Impact of Early Nutrient Restriction During Critical Illness on the Nonthyroidal Illness Syndrome and Its Relation With Outcome: A Randomized, Controlled Clinical Study
Abstract
CONTEXT: Both critical illness and fasting induce low circulating thyroid hormone levels in the absence of a rise in TSH, a constellation-labeled nonthyroidal illness syndrome (NTI). The contribution of restricted nutrition during critical illness in the pathophysiology of NTI remains unclear. OBJECTIVE: The objective of the study was to investigate the impact of nutrient restriction early during critical illness on the NTI, in relation to outcome. DESIGN AND PATIENTS: A preplanned subanalysis in a group of intensive care unit (ICU) patients admitted after complicated surgery and for whom enteral nutrition was contraindicated (n = 280) of a randomized controlled trial, which compared tolerating pronounced nutritional deficit for 1 week in the ICU [late parenteral nutrition (PN)] with early initiation of parenteral nutrition (early PN). MEASUREMENTS: Circulating TSH, total T4, T3, rT3, and leptin levels were quantified upon admission and on ICU day 3 or the last day when patients were discharged earlier. After correction for baseline risk factors, the role of these changes from baseline in explaining the outcome benefit of late PN was assessed with the multivariable Cox proportional hazard analysis. RESULTS: Late PN reduced complications and accelerated recovery. Circulating levels of TSH, total T4, T3, the T3 to rT3 ratio, and leptin levels were all further reduced by late PN. The further lowering of T4 appeared to reduce the outcome benefit of late PN, whereas the further reduction of T3 to rT3 ratio appeared to statistically explain part of the outcome benefit. CONCLUSIONS: Tolerating nutrient restriction early during critical illness, shown to accelerate recovery, further aggravated the NTI. The statistical analyses suggested that the more pronounced peripheral inactivation of the thyroid hormone with nutrient restriction during critical illness could be a beneficial adaptation, whereas the lowering of T4 could be deleterious.
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The response of DIO3 to illness might depend on energy status; fasting results in increased liver DIO3 activity in rodents and prolonged illness is associated with diminished food intake.
“The response of DIO3 to illness might depend on energy status; fasting results in increased liver DIO3 activity in rodents [23, 24] and prolonged illness is associated with diminished food intake [25].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [25]
Inactivation of T3 to rT3, as part of the fasting response, might be a beneficial adaptation during acute illness.
“The subanalysis suggested that the inactivation of T3 to rT3, as part of the fasting response, might be a beneficial adaptation during acute illness [25].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [25]
Late feeding enhances the changes in circulating concentrations of serum thyroid hormones.
“a subanalysis of this trial showed that late feeding enhanced the changes in circulating concentrations of serum TH.”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [25]
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- Authors
- Langouche, L., Vander Perre, S., Marques, M., Boelen, A., Wouters, P. J., Casaer, M. P., & Van den Berghe, G.
- Affiliations
- KU Leuven (BE)
- Clinical Department and Laboratory of Intensive Care Medicine (L.L., S.V.P., M.M., P.J.W., M.P.C., G.V.d.B.), Division Cellular and Molecular Medicine, University of Leuven (KU Leuven), B-3000 Leuven, Belgium
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Langouche, Lies
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-03-01
- Volume
- 98
- Issue
- 3
- Pages
- 1006-1013
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2164211218
- Cited by
- 79
- References
- 39
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 12 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 6 · 2013: 3
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lirias (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Surgery › Enhanced Recovery After Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- low T3 syndrome, nutrient restriction, critical illness, thyroid-stimulating hormone, thyroid hormones, reverse T3, leptin, postoperative intensive care, recovery outcomes
- MeSH terms
- Aged, Critical Care, Fasting, Female, Food Deprivation, Humans, Male, Middle Aged, Parenteral Nutrition, Prospective Studies, Risk Factors, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Proportional Hazards Models, Critical Illness, Treatment Outcome, Recovery of Function, Leptin
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