pp 1–13 | Cite as

Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function

  • Georgia Ntali
  • Stylianos TsagarakisEmail author



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.


Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series.


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.


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.


Traumatic brain injury (TBI) Post-traumatic hypopituitarism (PTHP) Anterior pituitary hormone deficiency Acute post-TBI period 


Compliance with ethical standards

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.


  1. 1.
    Dewan MC, Rattani A, Gupta S et al (2018) Estimating the global incidence of traumatic brain injury. J Neurosurg 27:1–18Google Scholar
  2. 2.
    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):712–721Google Scholar
  3. 3.
    Dusick JR, Wang C, Cohan P et al (2012) Pathophysiology of hypopituitarism in the setting of brain injury. Pituitary 15(1):2–9Google Scholar
  4. 4.
    Tanriverdi F, Schneider HJ, Aimaretti G et al (2015) Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr Rev 36(3):305–342Google Scholar
  5. 5.
    Ceballos R (1966) Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 3(2):185–198Google Scholar
  6. 6.
    Kornblum RN, Fisher RS (1969) Pituitary lesions in craniocerebral injuries. Arch Pathol 88(3):242–248Google Scholar
  7. 7.
    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):769–773Google Scholar
  8. 8.
    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):651–656Google Scholar
  9. 9.
    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):290–293Google Scholar
  10. 10.
    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):206–210Google Scholar
  11. 11.
    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):468–475Google Scholar
  12. 12.
    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):75–80Google Scholar
  13. 13.
    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):433–439Google Scholar
  14. 14.
    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):19–28Google Scholar
  15. 15.
    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):1216–1219Google Scholar
  16. 16.
    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):598–606Google Scholar
  17. 17.
    Krahulik D, Zapletalova J, Frysak Z et al (2010) Dysfunction of hypothalamic-hypophysial axis after traumatic brain injury in adults. J Neurosurg 113(3):581–584Google Scholar
  18. 18.
    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):80–84Google Scholar
  19. 19.
    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):772–778Google Scholar
  20. 20.
    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):2358–2366Google Scholar
  21. 21.
    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):871–888Google Scholar
  22. 22.
    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):3229–3237Google Scholar
  23. 23.
    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):627–636Google Scholar
  24. 24.
    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 20:21:33Google Scholar
  25. 25.
    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):193–205Google Scholar
  26. 26.
    Steinbok P, Thompson G (1979) Serum cortisol abnormalities after craniocerebral trauma. Neurosurgery 5(5):559–565Google Scholar
  27. 27.
    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):52–58Google Scholar
  28. 28.
    King LR, McLaurin RL, Lewis HP (1970) Plasma cortisol levels after head injury. Ann Surg 172(6):975–984Google Scholar
  29. 29.
    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):1245–1250Google Scholar
  30. 30.
    Barton RN, Stoner HB, Watson SM (1987) Relationships among plasma cortisol, adrenocorticotrophin, and severity of injury in recently injured patients. J Trauma 27(4):384–392Google Scholar
  31. 31.
    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):1368–1374Google Scholar
  32. 32.
    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):1419–1426Google Scholar
  33. 33.
    Cernak I, Savic VJ, Lazarov A et al (1999) Neuroendocrine responses following graded traumatic brain injury in male adults. Brain Inj 13(12):1005–1015Google Scholar
  34. 34.
    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):1411–1417Google Scholar
  35. 35.
    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):1435–1446Google Scholar
  36. 36.
    Arindom Kakati BI, Devi V, Bhadrinarayan et al (2013) Endocrine dysfunction following traumatic brain injury in acute stage. Indian J Neurotrauma 10(20):92–96Google Scholar
  37. 37.
    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):336–342Google Scholar
  38. 38.
    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):805–815Google Scholar
  39. 39.
    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):25–29Google Scholar
  40. 40.
    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):1262–1269Google Scholar
  41. 41.
    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):302–306Google Scholar
  42. 42.
    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):404–408Google Scholar
  43. 43.
    Agha A, Rogers B, Mylotte D et al (2004) Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf) 60(5):584–591Google Scholar
  44. 44.
    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):2105–2111Google Scholar
  45. 45.
    Jeevanandam M, Holaday NJ, Petersen SR (1995) Plasma levels of insulin-like growth factor binding protein-3 in acute trauma patients. Metabolism 44(9):1205–1208Google Scholar
  46. 46.
    Wagner J, Dusick JR, McArthur DL et al (2010) Acute gonadotroph and somatotroph hormonal suppression after traumatic brain injury. J Neurotrauma 27(6):1007–1019Google Scholar
  47. 47.
    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):741–747Google Scholar
  48. 48.
    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):1051–1057Google Scholar
  49. 49.
    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):201–208Google Scholar
  50. 50.
    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):113–116Google Scholar
  51. 51.
    Fleischer AS, Rudman DR, Payne NS et al (1978) Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma. J Neurosurg 49(5):650–657Google Scholar
  52. 52.
    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):747–754Google Scholar
  53. 53.
    Matsuura H, Nakazawa S, Wakabayashi I (1985) Thyrotropin-releasing hormone provocative release of prolactin and thyrotropin in acute head injury. Neurosurgery 16(6):791–795Google Scholar
  54. 54.
    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):1416Google Scholar
  55. 55.
    Woolf PD, Hamill RW, McDonald JV et al (1985) Transient hypogonadotropic hypogonadism caused by critical illness. J Clin Endocrinol Metab 60(3):444–450Google Scholar
  56. 56.
    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):277–287Google Scholar
  57. 57.
    Lee SC, Zasler ND, Kreutzer JS (1994) Male pituitary-gonadal dysfunction following severe traumatic brain injury. Brain Inj 8(6):571–577Google Scholar
  58. 58.
    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(Google Scholar
  59. 59.
    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):452–461Google Scholar
  60. 60.
    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.Google Scholar
  61. 61.
    Clark JD, Raggatt PR, Edwards OM (1988) Hypothalamic hypogonadism following major head injury. Clin Endocrinol (Oxf) 29(2):153–165Google Scholar
  62. 62.
    Srinivas R, Brown SD, Chang YF et al (2010) Endocrine function in children acutely following severe traumatic brain injury. Childs Nerv Syst 26(5):647–653Google Scholar
  63. 63.
    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):691–703Google Scholar
  64. 64.
    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):1021–1028Google Scholar
  65. 65.
    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):80–85Google Scholar
  66. 66.
    Bianchi VE, Locatelli V, Rizzi L (2017) Neurotrophic and Neuroregenerative Effects of GH/IGF1. Int J Mol Sci 18(11):2441Google Scholar
  67. 67.
    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):163–166Google Scholar
  68. 68.
    King LR, Knowles HC Jr, McLaurin RL et al (1981) Pituitary hormone response to head injury. Neurosurgery 9(3):229–235Google Scholar
  69. 69.
    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):813–822Google Scholar
  70. 70.
    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):1226–1242Google Scholar
  71. 71.
    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):2752–2756Google Scholar
  72. 72.
    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):1781–1792Google Scholar
  73. 73.
    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):716–725Google Scholar
  74. 74.
    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):401–402Google Scholar
  75. 75.
    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):971–981Google Scholar
  76. 76.
    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):6085–6092Google Scholar
  77. 77.
    Urban RJ (2006) Hypopituitarism after acute brain injury. Growth Horm IGF Res 16(Suppl A):S25–S29Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology and DiabetesEvangelismos HospitalAthensGreece

Personalised recommendations