Neuroendocrine Changes are common during the acute Phase of Traumatic Brain Injury and Subarachnoid Hemorrhage

Main Article Content

Pétur Sigurjónsson, MD Msc. Asta Dogg Jonasdottir, MD Msc. Ingvar H Olafsson, MD Sigurbergur Karason, MD, PhD, professor Gudmundur Sigthorsson, MD Msc PhD Helga A Sigurjonsdottir, MD, PhD, professor


Background and aims of the study: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) can cause death and long-term morbidity. Studies indicate that both TBI and SAH may affect pituitary function in both the acute and the chronic phase. The aims of this study were firstly to evaluate the nature of neuroendocrine changes in the acute phase of moderate and severe TBI and all SAH, to evaluate association between neuroendocrine disturbance and indicators of severity of insult as well as hypotension, desaturation and anemia and to evaluated the incidence of neuroendocrine changes after moderate and severe TBI and SAH in the acute phase. Purpose: To explore neuroendocrine disturbances in moderate traumatic brain injury (mTBI), severe TBI (sTBI) and subarachnoid hemorrhage (SAH) in the acute phase.

Methods: The study was a prospective single-center study. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on admission (day 0) with baseline hormone levels and on day 6 post insult with baseline hormone levels and a Synacthen test. From patient charts we recorded for all patients GCS, APACHEII score, length of ICU stay, pupil dilatation, documented hypotension, desaturation and hemoglobin value <80 g/dL. Hunt and Hess grade for SAH group and Injury severity score for TBI group. S100b was measured in all patients on admission. We included 21 TBI patient, 6 moderate TBI and 15 severe TBI, and 19 SAH patients. Anterior hypothalamic-pituitary (HP) hormone axis were assessed on day 0 and 6 post insult in Twenty-one TBI patient and 19 SAH patients.

Results: HP-adrenal axis: The TBI group had significantly lower mean cortisol than the SAH group on day 0, 23.8% of TBI patients had low cortisol and 0% of SAH patients. On day 6, one patient in each group had low cortisol, 6.7% of TBI and 9.1% of SAH. HP-gonadal axis: In males on day 0, 52.9% of TBI patients and 57.1% of SAH patients had suppressed HP-gonadal axis and on day 6, 84.6% of TBI patients and 90% of SAH patients. There was a greater suppression of LH/FSH in the TBI group. HP-thyroid axis: Only one TBI patient (5.9%) had secondary hypothyroidism on day 6. HP-somatotroph axis: On day 0, 52.4% of TBI patients and 35.7% of SAH patients had low IGF-1. On day 6 all but one TBI patient (5.9%) had normalized their IGF-1 but 25% of SAH patients still had low IGF-1. In general, when evaluating association there seemed to more suppression of the hypothalamic-pituitary (HP) gonadal and thyroid axis with more severe insult and adequately more activation of the hypothalamic-pituitary adrenal axis.

Conclusion: Neuroendocrine disturbances in the acute phase of TBI and SAH are common and seem to differ between the two groups. The clinical significance of these disturbances is uncertain.

Keywords: Traumatic brain injury, Subarachnoid hemorrhage, Neuroendocrine disturbances, hormonal change

Article Details

How to Cite
SIGURJÓNSSON, Pétur et al. Neuroendocrine Changes are common during the acute Phase of Traumatic Brain Injury and Subarachnoid Hemorrhage. Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 19 june 2024. doi:
Research Articles


1. Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien). 2006;148(3):255-268; discussion 268. doi:10.1007/s00701-005-0651-y
2. van Gijn J, Kerr RS, Rinkel GJE. Subarachnoid haemorrhage. Lancet. 2007;369(9558):306-318. doi:10.1016/S0140-6736(07)60153-6
3. Klose M, Juul A, Struck J, Morgenthaler NG, Kosteljanetz M, Feldt-Rasmussen U. Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study. Clin Endocrinol (Oxf). 2007;67(4):598-606. doi:10.1111/j.1365-2265.2007.02931.x
4. Hannon MJ, Crowley RK, Behan L a, et al. Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality. J Clin Endocrinol Metab. 2013;98(8):3229-3237. doi:10.1210/jc.2013-1555
5. Poll E, Bostro A, Bu U, et al. Cortisol Dynamics in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage : 2010;195(January):189-195.
6. Lanterna L a, Spreafico V, Gritti P, et al. Hypocortisolism in noncomatose patients during the acute phase of subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2013;22(7):e189-96. doi:10.1016/j.jstrokecerebrovasdis.2012.11.002
7. Agha A, Rogers B, Mylotte D, et al. Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf). 2004;60(5):584-591. doi:10.1111/j.1365-2265.2004.02023.x
8. Dimopoulou I, Tsagarakis S, Theodorakopoulou M, et al. Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors. Intensive Care Med. 2004;30(6):1051-1057. doi:10.1007/s00134-004-2257-x
9. Tanriverdi F, Dagli AT, Karaca Z, et al. High risk of pituitary dysfunction due to aneurysmal subarachnoid haemorrhage: a prospective investigation of anterior pituitary function in the acute phase and 12 months after the event. Clin Endocrinol (Oxf). 2007;67(6):931-937. doi:10.1111/j.1365-2265.2007.02989.x
10. Khursheed N, Ramzan A, Shoaib Y, Bashir I, Wani A, Shafiq A. Is hypothyroidism and hypogonadism an issue after aneurysmal subarachnoid hemorrhage-an institutional experience? Int J Endocrinol Metab. 2013;11(3):179-183. doi:10.5812/ijem.8241
11. Kleindienst A, Brabant G, Bock C, Maser-gluth C, Buchfelder M. Neuroendocrine Function following Traumatic Brain Injury and Subsequent Intensive Care Treatment : A Prospective Longitudinal Evaluation. 2009;1446(September):1435-1446.
12. Kronvall E. Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage Is Associated with Impaired Early Outcome. Published online 2014:529-537. doi:10.1016/j.wneu.2013.10.038
13. Klose M, Brennum J, Poulsgaard L, Kosteljanetz M, Wagner A, Feldt-Rasmussen U. Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage. Clin Endocrinol (Oxf). 2010;73(1):95-101. doi:10.1111/j.1365-2265.2010.03791.x
14. Hassan-Smith Z, Cooper MS. Overview of the endocrine response to critical illness: how to measure it and when to treat. Best Pract Res Clin Endocrinol Metab. 2011;25(5):705-717. doi:10.1016/j.beem.2011.04.002
15. Jonasdottir AD, Sigurjonsson P, Olafsson IH, Karason S, Sigthorsson G, Sigurjonsdottir HA. Hypopituitarism 3 and 12 months after traumatic brain injury and subarachnoid haemorrhage. Brain Inj. 2018;32(3). doi:10.1080/02699052.2017.1418906
16. Marik PE, Pastores SM, Annane D, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937-1949. doi:10.1097/CCM.0b013e31817603ba
17. Baker SP, O’Neill B, Haddon W, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma. 1974;14(3):187-196. Accessed April 16, 2015.
18. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-829. Accessed February 19, 2015.
19. Peeters B, Boonen E, Langouche L, Van den Berghe G. The HPA axis response to critical illness: New study results with diagnostic and therapeutic implications. Mol Cell Endocrinol. 2015;408:235-240. doi:10.1016/j.mce.2014.11.012
20. Cohan P, Wang C, McArthur DL, et al. Acute secondary adrenal insufficiency after traumatic brain injury: A prospective study*. Crit Care Med. 2005;33(10):2358-2366. doi:10.1097/01.CCM.0000181735.51183.A7
21. Tandon A, Suri A, Kasliwal MK, et al. Assessment of endocrine abnormalities in severe traumatic brain injury: A prospective study. Acta Neurochir (Wien). 2009;151(11). doi:10.1007/s00701-009-0444-9
22. Olivecrona Z, Dahlqvist P, Koskinen L-OD. Acute neuro-endocrine profile and prediction of outcome after severe brain injury. Scand J Trauma Resusc Emerg Med. 2013;21(1):33. doi:10.1186/1757-7241-21-33
23. Bendel S, Koivisto T, Ruokonen E, et al. Pituitary-adrenal function in patients with acute subarachnoid haemorrhage: a prospective cohort study. Crit Care. 2008;12(5):R126. doi:10.1186/cc7084
24. Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321-1328. doi:10.1016/S0140-6736(04)17188-2
25. Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev. 2005;(1):CD000196. doi:10.1002/14651858.CD000196.pub2
26. Feigin VL, Anderson N, Rinkel GJE, Algra A, van Gijn J, Bennett DA. Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane database Syst Rev. 2005;(3):CD004583. doi:10.1002/14651858.CD004583.pub2
27. Hannon MJ, Sherlock M, Thompson CJ. Pituitary dysfunction following traumatic brain injury or subarachnoid haemorrhage - in “Endocrine Management in the Intensive Care Unit”. Best Pract Res Clin Endocrinol Metab. 2011;25(5):783-798. doi:10.1016/j.beem.2011.06.001
28. Parenti G, Cecchi PC, Ragghianti B, et al. Evaluation of the anterior pituitary function in the acute phase after spontaneous subarachnoid hemorrhage. Published online 2011:361-365. doi:10.3275/7242
29. Tanriverdi F, Senyurek H, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F. High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma. J Clin Endocrinol Metab. 2006;91(6):2105-2111. doi:10.1210/jc.2005-2476
30. Tandon A, Suri A, Kasliwal MK, et al. Assessment of endocrine abnormalities in severe traumatic brain injury: a prospective study. Acta Neurochir (Wien). 2009;151(11):1411-1417. doi:10.1007/s00701-009-0444-9
31. Woolf PD, Lee LA, Hamill RW, McDonald J V. Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation. Am J Med. 1988;84(2):201-208. Accessed May 7, 2015.
32. Boonen E, Van den Berghe G. Endocrine responses to critical illness: novel insights and therapeutic implications. J Clin Endocrinol Metab. Published online March 11, 2014:jc20134115. doi:10.1210/jc.2013-4115
33. Bendel S, Koivisto T, Ryynänen O, Ruokonen E, Romppanen J, Kiviniemi V. Insulin like growth factor-I in acute subarachnoid hemorrhage : a prospective cohort study. Published online 2010.