Free Thyroxine (fT4) as a Potential Biomarker of Neurological and Functional Outcome in Acquired Brain Injury: A Prospective Multicenter Cohort Study

The potential involvement of thyroid hormones (THs) in the neurological and functional recovery of patients with brain damage has been hypothesized. We aimed at investigating the role of THs and their variations during the rehabilitation process as predictive biomarkers of neurological and functional outcome in patients with acquired brain injury (ABI). This prospective, multicenter cohort study included 220 patients with ABI consecutively admitted for a 6-month neurorehabilitation program. Data on the etiology of the brain injury, occurrence of seizures, neurosurgical procedures, and death during hospitalization were collected. Both at the baseline (T0) and at the end of the rehabilitation process (T1), the following variables were evaluated: thyroid function (TSH, fT4, and fT3) and outcome measure including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale-Extended (GOS-E), and Functional Independence Measure (FIM) scale. During neurorehabilitation, a significant decrease in fT4 levels was documented in the population as a whole and in patients with severe ABI (p < 0.0001), whereas no significant variations were found in TSH and fT3 levels. No significant associations were found between THs and seizure occurrence, while the neurological and functional outcomes were associated with the variation in fT4 levels during rehabilitation. In particular, a higher magnitude of decrease in fT4 levels emerged as an independent predictor of more severe neurological damage (OR = 3.48, CI 95% 1.04-11.69, p = 0.04) and a lower functional recovery (β = -0.22, p = 0.01). In conclusion, serum fT4 variation during neurorehabilitation could represent a potential biomarker of neurological and functional outcome in patients with ABI. Further studies are needed to investigate the mechanisms underlying this association.