Impact of early nutrient restriction during critical illness on the nonthyroidal illness syndrome and its relation with outcome: a randomized, controlled clinical study

J Clin Endocrinol Metab. 2013 Mar;98(3):1006-13. doi: 10.1210/jc.2012-2809. Epub 2013 Jan 24.


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.

Trial registration: NCT00512122.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Critical Care / methods*
  • Critical Illness / epidemiology
  • Critical Illness / therapy*
  • Fasting / physiology
  • Female
  • Food Deprivation / physiology*
  • Humans
  • Leptin / blood
  • Male
  • Middle Aged
  • Parenteral Nutrition / adverse effects
  • Parenteral Nutrition / methods*
  • Proportional Hazards Models
  • Prospective Studies
  • Recovery of Function / physiology
  • Risk Factors
  • Thyroid Gland / physiology*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Treatment Outcome
  • Triiodothyronine / blood


  • Leptin
  • Triiodothyronine
  • Thyrotropin
  • Thyroxine

Associated data