Is measurement of TT3 by immunoassay reliable at low concentrations? A comparison of the Roche Cobas 6000 vs. LC–MSMS
Open accessAbstract
Objectives Thyroid dysfunction is a common medical condition affecting an estimated 30 million people in the US alone. Employing gold standard Liquid chromatography-tandem mass spectrometry (LC-MSMS) methods we have examined the extent of inaccuracy of immunoassay (IA) measurement for total T3 (TT3) at low, normal and high concentrations. Design and methods 268 TT3 Roche Cobas 6000 immunoassay TT3 values (covering the low, normal, and high ranges) were compared with LC-MSMS results. Results At TT3 concentrations between 50 and 113ng/dL (conversion factor for TT3 to SI Units is ng/dL×0.0154=nmol/L), n=122, LC-MSMS values were lower than immunoassay with 72% found to be below the 2.5th percentile by LC-MSMS compared to 27% for immunoassay. Strikingly 45% of the patients classified as normal TT3 by immunoassay were defined as lower than the 2.5th percentile by LC-MSMS. Only 38 of the 122 patients with low T3's were not receiving T4. In this latter group all of whom had TSH's>3.7mIU/L, 74% of results by LC-MSMS were below the 2.5th percentile while only 21% were below the 2.5th percentile by IA. The clinical consequences of these inaccuracies may affect whether dosing with T4 or combination of T4 with T3 is selected for treatment. Finally the correlation of TT3 with TSH was far superior when TT3 was measured by LC-MSMS. A typical case which demonstrates our message is included. Conclusion T3 being the active hormone needs to be reliably measured and if the patient has low TT3 and hypothyroid symptoms persist; treatment with T3 should be considered. A typical case report is included to illustrate the problems of inaccurate immunoassay results for TT3. Measurement of TT3 by immunoassay at low concentrations is less than optimal and often provides the clinician with a normal result when the LC-MSMS method and the patient's clinical condition suggests that supplementation with T3 (as in combination therapy) may be required to optimize patient care.
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Other groups previously reported major deviations between immunoassay- and LC-MS-based methods for T3, rT3, or 3,3′T2 in human serum.
“Previously, other groups already reported major deviations between immunoassay- and LC-MS-based methods, if T3, rT3, or 3,3′T2 were analyzed in human serum (27, 76, 77).”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [77]
The Results and Discussion report substantial differences between immunoassay and LC-MS/MS measurements of total T3, especially at low concentrations. However, the Test Method section says this study analyzed lithium-heparin plasma, not serum, and it does not report a comparison for rT3 or 3,3′T2. (LLM, conf=0.86)
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Cites
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Ettleson, M. D., Prieto, W. H., Russo, P. S. T., de Sa, J., Wan, W., Laiteerapong, N., Maciel, R. M. B., & Bianco, A. C. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac725 · Cited by 25 · see citing works
Köhrle, J., Lehmphul, I., Pietzner, M., Renko, K., Rijntjes, E., Richards, K., Anselmo, J., Danielsen, M., & Jonklaas, J. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00787 · Cited by 23 · see citing works
Assessment of thyroid function tests and harmonization: opinion on thyroid hormone harmonization
Araque, K. A., Klubo-Gwiezdzinska, J., Nieman, L. K., Welsh, K., & Soldin, S. J. (2019) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018819897049 · Cited by 14 · see citing works
Self-citationThyroid hormone testing in the 21st century
Singh, R. J., & Kaur, P. (2016) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2016.06.007 · Cited by 10 · see citing works
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- Authors
- Masika, L. S., Zhao, Z., & Soldin, S. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Soldin, Steven John
- ORCID
- Zhao, Zhen
- Venue
- Clinical Biochemistry
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 49
- Issue
- 12
- Pages
- 846-849
- ISSN
- 0009-9120 (ISSN-L)
- PMC
- PMC4972640
- OpenAlex
- W2267879997
- Cited by
- 23
- References
- 5
- Citations by year
- 2025: 2 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 4
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Intramural Research Program of the National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Scientific Measurement and Uncertainty Evaluation
- Keywords
- total T3, triiodothyronine, low T3 syndrome, LC-MS/MS comparison, thyroid function tests, hypothyroidism
- MeSH terms
- Chromatography, Liquid, Female, Humans, Hypothyroidism, Immunoassay, Middle Aged, Prognosis, Triiodothyronine, Biomarkers, Tandem Mass Spectrometry
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