Impact of Early Nutrient Restriction During Critical Illness on the Nonthyroidal Illness Syndrome and Its Relation With Outcome: A Randomized, Controlled Clinical Study

Lies Langouche, Sarah Vander Perre, Mirna Marques, Anita Boelen, Pieter J. Wouters, Michael P. Casaer, Greet Van den Berghe
2013 Journal of Clinical Endocrinology and Metabolism  
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
more » ... lanned subanalysis in a group of intensive care unit (ICU) patients admitted after complicated surgery and for whom enteral nutrition was contraindicated (n ϭ 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 T 4 , T 3 , rT 3 , 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 T 4 , T 3 , the T 3 to rT 3 ratio, and leptin levels were all further reduced by late PN. The further lowering of T 4 appeared to reduce the outcome benefit of late PN, whereas the further reduction of T 3 to rT 3 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 T 4 could be deleterious. (J Clin Endocrinol Metab 98: 1006 -1013, 2013) C ritical illness is hallmarked by alterations in the thyroid axis (1). A decrease in circulating T 3 and a rise in rT 3 are the first and most characteristic changes that occur during critical illness. These changes are thought to be predominantly caused by a decreased activity of the type 1 deiodinase (D1) and/or a rapid increase of type 3 deiodinase (D3) activity (2, 3). When illness is more severe and prolonged intensive care is required, T 4 levels decrease
doi:10.1210/jc.2012-2809 pmid:23348400 fatcat:vrr2sds4rravvidvh36yadqlqm