Citation

Ranganathan P, Kumar RG, Oh BM, Rakholia MV, Berga S, Wagner AK. J. Neurotrauma 2019; 36(4): 538-547.

Affiliation

University of Pittsburgh , PM&R , 3471 Fifth Avenue Suite 202 , Pittsburgh, Pennsylvania, United States , 15213 ; wagnerak@upmc.edu.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2018.5677

PMID

30014751

Abstract

Early declines in gonadotropin production, despite elevated serum estradiol, among patients with severe traumatic brain injury (TBI) suggests amplified aromatization occurs post-injury. Our previous work identifies estradiol (E2) as a potent mortality marker. Androstenedione (Andro), a metabolic precursor to E2 and testosterone (T), is a steroid hormone, yet has not been explored in TBI. We evaluated daily serum Andro, estrone (E1), T, and E2 over the first three days post-injury for 82 subjects with severe TBI. Daily hormone values were calculated, and E2:Andro (E2:A) and E1:T ratios were generated and then averaged. After data inspection, mean E2:A values were categorized as above (high aromatization) and below (low aromatization) the 50th percentile for 30-day mortality assessment using Kaplan-Meier survival analysis and a multivariable Cox proportional hazard model adjusting for age, and Glasgow Coma Scale (GCS) to predict 30-day mortality status. Daily serum T, E1, and E2 were graphed by E2:A category. Serum E1 and E2 significantly differed over time (p<0.05); the high aromatization group had elevated levels. The high aromatization group had a significantly lower probability of survival within the first 30-days (p=0.0274). The multivariable Cox model showed a significant E2:A*GCS interaction (p=0.0129), wherein GCS predicted mortality only among those in the low aromatization group. E2:A may be a useful mortality biomarker representing enhanced aromatization after TBI. E2:A ratios represent non-neurological organ dysfunction after TBI and may be useful in defining injury subgroups in which GCS has variable capacity to serve as an accurate early prognostic marker.

Language: en

Keywords

BIOMARKERS; CLINICAL MANAGEMENT OF CNS INJURY; OUTCOME MEASURES; PROSPECTIVE STUDY; TRAUMATIC BRAIN INJURY