Abstract
Purpose
It is estimated that approximately 69 million individuals worldwide will sustain a TBI each year, which accounts for substantial morbidity and mortality in both children and adults. TBI may lead to significant neuroendocrine changes, if the delicate pituitary is ruptured. In this review, we focus on the anterior pituitary hormonal changes in the acute post-TBI period and we present the evidence supporting the need for screening of anterior pituitary function in the early post-TBI time along with current suggestions regarding the endocrine assessment and management of these patients.
Methods
Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series.
Results
Although TBI may motivate an acute increase of stress hormones, it may also generate a wide spectrum of anterior pituitary hormonal deficiencies. The frequency of post-traumatic anterior hypopituitarism (PTHP) varies according to the severity, the type of trauma, the time elapsed since injury, the study population, and the methodology used to diagnose pituitary hormone deficiency. Early neuroendocrine abnormalities may be transient, but additional late ones may also appear during the course of rehabilitation.
Conclusions
Acute hypocortisolism should be diagnosed and managed promptly, as it can be life-threatening, but currently there is no evidence to support treatment of acute GH, thyroid hormones or gonadotropins deficiencies. However, a more comprehensive assessment of anterior pituitary function should be undertaken both in the early and in the post-acute phase, since ongoing hormone deficiencies may adversely affect the recovery and quality of life of these patients.
Similar content being viewed by others
References
Dewan MC, Rattani A, Gupta S et al (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 27:1–18
Lauzier F, Turgeon AF, Boutin A et al (2014) Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review. Crit Care Med 42(3):712–721
Dusick JR, Wang C, Cohan P et al (2012) Pathophysiology of hypopituitarism in the setting of brain injury. Pituitary 15(1):2–9
Tanriverdi F, Schneider HJ, Aimaretti G et al (2015) Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr Rev 36(3):305–342
Ceballos R (1966) Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 3(2):185–198
Kornblum RN, Fisher RS (1969) Pituitary lesions in craniocerebral injuries. Arch Pathol 88(3):242–248
Harper CG, Doyle D, Adams JH et al (1986) Analysis of abnormalities in pituitary gland in non-missile head injury: study of 100 consecutive cases. J Clin Pathol 39(7):769–773
Salehi F, Kovacs K, Scheithauer BW et al (2007) Histologic study of the human pituitary gland in acute traumatic brain injury. Brain Inj 21(6):651–656
Chaturvedi D, Suri A, Kasliwal MK et al (2010) Factors affecting the development of hypothalamus and pituitary lesions in fatal closed head injury: a prospective study. J Trauma 69(2):290–293
Kibayashi K, Shimada R, Nakao K et al (2012) Analysis of pituitary lesions in fatal closed head injury. Am J Forensic Med Pathol 33(3):206–210
Maiya B, Newcombe V, Nortje J et al (2008) Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury. Intensive Care Med 34(3):468–475
Zheng P, He B, Guo Y et al (2015) Decreased apparent diffusion coefficient in the pituitary and correlation with hypopituitarism in patients with traumatic brain injury. J Neurosurg 123(1):75–80
Tanriverdi F, Ulutabanca H, Unluhizarci K et al (2007) Pituitary functions in the acute phase of traumatic brain injury: are they related to severity of the injury or mortality? Brain Inj 21(4):433–439
van der Eerden AW, Twickler MT, Sweep FC et al (2010) Should anterior pituitary function be tested during follow-up of all patients presenting at the emergency department because of traumatic brain injury? Eur J Endocrinol 162(1):19–28
Dimopoulou I, Tsagarakis S, Douka E et al (2004) The low-dose corticotropin stimulation test in acute traumatic and non-traumatic brain injury: incidence of hypo-responsiveness and relationship to outcome. Intensive Care Med 30(6):1216–1219
Klose M, Juul A, Struck J et al (2007) Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study. Clin Endocrinol (Oxf) 67(4):598–606
Krahulik D, Zapletalova J, Frysak Z et al (2010) Dysfunction of hypothalamic-hypophysial axis after traumatic brain injury in adults. J Neurosurg 113(3):581–584
Dalwadi PP, Bhagwat NM, Tayde PS et al (2017) Pituitary dysfunction in traumatic brain injury: is evaluation in the acute phase worth while? Indian J Endocrinol Metab 21(1):80–84
Hari Kumar KV, Swamy MN, Khan MA (2016) Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain injury. Indian J Endocrinol Metab 20(6):772–778
Cohan P, Wang C, McArthur DL et al (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33(10):2358–2366
Wagner AK, McCullough EH, Niyonkuru C et al (2011) Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury. J Neurotrauma 28(6):871–888
Hannon MJ, Crowley RK, Behan LA et al (2013) Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality. J Clin Endocrinol Metab 98(8):3229–3237
Bensalah M, Donaldson M, Aribi Y et al (2018) Cortisol evaluation during the acute phase of traumatic brain injury-A prospective study. Clin Endocrinol (Oxf) 88(5):627–636
Olivecrona Z, Dahlqvist P, Koskinen LO (2013) Acute neuro-endocrine profile and prediction of outcome after severe brain injury. Scand J Trauma Resusc Emerg Med 20:21:33
Tölli A, Borg J, Bellander BM et al (2017) Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage. J Endocrinol Invest 40(2):193–205
Steinbok P, Thompson G (1979) Serum cortisol abnormalities after craniocerebral trauma. Neurosurgery 5(5):559–565
Kôiv L, Merisalu E, Zilmer K et al (1997) Changes of sympatho-adrenal and hypothalamo-pituitary-adrenocortical system in patients with head injury. Acta Neurol Scand 96(1):52–58
King LR, McLaurin RL, Lewis HP (1970) Plasma cortisol levels after head injury. Ann Surg 172(6):975–984
Feibel J, Kelly M, Lee L et al (1983) Loss of adrenocortical suppression after acute brain injury: role of increased intracranial pressure and brain stem function. J Clin Endocrinol Metab 57(6):1245–1250
Barton RN, Stoner HB, Watson SM (1987) Relationships among plasma cortisol, adrenocorticotrophin, and severity of injury in recently injured patients. J Trauma 27(4):384–392
Chioléro R, Lemarchand T, Schutz Y et al (1988) Plasma pituitary hormone levels in severe trauma with or without head injury. J Trauma 28(9):1368–1374
Della Corte F, Mancini A, Valle D et al (1998) Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis. Crit Care Med 26(8):1419–1426
Cernak I, Savic VJ, Lazarov A et al (1999) Neuroendocrine responses following graded traumatic brain injury in male adults. Brain Inj 13(12):1005–1015
Tandon A, Suri A, Kasliwal MK et al (2009) Assessment of endocrine abnormalities in severe traumatic brain injury: a prospective study. Acta Neurochir (Wien) 151(11):1411–1417
Kleindienst A, Brabant G, Bock C et al (2009) Neuroendocrine function following traumatic brain injury and subsequent intensive care treatment: a prospective longitudinal evaluation. J Neurotrauma 26(9):1435–1446
Arindom Kakati BI, Devi V, Bhadrinarayan et al (2013) Endocrine dysfunction following traumatic brain injury in acute stage. Indian J Neurotrauma 10(20):92–96
Prasanna KL, Mittal RS, Gandhi A (2015) Neuroendocrine dysfunction in acute phase of moderate-to-severe traumatic brain injury: a prospective study. Brain Inj 29(3):336–342
Boonen E, Bornstein SR, Van den Berghe G (2015) New insights into the controversy of adrenal function during critical illness. Lancet Diabetes Endocrinol 3(10):805–815
Hackl JM, Gottardis M, Wieser C et al (1991) Endocrine abnormalities in severe traumatic brain injury–a cue to prognosis in severe craniocerebral trauma? Intensive Care Med 17(1):25–29
Hohl A, Ronsoni MF, Debona R et al (2014) Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury. Brain Inj 28(10):1262–1269
Alavi SA, Tan CL, Menon DK et al (2016) Incidence of pituitary dysfunction following traumatic brain injury: A prospective study from a regional neurosurgical centre. Br J Neurosurg 30(3):302–306
Dimopoulou I, Tsagarakis S, Kouyialis AT et al (2004) Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels. Crit Care Med 32(2):404–408
Agha A, Rogers B, Mylotte D et al (2004) Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf) 60(5):584–591
Tanriverdi F, Senyurek H, Unluhizarci K et al (2006) 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 91(6):2105–2111
Jeevanandam M, Holaday NJ, Petersen SR (1995) Plasma levels of insulin-like growth factor binding protein-3 in acute trauma patients. Metabolism 44(9):1205–1208
Wagner J, Dusick JR, McArthur DL et al (2010) Acute gonadotroph and somatotroph hormonal suppression after traumatic brain injury. J Neurotrauma 27(6):1007–1019
De Marinis L, Mancini A, Valle D et al (1999) Hypothalamic derangement in traumatized patients: growth hormone (GH) and prolactin response to thyrotrophin-releasing hormone and GH-releasing hormone. Clin Endocrinol (Oxf) 50(6):741–747
Dimopoulou I, Tsagarakis S, Theodorakopoulou M et al (2004) Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors. Intensive Care Med 30(6):1051–1057
Woolf PD, Lee LA, Hamill RW et al (1988) Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation. Am J Med 84(2):201–208
Malekpour B, Mehrafshan A, Saki F et al (2012) Effect of posttraumatic serum thyroid hormone levels on severity and mortality of patients with severe traumatic brain injury. Acta Med Iran 50(2):113–116
Fleischer AS, Rudman DR, Payne NS et al (1978) Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma. J Neurosurg 49(5):650–657
Rudman D, Fleischer AS, Kutner MH et al (1977) Suprahypophyseal hypogonadism and hypothyroidism during prolonged coma after head trauma. J Clin Endocrinol Metab 45(4):747–754
Matsuura H, Nakazawa S, Wakabayashi I (1985) Thyrotropin-releasing hormone provocative release of prolactin and thyrotropin in acute head injury. Neurosurgery 16(6):791–795
Agha A, Phillips J, O’Kelly P et al (2005) The natural history of post-traumatic hypopituitarism: implications for assessment and treatment. Am J Med 118(12):1416
Woolf PD, Hamill RW, McDonald JV et al (1985) Transient hypogonadotropic hypogonadism caused by critical illness. J Clin Endocrinol Metab 60(3):444–450
Barton DJ, Kumar RG, McCullough EH et al (2016) Persistent hypogonadotropic hypogonadism in men after severe traumatic brain injury: temporal hormone profiles and outcome prediction. J Head Trauma Rehabil 31(4):277–287
Lee SC, Zasler ND, Kreutzer JS (1994) Male pituitary-gonadal dysfunction following severe traumatic brain injury. Brain Inj 8(6):571–577
Van den Berghe G (2016) On the neuroendocrinopathy of critical illness. Perspectives for feeding and novel treatments. Am J Respir Crit Care Med 1(11):1337–1348 194(
Ranganathan P, Kumar RG, Davis K et al (2016) Longitudinal sex and stress hormone profiles among reproductive age and post-menopausal women after severe TBI: a case series analysis. Brain Inj 30(4):452–461
Hohl A, Zanela FA, Ghisi G et al Ronsoni MF, Diaz AP, Schwarzbold ML, Dafre AL, Reddi B, Lin K, Pizzol FD, Walz R (2018) Luteinizing hormone and testosterone levels during acute phase of severe traumatic brain injury: prognostic implications for adult male patients. Front Endocrinol (Lausanne) 9:13 29.
Clark JD, Raggatt PR, Edwards OM (1988) Hypothalamic hypogonadism following major head injury. Clin Endocrinol (Oxf) 29(2):153–165
Srinivas R, Brown SD, Chang YF et al (2010) Endocrine function in children acutely following severe traumatic brain injury. Childs Nerv Syst 26(5):647–653
Einaudi S, Matarazzo P, Peretta P et al (2006) Hypothalamo-hypophysial dysfunction after traumatic brain injury in children and adolescents: a preliminary retrospective and prospective study. J Pediatr Endocrinol Metab 19(5):691–703
Ulutabanca H, Hatipoglu N, Tanriverdi F et al (2014) Prospective investigation of anterior pituitary function in the acute phase and 12 months after pediatric traumatic brain injury. Childs Nerv Syst 30(6):1021–1028
Krahulik D, Aleksijevic D, Smolka V et al (2017) Prospective study of hypothalamo-hypophyseal dysfunction in children and adolescents following traumatic brain injury. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 161(1):80–85
Bianchi VE, Locatelli V, Rizzi L (2017) Neurotrophic and Neuroregenerative Effects of GH/IGF1. Int J Mol Sci 18(11):2441
Gottardis M, Nigitsch C, Schmutzhard E et al (1990) The secretion of human growth hormone stimulated by human growth hormone releasing factor following severe cranio-cerebral trauma. Intensive Care Med 16(3):163–166
King LR, Knowles HC Jr, McLaurin RL et al (1981) Pituitary hormone response to head injury. Neurosurgery 9(3):229–235
Marina D, Klose M, Nordenbo A et al (2015) Early endocrine alterations reflect prolonged stress and relate to 1-year functional outcome in patients with severe brain injury. Eur J Endocrinol 172(6):813–822
Wagner AK, Brett CA, McCullough EH et al (2012) Persistent hypogonadism influences estradiol synthesis, cognition and outcome in males after severe TBI. Brain Inj 26(10):1226–1242
Lieberman SA, Oberoi AL, Gilkison CR et al (2001) Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86(6):2752–2756
Annane D, Pastores SM, Arlt W et al (2017) Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). Intensive Care Med 43(12):1781–1792
Hamrahian AH, Fleseriu M, AACE Adrenal Scientific Committee (2017) Evaluation and management of adrenal insufficiency in critically Ill patients: disease state review. Endocr Pract 23(6):716–725
Annane D, Pastores SM, Rochwerg B et al (2017) Correction to: Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med 44(3):401–402
Tan CL, Alavi SA, Baldeweg SE et al (2017) The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance. J Neurol Neurosurg Psychiatry 88(11):971–981
Aimaretti G, Ambrosio MR, Di Somma C et al (2005) Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab 90(11):6085–6092
Urban RJ (2006) Hypopituitarism after acute brain injury. Growth Horm IGF Res 16(Suppl A):S25–S29
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
This paper does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ntali, G., Tsagarakis, S. Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function. Pituitary 22, 283–295 (2019). https://doi.org/10.1007/s11102-019-00944-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11102-019-00944-0