Higher Caloric Exposure in Critically Ill Patients Transiently Accelerates Thyroid Hormone Activation

J Clin Endocrinol Metab. 2020 Feb 1;105(2):523-533. doi: 10.1210/clinem/dgz077.


Introduction: The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients.

Objective: To explore the impact of calorie exposure on NTIS over time in critically ill patients.

Methods: Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio.

Results: Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1.

Conclusions: Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Trial registration: ClinicalTrials.gov NCT03085615.

Keywords: enteral nutrition; low t3 syndrome; nonthyroidal illness syndrome; nutrition support; prospective randomized controlled trial.

Publication types

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

MeSH terms

  • Critical Illness / therapy
  • Energy Intake / physiology*
  • Enteral Nutrition / methods*
  • Euthyroid Sick Syndromes / blood*
  • Euthyroid Sick Syndromes / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Regression Analysis
  • Respiration, Artificial
  • Thyrotropin / blood
  • Thyroxine / blood
  • Treatment Outcome
  • Triiodothyronine / blood
  • Triiodothyronine, Reverse / blood


  • Triiodothyronine
  • Triiodothyronine, Reverse
  • Thyrotropin
  • Thyroxine

Associated data

  • ClinicalTrials.gov/NCT03085615