Beyond Low Plasma T3: Local Thyroid Hormone Metabolism during Inflammation and Infection
Abstract
Decreased serum thyroid hormone concentrations in severely ill patients were first reported in the 1970s, but the functional meaning of the observed changes in thyroid hormone levels, together known as nonthyroidal illness syndrome (NTIS), remains enigmatic. Although the common view was that NTIS results in overall down-regulation of metabolism in order to save energy, recent work has shown a more complex picture. NTIS comprises marked variation in transcriptional and translational activity of genes involved in thyroid hormone metabolism, ranging from inhibition to activation, dependent on the organ or tissue studied. Illness-induced changes in each of these organs appear to be very different during acute or chronic inflammation, adding an additional level of complexity. Organ- and timing-specific changes in the activity of thyroid hormone deiodinating enzymes (deiodinase types 1, 2, and 3) highlight deiodinases as proactive players in the response to illness, whereas the granulocyte is a novel and potentially important cell type involved in NTIS during bacterial infection. Although acute NTIS can be seen as an adaptive response to support the immune response, NTIS may turn disadvantageous when critical illness enters a chronic phase necessitating prolonged life support. For instance, changes in thyroid hormone metabolism in muscle during critical illness may be relevant for the pathogenesis of myopathy associated with prolonged ventilator dependence. This review focuses on NTIS as a timing-related and organ-specific response to illness, occurring independently from the decrease in serum thyroid hormone levels and potentially relevant for disease progression.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Changes in DIO1, DIO2 and DIO3 expression and activity during NTIS have been reported in a variety of organs and tissues.
“Changes in DIO1, DIO2 and DIO3 expression and activity during NTIS have been reported in a variety or organs and tissues [3].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [3]
A variety of changes in TH transporters, deiodinase and TR action have been observed in different organs and tissues both during acute and chronic illness, while serum TH levels are uniformly downregulated.
“A variety of changes in TH transporters, deiodinase and TR action have been observed in different organs and tissues both during acute and chronic illness, while serum TH levels are uniformly downregulated [3, 11].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [3]
TR expression levels are affected in a differential way during NTIS.
“Like the TH transporters and the deiodinases, TR expression levels are also affected in a differential way during NTIS [3].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [3]
In granulocytes, the inactivating D3 is highly expressed, and release of inorganic iodide is related to improved killing of bacteria.
“In granulocytes, the inactivating D3 is highly expressed [136]. In these cells, the release of inorganic iodide was related to improved killing of bacteria [136].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [136]
During acute inflammation, in muscle, the hormone-activating deiodinase D2 increases whereas the hormone-inactivating D3 decreases, leading to higher muscular T3 levels and increased breakdown of energy-rich substrates in muscle only.
“For example, during acute inflammation, in the muscle, the hormone-activating deiodinase D2 increases whereas the hormone-inactivating D3 decreases, which would lead to higher muscular T3 levels, resulting in increased breakdown of energy-rich substrates in the muscle only [136].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [136]
Downregulation of the central part of the hypothalamic-pituitary-thyroid gland axis during acute and chronic inflammation does not necessarily induce decreased thyroid hormone levels in key metabolic organs such as liver, muscle, and adipose tissue.
“Importantly, recent experimental studies have shown that downregulation of the central part of this axis observed during acute and chronic inflammation does not necessarily induce decreased thyroid hormone levels in key metabolic organs such as liver, muscle, and adipose tissue (summarized in [136]).”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [136]
In chronic inflammation, D2 and D3 are elevated and the net effect on T3 is a reduction in active T3.
“This is different in chronic inflammation, where D2 and D3 are elevated and, as was described, the net effect on T3 is a reduction in active T3 [136].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [136]
Differential regulation of local thyroid hormone availability depends mainly on expression of activating (D1 or D2) and inactivating (D3) deiodinases.
“The differential regulation of local thyroid hormone availability depends mainly on expression of activating (D1 or D2) and inactivating (D3) deiodinases [136].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [136]
The citation lists haven’t been fetched yet
References 190 · Cited by 287
- Authors
- Boelen, A., Kwakkel, J., & Fliers, E.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Boelen, Anita
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2011-07-26
- Volume
- 32
- Issue
- 5
- Pages
- 670-693
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2167179294
- Cited by
- 287
- References
- 190
- Citations by year
- 2026: 26 · 2025: 23 · 2024: 19 · 2023: 18 · 2022: 21 · 2021: 20 · 2020: 16 · 2019: 16 · 2018: 19 · 2017: 17 · 2016: 25 · 2015: 23 · 2014: 24 · 2013: 13 · 2012: 5
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- low T3 syndrome, thyroid hormone metabolism, deiodinases, inflammation, infection, critical illness, granulocytes, muscle myopathies, ventilator dependence, organ-specific gene expression
- MeSH terms
- Acute Disease, Adipose Tissue, Bacterial Infections, Chronic Disease, Euthyroid Sick Syndromes, Granulocytes, Humans, Hypothalamus, Infections, Inflammation, Iodide Peroxidase, Liver, Muscles, Pituitary Gland, Receptors, Thyroid Hormone, Thyroid Gland, Thyroid Hormones, Triiodothyronine, Gene Expression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
