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.