title: The molecular basis of the non-thyroidal illness syndrome.
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.
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Emmely M
authors.initials: EM
authors.lastname: de Vries
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Fliers
authors.affiliation: Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands a.boelen@amc.uva.nl.
authors.forename: Anita
authors.initials: A
authors.lastname: Boelen
mesh_terms: D000818:Animals; D005067:Euthyroid Sick Syndromes / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D018836:Inflammation Mediators; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D007453:Iodide Peroxidase
keywords: deiodinases; nonthyroidal illness; thyroid hormone receptors; thyroid hormone transporters