH ratios >75%. Twenty serum samples were found to contain large molecular-sized TSH, five of which were due to interference by HAMA. The prevalence of macro TSH was eventually 0.79% (15/1901). Commercial immunoassay systems variably recognized macro TSH. The Architect TSH immunoassay platform was the least reactive to macro TSH, but still recognized it in 60% of macro TSH-containing serum samples. Conclusions: There were no commercial TSH immunoassay platforms that did not cross-react with macro TSH. Screening for macro TSH should be performed before hormone replacement therapy is initiated for subclinical hypothyroidism.
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MacroTSH will have a greater relative effect in the elderly.
“Whilst rare, macroTSH is thought to be more common in the elderly and therefore will have a greater relative effect in this group [114].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [114]
MacroTSH is thought to be more common in the elderly.
“Whilst rare, macroTSH is thought to be more common in the elderly and therefore will have a greater relative effect in this group [114].”
From Age-related variation in thyroid function – a narrative review highlighting important implications for research and clinical practice (2023) · cites this paper as [114]
People with hypothyroidism may produce a form of TSH, macro-TSH, made up of TSH coupled with IgG autoantibodies, which may be recognised to different extents by different commercial assays for TSH.
“People with hypothyroidism may produce a form of TSH, “macro-TSH,” made up of TSH coupled with IgG autoantibodies, which may be recognised to different extents by different commercial assays for TSH [34].”
From Challenges in Interpreting Thyroid Stimulating Hormone Results in the Diagnosis of Thyroid Dysfunction (2019) · cites this paper as [34]
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- Authors
- Hattori, N., Ishihara, T., & Shimatsu, A.
- Affiliations
- Ritsumeikan University (JP)
- Kyoto Medical Center (JP)
- Corresponding author
- Hattori, Naoki
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-01
- Volume
- 174
- Issue
- 1
- Pages
- 9-15
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2177853440
- Cited by
- 57
- References
- 13
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 2 · 2017: 1 · 2016: 2 · 2014: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (25460232)
- 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 › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- subclinical hypothyroidism, human anti-mouse antibodies, assay interference, polyethylene glycol precipitation, TSH receptor antibodies
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Antibodies, Anti-Idiotypic, Chromatography, Gel, False Negative Reactions, Female, Humans, Hypothyroidism, Immunoglobulin G, Immunoassay, Male, Middle Aged, Molecular Weight, Polyethylene Glycols, Chemical Precipitation, Sensitivity and Specificity, Thyroid Hormones, Thyrotropin, Mice
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