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Year : 2016  |  Volume : 5  |  Issue : 1  |  Page : 57-58

Can low T3predict clinical outcome in critically ill patients? Reality or hype

Department of Biochemistry, JSS Medical College, JSS University, Mysore, Karnataka, India

Date of Web Publication13-Jan-2016

Correspondence Address:
Parveen Doddamani
Department of Biochemistry, JSS Medical College, JSS University, S.S Nagar, Mysore, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-344X.173872

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How to cite this article:
Swetha N K, Doddamani P. Can low T3predict clinical outcome in critically ill patients? Reality or hype. Int J Health Allied Sci 2016;5:57-8

How to cite this URL:
Swetha N K, Doddamani P. Can low T3predict clinical outcome in critically ill patients? Reality or hype. Int J Health Allied Sci [serial online] 2016 [cited 2024 Mar 5];5:57-8. Available from: https://www.ijhas.in/text.asp?2016/5/1/57/173872


Low T3 syndrome or euthyroid sick syndrome or nonthyroidal illness (NTIS) is commonly seen in acute and chronic systemic illness. This syndrome is characterized by low free or total T3 and high levels of reverse T3 along with normal or low levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Studies have shown that the prevalence of NTIS is about 11–18% in nonselected hospitalized patients and about 60–70% of critically ill patients. Among these critically ill patients, more than 70% of patients showed low total T3 and around 50% with low total T4.[1],[2]

The exact mechanism of pathogenesis of low T3 syndrome is not known. The changes in serum thyroid hormone levels in the critically ill patients have been attributed to various reasons:

  • Decreased activity/inhibition of 5'-deiodinase: Increase in cytokines such as tumor necrosis factor-α, interleukin (IL)-1, and IL-6, in these patients, has been found to inhibit deiodinase. Drugs such as amiodarone, steroids, and beta-blockers have been found to inhibit deiodinase, as the cofactors of deiodinase such as glutathione and selenium are spared to combat the stress in critically ill patients
  • Alterations in the binding of thyroid hormone to thyronine-binding protein in presence of inhibitors
  • Stress-induced hormones and cytokines cause a decrease in hypothalamus and pituitary response to thyroid hormones
  • Starvation-induced decrease in T3 levels is due to inhibition of conversion of T4 to T3 in the liver and a decrease in basal metabolic rate. These changes are attributable to an adaptive response by the body to spare the proteins, calories, and cofactors to combat the stress in critically ill patients.[3]

Previous reports have shown that low T3 levels are commonly seen in critically ill patients and are associated with unfavorable clinical outcomes. A study conducted by Suvarna and Fande observed that the mean serum T3 levels at the time of admission were lower in the critically ill patients who subsequently attained mortality, when compared to critically ill patients who survived and hence, concluded that serum T3 levels at the time of admission can be considered as the best discriminator between survivors and nonsurvivors. And thus, serum T3 can be used as a prognostic marker to predict the clinical outcome of critically ill patients.[4]

Inflammation and malnutrition are found to be involved in low T3 syndrome wherein a strong relationship was reported between free T3, TSH, C-reactive protein, and serum albumin. Low T3 has also been a strong predictor of death and low cardiac output in coronary artery bypass graft surgery patients and brain tumor surgeries, and thus, these patients should be considered at higher risk and treated accordingly. Low T3 syndrome, thus impacts all-cause mortality partly via malnutrition, hormonal changes, and cardiac dysfunction. Patients with combined low T3 and T4 levels have a 30 times increased risk of mortality.[5],[6]

Low T3 syndrome is very common in acutely ill, hospitalized older patients, and when assessed according to the acute physiology and chronic health evaluation (APACHE) II, some studies have reported FT3 as the most sensitive independent predictor of short-term survival, and thus, serum FT3 determination can be even included in the assessment of short-term prognosis and Intensive Care Unit (ICU) mortality.[7],[8]

However, controversy remains whether NTIS should be treated or it needs to be considered as an adaptive response to illness. It has been much debated whether these changes are representative of an associated pathology requiring thyroid hormone replacement therapy or indeed an adaptive response to stress. Only a few studies have examined the use of supplemental thyroid hormone therapy in critically ill patients. One of the studies showed that administration of T4 did not show any improvement in these patients, which could be due to the impaired conversion of T4 to T3. A few studies suggested that use of T3 in addition to T4 would be beneficial in these patients. It was proved in an animal experimental study that combined use of T3 and T4 induces euthyroidism in all tissues, which was said to be due to local regulatory mechanisms of tissue-specific deiodinases. In another study, instead of replacing the thyroid hormones, a continuous infusion of thyrotropin-releasing hormone (TRH) together with a growth hormone (GH) secretagogue was used which successfully restored both thyroid hormone and TSH concentration. TRH infusion is thus said to have advantageous effects, thereby normalizing the thyroid hormones in the circulation and the tissues. Coinfusion of TRH and GH secretagogues increased the levels of T3, T4, insulin-like growth factor (IGF)-1, IGF binding protein-3, and other binding proteins, which is said to be due to normalization of thyroid axis.[9] However, further large-scale studies are required to prove the usefulness of T3 in predicting the clinical outcome, and whether thyroid hormone replacement would be beneficial in these patients.

  Conclusion Top

Low T3 is very useful in predicting the clinical outcome in critically ill patients. Thyroid hormones can therefore be routinely used in risk stratification of these patients by addition of FT3/T3 levels to APACHE II scores, which would significantly improve the ability to predict ICU mortality. Early risk stratification would help in initiating a more aggressive therapy, thereby resulting in better management of these patients. The need of the hour is large-scale prospective studies which would focus on two aspects of low T3 syndrome, first whether low T3 could be essentially used as a prognostic marker in critically ill patients, and second, whether the thyroid hormone replacement therapy would actually be beneficial to manage such patients.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Abdel Naby EA, Selim S, Mohsen M, Helmy M. Thyroid function in mechanically ventilated patients with acute respiratory failure. Egypt J Chest Dis Tuberc 2015;64:175-81.  Back to cited text no. 1
Warner MH, Beckett GJ. Mechanisms behind the non-thyroidal illness syndrome: An update. J Endocrinol 2010;205:1-13.  Back to cited text no. 2
Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A. Thyroid function during critical illness. Hormones (Athens) 2011;10:117-24.  Back to cited text no. 3
Suvarna JC, Fande CN. Serum thyroid hormone profile in critically Ill children. Indian J Pediatr 2009;76:1217-21.  Back to cited text no. 4
Cerillo AG, Storti S, Kallushi E, Haxhiademi D, Miceli A, Murzi M, et al. The low triiodothyronine syndrome: A strong predictor of low cardiac output and death in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 2014;97:2089-95.  Back to cited text no. 5
Enia G, Panuccio V, Cutrupi S, Pizzini P, Tripepi G, Mallamaci F, et al. Subclinical hypothyroidism is linked to micro-inflammation and predicts death in continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 2007;22:538-44.  Back to cited text no. 6
Tognini S, Marchini F, Dardano A, Polini A, Ferdeghini M, Castiglioni M, et al. Non-thyroidal illness syndrome and short-term survival in a hospitalised older population. Age Ageing 2010;39:46-50.  Back to cited text no. 7
Wang F, Pan W, Wang H, Wang S, Pan S, Ge J. Relationship between thyroid function and ICU mortality: A prospective observation study. Crit Care 2012;16:R11.  Back to cited text no. 8
Van den Berghe G. Endocrine evaluation of patients with critical illness. Endocrinol Metab Clin North Am 2003;32:385-410.  Back to cited text no. 9


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