Early Serum Thyroxine as a Prognostic and Psychoneuroendocrine Marker after Moderate-to-Severe Traumatic Brain Injury

Abstract This article evaluates whether early serum thyroxine (T4) concentrations predict neurological and psychological outcomes following moderate-to-severe traumatic brain injury (TBI). This prospective cohort enrolled 56 adults (44 men) with moderate (Glasgow Coma Scale [GCS] 9–12; n = 19) or severe (GCS ≤ 8; n = 37) TBI at a tertiary trauma center. Total T4 and free T4 (fT4) were measured within 10 days of injury, then at 6 and 12 months. Neurological outcome was assessed using Glasgow Outcome Scale-Extended (GOSE); depression and anxiety were evaluated with Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) at 1 year. Multivariable logistic regression examined independent associations between baseline T4 and unfavorable outcome (GOSE ≤ 4), as well as clinically significant depressive (PHQ-9 ≥ 10) or anxiety (GAD-7 ≥ 10) symptoms. Median baseline fT4 was significantly lower in severe versus moderate TBI (0.77 vs. 0.89 ng/dL, p = 0.021) and correlated positively with admission GCS (ρ = 0.34, p = 0.010). Unfavorable neurological outcome at 6 months occurred in 26/54 evaluable patients (48%). After adjusting for age, sex, admission GCS, and cranial computed tomography score, each 0.1 ng/dL decrease in baseline fT4 increased odds of unfavorable outcome by 28% (adjusted odds ratio [OR] 1.28; 95% confidence interval 1.07-1.55; p = 0.007). At 1 year, 18/50 (36%) and 15/50 (30%) screened positive for depression and anxiety, respectively. Lower early fT4 independently predicted both depressive (adjusted OR 1.35 per 0.1 ng/dL decrease; p = 0.004) and anxiety symptoms (adjusted OR 1.29; p = 0.017). Serial measurements demonstrated spontaneous T4 normalization in most survivors by 6 months. Early reduction in serum fT4 frequently occurs after moderate-to-severe TBI and independently predicts functional recovery and subsequent affective morbidity. Routine fT4 measurement during the acute phase may enhance prognostication and identify patients requiring endocrine and psychological surveillance.