title: 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.
authors.affiliation: Department of Endocrinology and Metabolism, F5-165, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. a.boelen@amc.uva.nl
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
authors.forename: Joan
authors.initials: J
authors.lastname: Kwakkel
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
mesh_terms: D000208:Acute Disease; D000273:Adipose Tissue / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism; D002908:Chronic Disease; D005067:Euthyroid Sick Syndromes / Q000503:physiopathology*; D015870:Gene Expression; D006098:Granulocytes / Q000201:enzymology; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology; D007239:Infections / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010902:Pituitary Gland / Q000503:physiopathology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D013961:Thyroid Gland / Q000503:physiopathology; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014284:Triiodothyronine / Q000097:blood*
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D014284:Triiodothyronine; D007453:Iodide Peroxidase