Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients

Arvind Mishra; Rohin Saini; Madhukar Mittal; Dandu Himanshu; Kamlesh Kumar Gupta; Abbas Ali Mahdi

doi:10.4103/trp.trp_17_19

ORIGINAL ARTICLE

Year : 2019 | Volume : 16 | Issue : 3 | Page : 113-120

Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients

Arvind Mishra¹, Rohin Saini¹, Madhukar Mittal¹, Dandu Himanshu¹, Kamlesh Kumar Gupta¹, Abbas Ali Mahdi²
¹ Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh, India
² Department of Biochemistry, Era Medical College, Lucknow, Uttar Pradesh, India

Date of Submission	18-May-2019
Date of Acceptance	28-Jul-2019
Date of Web Publication	18-Nov-2019

Correspondence Address:
Dr. Madhukar Mittal
Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/trp.trp_17_19

Abstract

Introduction and Objectives: Thyroid hormone changes in critically ill patients are commonly observed phenomenon. This is known as sick euthyroid syndrome. Sequential organ faillure assessment (SOFA) score is used to track and determine the extent of a person's organ function or its rate of failure. We performed a prospective observation study to analyze the prognostic rather than diagnostic efficacy of thyroid function test (TFT) (T3, T4, thyroid-stimulating hormone [TSH], free triiodothyronine [fT3], and free thyroxine [fT4]) in unselected critically ill patients and compare the prognostic efficacy of fT3, fT4, TSH, T3, and T4 with SOFAS in predicting mortality in critically ill patients.
Materials and Methods: We studied a sample of unselected 338 patients admitted in the intensive care unit (ICU) and measured their TFT, routine biochemical parameters within 48 h of admission along with SOFA scores and assessed their individual and combined efficacy in predicting mortality. All patients with known thyroid illness were excluded from this study.
Results: There were 200 survivors and 138 nonsurvivors, the nonsurvivors had higher SOFAS score and lower free T3 levels and lower T3 levels compared to survivors. ICU survival was predicted using SOFAS score alone and a combination of TFT with SOFA score.
Conclusions: In critically ill patients with higher SOFA score, lower values of serum fT3 and T3 levels were clinically significantly associated with mortality and free T3 have additional powers to improve predictive ability to SOFAS in predicting mortality in ICU patients.

Keywords: Critically ill patients, sick euthyroid syndrome, SOFAS, thyroid dysfunction

How to cite this article:
Mishra A, Saini R, Mittal M, Himanshu D, Gupta KK, Mahdi AA. Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients. Thyroid Res Pract 2019;16:113-20

How to cite this URL:
Mishra A, Saini R, Mittal M, Himanshu D, Gupta KK, Mahdi AA. Prognostic efficacy of thyroid profile with sequential organ failure assessment score in predicting mortality in intensive care unit patients. Thyroid Res Pract [serial online] 2019 [cited 2021 Dec 8];16:113-20. Available from: https://www.thetrp.net/text.asp?2019/16/3/113/271149

Introduction

Intensive care unit (ICU) scoring systems have been in use for more than three decades to objectify and quantify the physician's clinical decision in critically ill patients.^[1] These performance indicators, however, cannot exactly predict actual mortality probability. The changes in hormone axis of critically ill patients are common, however rarely have been given emphasis with regard to its ability to predict mortality. Changes in thyroid function test (TFT) are commonly seen in critically ill patients. These changes are referred to as sick euthyroid syndrome.^[2] It is commonly associated with low levels of total triiodothyronine and low free triodothyronine with changes in levels of thyroxine and free thyroxine in prolonged critical illnesses. These changes have been attributed to decreased peripheral deiodination of thyroid hormones along with altered binding to thyroid hormone-binding proteins. Although nonthyroidal illness syndrome has been associated with poor outcomes in patients, it has been associated with conflicting views as to whether they can be used to predict clinical outcome in critically ill patients.^[3] While some studies are of the opinion that sick euthyroid syndrome is a marker of poor outcome,^[4] others remain mute on the opinion^[5] and some deny any association of poor outcome and sick euthyroid syndrome.^[6] Acute physiology and chronic health evaluation II (APACHE II) score and sepsis-related organ failure assessment (SOFAS) score have been used in multiple studies to predict hospital-associated mortality.^[7] This study has been under taken clarify whether TFT can independently predict mortality in ICU patients and whether incorporation of TFT with SOFAS score can improve the ability of SOFA score to predict mortality in critically ill patients. Thus assess the prognostic accuracy of SOFAS score and T3, T4, thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) parameters to predict mortality of critically ill patients individually and in combination.

Materials and Methods

This descriptive prospective observational study was conducted for a period of 1 year from September 2017 to September 2018 in King George's Medical University, Lucknow, after approval of ethical committee. Written informed consent was taken from patients and/or their next of kin for all patients. 338 patients were enrolled for this study. Following was kept as exclusion criteria: (1) age <18 years (2) patients with known history of thyroid illness (3) pregnant patients and pregnancy within last 6 months (4) patients who expired within 24 h of admission. Demographic data along with routine biochemical parameters and TFTs were recorded for all the patients along with their primary outcome as mortality. Patients under the age of 18 years and mortality within first 24 h and patients receiving medications known to alter thyroid hormone profile were excluded [Table 1] and [Figure 1], [Figure 2], [Figure 3], [Figure 4]. APACHE II and SOFAS score used to determine severity of illness. It was calculated from all patients along with their thyroid hormone profile. Venous blood samples were collected along with arterial blood gas analysis for all patients. TFTs were measured by radioimmunoassay. Range of TFT were as follows: Total T3: 0.58–1.59 ng/mL, Total T4: 4.8–11.7 Ug/dL, TSH: 0.35–4.94 UIU/ml, fT3: 1.4–4.2 pg/ml, fT4: 0.8–2.2 ng/ml, and anti-TPO: 0–6. This was a single-center study, and there was no availability of data on the use of medications which can alter TFT in previous hospitalization prereferral. Statistical analysis was done using SPSS version 21.0 (Armonk, NY: IBM Corp.)statistical analysis software. The values were represented as number (%) and mean ± standard deviation (SD). The results are presented in frequencies, percentages for categorical variables, and mean ± SD for continuous variables. The Chi-square test was used to assess the association between categorical variables. The binary logistic regression was used to find the strength of associations. The odds ratio with its 95% confidence interval (CI) was calculated. The sensitivity, specificity, positive predictive value, and negative predictive value with 95% CI was calculated. Parameters which showed significant difference between survivors and nonsurvivors were analyzed using receiver operating characteristic (ROC) curve analysis. ROC curves were constructed to examine the performance of indicators as predictors of ICU mortality. Area under curve (AUC) for each indicator was calculated. The AUC, optimal cutoff value sensitivity and specificity of each indicator was calculated [Table 2] and [Figure 2]. We further performed univariate logistic regression analysis to assess the association between ICU mortality and each of the mortality predictors. P < 0.05 was considered statistically significant. We also conducted forward stepwise multivariate logistic regression analysis to determine the independent predictors of ICU mortality. SOFAS score alone was contested against SOFAS score with TFT.

Table 1: Demographic profile and clinical profile of patients according to their survival status

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Figure 1: (a) Gender profile of survivors and nonsurvivors, (b) comparison of mean age blood pressure parameters between survivors and nonsurvivors, (c) comparison of mean Glasgow Coma Scale, acute physiology and chronic health evaluation II and pH scores between survivors and nonsurvivors, (d) comparison of mean thyroid hormone levels between survivors and nonsurvivors, (e) comparison of mean hemoglobin, hematocrit, serum urea, creatinine, total protein and total albumin levels between survivors and nonsurvivors

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Figure 2: Receiver operator characteristic curves showing area under curve for different parameters for the outcome survival

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Figure 3: (a) Distribution of cases according to system involved, (b) mortality rates for different systems involved

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Figure 4: (a) Association between SOFA risk scores and T3 levels, (b) association between SOFA risk scores and T4 levels, (c) association between SOFA risk scores and thyroid-stimulating hormone levels, (d)association between SOFA assessment risk scores and free triiodothyronine levels, (e) association between SOFA assessment risk scores and free thyroxine levels, (f) association between SOFA assessment risk scores and thyroid peroxidase levels

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Table 2: Area under the curve (for prediction of survival)

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Results

A total of 338 patients admitted to the ICU during the study period and were analyzed. There were 200 survivors and 138 nonsurvivors. There was a significant correlation between T3 and fT3 and mortality of patients. The survivors had a higher systolic blood pressure (SBP), diastolic blood pressure, mean arterial blood pressure, higher Glasgow coma scale score, longer duration of illness, higher T3 and fT3 levels and lower APACHE II and SOFA score. ROC curves were constructed and area under the curve was derived for independent variables along with its optimal cutoff and sensitivity and specificity. AUC values ranged from 0.571 (SBP) to 0.772 (fT3). Among different parameters analyzed fT3 had maximum sensitivity (71.8%) as well as specificity (78.7%). Close to fT3 were SOFAS and T3 levels which had a sensitivity and specificity of 53.3% and 67.4% and 63.6% and 69.7% respectively [Table 3], [Table 4], [Table 5], [Table 6] and [Figure 3], [Figure 4], [Figure 5]. Univariate logistic regression analyses association of each indicator with mortality in ICU was further calculated along with odds ratio and standardized coefficient which showed fT3 and T3 had higher absolute values of standardization and were better predictors of ICU mortality than other variables [Table 7]. Multivariate logistic regression was done to determine the independent predictive power of ICU mortality and results were shown. Comparison of two models were done one with SOFAS alone versus SOFAS with fT3 and T3 was done. This model revealed that combination of T3 and fT3 with SOFA score improved the predictive ability of SOFA score.

Table 3: Association between system involved and survival status

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Table 4: Association between sequential organ failure assessment scores and different thyroid function parameters

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Table 5: Association between mortality and different thyroid function parameters

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Table 6: Univariate odds ratios of variables for predicting intensive care unit mortality

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Figure 5: (a) Association between survival and T3 levels, (b) association between survival and T4 levels, (c) association between survival and thyroid-stimulating hormone levels, (d) association between survival and free triiodothyronine levels, (e) Association between survival and free thyroxine levels, (f) association between survival and thyroid peroxidase levels

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Table 7: Independent predictors of intensive care unit mortality by multivariate logistic regression

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Discussion

To the best of our knowledge, this study is the first study done in the Indian population in a tertiary care hospital to assess the prognostic efficacy of TFT individually and along with SOFA score in ICU patients. Hormonal changes in and during sepsis or critically ill state is a commonly witnessed phenomenon.^[8] ICU studies have demonstrated the association between hormones and mortality. Studies have shown that plasma cortisol, aldosterone, and androstenedione are increased in ICU patients compared to normal subjects while T3 and fT3 values are commonly low. The latter is referred to as sick euthyroid phenomenon as changes in thyroid hormone parameters reflects apparent alterations in thyroid hormone metabolism and are not associated with pathology in the gland itself.^[9] Patients in ICU are predominantly catabolic and have decreased conversion of T4 to T3 in peripheral tissue. The initial response in acute stress is to decrease serum tri-iodothyronine levels (T3) to counteract biochemical catabolism. This helps in preventing unnecessary energy expenditure. However, in those with a prolonged critical illness, the normal physiologic response of the hypothalamus-pituitary-thyroid axis is altered, leading to low levels of both T3 and thyrotropin (TSH).^[10] As it is unclear whether this acute endocrine phenomenon is a protective or an adaptive compensatory mechanism of coping with stress the benefits of hormone in critically ill patients of ICU with low thyroid levels are still under speculation.^[11] However, one can make the argument that for ICU patients, the risk-benefit ratio favors hormone supplementation given its potential for efficacy and low likelihood for harm.^[12] This shall also greatly benefit those who have subclinical deficiencies which becomes overt in times of acute illness. These dynamic changes in the hormone axes also suggest that hormones can be used as supplements for understanding the effect of stress in ICU patients.

Sick euthyroid syndrome is associated with poor outcomes in patients.^[13] Different theories have been propagated to explain the mechanism and significance of the euthyroid sick syndrome. Acute and sustained critical illness results in complex alterations in the thyroid axis in a bimodal pattern.^{[10],[11],[14]} The acute initial phase is primarily characterized by changes in the peripheral metabolism and receptor binding of thyroid hormones, whereas in the chronic phase, a diminished hypothalamic-pituitary-activity with a timely overlap of the two conditions is found.^{[10],[11],[15]} The chronic phase of the euthyroid sick syndrome is characterized by reversibly diminished secretion of TSH.

In our study, we found that low T3 and fT3 were associated with poor outcomes. Nonsurvivors had a poor blood pressure parameters (systolic, diastolic, and mean arterial blood pressure). These patients also had a poor Glasgow coma score even patients with higher Sofas score had lower normal TSH levels. These factors which showed a significant difference between survivor and nonsurvivor were further analyzed using ROC curves. Among different parameters analyzed fT3 had maximum sensitivity (71.8%) as well as specificity (78.7%). Close to fT3 were SOFAS and T3 levels which had a sensitivity and specificity of 53.3% and 67.4% and 63.6% and 69.7% respectively. It was observed that with increasing SOFA score, the proportion of those with below normal T3 and fT3 levels significantly increased. Except for T3 and fT3 levels, none of the other thyroid function parameters showed a significant association with survival status. Below normal T3 levels were seen in a significantly higher proportion of those who died (90.6%) as compared to those who survived (63.5%) (P = 0.001). With respect to fT3 levels, these were also below normal in significantly higher proportion of those who died (94.2%) as compared to those who survived (72.5%) (P< 0.001). Odds ratios for predicting ICU mortality ranged from 0.034 (T3) to 0.985 (SOFA score). All the variables tested for univariate association showed a significant association with ICU mortality. Between model of comparison between SOFAS alone versus SOFAS and T3 and fT3, the latter were found to be significantly stronger than former.

Very few studies have been done in the Indian background to compare the TFT with prognosis of ICU patients. While there have been studies to depict comparison of TFT with multivariable APACHE II (12 variables), there have been few studies involving SOFA score and thyroid function. Further studies are required for understanding and verification of prognostic capabilities of TFT in critically patients alone and with SOFA score within the Indian scenario.

Conclusions

We would like to conclude that fT3 and SOFA score can be used independently to predict mortality of critically ill patients admitted in the ICU. The addition of fT3 T3 to SOFA score can significantly improve its ability to predict mortality.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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