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Hypothalamic-pituitary dysfunction in critically ill patients with traumatic and nontraumatic brain injury

  • Ioanna Dimopoulou
  • Stylianos Tsagarakis
Chapter

Abstract

Background: A significant number of studies have shown that critically ill patients with brain injury (BI) frequently exhibit abnormal pituitary hormonal responses during the immediate postinjury period. Discussion: The elucidation of endocrine alterations depends on the criteria used, the diagnostic tests applied, and the timing of testing in relation to BI. The pattern of the detected hormonal abnormalities shows considerable variability. Altered endocrine responses are due mostly to hypothalamic changes rather than to pituitary dysfunction. Several studies have examined the correlation between hormonal alterations and BI severity, but the results are inconsistent. Furthermore, it remains currently unclear whether and how pituitary abnormalities adversely affect the clinical course of BI patients during the period of critical illness. On the basis of current knowledge, with the exception of clinically significant relative adrenal deficiency and diabetes insipidus, the other endocrine alterations do not seem to require any therapeutic intervention in severely ill BI patients. It is also uncertain whether hormonal abnormalities detected in the early post-BI period persist for the rest of these patients' lives. Conclusions: In view of current evidence indicating a high incidence of pituitary dysfunction even years following BI it is recommended that repetition of endocrine evaluation should be performed during the rehabilitation phase in all patients.

Keywords

Brain injury Critical illness Endocrine alterations Treatment Outcome Recovery 

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References

  1. 1.
    Marik PE, Varon J, Trask T (2002) Management of head trauma. Chest 122:699-711PubMedCrossRefGoogle Scholar
  2. 2.
    Warlow C, Sudlow C, Dennis M, Wardlaw J, Sandercock P (2003) Stroke. Lancet 362:1211-1224PubMedCrossRefGoogle Scholar
  3. 3.
    Fahy BG, Sivaraman V (2002) Current concepts in neurocritical care. Anesthesiol Clin North America 20:441-462PubMedCrossRefGoogle Scholar
  4. 4.
    Crompton MR (1971) Hypothalamic lesions following closed head injury. Brain 94:165-172PubMedCrossRefGoogle Scholar
  5. 5.
    Edwards OM, Clark JD (1986) Post-traumatic hypopituitarism. Six cases and review of the literature. Medicine (Baltimore) 65:281-290Google Scholar
  6. 6.
    Benvega S, Campenni A, Ruggeri RM, Trimarchi F (2000) Clinical Review 113. Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85:1353-1361CrossRefGoogle Scholar
  7. 7.
    Lamberts SWJ, de Herder WW, van der Lely AJ (1998) Pituitary insufficiency. Lancet 352:127-134PubMedGoogle Scholar
  8. 8.
    Amar AP, Weiss MH (2003) Pituitary anatomy and physiology. Neurosurg Clin N Am 13:11-23CrossRefGoogle Scholar
  9. 9.
    Oelkers W (1996) Adrenal insufficiency. N Engl J Med 335:1206-1212PubMedCrossRefGoogle Scholar
  10. 10.
    Cooper MS, Stewart PM (2003) Corti-costeroid insufficiency in acutely ill patients. N Engl J Med 348:727-734PubMedCrossRefGoogle Scholar
  11. 11.
    McKeating EG, Andrews PJD (1998) Cytokines and adhesion molecules in acute brain injury. Br J Anaesth 80:77-84PubMedGoogle Scholar
  12. 12.
    Bornstein SR, Chroussos GP (1999) Clinical review 104. Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab 84:1729-1736PubMedCrossRefGoogle Scholar
  13. 13.
    Kelly DF, Gaw Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C (2000) Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report. J Neurosurg 93:743-752PubMedCrossRefGoogle Scholar
  14. 14.
    Chroussos GP (2000) The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuroendocrine and target tissue-related causes. Int J Obes Relat Metab Disord 24:S50-S55CrossRefGoogle Scholar
  15. 15.
    Vanltallie TB (2002) Stress: a risk factor for serious illness. Metabolism 51 [Suppl 1]:40-45CrossRefGoogle Scholar
  16. 16.
    Charmandari E, Tsigos C, Chrousos G (2005) Endocrinology of the stress response. Annu Rev Physiol 67:259-284PubMedCrossRefGoogle Scholar
  17. 17.
    Fleischer AS, Rudman DR, Payne NS, Tindall GT (1978) Hypothalamic hypothyroidism and hypogonadism in prolonged traumatic coma. J Neurosurg 49:650-657PubMedCrossRefGoogle Scholar
  18. 18.
    Steinbok P, Thompson G (1979) Serum cortisol abnormalities after craniocerebral trauma. Neurosurgery 5:559-565PubMedCrossRefGoogle Scholar
  19. 19.
    King LR, Knowles HC, McLaurin RL, Brielmaier J, Perisutti G, Piziak VK (1981) Pituitary response to head injury. Neurosurgery 9:229-235PubMedCrossRefGoogle Scholar
  20. 20.
    Feibel J, Kelly M, Lee L, Woolf P (1983) Loss of adrenocortical suppression after acute brain injury: role of increased intracranial pressure and brain stem function. J Clin Endocrinol Metab 57:1245-1250PubMedGoogle Scholar
  21. 21.
    Matsuura H, Nakazawa S, Wakabayashi I (1985) Thyrotropin-releasing hormone provocative release of prolactin and thyrotropin in acute head injury. Neurosurgery 16:791-795PubMedCrossRefGoogle Scholar
  22. 22.
    Woolf PD, Hamill RW, McDonald JV, Lee LA, Kelly M (1985) Transient hypogonadotropic hypogonadism caused by critical illness. J Clin Endocrinol Metab 60:444-450PubMedCrossRefGoogle Scholar
  23. 23.
    Woolf PD, Hamill RW, McDonald JV, Lee LA, Kelly M (1986) Transient hypogonadotrophic hypogonadism after head trauma: effects on steroid precursors and correlation with sympathetic nervous system activity. Clin Endocrinol (Oxf) 25:265-274CrossRefGoogle Scholar
  24. 24.
    Clark JD, Raggatt PR, Edwards OM (1988) Hypothalamic hypogonadism following major head injury. Clin Endocrinol (Oxf) 29:153-165CrossRefGoogle Scholar
  25. 25.
    Woolf PD, Lee LA, Hamill RW, McDonald JV (1988) Thyroid test abnormalities in traumatic brain injury: correlation with neurologic impairment and sympathetic nervous system activation. Am J Med 84:201-208PubMedCrossRefGoogle Scholar
  26. 26.
    Chiolero RL, Lemarchand-Beraud T, Schutz Y, de Tribolet N, Bayer-Berger M, Freeman J (1988) Thyroid function in severely traumatized patients with or without head injury. Acta Endocrinol (Copenh) 117:80-86Google Scholar
  27. 27.
    Chiolero R, Lemarchand T, Schutz Y, de Tribolet N, Felber JP, Freeman J, Jequier E (1988) Plasma pituitary hormone levels in severe trauma with or without head injury. J Trauma 28:1368-1374PubMedCrossRefGoogle Scholar
  28. 28.
    Woolf PD, Cox C, Kelly M, Nichols D, McDonald JV, Hamill RW (1990) The adrenocortical response to brain injury: correlation with the severity of neurologic dysfunction, effects of intoxication, and patient outcome. Alcohol Clin Exp Res 14:917-921PubMedCrossRefGoogle Scholar
  29. 29.
    Ziegler MG, Morrissey EC, Marshall LF (1990) Catecholamine and thyroid hormones in traumatic injury. Crit Care Med 18:253-258PubMedCrossRefGoogle Scholar
  30. 30.
    Gottardis M, Nigitsch C, Schmutzhard E, Neumann M, Putensen C, Hackl JM, Koller W (1990) The secretion of human growth hormone stimulated by human growth hormone releasing factor following severe cranio-cerebral trauma. Intensive Care Med 16:163-166PubMedCrossRefGoogle Scholar
  31. 31.
    Hackl JM, Gottardis M, Wieser C, Rumpl E, Stadler C, Schwarz S, Monkayo R (1991) Endocrine abnormalities in severe traumatic brain injury-a cue to prognosis in severe craniocerebral trauma? Intensive Care Med 17:25-29PubMedCrossRefGoogle Scholar
  32. 32.
    Pentelenyi T (1992) Significance of endocrine studies in the general assessment and prediction of fatal outcome in head injury. Acta Neurochir Suppl 55:21-24Google Scholar
  33. 33.
    Mocchegiani E, Imberti R, Testasecca D, Zandri M, Santarelli L, Fabris N (1995) Thyroid and thymic endocrine function and survival in severely traumatized patients with or without head injury. Intensive Care Med 21:334-341PubMedCrossRefGoogle Scholar
  34. 34.
    Koiv L, Merisalu E, Zilmer K, Tomberg T, Kaasik AE (1997) Changes of sympatho-adrenal and hypothalamo-pituitary-adrenocortical system in patients with head injury. Acta Neurol Scand 96:52-58PubMedGoogle Scholar
  35. 35.
    Della Corte F, Mancini A, Valle D, Gallizzi F, Carducci P, Mignani V, De Marinis L (1998) Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis. Crit Care Med 26:1419-1426PubMedCrossRefGoogle Scholar
  36. 36.
    Hoen S, Asehnoune K, Brailly-Tabart S, Mazoit JX, Benhamou D, Moine P, Edouard AR (2002) Cortisol response to corticotropin stimulation in trauma patients: influence of hemorrhagic shock. Anesthesiology 97:807-813PubMedCrossRefGoogle Scholar
  37. 37.
    Dimopoulou I, Tsagarakis S, Theodorakopoulou M, Douka E, Zervou M, Kouyialis AT, Thalassinos N, Roussos C (2004) Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors. Intensive Care Med 30:1051-1057PubMedCrossRefGoogle Scholar
  38. 38.
    Agha A, Rogers B, Mylotte D, Taleb F, Tormey W, Phillips J, Thompson CJ (2004) Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol (Oxf) 60:584-591CrossRefGoogle Scholar
  39. 39.
    Savaridas T, Andrews PJD, Harris B (2004) Cortisol dynamics following acute severe brain injury. Intensive Care Med 30:1479-1483PubMedCrossRefGoogle Scholar
  40. 40.
    Lamberts SWJ, Bruining HA, de Jong FH (1997) Drug therapy: corticosteroid therapy in severe illness. N Engl J Med 337:1285-1292PubMedCrossRefGoogle Scholar
  41. 41.
    Dimopoulou I, Tsagarakis S, Anthi A, Milou E, Ilias I, Stavrakaki K, Charalambidis C, Tzanela M, Orfanos S, Mandragos K, Thalassinos N, Roussos C (2003) High incidence of decreased cortisol reserve in brain-dead potential organ donors. Crit Care Med 31:1113-1117PubMedCrossRefGoogle Scholar
  42. 42.
    Hamrahian AH, Oseni TS, Arafah B (2004) Measurements of serum free cortisol in critically ill patients. N Engl J Med 350:1629-1638PubMedCrossRefGoogle Scholar
  43. 43.
    Dimopoulou I, Tsagarakis S, Kouyialis AT, Roussou P, Assithianakis G, Christoforaki M, Ilias I, Sakas DE, Thalassinos N, Roussos C (2004) Hypothalamic-pituitary-adrenal dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels. Crit Care Med 32:404-408PubMedCrossRefGoogle Scholar
  44. 44.
    Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, Adawi F, Lahav M (1991) Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 72:773-778PubMedGoogle Scholar
  45. 45.
    Stavrou S, Kleinberg DL (2001) Diagnosis and management of growth hormone deficiency in adults. Endocrinol Metab Clin North Am 30:545-563PubMedCrossRefGoogle Scholar
  46. 46.
    Clark JDA, Raggatt PR, Edwards OM (1992) Abnormalities of the hypothalamo-pituitary-gonadal axis after head injury. Clin Endocrinol (Oxf) 36:481-485CrossRefGoogle Scholar
  47. 47.
    Schwarz S, Schwab S, Klinga K, Maser-Gluth C, Bettendorf M (2003) Neuroendocrine changes in patients with acute space occupying ischemic stroke. J Neurol Neurosurg Psychiatry 74:725-727PubMedCrossRefGoogle Scholar
  48. 48.
    Dimopoulou I, Tsagarakis S, Douka E, Zervou M, Kouyialis AT, Dafni U, Thalassinos N, Roussos C (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 30:1216-1219PubMedCrossRefGoogle Scholar
  49. 49.
    Fassbender K, Schmidt R, Mossner R, Daffertshofer M, Hennerici M (1994) Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome. Stroke 25:1105-1108PubMedGoogle Scholar
  50. 50.
    Johansson A, Ahren B, Nasman B, Carlstrom K, Olsson T (2000) Cortisol axis abnormalities early after stroke—relationships to cytokines and leptin. J Intern Med 247:179-187PubMedCrossRefGoogle Scholar
  51. 51.
    Olsson T, Marklund N, Gustafson Y, Nasman B (1992) Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke. Stroke 23:1573-1576PubMedGoogle Scholar
  52. 52.
    Hagg E, Asplund K, Eriksson S, Lithner F, Strand T, Wester PO (1986) Serum thyroid-stimulating hormone in cerebrovascular disease. Acta Med Scand 219:53-58PubMedGoogle Scholar
  53. 53.
    Pepper GM, Koenigsberg R, Zito JL, Deutsch S (1993) Alterations of serum pituitary hormone levels in postmenopausal women with stroke. Stroke 24:805-808PubMedGoogle Scholar
  54. 54.
    Jeppesen LL, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K (1996) Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol 16:749-754PubMedGoogle Scholar
  55. 55.
    Schwab S, Spranger M, Krempien S, Hacke W, Bettendorf M (1997) Plasma insulin-like growth factor I and IGF binding protein 3 levels in patients with acute cerebral ischemic injury. Stroke 28:1744-1748PubMedGoogle Scholar
  56. 56.
    Mangieri P, Suzuki K, Ferreira M, Domingues L, Casulari LA (2003) Evaluation of pituitary and thyroid hormones in patients with subarachnoid hemorrhage due to ruptured intracranial aneurysm. Arq Neuropsiquiatr 61:14-19PubMedGoogle Scholar
  57. 57.
    Brandt L, Saveland H, Valdenmarsson S, Sjoholm H, Reinstrup P (2004) Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function and 3D-CBF. Acta Neurol Scand 109:91-96PubMedCrossRefGoogle Scholar
  58. 58.
    Aimaretti G, Ambrosio MR, Di Somma C, Fusco A, Cannavo S, Gasperi M, Scaroni C, De Marinis L, Benvega S, Degli Uberti EC, Lombardi G, Mantero F, Martino E, Giordano G, Ghigo E (2004) 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) 61:320-326CrossRefGoogle Scholar
  59. 59.
    Kreitschmann-Andermahr I, Hoff C, Saller B, Niggemeier S, Pruemper S, Hutter BO, Rohde V, Gressner A, Matern S, Gilsbach JM (2004) Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 89:4986-4992PubMedCrossRefGoogle Scholar
  60. 60.
    Dimopoulou I, Kouyialis AT, Tzanella M, Armaganidis A, Thalassinos N, Sakas DE, Tsagarakis S (2004) High incidence of neuroendocrine dysfunction in long-term survivors of aneurysmal subarachnoid hemorrhage. Stroke 35:2884-2889PubMedCrossRefGoogle Scholar
  61. 61.
    Bondanelli M, De Marinis L, Ambrosio MR, Monesi M, Valle D, Zatelli MC, Fusco A, Bianchi A, Farneti M, Degli Uberti EC (2004) Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 21:685-696PubMedCrossRefGoogle Scholar
  62. 62.
    Agha A, Thornton E, O'Kelly P, Tormey W, Phillips J, Thompson CJ (2004) Posterior pituitary dysfunction after traumatic brain injury. J Clin Endocrinol Metab 89:5987-5992PubMedCrossRefGoogle Scholar
  63. 63.
    Agha A, Sherlock M, Phillips J, Tormey W, Thompson CJ (2005) The natural history of post-traumatic neurohypophysial dysfunction. Eur J Endocrinol 152:371-377PubMedCrossRefGoogle Scholar
  64. 64.
    Van den Berghe G (2000) Novel insights into the neuroendocrinology of critical illness. Eur J Endocrinol 143:1-13PubMedCrossRefGoogle Scholar
  65. 65.
    Spratt DI (2001) Altered gonadal steroidogenesis in critical illness: is treatment with anabolic steroids indicated? Baillieres Best Pract Res Clin Endocrinol Metab 15:479-494CrossRefGoogle Scholar
  66. 66.
    Stathatos N, Levetan C, Burman KD, Wartofsky L (2001) The controversy of the treatment of critically ill patients with thyroid hormone. Baillieres Best Pract Res Clin Endocrinol Metab 15:465-478CrossRefGoogle Scholar
  67. 67.
    Takala J, Ruokonen E, Webster NR, Nielsen MS, Zandstra DF, Vundelinckx G, Hinds CJ (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785-792PubMedCrossRefGoogle Scholar
  68. 68.
    Carroll PV (2001) Treatment with growth hormone and insulin like growth factor-I in critical illness. Baillieres Best Pract Res Clin Endocrinol Metab 15:435-451CrossRefGoogle Scholar
  69. 69.
    Ligtenberg JJM, Zijlstra JG (2004) The relative adrenal insufficiency syndrome revisited: which patients will benefit from low-dose steroids? Curr Opin Crit Care 10:456-460PubMedCrossRefGoogle Scholar
  70. 70.
    CRASH trial collaborators (2204) Effect of intravenous corticosteroids on death within 14 days in 10.008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 364:1321-1328Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Ioanna Dimopoulou
    • 1
  • Stylianos Tsagarakis
    • 2
  1. 1.Second Department of Critical Care MedicineAttikon Hospital, Medical School National and Kapodistrian University of AthensKifissiaGreece
  2. 2.Department of EndocrinologyAthens PolyclinicAthensGreece

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