Some aspects of the humoral dysfunctions in patients with chronic disorders of consciousness (literature review)
https://doi.org/10.24884/2078-5658-2026-23-2-111-120
Abstract
The objective was to analyze the literature on neuroendocrine dysfunctions in patients with chronic disorders of consciousness (DoC), who are in intensive care units due to their chronic critical condition.
Materials and methods. We conducted a systematic review of Englishand Russian-language sources (PubMed, Scopus, Web of Science, etc.) from 2006 to 2024. Fifty publications (systematic reviews) were included that provided data on hormonal status in patients with DoC and chronic critical illness (CCI).
Results. In most cases, the authors indicated hypothalamic-pituitary-adrenal axis (HPA-axis) dysregulation (blunted diurnal cortisol variation, ACTH-cortisol dissociation, secondary adrenal insufficiency). The HPT-axis dysregulation frequently shows non-thyroidal illness syndrome («low T3»), associated with severity and mortality. The HPG-axis dysregulation is frequently accompanied by the development of hypogonadotropic hypogonadism. Many endocrine dysfunctions are associated, among other things, with circadian rhythm disorders. Paroxysmal sympathetic hyperactivity (PSH) is a major modifier of both endocrine profiles and clinical expression. Suggested practices include screening for adrenal insufficiency, hormone replacement therapy.
Conclusions. In patients with chronic disorders of consciousness, various endocrine dysfunctions commonly occur and may have a significant impact on disease course and prognosis. Early identification and multidisciplinary management of hormonal dysfunctions potentially improve functional outcomes. Prospective, multicenter studies are warranted to standardize diagnostics for central adrenal insufficiency and to assess the effectiveness of hormone-directed interventions.
About the Authors
P. Pradhan
Federal Scientific and Clinical Center for Intensive Care and Rehabilitation;
Peoples’ Friendship University of Russia named after Patrice Lumumba
Russian Federation
Russian Federation
Pradhan Pranil, Junior Research Fellow, Federal Research and Clinical Center of Intensive Care and Rehabilitation, Assistant of the Department of Anesthesiology and Intensive Care with the course of Medical Rehabilitation, Peoples’ Friendship University of Russia named after Patrice Lumumba
Moscow
M. V. Petrova
Federal Scientific and Clinical Center for Intensive Care and Rehabilitation;
Peoples’ Friendship University of Russia named after Patrice Lumumba
Russian Federation
Russian Federation
Petrova Marina V., Dr. of Sci. (Med.), Professor, Deputy Director for Scientific and Clinical Work, Federal Research and Clinical Center of Intensive Care and Rehabilitation (Moscow, Russia), Head of the Department of Anesthesiology and Intensive Care with the course of Medical Rehabilitation, Peoples’ Friendship University of Russia named after Patrice Lumumba
Moscow
I. V. Borisov
Federal Scientific and Clinical Center for Intensive Care and Rehabilitation
Russian Federation
Russian Federation
Borisov Ilya V., Research Fellow
Moscow
A. M. Fisun
Saratov State Medical University named after V. I. Razumovsky
Russian Federation
Russian Federation
Fisun Alexey M., Cand. of Sci. (Med.), Associate Professor of the Department of Emergency and Intensive Care Medicine and Simulation Technologies in Medicine
Saratov
D. V. Protasova
Almazov National Medical Research Centre
Russian Federation
Russian Federation
Protasova Diana V., Postgraduate Student of the Department of Anesthesiology and Intensive Care with the Clinic of the Institute of Medical Education
Saint Petersburg
L. M. Tsentsiper
Peoples’ Friendship University of Russia named after Patrice Lumumba;
Almazov National Medical Research Centre;
Polenov Russian Scientific Research Neurosurgical Institute – Almazov National Medical Research Centre;
Saint Petersburg State Pediatric Medical University
Russian Federation
Russian Federation
Tsentsiper Lubov M., Dr. of Sci. (Med.), Professor of the Department of Anesthesiology and Intensive Care with the Clinic of the Institute of Medical Education, Almazov National Medical Research Center, Anesthesiologist and Intensivist, Endocrinologist, Polenov Russian Scientific Research Neurosurgical Institute – Almazov National Medical Research Centre, Professor of the Department of Anesthesiology, Intensive Care and Emergency Pediatrics at the Faculty of Postgraduate and Additional Professional Education, Saint Petersburg State Pediatric Medical University, Professor of the Department of Anesthesiology and Intensive Care with the course of Medical Rehabilitation at the Medical Institute, Peoples’ Friendship University of Russia named after Patrice Lumumba
Saint Petersburg, Moscow
References
1. Belkin A. A., Aleksandrova E. V., Akhutina T. V. et al. Chronic Disorders of Consciousness: guidelines of the All-Russian public organization “Federation of Anesthesiologists and Reanimatologists”. Annals of Critical Care, 2023, no. 3, pp. 7–42. http://doi.org/10.21320/1818-474X-2023-3-7-42.
2. Ivanova A. O., Kondratyeva E. A., Yarmolinskaya M. I. et al. Case reports of patients with chronic disorders of consciousness in obstetric and gynecological practice. Journal of obstetrics and women’s diseases, 2020, vol. 69, no. 6, pp. 31–42. http://doi.org/10.17816/JOWD69631-42.
3. Ivanova A. O., Yarmolinskaya M. I., Kondratyeva E. A. The hormonal status and the possibility of predicting outcomes in patients with different types of chronic disorders of consciousness. Journal of obstetrics and women’s diseases, 2023, vol. 72, no. 3, pp. 39–51. http://doi.org/10.17816/JOWD370684.
4. Nekrasova I. Y., Grechko A. V., Kanarskii M. М. et al. Three-year survival rate and changes in the level of consciousness in outpatients after severe brain injuries. Annals of Clinical and Experimental Neurology, 2023, vol. 17, no. 3, pp. 31–40. http://doi.org/10.54101/ACEN.2023.3.4.
5. Rybakov G. Yu., Kondratyeva E. A., Tsentsiper L. M. et al. Some Aspects of Pituitary-Adrenal and Autonomic Nervous Systems Functioning in Patients with Chronic Consciousness Disorders. Messenger of anesthesiology and resuscitation, 2022, vol. 19, no. 5, pp. 63–70. http://doi.org/10.21292/2078-5658-2022-19-5-63-70.
6. Tsentsiper L. M., Terekhov I. S., Shevelev O. A. et al. Paroxysmal Sympathetic Hyperactivity Syndrome (Review). General Reanimatology, 2022, vol. 18, no. 4, pp. 55–67. (In Russ.). http://doi.org/10.15360/1813-9779-2022-4-55-67.
7. Alfawares Y., Yang G. L., Lamichhane R. et al. Neuroendocrine dysfunction after TBI. hot topics in acute care surgery and trauma. Springer, Cham, 2024, pp. 419–427. http://doi.org/10.1007/978-3-031-50117-3_25.
8. Bao W., Li X., Luo B. A novel prognostic approach to predict recovery in patients with chronic disorders of consciousness. Neurosci Bull, 2019, vol. 35, no. 5, pp. 953–954. http://doi.org/10.1007/S12264-019-00369-6.
9. Bernat J. L. Editorial: The natural history of chronic disorders of consciousness. Neurology, 2010, vol. 75, no. 3, pp. 206–207. http://doi.org/10.1212/WNL.0B013E3181E8E960.
10. Boonen E., Vervenne H., Meersseman P. et al. Reduced cortisol metabolism during critical illness. N Engl J Med, 2013, vol. 368, no. 16, pp. 1477–1488. http://doi.org/10.1056/NEJMoa1214969.
11. Borresen S. W., Klose M., Glintborg D. et al. Approach to the patient with glucocorticoid-induced adrenal insufficiency. J Clin Endocrinol Metab, 2022, vol. 107, no. 7, pp. 2065–2076. http://doi.org/10.1210/clinem/dgac151.
12. Chethan Kumar K. L., Shivakumar K. M. Thyroid status among critically ill patients admitted in the intensive care unit of the government tertiary care hospital in Mandya: a retrospective study. International Journal of Advances in Medicine, 2020, vol. 7, no. 3, pp. 401–403. http://doi.org/10.18203/2349-3933.IJAM20200527.
13. Challet E., Pévet P. Melatonin in energy control: Circadian time-giver and homeostatic monitor. J Pineal Res, 2024, vol. 76, no. 4, e12961. http://doi.org/10.1111/JPI.12961.
14. Chrétien M., Mbikay M. 60 years of POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9). J Mol Endocrinol, 2016, vol. 56, no. 4, pp. 49–62. http://doi.org/10.1530/JME-15-0261.
15. Gobert F., Luauté J., Raverot V. et al. Is circadian rhythmicity a prerequisite to coma recovery? Circadian recovery concomitant to cognitive improvement in two comatose patients. J. Pineal Res, 2019, vol. 66, no. 3, e12555. http://doi.org/10.1111/JPI.12555.
16. Gosseries O., Boly M., Laureys S. Transcranial magnetic stimulation coupled to EEG: a new tool to assess brain function in coma. In: Vincent J. L. (eds) Annual Update in Intensive Care and Emergency Medicine 2013. Springer. http://doi.org/10.1007/978-3-642-35109-9_63.
17. Guo L. Z. A Review on the interaction between neuroendocrinology and immunology: hypothalamic-pituitary-thyroid axis in immunoendocrinology. Cutting Edge Research in Biology, 2023, vol. 5, pp. 70–78. https://stm.bookpi.org/CERB-V5/article/view/9796.
18. Hassamal S. Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories. Front Psychiatry, 2023, vol. 14, 1130989. http://doi.org/10.3389/FPSYT.2023.1130989/PDF.
19. He J., Dang Y. Disorders of Consciousness. In: therapeutics of neural stimulation for neurological disorders. Springer, singapore, 2023, pp. 379–384. http://doi.org/10.1007/978-981-99-4538-2_27.
20. Jagota A., Thummadi N. B., Kukkemane K. Circadian regulation of hormesis for health and longevity. The science of hormesis in health and longevity, 2019, pp. 223–233. http://doi.org/10.1016/B978-0-12-814253-0.00020-6.
21. John C. D., Gavins F. N., Buss N. A. et al. Annexin A1 and the formyl peptide receptor family: neuroendocrine and metabolic aspects. Curr Opin Pharmacol, 2008, vol. 8, no. 6, pp. 765–776. http://doi.org/10.1016/j.coph.2008.09.005.
22. Kanarskii M., Nekrasova J., Kondatieva E. et al. Are circadian rhythms in disarray in patients with chronic critical illness? Sleep Med X, 2023, vol. 7, 100101. http://doi.org/10.1016/J.SLEEPX.2023.100101.
23. Kanarskii M., Nekrasova J., Vitkovskaya V. et al. Effect of retinohypothalamic tract dysfunction on melatonin level in patients with chronic disorders of consciousness. Brain Sci, 2021 – Vol. 11, no. 5, pp. 559. http://doi.org/10.3390/BRAINSCI11050559.
24. Kovacevic M., Nesek-Adam V., Klokic S. et al. Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study. World. J Crit Care Med, 2024, vol. 13, no. 3, pp. 96132. http://doi.org/10.5492/WJCCM.V13.I3.96132.
25. Langouche L., Téblick A., Gunst J. et al. The hypothalamus-pituitary-adrenocortical response to critical illness: a concept in need of revision. Endocr Rev, 2023, vol. 44, no. 6, pp. 1096–1106. http://doi.org/10.1210/endrev/bnad021.
26. Lirio P., Santos M., Silva I. et al. Oxidative stress in substance use disorders: endogenous and exogenous mechanisms of repair. Biochemistry. May 2023. http://doi.org/10.5772/INTECHOPEN.108886 https://www.intechopen.com/chapters/85059.
27. Llorens R., Ippoliti C., Navarro M. D. et al. Minimally conscious state plus versus minus: Likelihood of emergence and long-term functional independence. Ann Clin Transl Neurol, 2024, vol. 11, no. 3, pp. 719–728. http://doi.org/10.1002/ACN3.51993.
28. Lucca L. F., Lofaro D., Pignolo L. et al. Outcome prediction in disorders of consciousness: the role of coma recovery scale revised. BMC Neurol, 2019, vol. 19, 68. http://doi.org/10.1186/s12883-019-1293-7.
29. Medina II W. A., Conermann T. Opioid-induced endocrinopathy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; PMID: 32644637. https://www.ncbi.nlm.nih.gov/books/NBK559211.
30. Minnetti M., Hasenmajer V., Pofi R. et al. Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy. Journal of Endocrinology, 2020, vol. 246, no. 2, R13–R31. http://doi.org/10.1530/JOE-20-0066.
31. Nathan A. Malnutrition: Impact on long-term conditions. InnovAiT, 2021, vol. 14, №4, pp. 263–265. http://doi.org/10.1177/1755738020919143.
32. Nicolaides N. C., Charmandari E., Chrousos G. P. The hypothalamic-pituitary-adrenal axis in human health and disease. Introduction to translational cardiovascular research, 2015, pp. 91–107. http://doi.org/10.1007/978-3-319-08798-6_6.
33. Oyola M. G., Handa R. J. Hypothalamic-pituitaryadrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity. Stress, 2017, vol. 20, no. 5, pp. 476–494. http://doi.org/10.1080/10253890.2017.1369523.
34. Peeters B., Meersseman P., Vander Perre S. et al. Adrenocortical function during prolonged critical illness and beyond: a prospective observational study. Intensive Care Med, 2018, vol. 44, no. 10, pp. 1720–1729. http://doi.org/10.1007/s00134-018-5366-7.
35. Piradov M. A., Suponeva N. A., Ryabinkina Y. V. et al. Study of chronic post-comatose states: on the way to understanding the phenomenon of consciousness. Velichkovsky B. M., Balaban P. M., Ushakov V. L. (eds). Advances in Cognitive Research, Artificial Intelligence and Neuroinformatics. Intercognsci 2020. Advances in Intelligent Systems and Computing, vol. 1358. Springer, Cham. http://doi.org/10.1007/978-3-030-71637-0_60.
36. Praveen N. S., Modi K., Sethi B. et al. Study of non-thyroidal illness syndrome and its recovery in critically ill patients at a tertiary care centre in South India. Indian. J Endocrinol Metab, 2023, vol. 27, no. 1, pp. 50–55. http://doi.org/10.4103/ijem.ijem_349_22.
37. Robayo A. M. M. Hypotalamus-Pituitary-Adrenal (HPA) axes and their relationship with stress, mood, personality, and neurocognitive functioning. Logic, argumentation & reasoning, 2023, vol. 34, pp. 341–365. http://doi.org/10.1007/978-3-031-46742-4_11.
38. Şahin Ş. K., Aslan E. Inflammation as a neurobiological mechanism of cognitive impairment in psychological stress. J Integr Neurosci, 2024, vol. 23, no. 5, pp. 101. http://doi.org/10.31083/J.JIN2305101.
39. Secci S., Liuzzi P., Hakiki B. et al. Low-density EEG-based functional connectivity discriminates minimally conscious state plus from minus. Clin Neurophysiol, 2024, vol. 163, pp. 197–208. http://doi.org/10.1016/j.clinph.2024.04.021.
40. Song J. H., Kim J. H., Lee S. M. et al. prognostic implication of adrenocortical response during the course of critical illness. Acute and Critical Care, 2019, vol. 34, no. 1, pp. 38–45. http://doi.org/10.4266/ACC.2018.00339.
41. Téblick A., Langouche L., Van den Berghe G. Anterior pituitary function in critical illness. Endocr Connect, 2019, vol. 8, no. 8, R131–R143. http://doi.org/10.1530/EC-19-0318.
42. Téblick A., Gunst J., Van den Berghe G. Critical illness-induced corticosteroid insufficiency: what it is not and what it could be. J Clin Endocrinol Metab, 2022, vol. 107, №7, pp. 2057–2064. http://doi.org/10.1210/clinem/dgac201.
43. Thibaut A., Bodien Y. G., Laureys S. et al. Minimally conscious state “plus”: diagnostic criteria and relation to functional recovery. J Neurol, 2020, vol. 267, pp. 1245–1254. http://doi.org/10.1007/s00415-019-09628-y.
44. Usami N., Asano Y., Ikegame Y. et al. Cerebral glucose metabolism in patients with chronic disorders of consciousness. Canadian Journal of Neurological Sciences, 2023, vol. 50, no. 5, pp. 719–729. http://doi.org/10.1017/cjn.2022.301.
45. Vanhorebeek I., Langouche L., Van den Berghe G. Endocrine aspects of acute and prolonged critical illness. Nat Clin Pract Endocrinol Metab, 2006, vol. 2, no. 1, pp. 20–31. http://doi.org/10.1038/ncpendmet0071.
46. Vanwijngaerden Y. M., Wauters J., Langouche L. et al. Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. Hepatology, 2011, vol. 54, no. 5, pp. 1741–1752. http://doi.org/10.1002/hep.24582.
47. Villar J., Ferrando C., Martínez D. et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med, 2020, vol. 8, no. 3, pp. 267–276. http://doi.org/10.1016/S2213-2600(19)30417-5.
48. Wu H., Lv W., Jiang L. et al. Increased adrenocorticotropic hormone levels predict recovery of consciousness in patients with disorders of consciousness. J. Neurotrauma, 2024, vol. 41, no. 15–16, e1976–e1985. http://doi.org/10.1089/NEU.2023.0501.
49. Yang Y., Yang Yi., Tang Y. et al. Analysis of pituitary-related hormone changes and influencing factors in patients with chronic consciousness disorders. Journal of the Third Military Medical University, 2021, vol. 43, no. 15, pp. 1430–1436. http://doi.org/10.16016/J.1000-5404.202103120.
50. Zhong Y. H., Wu H. Y., He R. H. et al. Sex differences in sex hormone profiles and prediction of consciousness recovery after severe traumatic brain injury. Front Endocrinol (Lausanne), 2019, vol. 10, pp. 261. http://doi.org/10.3389/FENDO.2019.00261.
Review
For citations:
Pradhan P., Petrova M.V., Borisov I.V., Fisun A.M., Protasova D.V., Tsentsiper L.M. Some aspects of the humoral dysfunctions in patients with chronic disorders of consciousness (literature review). Messenger of ANESTHESIOLOGY AND RESUSCITATION. 2026;23(2):111-120. (In Russ.) https://doi.org/10.24884/2078-5658-2026-23-2-111-120
Email this article 