Hypothalamo-Pituitary Dysfunction Following Traumatic Brain Injury and Spontaneous Subarachnoid Haemorrhage

Authors: M. Kosák;  V. Hána
Authors‘ workplace: III. interní klinika 1. LF UK a VFN v Praze
Published in: Cesk Slov Neurol N 2011; 74/107(3): 286-291
Category: Review Article


The authors provide a review of observed hypothalamo-pituitary dysfunction following traumatic brain injury (TBI) and spontaneous subarachnoid haemorrhage (SAH) based on studies published in peer-reviewed journals. In most of the studies published in the last ten years, neuro-endocrine dysfunction after TBI and SAH appeared more often than previously. Impaired secretion of anterior pituitary hormones was diagnosed after TBI in up to 28.9% of cases and after SAH in up to 56.8%. Diabetes insipidus centralis was observed after TBI in acute phase in 26% and in chronic phase in 6.9%. Some recent studies did not confirm such high frequency. Currently we cannot predict the potential risk of neuro-endocrine sequelae of TBI in the individual patient. Although guidelines for endocrine evaluation of patients after TBI and SAH have been published, it appears that they have not yet become part of routine practice.

Key words:
hypothalamo-pituitary dysfunction – hypopituitarism – diabetes insipidus centralis – traumatic brain injury – subarachnoid haemorrhage


1. Tagliaferri F, Compagnone C, Korsic M, Servadei F, Kraus J. A systematic review of brain injury epidemiology in Europe. Acta Neurochir 2006; 148(3): 255–268.

2. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet 2007; 369(9558): 306–318.

3. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 2007; 298(12): 1429–1438.

4. 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.

5. Ghigo E, Masel B, Aimaretti G, Léon-Carrión J, Casanueva FF, Dominguez-Morales MR et al. Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj 2005; 19(9): 711–724.

6. Čáp J. Hormonální poruchy po úrazu mozku. Vnitř Lék 2006; 52(10): 941–946.

7. De Marinis L, Fusco A, Bianchi A, Aimaretti G, Ambrosio MR, Scaroni C et al. Hypopituitarism findings in patients with primary brain tumors 1 year after neurosurgical treatment: preliminary report. J Endocrinol Invest 2006; 29(6): 516–522.

8. McKinlay A, Grace RC, Horwood LJ, Fergusson DM, Ridder EM, MacFarlane MR. Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort. Brain Inj 2008; 22(2): 175–181.

9. Parslow RC, Morris KP, Tasker RC, Forsyth RJ, Hawley CA; UK Paediatric Traumatic Brain Injury Study Steering Group; Paediatric Intensive Care Society Study Group. Epidemiology of traumatic brain injury in children receiving intensive care in the UK. Arch Dis Child 2005; 90(11): 1182–1187.

10. Brichtová E. Kraniocerebrální poranění v dětském věku. Praha: Triton 2008: 16–23.

11. Park E, Bell JD, Baker AJ. Traumatic brain injury: can the consequences be stopped? CMAJ 2008; 178(9): 1163–1170.

12. Smrčka M et al. Poranění mozku. Praha: Grada 2001.

13. Cernak I, Savic VJ, Lazarov A, Joksimovic M, Markovic S. Neuroendocrine responses following graded traumatic brain injury in male adults. Brain Inj 1999; 13(12): 1005–1015.

14. Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 2005; 33(10): 2358–2366.

15. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W 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.

16. Arem R, Ghusn H, Ellerhorst J, Comstock JP. Effect of decreased plasma low-density lipoprotein levels on adrenal and testicular function in man. Clin Biochem 1997; 30(5): 419–424.

17. Roberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G 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.

18. Lee SC, Zasler ND, Kreutzer JS. Male pituitary-gonadal dysfunction following severe traumatic brain injury. Brain Inj 1994; 8(6): 571–577.

19. Fleischer AS, Rudman DR, Payne NS, Tindall GT. Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma. J Neurosurg 1978; 49(5): 650–657.

20. Woolf PD, Lee LA, Hamill RW, McDonald JV. Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation. Am J Med 1988; 84(2): 201–208.

21. King LR, Knowles HC Jr, McLaurin RL, Brielmaier J, Perisutti G, Piziak VK. Pituitary hormone response to head injury Neurosurgery 1981; 9(3): 229–235.

22. Matsuura H, Nakazawa S, Wakabayashi I. Thyro­tropin-releasing hormone provocative release of prolactin and thyrotropin in acute head injury. Neurosurgery 1985; 16(6): 791–795.

23. Agha A, Rogers B, Mylotte D, Taleb F, Tormey W, Phillips J et al. Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf) 2004; 60(5): 584–591.

24. Agha A, Rogers B, Sherlock M, O’Kelly P, Tormey W, Phillips J et al. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 2004; 89(10): 4929–4936.

25. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavò S, Scaroni C et al. Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab 2005; 90(11): 6085–6092.

26. Aimaretti G, Ambrosio MR, Di Somma C, Fusco A, Cannavò S, Gasperi et al. Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury. Clin Endocrinol (Oxf) 2004; 61(3): 320–326.

27. Kreitschmann-Andermahr I, Hoff C, Saller B, Niggemeier S, Pruemper S, Hütter BO, et al. Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 2004; 89(10): 4986–4992.

28. Dimopoulou I, Kouyialis AT, Tzanella M, Armaganidis A, Thalassinos N, Sakas DE et al. High incidence of neuroendocrine dysfunction in long-term survivors of aneurysmal subarachnoid hemorrhage. Stroke 2004; 35(12): 2884–2889.

29. Tanriverdi F, Dagli AT, Karaca Z, Unluhizarci K, Selcuklu A, Casanueva FF 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.

30. Kaulfers AM, Backeljauw PF, Reifschneider K, Blum S, Michaud L, Weiss M et al. Endocrine dysfunction following traumatic brain injury in children. J Pediatr 2010; 157(6): 894–899.

31. Khadr SN, Crofton PM, Jones PA, Wardhaugh B, Roach J, Drake AJ et al. Evaluation of pituitary function after traumatic brain injury in childhood. Clin Endocrinol (Oxf) 2010; 73(5): 637–643.

32. Sockalosky JJ, Kriel RL, Krach LE, Sheehan M. Precocious puberty after traumatic brain injury. J Pediatr 1987; 110(3): 373–377.

33. Aleksijevič D, Zapletalová J, Smolka V, Klásková E, Wiedermann J, Krahulík D et al. Neuroendokrinní dysfunkce u dětí a dospívajících po úrazu mozku. Cesk Slov Neurol N 2010; 73/106(4): 409–414.

34. Zapletalová J, Aleksijevič D, Smolka V, Krahulík D, Fryšák Z. Posttraumatický hypopituitarizmus u dětí a dospívajících. Cesk Slov Neurol N 2010; 73/106(4): 398–401.

35. Agha A, Thornton E, O’Kelly P, Tormey W, Phillips J, Thompson CJ. Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab 2004; 89(12): 5987–5992.

36. Becker RM, Daniel RK. Increased antidiuretic hormone production after trauma to the craniofacial complex. J Trauma 1973; 13(2): 112–115.

37. Twijnstra A, Minderhoud JM. Inappropriate secretion of antidiuretic hormone in patients with head injuries. Clin Neurol Neurosurg 1980; 82(4): 263–268.

38. Dóczi T, Tarjányi J, Huszka E, Kiss J. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after head injury. Neurosurgery 1982; 10(6): 685–688.

39. Born JD, Hans P, Smitz S, Legros JJ, Kay S. Syndrome of inappropriate secretion of antidiuretic hormone after severe head injury. Surg Neurol 1985; 23(4): 383–387.

40. Bondanelli M, De Marinis L, Ambrosio MR, Monesi M, Valle D, Zatelli MC et al. Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 2004; 21(6): 685–696.

41. Agha A, Sherlock M, Thompson CJ. Post-traumatic hyponatraemia due to acute hypopituitarism. QJM 2005; 98(6): 463–464.

42. Ceballos R. Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 1966; 3(2): 185–198.

43. Kornblum RN, Fisher RS. Pituitary lesions in cranio­cerebral injuries. Arch Pathol 1969; 88(3): 242–248.

44. Pierucci G, Gherson G, Tavani M. Pituitary changes especially necrotic-following cranio-cerebra injuries. Pathologica 1971; 63(917): 71–88.

45. Crompton MR. Hypothalamic lesions following closed head injury. Brain 1971; 94(1): 165–172.

46. Harper CG, Doyle D, Adams JH, Graham DI. Analysis of abnormalities in pituitary gland in non-missile head injury: study of 100 consecutive cases. J Clin Pathol 1986; 39(7): 769–773.

47. Salehi F, Kovacs K, Scheithauer BW, Pfeifer EA, Cusimano M. Histologic study of the human pituitary gland in acute traumatic brain injury. Brain Inj 2007; 21(6): 651–656.

48. Yuan XQ, Wade CE. Neuroendocrine abnormalities in patients with traumatic brain injury. Front Neuroendocrinol 1991; 12(3): 209–230.

49. Benvenga S, Campenní A, Ruggeri RM, Trimarchi F. Clinical review 113: hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 2000; 85(4): 1353–1361.

50. Kornblum RN, Fisher RS. Pituitary lesions in cranio­cerebral injuries. Arch Pathol 1969; 88(3): 242–248.

51. Maiya B, Newcombe V, Nortje J, Bradley P, Bernard F, Chatfield D et. Al. Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury. Intensive Care Med 2008; 34(3): 468–475.

52. Krahulik D, Zapletalova J, Frysak Z, Vaverka M. Dysfunction of hypothalamic-hypophysial axis after traumatic brain injury in adults. J Neurosurg 2010; 113(3): 581–584.

53. Tanriverdi F, De Bellis A, Bizzarro A, Sinisi AA, Bellastella G, Pane E et al. Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity? Eur J Endocrinol 2008; 159(1): 7–13.

54. Jovanovic V, Pekic S, Stojanovic M, Tasic G, Djurovic B, Soldatovic I et al. Neuroendocrine dysfunction in patients recovering from subarachnoid hemorrhage. Hormones (Athens) 2010; 9(3): 235–244.

55. 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.

56. Klose M, Juul A, Poulsgaard L, Kosteljanetz M, Brennum J, Feldt-Rasmussen U. Prevalence and predictive factors of post-traumatic hypopituitarism. Clin Endocrinol (Oxf) 2007; 67(2): 193–201.

57. Schneider M, Schneider HJ, Yassouridis A, Saller B, von Rosen F, Stalla GK. Predictors of anterior pituitary insufficiency after traumatic brain injury. Clin Endocrinol (Oxf) 2008; 68(2): 206–212.

58. Herrmann BL, Rehder J, Kahlke S, Wiedemayer H, Doerfler A, Ischebeck W et al. Hypopituitarism following severe traumatic brain injury. Exp Clin Endocrinol Diabetes 2006; 114(6): 316–321.

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