Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes

Abstract

Purpose That thyroid hormones exert pleiotropic effects and have a contributory role in triggering seizures in patients with traumatic brain injury (TBI) can be hypothesized. We aimed at investigating thyroid function tests as prognostic factors of the development of seizures and of functional outcome in TBI. Methods This retrospective study enrolled 243 adult patients with a diagnosis of mild-to-severe TBI, consecutively admitted to our rehabilitation unit for a 6-month neurorehabilitation program. Data on occurrence of seizures, brain imaging, injury characteristics, associated neurosurgical procedures, neurologic and functional assessments, and death during hospitalization were collected at baseline, during the workup and on discharge. Thyroid function tests (serum TSH, fT4, and fT3 levels) were performed upon admission to neurorehabilitation. Results Serum fT3 levels were positively associated with an increased risk of late post-traumatic seizures (LPTS) in post-TBI patients independent of age, sex and TBI severity (OR = 1.85, CI 95% 1.22–2.61, p < 0.01). Measured at admission, fT3 values higher than 2.76 pg/mL discriminated patients with late post-traumatic seizures from those without, with a sensitivity of 74.2% and a specificity of 60.9%. Independently from the presence of post-traumatic epilepsy and TBI severity, increasing TSH levels and decreasing fT3 levels were associated with worse neurological and functional outcome, as well as with higher risk of mortality within 6 months from the TBI event. Conclusions Serum fT3 levels assessed in the subacute phase post-TBI are associated with neurological and functional outcome as well as with the risk of seizure occurrence. Further studies are needed to investigate the mechanisms underlying these associations.

The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19

“…What is surprising is that in the overall trend of laboratory findings of inflammation/coagulopathy/fibrinolysis in ESS patients at different time points, most parameters emerged a turning point at T3 (D9-D11 after admission), which is almost certainly a critical period related to prognosis. CRP, D-dimer, and fibrinogen (FIB) increased at the initial phase of SARS-COV-2 infection, with two peaks at day 5 and day 9 (30). CRP played an important role in inflammation, the tissue factor (TF) pathway, blood coagulation, endogenous fibrinolytic capacity, and the susceptibility of venous thromboembolism (31,32).…”

Thyrotropic Axis and Disorders of Consciousness in Acquired Brain Injury: A Potential Intriguing Association?

“…In this pioneering study we found that, independently from confounders, lower baseline TSH levels and higher TSH increments during 6-months inpatient neurorehabilitation predicted an improvement of DoC, while baseline fT4 and fT3 levels and their variations during rehabilitation did not appear to play a role in DoC changes. Although serum TSH levels are usually normal during the post-acute phase of ABI, we were unable to find a correlation between TSH and THs, suggesting a central derangement of pituitary TSH secretion ( 33 ). It is known that thyrotropic axis signaling in the brain can be disrupted by a severe damage ( 34 ), likely through mechanisms that involved both THs signaling deregulation and alterations in TRH and TSH secretion and feedbacks ( 32 , 35 ).…”

“…The role of thyrotropic axis on rehabilitation and mortality after acquired brain injuries is still debated. In a previous study on patients with mild-to-severe TBI, we observed that increasing TSH and declining fT3 levels were associated with worst neurological and functional outcomes, as well as with a higher risk of mortality within 6 months following TBI ( 33 ). In this cohort, a narrower variation of fT4 levels was associated with an improvement in functional disability level and cognitive functions.…”

“…Although we found no associations between serum fT4 and fT3 levels and DoC evolution, we hypothesize that serum levels of THs are not able to reflect the local alterations of THs in the brain. Alternatively, an altered permeability of blood brain barrier (BBB) could allow an abnormal entry of THs from the bloodstream to the brain, but this remains difficult to be quantified ( 33 ).…”

“…In this context, the effect of the thyrotropic axis on consciousness is unknown so far. Thyroid function is essential for adult brain function and yields a key role in controlling neural stem cells function in the hippocampus and the subventricular zone, main sites of neurogenesis, as well as in processes modulating neuronal plasticity after injuries (30)(31)(32)(33). Further, THs signaling influences activation of ARAS and promotes cortical function, while TRH is known to influence the state of consciousness (19).…”