ENDOCRINE AND IMMUNOLOGICAL ALTERATIONS IN SEVERE TRAUMA: CONTEMPORARY BIOMARKERS, PROGNOSTIC FACTORS, AND CLINICAL IMPLICATIONS
Abstract
Severe trauma triggers a complex and dynamic response of the organism that includes simultaneous endocrine, immunological and metabolic alterations with a direct impact on the clinical course and treatment outcome. Hypothalamic-Pituitary-Adrenal (HPA) axis activation, changes in the secretion of catecholamine, disorders of the thyroid function and imbalance of the inflammatory response are key components of the systemic response to traumatic stress. The aim of this review article was to systematize endocrine and immunological biomarkers that have prognostic relevance in patients with severe trauma based on contemporary literature, as well as to review their clinical implications in intensive care medicine. Relevant papers published in the period 2014 to 2025 were reviewed in order to analyze changes in cortisol and catecholamine concentrations, Critical Illness-related Corticosteroid Insufficiency (CIRCI) Syndrome, Non-Thyroid Illness Syndrome (NTIS), as well as inflammatory biomarkers such as Interleukin-6 and C-reactive protein. Special attention was paid to their role in predicting mortality, development of multiple organ dysfunction, respiratory deterioration and septic complications. Available data indicate that early disorders of endocrine axes, especially abnormal patterns of cortisol and thyroid reactions have a significant prognostic values, while inflammatory and transcriptomic biomarkers allow more precise risk stratification in the early stages of critical disease. The integration of endocrine, immunological and metabolic biomarkers with clinical parameters and demographic characteristics of patients is the basis of a modern, personalized approach in the treatment of severe trauma. Further research should be directed towards standardization of diagnostic criteria, optimal sampling time and evaluation of therapeutic interventions, with the aim of improving outcomes and reducing mortality in critically ill patients.
References
Brauckmann V., Enke S.R., Dietrich A.K.I.M., Roth S., Wilhelmi M. Patterns of sex-specific outcomes and mortality in polytrauma: a demographic and epidemiologic analysis by injury severity score. Eur J Trauma Emerg Surg 2025;51:250. Available at: https://doi.org/10.1007/s00068-025-02930-7
Maas A. I. R., Menon D. K., Manley G. T., Abrams M., Åkerlund C., Andelic N. et al. InTBIR Participants and Investigators (2022). Traumatic brain injury: progress and challenges in prevention, clinical care, and research. The Lancet. Neurology, 21(11), 1004–1060. https://doi.org/10.1016/S1474-4422(22)00309-XKwok AM, Davis JW, Dirks RC, Sue LP, Wolfe MM, Kaups K. Prospective evaluation of admission cortisol in trauma. Trauma Surg Acute Care Open. 2020;5(1):e000386. doi:10.1136/tsaco-2019-000386
Engel S, Laufer S, Klusmann H, Schulze L, Schumacher S, Knaevelsrud C. Cortisol response to traumatic stress to predict PTSD symptom development - a systematic review and meta-analysis of experimental studies. Eur J Psychotraumatol. 2023;14(2):2225153. doi:10.1080/20008066.2023.2225153
Sobolewska J, Dzialach L, Kuca P, Witek P. Critical illness-related corticosteroid insufficiency (CIRCI) - an overview of pathogenesis, clinical presentation and management. Front Endocrinol (Lausanne). 2024;15:1473151. doi:10.3389/fendo.2024.1473151
Prete A., Yan Q., Al-Tarrah K., Akturk H. K., Prokop L. J., Alahdab F. (2018). The cortisol stress response induced by surgery: A systematic review and meta-analysis. Clinical endocrinology, 89(5), 554–567. https://doi.org/10.1111/cen.13820
Duran I., Banerjee A., Flaherty P. J., Que Y. A., Ryan C. M., Rahme L. G. et al. (2024). Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome. Annals of intensive care, 14(1), 134. https://doi.org/10.1186/s13613-024-01364-5
Trancă SD, Petrişor CL, Hagău N. Biomarkers in polytrauma induced systemic inflammatory response syndrome and sepsis - a narrative review. Rom J Anaesth Intensive Care. 2014;21(2):118-122.
Marta R, Svitlana Y, Konstiantyn K, Maryna M, Andriy D, Oleksandr O. Potential Predictors of Mortality in Adults with Severe Traumatic Brain Injury. Brain Sciences. 2025; 15(9):1014. Available at: https://doi.org/10.3390/brainsci15091014
Goder N., Gerstenhaber F., Gal Oz A., Stavi D., Angel Y., Nini A., et al. (2024). Cortisol Levels During First Admission Day Are Associated With Clinical Outcomes in Surgical Critically Ill Patients. Critical care explorations, 6(5), e1086. https://doi.org/10.1097/CCE.0000000000001086
Menger MM, Histing T, Laschke MW, Ehnert S, Viergutz T, Fontana J. Cortisol stress response after musculoskeletal surgery: a narrative review. EFORT Open Rev. 2025;10(4):186-192. doi:10.1530/EOR-2024-0126
Suh JI, da Roza DL, Cadamuro FM, Malbouisson LMS, Sanches TR, Andrade L. Catecholamine concentration as a predictor of mortality in emergency surgical patients. Int J Emerg Med. 2024;17(1):95. doi:10.1186/s12245-024-00676-4
Voelckel WG. Vasopressin in traumatic hemorrhagic shock. Curr Opin Anaesthesiol. 2025;38(2):81-92. doi:10.1097/ACO.0000000000001456
Nesek Adam V, Keranović A, Simić A, Matolić M, Murselović T. Vasopressors in Trauma Patients: A Review of Indications, Benefits, and Controversies. ANNALES MEDICINAE URGENTIS;1(1):60-66. Available at: https://doi.org/10.64266/amu.1.1.10
Gauss T., Gayat E., Harrois A., Raux M., Follin A., Daban J. L. et al.(2018). Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. British journal of anaesthesia, 120(6), 1237–1244. https://doi.org/10.1016/j.bja.2018.02.032
Morabito LA, Corica D, Pepe G, Li Pomi A, Aversa T, Wasniewska MG. Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge. Ital J Pediatr. 2024;50(1):46. Published 2024 Mar 11. doi:10.1186/s13052-024-01616-x
Vidart J, Jaskulski P, Kunzler AL, Marschner RA, Ferreira de Azeredo da Silva A, Wajner SM. Non-thyroidal illness syndrome predicts outcome in adult critically ill patients: a systematic review and meta-analysis. Endocr Connect. 2022;11(2):e210504. doi:10.1530/EC-21-0504
Elmas D, Kizilarslanoglu MC. Non-Thyroidal Illness Syndrome: A Predictor of Non-Invasive Ventilation Failure and Mortality in Critically Ill Patients. Medicina. 2025;61(5):927. Available at: https://doi.org/10.3390/medicina61050927
Sciacchitano S, Capalbo C, Napoli C, Anibaldi P, Salvati V, De Vitis C, et al. Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses. Front Endocrinol. 2022;13:850328. doi: 10.3389/fendo.2022.850328
Wu H, Mu Y, Liu Y, Zhang R, Xu Y, Zhang Y, et al. The Impact of Non-Thyroidal Illness Syndromes on The Prognosis and Immune Profile in Severe Fever with Thrombocytopenia Syndrome Patients. Infect Drug Resist. 2025;18:1439-1449.
Available at: https://doi.org/10.2147/IDR.S506378
Hifumi T., Okada I., Kiriu N., Hasegawa E., Ogasawara T., Kato H. Et al. Thyroid hormone alterations in trauma patients requiring massive transfusion: An observational study. World journal of emergency medicine, 5(4), 270–274. https://doi.org/10.5847/wjem.j.issn.1920-8642.2014.04.005 (2014).
Armanious TR, Khalifa AA, Abubeih H, Badran M, Adam FF, Farouk O. Admission Blood Glucose Level with a Cutoff Value of 15 mmol/L Is a Reliable Predictor of Mortality in Polytraumatized Patients—a Prospective, Observational, Longitudinal Study From a North African Level One Trauma Center. Orthop Res Rev. 2025;17:43-54.