Discussion
Our study showed that lower FT3 levels were associated with poor outcome at 3 months after acute ischemic stroke, and this association remained significant after adjusting for the effect of risk factors and comorbidities. There were two previous studies consistent with our findings. Ambrosius et al (16) found that in acute ischemic stroke patients lower free T3 levels were an important factor related to unfavorable outcome. Zhang et al (14)found that FT3 was significantly decreased in AIS patients with poor outcome and served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38pmol/L. However, O’Keefe et al (11) enrolled 129 ischemic stroke patients and found that low FT3 value was not associated with poor outcome at 3 months in the multivariate analysis when other known predictors of outcome such as stroke severity (NIHSS) were controlled. The contradictory findings could be due to the relatively small sample size of the study. In addition, our study also showed that the detrimental effect of FT3 level on functional outcome increased as FT3 level decreased and neither TSH nor FT4 were associated with poor outcome at 3 months after ischemic stroke. There was one previous study to confirm and strengthen our findings. Satoshi et al (21)retrospectively enrolled 398 consecutive ischemic stroke patients to investigate the association of admission serum thyroid hormone concentration with functional outcomes and a dose-effect relationship between FT3 levels upon admission and poor outcome was noticed. In addition, critical illness could result in decreased peripheral conversion of FT4 to FT3 in the absence of a primary thyroid disorder indicating that FT3 might be more sensitive to the influence of critical illness than FT4, TSH(22), which indirectly supported our findings as well.
The potential pathophysiological mechanism linking low levels of FT3 to poor outcome is not well established. Previous study indicates that low T3 syndrome is independently associated with the risk of hemorrhagic transformation in acute ischemic stroke (23). Low FT3 levels at admission are independently associated with Post-stroke infection occurrence and may contribute to poor outcome(24).Although it is unknown whether administration of exogenous thyroid hormone in ischemic stroke patients improves outcomes, in animal experiment demonstrate that administration of T3 could modulate neuronal plasticity mechanisms to enhance functional outcome after stroke(25). Therefore, further well-designed studies and randomized controlled trials are needed to demonstrate the underlying mechanism between FT3 and functional outcome and whether supplementation of T3 could reduce disability after acute ischemic stroke.
Several limitations should be considered in the interpretation of our study. First, it was based on single center data, thus inevitably leading to selection bias. Second, we only measured the thyroid hormone levels once and not dynamically as a function of time. Another limitation was that we did not have the opportunity to measure total T3 and T4 levels, which might have given slightly different results.