Assessment of thyroid function in intensive care unit patients by liquid chromatography tandem mass spectrometry methods
Open accessAbstract
Objectives Patients with non-thyroidal illness syndrome have many abnormalities in thyroid hormone tests. Such patients have medical comorbidities associated with low serum proteins and are on multiple medications that interfere with thyroid hormone measurement by immunoassay platforms. It is unknown if these thyroid hormone measurements reflect physiologic conditions or if they are artifacts of testing methodology. Methods Fifty patients were selected from the intensive care unit (ICU) from our institution. Total and free thyroid hormones in plasma were measured by gold standard liquid chromatography-tandem mass spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000. Patient medical comorbidities and binding protein levels were assessed. Results Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4) were significantly more likely to be low by LC-MSMS compared to immunoassay. Free 3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS. However, FT4 concentrations were mildly elevated for many patients when measured by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were common and patients were on an average of 11.7±5.0 medications, all factors known to interfere with results found on immunoassays. Conclusions Marked discrepancies in thyroid hormone measurement were noted between reference LC-MSMS and a common immunoassay platform. It is hypothesized that T4 binding to low affinity albumin is displaced by several drugs, raising concentrations of FT4 by LC-MSMS compared to immunoassay, and that the immunoassay values are falsely decreased due to low binding proteins in our patient population.
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Several laboratories have developed procedures to accurately determine total T4 and total T3 in human plasma or serum and largely agree on concentration ranges, but this consensus has not been achieved for most other TH metabolites.
“While meanwhile several laboratories developed procedures to accurately determine total T4 and total T3 in human plasma or serum and largely agree on concentrations ranges (25, 67–73), this consensus has not been achieved yet for most of the other TH metabolites, which occur at much lower concentrations.”
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 [67]
The Methods (Laboratory methods; page unavailable) describe a validated LC-MSMS procedure for measuring total T3 and T4 in human plasma and give reference intervals. The paper does not establish agreement on concentration ranges across laboratories or address whether a consensus exists for most other thyroid hormone metabolites. (LLM, conf=0.84)
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Cites
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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
- Authors
- Welsh, K. J., Stolze, B. R., Yu, X., Podsiadlo, T. R., Kim, L. S., & Soldin, S. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Soldin, Steven J.
- Venue
- Clinical Biochemistry
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 50
- Issue
- 6
- Pages
- 318-322
- ISSN
- 0009-9120 (ISSN-L)
- PMC
- PMC5429196
- OpenAlex
- W2552087489
- Cited by
- 17
- References
- 3
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2017: 1
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- NIH Clinical Center (ZIACL010355)
- 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
- thyroid function, low T3 syndrome, intensive care unit patients, thyroid hormone measurement, free thyroxine, total thyroxine, triiodothyronine, immunoassay interference, drug interference, thyroxine-binding globulin, binding proteins
- MeSH terms
- Adult, Aged, Chromatography, Liquid, Female, Humans, Immunoassay, Intensive Care Units, Male, Middle Aged, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland, Thyroxine, Triiodothyronine, Biomarkers, Tandem Mass Spectrometry, Young Adult
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