, Volume 11, Issue 3, pp 255–261 | Cite as

Does the type and severity of brain injury predict hypothalamo–pituitary dysfunction? Does post-traumatic hypopituitarism predict worse outcome?



Several studies have reported a close association between traumatic brain injury (TBI) and pituitary dysfunction, and expert panels have recently proposed recommendations for hormone assessment and replacement for pituitary insufficiency after TBI. Given the high incidence of TBI, identification of reliable predictors is of utmost importance in order to secure a cost-effective screening strategy. It has not yet been possible to identify early hormone alterations as a useful tool for the prediction of long-term post-traumatic hypopituitarism, whereas indicators of increased trauma severity have been reported as predictive in an increasing number of studies. Outcome studies have moreover indicated that post-traumatic hypopituitarism is of clinical significance, which may justify introduction of neuroendocrine screening in TBI. Much larger cohorts are, however, still needed for further evaluation and confirmation of reliable screening markers, and future studies should be designed to ensure a high diagnostic robustness for proper identification of reliable predictors, as the results may be highly dependent on diagnostic pitfalls.


Hypopituitarism Traumatic brain injury Predictors Outcome 


  1. 1.
    Schneider HJ, Kreitschmann-Andermahr I, Ghigo E et al (2007) Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 298:1429–1438 Medline. doi: 10.1001/jama.298.12.1429 PubMedCrossRefGoogle Scholar
  2. 2.
    Ho KK (2007) Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol 157:695–700. doi: 10.1530/EJE-07-0631 PubMedCrossRefGoogle Scholar
  3. 3.
    Ghigo E, Masel B, Aimaretti G et al (2005) Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj 19:711–724 Medline. doi: 10.1080/02699050400025315 PubMedCrossRefGoogle Scholar
  4. 4.
    Engberg AW, Teasdale TW (2001) Traumatic brain injury in Denmark 1979–1996. A national study of incidence and mortality. Eur J Epidemiol 17:437–442 Medline. doi: 10.1023/A:1013733107520 CrossRefGoogle Scholar
  5. 5.
    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 118:1416 Medline. doi: 10.1016/j.amjmed.2005.02.042 PubMedCrossRefGoogle Scholar
  6. 6.
    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 91:2105–2111 Medline. doi: 10.1210/jc.2005-2476 PubMedCrossRefGoogle Scholar
  7. 7.
    Van den BG, de Zegher F, Bouillon R (1998) Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab 83:1827–1834Google Scholar
  8. 8.
    Beishuizen A, Thijs LG, Vermes I (2001) Patterns of corticosteroid-binding globulin, the free cortisol index during septic shock and multitrauma. Intensive Care Med 27:1584–1591 Medline. doi: 10.1007/s001340101073 PubMedCrossRefGoogle Scholar
  9. 9.
    Annane D, Sebille V, Troche G et al (2000) A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 283:1038–1045 Medline. doi: 10.1001/jama.283.8.1038 PubMedCrossRefGoogle Scholar
  10. 10.
    Hamrahian AH, Oseni TS, Arafah BM (2004) Measurements of serum free cortisol in critically ill patients. N Engl J Med 350:1629–1638 Medline. doi: 10.1056/NEJMoa020266 PubMedCrossRefGoogle Scholar
  11. 11.
    Jochberger S, Morgenthaler NG, Mayr VD et al (2006) Copeptin and arginine vasopressin concentrations in critically ill patients. J Clin Endocrinol Metab 91:4381–4386 Medline. doi: 10.1210/jc.2005-2830 PubMedCrossRefGoogle Scholar
  12. 12.
    Morgenthaler NG, Struck J, Alonso C et al (2006) Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem 52:112–119 Medline. doi: 10.1373/clinchem.2005.060038 PubMedCrossRefGoogle Scholar
  13. 13.
    Vanhorebeek I, Peeters RP, Vander PS et al (2006) Cortisol response to critical illness: effect of intensive insulin therapy. J Clin Endocrinol Metab 91:3803–3813 Medline. doi: 10.1210/jc.2005-2089 PubMedCrossRefGoogle Scholar
  14. 14.
    Molijn GJ, Spek JJ, van Uffelen JC et al (1995) Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock. J Clin Endocrinol Metab 80:1799–1803 Medline. doi: 10.1210/jc.80.6.1799 PubMedCrossRefGoogle Scholar
  15. 15.
    Cooper MS, Stewart PM (2003) Corticosteroid insufficiency in acutely ill patients. N Engl J Med 348:727–734 Medline. doi: 10.1056/NEJMra020529 PubMedCrossRefGoogle 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) 67:598–606 Medline. doi: 10.1111/j.1365-2265.2007.02860.x CrossRefGoogle Scholar
  17. 17.
    Klose M, Juul A, Poulsgaard L et al (2007) Prevalence and predictive factors of post-traumatic hypopituitarism. Clin Endocrinol (Oxf) 67:193–201 Medline. doi: 10.1111/j.1365-2265.2007.02860.x CrossRefGoogle Scholar
  18. 18.
    Bondanelli M, De Marinis L, Ambrosio MR et al (2004) Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 21:685–696 Medline. doi: 10.1089/0897715041269713 PubMedCrossRefGoogle Scholar
  19. 19.
    Kelly DF, Gonzalo IT, Cohan P et al (2000) Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report. J Neurosurg 93:743–752 MedlinePubMedCrossRefGoogle Scholar
  20. 20.
    Agha A, Rogers B, Sherlock M et al (2004) Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 89:4929–4936 Medline. doi: 10.1210/jc.2004-0511 PubMedCrossRefGoogle Scholar
  21. 21.
    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 90:6085–6092PubMedCrossRefGoogle Scholar
  22. 22.
    Leal-Cerro A, Flores JM, Rincon M et al (2005) Prevalence of hypopituitarism and growth hormone deficiency in adults long-term after severe traumatic brain injury. Clin Endocrinol (Oxf) 62:525–532 Medline. doi: 10.1111/j.1365-2265.2005.02250.x CrossRefGoogle Scholar
  23. 23.
    Schneider HJ, Schneider M, Saller B et al (2006) Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol 154:259–265 Medline. doi: 10.1530/eje.1.02071 PubMedCrossRefGoogle Scholar
  24. 24.
    Schneider M, Schneider HJ, Yassouridis A et al (2008) Predictors of anterior pituitary insufficiency after traumatic brain injury. Clin Endocrinol (Oxf) 68:206–212 MedlineGoogle Scholar
  25. 25.
    Crompton MR (1971) Hypothalamic lesions following closed head injury. Brain 94:165–172 Medline. doi: 10.1093/brain/94.1.165 PubMedCrossRefGoogle Scholar
  26. 26.
    Ceballos R (1966) Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 3:185–198 MedlinePubMedGoogle Scholar
  27. 27.
    Kornblum RN, Fisher RS (1969) Pituitary lesions in craniocerebral injuries. Arch Pathol 88:242–248 MedlinePubMedGoogle Scholar
  28. 28.
    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):468–475PubMedCrossRefGoogle Scholar
  29. 29.
    Bonnefont X, Lacampagne A, Sanchez-Hormigo A et al (2005) Revealing the large-scale network organization of growth hormone-secreting cells. Proc Natl Acad Sci USA 102:16880–16885 Medline. doi: 10.1073/pnas.0508202102 PubMedCrossRefGoogle Scholar
  30. 30.
    Schneider HJ, Samann PG, Schneider M et al (2007) Pituitary imaging abnormalities in patients with and without hypopituitarism after traumatic brain injury. J Endocrinol Invest 30:RC9–RC12 MedlinePubMedGoogle Scholar
  31. 31.
    Bonert VS, Elashoff JD, Barnett P et al (2004) Body mass index determines evoked growth hormone (GH) responsiveness in normal healthy male subjects: diagnostic caveat for adult GH deficiency. J Clin Endocrinol Metab 89:3397–3401 Medline. doi: 10.1210/jc.2003-032213 PubMedCrossRefGoogle Scholar
  32. 32.
    Rasmussen MH, Hvidberg A, Juul A et al (1995) Massive weight loss restores 24-h growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 80:1407–1415 Medline. doi: 10.1210/jc.80.4.1407 PubMedCrossRefGoogle Scholar
  33. 33.
    Miller KK, Biller BM, Lipman JG et al (2005) Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk. J Clin Endocrinol Metab 90:768–774 Medline. doi: 10.1210/jc.2004-0894 PubMedCrossRefGoogle Scholar
  34. 34.
    Cansu A, Serdaroglu A, Camurdan O et al (2006) The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate. Epilepsia 47:1855–1859 Medline. doi: 10.1111/j.1528-1167.2006.00821.x PubMedCrossRefGoogle Scholar
  35. 35.
    Isojarvi JI, Turkka J, Pakarinen AJ et al (2001) Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia 42:930–934 Medline. doi: 10.1046/j.1528-1157.2001.042007930.x PubMedCrossRefGoogle Scholar
  36. 36.
    Herzog AG, Fowler KM (2005) Sexual hormones and epilepsy: threat and opportunities. Curr Opin Neurol 18:167–172 Medline. doi: 10.1097/01.wco.0000162859.42218.fd PubMedCrossRefGoogle Scholar
  37. 37.
    Annegers JF, Hauser WA, Coan SP et al (1998) A population-based study of seizures after traumatic brain injuries. N Engl J Med 338:20–24 Medline. doi: 10.1056/NEJM199801013380104 PubMedCrossRefGoogle Scholar
  38. 38.
    Benedetti MS, Whomsley R, Baltes E et al (2005) Alteration of thyroid hormone homeostasis by antiepileptic drugs in humans: involvement of glucuronosyltransferase induction. Eur J Clin Pharmacol 61:863–872 Medline. doi: 10.1007/s00228-005-0056-0 PubMedCrossRefGoogle Scholar
  39. 39.
    Isojarvi JI, Tauboll E, Herzog AG (2005) Effect of antiepileptic drugs on reproductive endocrine function in individuals with epilepsy. CNS Drugs 19:207–223 Medline. doi: 10.2165/00023210-200519030-00003 PubMedCrossRefGoogle Scholar
  40. 40.
    Herzog AG, Seibel MM, Schomer DL et al (1986) Reproductive endocrine disorders in men with partial seizures of temporal lobe origin. Arch Neurol 43:347–350 MedlinePubMedGoogle Scholar
  41. 41.
    Teasdale TW, Engberg AW (2005) Subjective well-being and quality of life following traumatic brain injury in adults: a long-term population-based follow-up. Brain Inj 19:1041–1048 Medline. doi: 10.1080/02699050500110397 PubMedCrossRefGoogle Scholar
  42. 42.
    Pierce CA, Hanks RA (2006) Life satisfaction after traumatic brain injury and the World Health Organization model of disability. Am J Phys Med Rehabil 85:889–898 Medline. doi: 10.1097/01.phm.0000242615.43129.ae PubMedCrossRefGoogle Scholar
  43. 43.
    Carroll PV, Christ ER, Bengtsson BA et al (1998) Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 83:382–395PubMedCrossRefGoogle Scholar
  44. 44.
    Bengtsson BA, Eden S, Lonn L et al (1993) Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 76:309–317 Medline. doi: 10.1210/jc.76.2.309 PubMedCrossRefGoogle Scholar
  45. 45.
    Feldt-Rasmussen U, Wilton P, Jonsson P (2004) Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults. Growth Horm IGF Res 14(Suppl A):S51–S58PubMedCrossRefGoogle Scholar
  46. 46.
    Popovic V, Pekic S, Pavlovic D et al (2004) Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress. J Endocrinol Invest 27:1048–1054 MedlinePubMedGoogle Scholar
  47. 47.
    Kelly DF, McArthur DL, Levin H et al (2006) Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma 23:928–942 Medline. doi: 10.1089/neu.2006.23.928 PubMedCrossRefGoogle Scholar
  48. 48.
    Bondanelli M, Ambrosio MR, Cavazzini L et al (2007) Anterior pituitary function may predict functional and cognitive outcome in patients with traumatic brain injury undergoing rehabilitation. J Neurotrauma 24:1687–1697 Medline. doi: 10.1089/neu.2007.0343 PubMedCrossRefGoogle Scholar
  49. 49.
    Klose M, Watt T, Brennum J et al (2007) Posttraumatic hypopituitarism is associated with an unfavorable body composition and lipid profile, and decreased quality of life 12 months after injury. J Clin Endocrinol Metab 92:3861–3868 Medline. doi: 10.1210/jc.2007-0901 PubMedCrossRefGoogle Scholar
  50. 50.
    Lieberman SA, Oberoi AL, Gilkinson CR, Masel BE, Urban RJ (2001) Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86:2752–2756PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of Medical Endocrinology, PE2131Copenhagen University HospitalCopenhagenDenmark

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