Savvidis C, Ragia D, Kallistrou E, Kouroglou E, Tsiama V, Proikaki S, Belis K, Ilias I. Critical illness-implications of non-thyroidal illness syndrome and thyroxine therapy. World J Crit Care Med 2025; 14(3): 102577 [DOI: 10.5492/wjccm.v14.i3.102577]
Corresponding Author of This Article
Ioannis Ilias, MD, PhD, Department of Endocrinology, Hippocration General Hospital, 63 Evrou Street, Athens GR-11527, Greece. iiliasmd@yahoo.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Christos Savvidis, Dimitra Ragia, Efthymia Kallistrou, Eleni Kouroglou, Vasiliki Tsiama, Stella Proikaki, Konstantinos Belis, Ioannis Ilias, Department of Endocrinology, Hippocration General Hospital, Athens GR-11527, Greece
Co-first authors: Christos Savvidis and Dimitra Ragia.
Author contributions: Savvidis C, Ragia D, and Ilias I designed the research study; Savvidis C, Ragia D, Kallistrou E, Kouroglou E, Tsiama V, Proikaki S, Belis K and Ilias I performed the research; Savvidis C, Ragia D, Kallistrou E, Kouroglou E, Tsiama V, Proikaki S, Belis K and Ilias I wrote the manuscript.
Conflict-of-interest statement: All the Authors declare that they have no conflict of interest to disclose.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ioannis Ilias, MD, PhD, Department of Endocrinology, Hippocration General Hospital, 63 Evrou Street, Athens GR-11527, Greece. iiliasmd@yahoo.com
Received: October 23, 2024 Revised: March 17, 2025 Accepted: March 27, 2025 Published online: September 9, 2025 Processing time: 269 Days and 6.8 Hours
Abstract
Nonthyroidal illness syndrome (NTIS) is a common finding in critically ill patients, characterized by disruptions in the hypothalamus-pituitary-thyroid axis, resulting in altered levels of thyroxine (T4), triiodothyronine (T3), and reverse T3. This condition, often considered to be an adaptive response aimed at conserving energy, can become maladaptive in prolonged critical illness, contributing to poor outcomes in intensive care unit patients. The pathophysiology of NTIS involves cytokine-driven alterations in thyroid hormone (TH) metabolism, impaired hormone transport, and reduced receptor sensitivity, which-collectively-suppress thyroid function. Despite these insights, the therapeutic role of TH replacement in patients with NTIS remains uncertain. Low doses of levothyroxine and T3 have been trialed, particularly in patients with cardiovascular comorbidities, but clinical studies report conflicting results regarding their impact on mortality and overall patient outcomes. While some evidence suggests potential benefits of T3 administration in specific subgroups, such as patients with septic shock or severe coronavirus disease 2019, robust clinical trials have yet to conclusively demonstrate improved survival or recovery. The heterogeneity in NTIS presentation and treatment protocols, as well as the complex nature of TH regulation in critically ill patients, complicates efforts to establish clear guidelines for hormone therapy. Future research should prioritize individualized approaches, optimizing hormone dosing and timing, while aiming to elucidate the long-term effects of such interventions on critically ill patients to improve morbidity and mortality outcomes.
Core Tip: Nonthyroidal illness syndrome, common in critically ill patients, disrupts thyroid function through cytokine-driven mechanisms. While thyroid hormone replacement therapy shows potential in certain subgroups, such as in patients with septic shock, evidence on its benefits remains inconclusive. Future research should focus on individualized treatment approaches to improve outcomes.
