Low Free T 3 Is Associated With Worse Outcomes in Patients in the ICU Requiring Invasive Mechanical Ventilation

Abstract

Objective:

Critical illness causes a decrease in serum free triiodothyronine (T₃) levels. This condition, known as nonthyroidal illness syndrome (NTIS), is associated with poor outcomes. The association of NTIS and outcomes in patients in the intensive care unit (ICU) requiring mechanical ventilation has not been well studied. This study aimed to determine the impact of NTIS on the outcomes of these patients.

Methods:

This prospective study included 162 patients in the ICU who underwent mechanical ventilation. Serum free T₃ levels were tested on the day of initiation of mechanical ventilation. The rates of in-hospital mortality and ventilator-free days (VFDs) at day 28 after the initiation of mechanical ventilation were compared between patients with low (<2.3 pg/mL) and normal (≥2.3 pg/mL) free T₃ levels. Patients who died while on mechanical ventilation were assigned a VFD of 0.

Results:

Low T₃ was present in 60% of study patients. The in-hospital mortality rate of the entire cohort was 39%, and the mean and median VFDs at day 28 were 13.5 and 21 days, respectively. Compared to patients with normal free T₃, patients with low free T₃ had higher in-hospital mortality (52% vs 19%, P < .001) and less mean and median VFDs at day 28 (10.7 vs 18 and 0 vs 23, respectively. P < .001 for both mean and median VFDs).

Conclusions:

The presence of low T₃ due to NTIS in patients in the ICU requiring mechanical ventilation is associated with poor outcomes.

Keywords

thyroid triiodothyronine nonthyroidal illness syndrome mortality ventilator-free days

Get full access to this article

View all access options for this article.

References

Bermudez

Surks

Oppenheimer

. High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab.1975;41(1):27–40.

Warner

Beckett

. Mechanisms behind the non-thyroidal illness syndrome: an update. J Endocrinol. 2010;205(1):1–13.

Wartofsky

Burman

. Alterations in thyroid function in patients with systemic illnesses: the “euthyroid sick syndrome”. Endocr Rev.1982;3(2):164–217.

De Groot

. Dangerous dogmas in medicine: the nonthyroidal illness syndrome. J Clin Endocrinol Metab. 1999;84(1):151–164.

Farwell

. Thyroid hormone therapy is not indicated in the majority of patients with the sick euthyroid syndrome. Endocr Pract. 2008;14(9):1180–1187.

De Groot

. Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006;22(1):57–86.

Rothberger

Gadhvi

Michelakis

Kumar

Calixte

Shapiro

. Usefulness of serum triiodothyronine (T3) to predict outcomes in patients hospitalized with acute heart failure. Am J Cardiol. 2017;119(4):599–603.

Maldonado

Murata

Hershman

Braunstein

. Do thyroid function tests independently predict survival in the critically ill? Thyroid. 1992;2(2):119–123.

Wang

Pan

Wang

Pan

. Relationship between thyroid function and ICU mortality: a prospective observational study. Crit Care. 2012;16(1):R11.

10.

Yasar

Kirakli

Cimen

Ucar

Talay

Tibet

. Is non-thyroidal illness syndrome a predictor for prolonged weaning in intubated chronic obstructive pulmonary disease patients? Int J Clin Exp Med. 2015;8(6):10114–10121.

11.

Slag

Morley

Elson

Crowson

Nuttall

Shafer

. Hypothyroxinemia in critically ill patients as a predictor of high mortality. JAMA. 1981;245(1):43–45.

12.

Chinga-Alayo

Villena

Evans

Zimic

. Thyroid hormone levels improve the prediction of mortality among patients admitted to the intensive care unit. Intensive Care Med. 2005;31(10):1356–1361.

13.

Peeters

Wouters

Van Toor

Kaptein

Visser

Van den Berghe

. Serum 3,3′,5′-Triiodothyronine (rT₃) and 3,5,3′-Triiodothyronine/rT₃ are prognostic markers in critically ill patients and are associated with postmortem tissue deiodinase activities. J Clin Endocrinol Metab. 2005;90(8):4559–4565.

14.

Ture

Memis

Kurt

Pamukcu

. Predictive value of thyroid hormones on the first day in adult respiratory distress syndrome patients admitted to ICU: comparison with SOFA and APACHE II scores. Ann Saudi Med. 2005;25(6):466–472.

15.

Meyer

Schuetz

Wieland

Nusbaumer

Mueller

Christ-Crain

. Low triiodothyronine syndrome: a prognostic marker for outcome in sepsis? Endocrine. 2011;39(2):167–174.

16.

Bello

Pennisi

Montini

, et al. Nonthyroidal illness syndrome and prolonged mechanical ventilation in patients admitted to the ICU. Chest. 2009;135(6):1448–1454.

17.

Scoscia

Baglioni

Eslami

Iervasi

Monti

Todisco

. Low triiodothyronine (T3) state: a predictor of outcome in respiratory failure? Results of a clinical pilot study. Eur J Endocrinol. 2004;151(5):557–560.

18.

Custro

Scafidi

Costanzo

Notarbartolo

. Prospective study on thyroid function anomalies in severely ill patients. Ann Ital Med Int. 1992;7(1):13–18.

19.

Plikat

Langgartner

Buettner

, et al. Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism. 2007;56(2):239–244.

20.

Vincent

de Mendonça

Cantraine

, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–1800.

21.

Ferreira

Bota

Bross

Melot

Vincent

. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286(14):1754–1758.

22.

Fliers

Bianco

Langouche

Boelen

. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol. 2015;3(10):816–825.

23.

Brent

Hershman

. Thyroxine therapy in patients with severe nonthyroidal illnesses and low serum thyroxine concentration. J Clin Endocrinol Metab. 1986;63(1):1–8.

24.

Acker

Singh

Flick

Bernardini

Greenberg

Johnson

. A trial of thyroxine in acute renal failure. Kidney Int. 2000;57(1):293–298.

25.

Becker

Vaughan

Ziegler

, et al. Hypermetabolic low triiodothyronine syndrome of burn injury. Crit Care Med. 1982;10(12):870–875.

26.

Pingitore

Mastorci

Piaggi

, et al. Usefulness of triiodothyronine replacement therapy in patients with ST elevation myocardial infarction and borderline/reduced triiodothyronine levels (from the THIRST Study). Am J Cardiol. 2019;123(6):905–912.

27.

Siafakas

Salesiotou

Filaditaki

Tzanakis

Thalassinos

Bouros

. Respiratory muscle strength in hypothyroidism. Chest. 1992;102(1):189–194.

28.

Datta

Scalise

. Hypothyroidism and failure to wean in patients receiving prolonged mechanical ventilation at a regional weaning center. Chest. 2004;126(4):1307–1312.