Low free triiodothyronineis predicts worsen neurological outcome of patients with acute ischemic stroke: a retrospective study with bioinformatics analysis

Abstract

BackgroudPatients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear.MethodsWe retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed.ResultsFT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes.ConclusionsLow FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

Thyroid Function in Patients with Acute Ischemic Stroke

“…Moreover, studies suggests that thyroid status may influence recovery, prognosis, and outcomes of rehabilitation in stroke patients, but published data provide partially inconsistent results [8][9][10][11][12]. Therefore, the complex interrelationships between the thyroid, the heart and the brain remain an area of interest with a potential for future prevention and treatment approaches.…”

Risk Factors Associated with Ischemic Stroke in a Young Non-Diabetic and Non-Hypertensive Population: A Retrospective Case-Control Study

“…We also found that FT3 levels were negatively correlated with IS incidence among young adults. This is the rst study to our knowledge to have reported such a relationship, as prior studies and meta-analysis have largely focused on correlations between low FT3 levels and severity/mortality among acute IS patients [23][24][25][26][27]. These prior studies have reported such a relationship even for low FT3 values within the standard reference range [28,29].…”

“…One study, however, found that this relationship was age-dependent, such that TT3 and FT3 levels were unrelated to IS outcomes in patients < 65 years old, whereas TT3 levels were independently predictive of poor outcomes among older patients [30]. In these prior studies, the average population ages ranged from 61.4-81.5 years [23][24][25][26][27][28], with the exception of one study with a median population age of 48 years [29]. Serum TT3 and FT3 levels are lower among healthy older individuals [31], and FT3 levels decline over time [32].…”

T3 as predictor of mortality in any cause non-critically ill patients

“…We also observed a shorter readmission-free period on low T3 patients, but no difference was detected in the length of stay or readmissions rate in the 6 month period. Other studies found a longer length of stay in patients in ICU ( 15 , 17 ). Besides, considering that the comparison is made with ICU patients, our finding suggests that low T3 levels could be seen as a marker of the severity of the disease as well as the metabolic alterations caused by it.…”

“…This pattern of thyroid hormone alterations was described in several scenarios of acute or chronic illness ( 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ). In addition, there is a significant correlation between altered thyroid hormone levels and the severity and duration of disease ( 9 , 10 , 11 , 12 , 17 , 18 , 19 , 20 ).…”