title: Contribution of nutritional deficit to the pathogenesis of the nonthyroidal illness syndrome in critical illness: a rabbit model study.
abstract: Both starvation and critical illness are hallmarked by changes in circulating thyroid hormone parameters with typically low T(3) concentrations in the absence of elevated TSH. This constellation is labeled nonthyroidal illness (NTI). Because critical illness is often accompanied by anorexia and a failing gastrointestinal tract, the NTI of critical illness may be confounded by nutrient deficiency. In an experimental study performed in a rabbit model, we investigated the impact of nutritional deficit on the NTI of sustained critical illness. Critically ill rabbits were randomly allocated to parenteral nutrition (moderate dose 270 kcal/d) initiated on the day after injury and continued until d 7 of illness or to infusing a similar volume of dextrose 1.4% (14 kcal/d). With early parenteral nutrition during illness, the decrease in serum T(3) observed with fasting was reversed, whereas the fall in T(4) was not significantly affected. The rise in T(3) with parenteral nutrition paralleled an increase of liver and kidney type-1 and a decrease of liver and kidney type-3 deiodinase activity and an increase in circulating and central leptin. Nuclear staining of constitutive androstane receptor and its downstream expression of sulfotransferases were reduced in fasting ill animals. TRH expression in the hypothalamus was not different in fasted and fed ill rabbits, although circulating TSH levels were higher with feeding. In conclusion, in this rabbit model of sustained critical illness, reduced circulating T(3), but not T(4), levels could be prevented by parenteral nutrition, which may be mediated by leptin and its actions on tissue deiodinase activity.
authors.affiliation: Laboratory of Intensive Care Medicine, University of Leuven, Herestraat 49, bus 503, B-3000 Leuven, Belgium.
authors.forename: Liese
authors.initials: L
authors.lastname: Mebis
authors.forename: An
authors.initials: A
authors.lastname: Eerdekens
authors.forename: Fabian
authors.initials: F
authors.lastname: Güiza
authors.forename: Leslie
authors.initials: L
authors.lastname: Princen
authors.forename: Sarah
authors.initials: S
authors.lastname: Derde
authors.forename: Yoo-Mee
authors.initials: YM
authors.lastname: Vanwijngaerden
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Veerle M
authors.initials: VM
authors.lastname: Darras
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
mesh_terms: D000818:Animals; D000090702:Constitutive Androstane Receptor; D016638:Critical Illness; D004195:Disease Models, Animal; D004229:Dithiothreitol; D005067:Euthyroid Sick Syndromes / Q000209:etiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D009748:Nutrition Disorders / Q000150:complications*; D057947:Parenteral Nutrition Solutions / Q000008:administration & dosage; D011817:Rabbits; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D000090702:Constitutive Androstane Receptor; D020738:Leptin; D057947:Parenteral Nutrition Solutions; D018160:Receptors, Cytoplasmic and Nuclear; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D013974:Thyroxine; D004229:Dithiothreitol