Cited by 192Thyroid Disorders and TreatmentsGrowth Hormone and Insulin-like Growth FactorsAdrenal Hormones and Disorders

The molecular basis of the non-thyroidal illness syndrome

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de Vries, Emmely M, Fliers, Eric, Boelen, Anita·2015·Journal of Endocrinology

Abstract

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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  1. Taurog A, Briggs FN & Chaikoff IL 1952 I 131 -labeled 1-thyroxine. II. Nature of the excretion product in bile. Journal of Biological Chemistry 194 655-668.

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Authors
de Vries, E. M., Fliers, E., & Boelen, A.
Affiliations
Amsterdam UMC Location University of Amsterdam (NL)
Venue
Journal of Endocrinology
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
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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