The molecular basis of the non-thyroidal illness syndrome
Open accessAbstract
The ‘sick euthyroid syndrome’ or ‘non-thyroidal illness syndrome’ (NTIS) occurs in a large proportion of hospitalized patients and comprises a variety of alterations in the hypothalamus–pituitary–thyroid (HPT) axis that are observed during illness. One of the hallmarks of NTIS is decreased thyroid hormone (TH) serum concentrations, often viewed as an adaptive mechanism to save energy. Downregulation of hypophysiotropic TRH neurons in the paraventricular nucleus of the hypothalamus and of TSH production in the pituitary gland points to disturbed negative feedback regulation during illness. In addition to these alterations in the central component of the HPT axis, changes in TH metabolism occur in a variety of TH target tissues during NTIS, dependent on the timing, nature and severity of the illness. Cytokines, released during illness, are known to affect a variety of genes involved in TH metabolism and are therefore considered a major determinant of NTIS. The availability of in vivo and in vitro models for NTIS has elucidated part of the mechanisms involved in the sometimes paradoxical changes in the HPT axis and TH responsive tissues. However, the pathogenesis of NTIS is still incompletely understood. This review focusses on the molecular mechanisms involved in the tissue changes in TH metabolism and discusses the gaps that still require further research.
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Proinflammatory cytokines can downregulate various components of TH synthesis and metabolism in thyrocytes and hepatocytes.
“Cellular studies clearly showed that proinflammatory cytokines can downregulate various components of TH synthesis and metabolism in thyrocytes [58] and hepatocytes [59–61].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [58]
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An update on non-thyroidal illness syndrome
Fliers, E., & Boelen, A. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01482-4 · Cited by 199 · see citing works
Self-citationThe classic pathways of thyroid hormone metabolism
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Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study
Pearce, S. H. S., Razvi, S., Yadegarfar, M. E., Martin-Ruiz, C., Kingston, A., Collerton, J., Visser, T. J., Kirkwood, T. B., & Jagger, C. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1935 · Cited by 91 · see citing works
- Authors
- de Vries, E. M., Fliers, E., & Boelen, A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2015-05-13
- Volume
- 225
- Issue
- 3
- Pages
- R67-R81
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2121452730
- Cited by
- 192
- References
- 135
- Citations by year
- 2026: 22 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 18 · 2021: 22 · 2020: 22 · 2019: 23 · 2018: 19 · 2017: 19 · 2016: 12 · 2015: 3
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- low T3 syndrome, hypothalamic-pituitary-thyroid axis, thyroid hormone metabolism, thyroid-stimulating hormone, thyrotropin-releasing hormone, paraventricular nucleus, negative feedback regulation, cytokines, energy conservation, hospitalized patients
- MeSH terms
- Animals, Euthyroid Sick Syndromes, Gene Expression Regulation, Humans, Hypothalamo-Hypophyseal System, Iodide Peroxidase, Isoenzymes, Models, Biological, Nerve Tissue Proteins, Neurons, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal System, Severity of Illness Index, Inflammation Mediators
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