, Volume 14, Issue 3, pp 383–391 | Cite as

Predictors of post-traumatic pituitary failure during long-term follow-up

  • Orsolya Nemes
  • Noemi Kovacs
  • Endre Czeiter
  • Peter Kenyeres
  • Zita Tarjanyi
  • Laszlo Bajnok
  • Andras Buki
  • Tamas Doczi
  • Emese MezosiEmail author



There is increasing awareness among physicians of the risks of traumatic brain injury (TBI)-induced hypopituitarism. We have assessed the prevalence and risk factors of posttraumatic hypopituitarism by analyzing the TBI database of the University of Pecs.


This consecutive analysis of 126 TBI survivors (mean age: 42.4 years, average follow-up time: 48 months) revealed that 60.3% had severe and 39.7% moderately severe trauma based on GCS score. Subdural hemorrhage (29.3%) and diffuse injury (27%) were the most common types of injury; 17.5% of patients suffered basal skull fractures.


The prevalence of major anterior pituitary failure was 57.1%. Occurrence of total and partial growth hormone deficiency (GHD/GHI) was 39.7%, while LH/FSH, TSH and ACTH deficiencies were less frequent, namely 23.0%, 16.7% and 10.3%, respectively. Of the 82 patients with multiple endocrine evaluations, 31.7% presented significant changes in hormonal deficiencies during the follow-up period: new hormone deficiencies developed in 16 patients, while hormonal disturbances resolved in 10 subjects. Looking for factors influencing the prevalence of pituitary dysfunction, endocrine results were analyzed in relation to age, gender, GCS scores, injury types, basal skull fracture, ventricular drain insertion and necessity of neurosurgical intervention. All hormonal disturbances were more prevalent after severe trauma (OR: 3.25, p = 0.002), while the need for surgery proved to be an independent determinant of multiple and GH deficits (OR: 3.72 (p = 0.004) and 9.33 (p = 0.001)).


Post-traumatic hypopituitarism is common and may evolve or resolve over time. Victims of severe TBI and/or patients who have undergone neurosurgical intervention for head injury are the most prone to post-traumatic hypopituitarism.

Key words

Traumatic brain injury Hypopituitarism GCS Growth hormone deficiency 


  1. 1.
    Tagliaferri F, Comapagnone C, Korsic M, Servadei F, Kraus J, 2006 A systematic review of brain injury epidemiology in Europe. Acta Neurochir (Wien) 148: 255–268.CrossRefGoogle Scholar
  2. 2.
    Van Baalen B, Odding E, Maas AI, Ribbers GM, Bergen MP, Stam HJ, 2003 Traumatic brain injury: classification of initial severity and determination of functional outcome. Disabil Rehabil 25: 9–18.CrossRefGoogle Scholar
  3. 3.
    Benvenga S, Campenni A, Ruggeri RM, Trimarchi F, 2000 Clinical review 113: Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85: 1353–1361.CrossRefGoogle Scholar
  4. 4.
    Daniel PM, Prichard MM, Treip CS, 1959 Traumatic infarcion of the anterior lobe of the pituitary gland. Lancet 2: 927–931.CrossRefGoogle Scholar
  5. 5.
    Aimaretti G, Ambrosio MR, Benvenga S, et al, 2004 Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI). Growth Horm IGF Res 14: Suppl 1: 114–117.CrossRefGoogle Scholar
  6. 6.
    Kornblum RN, Fischer RS, 1969 Pituitary lesions in craniocerebral injuries. Arch Pathol 88: 242–248.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Crompton MR, 1971 Hypothalamic lesions following closed head injury. Brain 94: 165–172.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Bavisetty S, Mc Arthur DL, Dusick JR, et al, 2008 Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62: 1080–1094.CrossRefGoogle Scholar
  10. 10.
    Krahulik D, Zapletalova J, Frysak Z, Vaverka Z, 2010 Dysfunction of hypothalamic-hypophysial axis after TBI in adults. J Neurosurg 113: 581–584.CrossRefGoogle Scholar
  11. 11.
    Kelly DF, Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C, 2000 Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a prelimiary report. J Neurosurg 93: 743–752.CrossRefGoogle Scholar
  12. 12.
    Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ, 2001 Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86: 2752–2756.PubMedGoogle Scholar
  13. 13.
    Bondanelli M, De Marinis L, Ambrosio MR, et al, 2004 Occurence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 21: 685–696.CrossRefGoogle Scholar
  14. 14.
    Aimaretti G, Ambrosio MR, Di Somma C, et al, 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: 320–326.CrossRefGoogle Scholar
  15. 15.
    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: 6085–6092.CrossRefGoogle Scholar
  16. 16.
    Tanriverdi F, Senyurek H, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F, 2006 High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and at 12 months after the trauma. J Clin Endocrionol Metab 91: 2105–2111.CrossRefGoogle Scholar
  17. 17.
    Hermann BL, Rehder J, Kahlke S, et al, 2006 Hypopituitarism following severe traumatic brain injury. Exp Clin Endocrinol Diabetes 114: 316–321.CrossRefGoogle Scholar
  18. 18.
    Klose M, Juul A, Poulsgaard L, Kosteljanetz M, Brennum J, Feldt-Rasmussen U, 2007 Prevalence and predictive factors of post-traumatic hypopituitarism. Clin Endocrinol (Oxf) 67: 193–201.CrossRefGoogle Scholar
  19. 19.
    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.CrossRefGoogle 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.CrossRefGoogle Scholar
  21. 21.
    Schneider HJ, Schneider M, Sailer B, et al, 2006 Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol 154: 259–265.CrossRefGoogle Scholar
  22. 22.
    Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A, 2007 Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA 298: 1429–1438.CrossRefGoogle Scholar
  23. 23.
    Schneider M, Schneider HJ, Yassouridis A, Saller B, von Rosen F, Stalla GK, 2008 Predictors of anterior pituitary insufficiency after traumatic brain injury. Clin Endocrinol (Oxf) 68: 206–212.Google Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    Agha A, Ryan J, Sherlock M, Thompson CJ, 2005 Spontaneous recovery from post-traumatic hypopituitarism. Am J Phys Med Rahabil 84: 381–385.CrossRefGoogle Scholar
  26. 26.
    Agha A, Sherlok M, Phililips J, Tormey W, Thompson CJ, 2005 The natural history of post-traumatic neurohypophysial dysfunction. Eur J Endocrinol 152: 371–377.CrossRefGoogle Scholar
  27. 27.
    Schneider HJ, Schneider M, Kreitschmann-Andermahr I, et al, 2011 Structured assessment of hypopituitarism after traumatic brain injury and aneurysmal subarachnoid hemorrhage in 1242 patients: the German interdisciplinary database. J Neurotrauma 28: 1693–1698.CrossRefGoogle Scholar
  28. 28.
    Secco A, di Lorgi N, Napoli F, et al, 2009 Reassessment of the growth hormone status in young adults in childhood-onset growth hormone deficiency: reappraisal of insulin tolerance testing. J Clin Endocrinol Metab 94: 4195–4204.CrossRefGoogle Scholar
  29. 29.
    Murray RD, Adams JE, Shalet SM, 2004 Adults with partial growth hormone deficiency have an adverse body composition. J Clin Endocrinol Metab 89: 1586–1591.CrossRefGoogle Scholar
  30. 30.
    Glynn N, Agha A, 2013 Which patients requires neuroendocrine assessment following traumatic brain injury, when and how? Clin Endocrinol (Oxf) 78: 17–20.CrossRefGoogle Scholar
  31. 31.
    Ulfarsson T, Gudnaso GA, Rosén T, et al, 2013 Pituitary function and functional outcome in adults after severe traumatic brain injury: the long-term perspective. J Neurotrauma 30: 271–280.CrossRefGoogle Scholar
  32. 32.
    Ghigo E, Aimaretti G, Corneli G, 2008 Diagnosis of adult GH deficiency. Growth Horm IGF1 Res 18: 1–16.CrossRefGoogle Scholar
  33. 33.
    Blair JC, 2010 Prevalence, natural history and consequences of posttraumatic hypopituitarism:a case for endocrine surveillance. Br J Neurosurg 24: 10–17.CrossRefGoogle Scholar
  34. 34.
    Tanriverdi F, Agha A, Aimaretti G, et al, 2011 Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism. J Endocrinol Invest 34: 541–543.PubMedGoogle Scholar
  35. 35.
    Tanriverdi F, Taheri S, Ulutabanca H, et al, 2008 Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after traumatic brain injury due to varios causes: preliminary data. J Neurotrauma 25: 1071–1077.CrossRefGoogle Scholar
  36. 36.
    Tanriverdi F, De Bellis A, Bizzarro A, et al, 2008 Anti-pituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity? Eur J Endocrinol 159: 7–13.CrossRefGoogle Scholar
  37. 37.
    Tanriverdi F, De Bellis A, Battaglia M, et al, 2010 Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity? Eur J Endocrinol 162: 861–867.CrossRefGoogle Scholar
  38. 38.
    Kokshoorn NE, Wassenaar MJ, Biermasz NR, et al, 2010 Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values. Eur J Endocrinol 162: 11–18.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Orsolya Nemes
    • 1
  • Noemi Kovacs
    • 2
  • Endre Czeiter
    • 2
  • Peter Kenyeres
    • 1
  • Zita Tarjanyi
    • 1
  • Laszlo Bajnok
    • 1
  • Andras Buki
    • 2
  • Tamas Doczi
    • 2
  • Emese Mezosi
    • 1
    Email author
  1. 1.1st Department of Internal MedicineUniversity of PecsPecsHungary
  2. 2.Department of NeurosurgeryUniversity of PecsPecsHungary

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