ORIGINAL RESEARCH published: 09 June 2021 doi: 10.3389/fendo.2021.656641 Analysis of the Incidence of Euthyroid Sick Syndrome in Comprehensive Intensive Care Units and Related Risk Factors Jianying Guo 1,2*, Yanyan Hong 3, Zhiyong Wang 2 and Yukun Li 1* 1 Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, China, 2 Department of Critical Care Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, China, 3 Department of School Infirmary, Infirmary of Shijiazhuang Institute of Technology, Shijiazhuang, China Objective: A low concentration of plasma triiodothyronine (T3) indicates euthyroid sick syndrome (ESS), which could be associated with a poor outcome in patients in intensive Edited by: care units (ICUs). This study evaluated the relationship between ESS and prognostic Trevor Edmund Angell, indicators in patients admitted to an ICU and examined the free T3 (FT3) cut-off points that University of Southern California, United States could be associated with 28-day mortality. Reviewed by: Methods: This prospective observational study included patients admitted to the ICU of Yanjun Zhong, Central South University, The Third Hospital of Hebei Medical University between February and November 2018. China Baseline variables and data on the occurrence of low FT3 were collected. The patients Madan Madhav Godbole, were divided into ESS (FT3 < 3.28 pmol/L) and non-ESS groups. The relationship Sanjay Gandhi Post Graduate Institute of Medical Sciences between ESS and prognostic indicators in patients admitted to the ICU was evaluated, (SGPGI), India and the FT3 cut-off points that could be associated with 28-day mortality were examined. *Correspondence: Yukun Li Results: Out of a total of 305 patients, 118 (38.7%) were in the ESS group. Levels of FT3 [email protected] (P < 0.001) and FT4 (P = 0.001) were lower, while the 28-day mortality rate (P < 0.001) and Jianying Guo hospitalization expenses in the ICU (P = 0.001) were higher in the ESS group. A univariable [email protected] analysis identified ESS, FT3, free thyroxine (FT4)/FT3, the APACHE II score, the sequential Specialty section: organ failure (SOFA) score, the duration of mechanical ventilation, creatinine (CREA) levels, This article was submitted to the oxygenation index (HGB), white blood cells, albumin (ALB) levels, age, and brain Thyroid Endocrinology, a section of the journal natriuretic peptide (BNP) levels as factors associated with 28-day mortality (all P < 0.05). Frontiers in Endocrinology The cut-off value of FT3 for 28-day mortality was 2.88 pmol/L, and the 28-day mortality Received: 21 January 2021 rate and hospitalization expenses in the ICU were higher in patients with ESS. The Accepted: 27 April 2021 syndrome was confirmed to be independently associated with 28-day mortality. Published: 09 June 2021 Citation: Conclusion: This study determined the incidence of ESS in the comprehensive ICU to be Guo J, Hong Y, Wang Z and Li Y 38.7%. APACHE II, SOFA, BNP, APTT, HGB, PLT, CREA, ALB, FT4, SBP, and DBP are (2021) Analysis of the Incidence of Euthyroid Sick Syndrome closely related to ESS, while BNP, PLT, and ALB are independent risk factors for in Comprehensive Intensive Care the syndrome. Units and Related Risk Factors. Front. Endocrinol. 12:656641. Keywords: low plasma triiodothyronine, nonthyroidal illness syndrome, thyroid-stimulating hormone, thyroid doi: 10.3389/fendo.2021.656641 hormone, intensive care unit Frontiers in Endocrinology | www.frontiersin.org 1 June 2021 | Volume 12 | Article 656641 Guo et al. Euthyroid Sick Syndrome in ICU PREFACE donation or organ function maintenance, (3) pregnant or lactating women, (4) presence of tumors with endocrine Thyroid hormones act on various organ systems throughout the dysfunction, and (5) use of anti-thyroid drugs, T4, or long- body and are essential for maintaining basic physiological term use of iodine-containing preparations, such as long-term activities. The concept of euthyroid sick syndrome (ESS) was oral amiodarone. proposed in the 1970s. It means that under the influence of many factors, including trauma, infection, surgery, and inflammation, Data Collection patients with normal thyroid function are affected by a series of The collection of all the clinical data in this study was carried out thyroid hormone level disorders. The main manifestations of ESS by full-time ICU doctors and respiratory therapists. The are a decrease in the level of triiodothyronine (T3) or free researchers uniformly trained the data collection personnel. triiodothyronine (FT3), an increase in the level of thyroid The main data sources included on-site collection, case and hormone reverse T3, and normal or decreased levels of nursing data, monitoring data, and related laboratory tests. thyroxine (T4)/free T4 (FT4) and thyroid-stimulating hormone The researcher performed/obtained an acute physiology and (TSH) (1). Because the decline in T3 is the most prominent and chronic health evaluation score (APACHE II), the Glasgow easy to detect in ESS, the disorder is also known as low T3 coma scale (GCS), and the sequential organ failure score syndrome (2). Thyroid hormone level disorder is secondary to (SOFA); these were reviewed by another researcher to ensure various clinical diseases because of the normal primary thyroid the accuracy of the scores. function. ESS is also known as nonthyroidal illness syndrome The patient’s body temperature, respiration, heart rate, and (NTIS) (2–8). blood pressure were measured upon admission to the ICU. The Intensive care units (ICUs) are dominated by critically ill body temperature was measured with a mercury thermometer, patients, and ESS is a common disease in these facilities (2). Few and the remaining parameters were measured with a monitor studies have been conducted on the incidence of ESS and related (Philips MP series). When patients underwent invasive blood factors in ICU patients, and the subject has received little attention. pressure monitoring, the invasive blood pressure was preferred Studiesare availableonthe incidenceofESSin ICUs,but most ofthe as the blood pressure value. When invasive blood pressure sample sizes are small, and the type of disease is relatively specific(9, monitoring was not performed, the patient’snon-invasive 10). There has been a lack of investigation and in-depth analysis of (cuff) blood pressure was used to record the systolic and large samples concerning the incidence of ESS in comprehensive diastolic blood pressures, respectively. ICUs. Therefore, this study aims to explore the incidence of ESS in a comprehensive ICU and to analyze and investigate the clinical risk Specimen Collection and factors of the syndrome. Laboratory Testing The blood samples required for the test were collected by a full-time ICU nurse via the peripheral or central vein. The blood sample MATERIALS AND METHODS required for arterial blood gas analysis was obtained either by percutaneous puncture through the radial or femoral artery or Research Subjects was drawn throughthe arterial catheter. When drawingthroughthe All eligible patients were admitted to the comprehensive ICU of arterial catheter, 5–10 ml of blood was drawn out in advance to the Third Hospital of Hebei Medical University between prevent interference with the liquid in the pipeline. Arterial blood February 2018 and November 2018. This study was approved sampling was performed by a full-time ICU nurse. The enrolled by the Ethics Committee of the Third Hospital of Hebei Medical patients were monitored for FT3, FT4, and TSH levels within University (approval No. 2018-019-1). After being informed of 24 hours of admission to the ICU. The nuclear medicine the study’s procedures, all patients or authorized family members physicians at the hospital used radioimmunoassays to analyze the signed a written informed consent form before enrolment. blood samples (Beckman DXI800). The normal laboratory values of thyroid function in the hospital were: FT3: 3.28–6.47 pmol/L, FT4: Inclusion Criteria 7.64–16.3 pmol/L, and TSH: 0.49–4.91 mIU/L. The inclusion criteria were as follows: (1) aged between 16 and 80 years, (2) admitted to the ICU for various reasons, and Scores (3) normal past thyroid function with no history of thyroid According to the standard requirements for each scoring scheme, disease, such as hyperthyroidism, hypothyroidism, or thyroid the APACHE II, GCS, and SOFA score tests were performed on tumor. According to the level of thyroid hormone FT3, patients the enrolled patients; they were scored by a professional ICU were divided into the ESS group and the non-ESS group. The doctor and reviewed by another physician. The scoring rules are normal value of FT3 is 3.28–6.47 pmol/L; patients with FT3 < shown in the attached table. 3.28 pmol/L were assigned to the ESS group, and those with FT3 ≥ 3.28 pmol/L were assigned to the non-ESS group. Statistical Methods All data were statistically analyzed using SPSS 24.0 software Exclusion Criteria (IBM). Measurement data conforming to the normal distribution The exclusion criteria were as follows: (1) hospitalization in the were expressed as x±s, and measurement data not conforming ICU for less than 24 hours, (2) admission to the ICU for organ to the normal distribution were expressed in the median form Frontiers in Endocrinology | www.frontiersin.org 2 June 2021 | Volume 12 | Article 656641 Guo et al. Euthyroid Sick Syndrome in ICU (the interquartile range). An independent sample t-test was used Comparison of Vital Signs at Enrolment for the comparison of measurement data conforming to the Between the ESS and Non-ESS Groups – normal distribution, and the Mann Whitney rank sum test was At the time of enrolment, the body temperature of the ESS group used for the abnormal distribution. The count data were was 37.33°C ± 0.92°C, while that of the non-ESS group was 37.26°C ± ’ expressed as the number of cases (percentage), and Pearson s 0.84°C.