Endocrine changes after pediatric traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a very common occurrence in childhood, and can lead to devastating long term consequences. Recent research has focused on the potential endocrine consequences of TBI in adults. The research in children is less robust. This paper reviews current literature regarding TBI and possible hypothalamic and pituitary deficiencies in childhood. Acute endocrine changes are commonly found after TBI in pediatric patients, which can include changes in hypothalamic–pituitary–adrenal axis and antidiuretic hormone production and release. In the long term, both temporary and permanent alterations in pituitary function have been found. About 30% of children have hypopituitarism up to 5 years after injury. Growth hormone deficiency and disturbances in puberty are the most common, but children can also experience ACTH deficiency, diabetes insipidus, central hypothyroidism, and elevated prolactin. Every hormonal axis can be affected after TBI in children, although growth hormone deficiency and alterations in puberty are the most common. Because transient and permanent hypopituitarism is common after TBI, survivors should be screened serially for possible endocrine disturbances. These children should undergo routine surveillance at least 1 year after injury to ensure early detection of deficiencies in hormonal production in order to permit normal growth and development.

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References

  1. 1.

    Bruns J Jr, Hauser WA (2003) The epidemiology of traumatic brain injury: a review. Epilepsia 44(suppl 10):2–10

    PubMed  Article  Google Scholar 

  2. 2.

    Schneier AJ, Shields BJ, Hostetler SG, Xiang H, Smith GA (2006) Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics 118:483–492

    PubMed  Article  Google Scholar 

  3. 3.

    Keenan HT, Runyan DK, Nocera M (2006) Longitudinal follow-up of families and young children with traumatic brain injury. Pediatrics 117:1291–1297

    PubMed  Article  Google Scholar 

  4. 4.

    McCarthy ML, MacKenzie EJ, Durbin DR, Aitken ME, Jaffe KM, Paidas CN et al (2006) Health-related quality of life during the first year after traumatic brain injury. Arch Pediatr Adolesc Med 160:252–260

    PubMed  Article  Google Scholar 

  5. 5.

    Acerini CL, Tasker RC (2008) Neuroendocrine consequences of traumatic brain injury. J Pediatr Endocrinol Metab 21:611–619

    PubMed  Article  Google Scholar 

  6. 6.

    Popovic V, Pekic S, Pavlovic D, Maric N, Jasovic-Gasic M, Djurovic B 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

    PubMed  CAS  Google Scholar 

  7. 7.

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

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Agha A, Phillips J, Thompson CJ (2007) Hypopituitarism following traumatic brain injury (TBI). Br J Neurosurg 21:210–216

    PubMed  Article  Google Scholar 

  9. 9.

    Bushnik T, Englander J, Katznelson L (2007) Fatigue after TBI: association with neuroendocrine abnormalities. Brain Inj 21:559–566

    PubMed  Article  Google Scholar 

  10. 10.

    Tanrverdi F, De Bellis A, Bizzarro A, Sinisi AA, Bellastella G, Pane E, Bellastella A, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F (2008) Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity? Eur J Endocrinol 159:7–13

    Article  Google Scholar 

  11. 11.

    Pavlovic D, Pekic S, Stojanovic M, Zivkovic V, Djurovic B, Jovanovic V, Miljic N, Medic-Stojanoska M, Doknic M, Miljic D, Djurovic M, Casanueva F, Popovic V (2010) Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults. Eur J Neurol 17:696–702

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Berg C, Oeffner A, Schumm-Draeger PM, Badorrek F, Brabant G, Gerbert B, Bornstein S, Zimmermann A, Weber M, Broecker-Preuss M, Mann K, Herrmann BL (2010) Prevalence of anterior pituitary dysfunction in patients following traumatic brain injury in a German multi-centre screening program. Exp Clin Endocrinol Diabetes 118:139–144

    PubMed  Article  CAS  Google Scholar 

  13. 13.

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

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Barton RN, Stoner HB, Watson SM (1987) Relationships among plasma cortisol, adrenocorticotrophin, and severity of injury in recently injured patients. J Trauma 27:384–392

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    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 14:917–921

    PubMed  Article  CAS  Google Scholar 

  16. 16.

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

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Srinivas R, Brown SD, Chang YF, Garcia-Fillion P, Adelson PD (2010) Endocrine function in children acutely following severe traumatic brain injury. Childs Nerv Syst 26:647–653

    PubMed  Article  Google Scholar 

  18. 18.

    Behan LA, Phillips J, Thompson CJ, Agha A (2008) Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry 79:753–759

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Einaudi S, Matarazzo P, Peretta P, Grossetti R, Giordano F, Altare F et al (2006) Hypothalamo-hypophysial dysfunction after traumatic brain injury in children, adolescents: a preliminary retrospective and prospective study. J Pediatr Endocrinol Metab 19:691–703

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Morares RB, Czepielewski M, Friedman G, de Borba EL (2011) Diagnosis of adrenal failure in critically ill patients. Arq Bras Endocrinol Metab 55:295–302

    Article  Google Scholar 

  21. 21.

    Barzilay Z, Somekh E (1998) Diabetes insipidus in severely brain damaged children. J Med 19:47–64

    Google Scholar 

  22. 22.

    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 12 months after trauma. J Clin Endocrinol Metab 91:2105–2111

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Kokshoorn NE, Wassenaar MJE, Biermasz NR, Roelfsema F, Smit JWA, Romijn JA, Pereira AM (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

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavo S, Scaroni C et al (2005) Hypopituitarism induced by traumatic brain injury in the transition phase. J Endocrinol Invest 28:984–989

    PubMed  CAS  Google Scholar 

  25. 25.

    Bruce DA, Schut L, Bruno LA, Wood JH, Sutton LN (1978) Outcome following severe head injuries in children. J Neurosurg 48:679–688

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Niederland T, Makovi H, Gal V, Andreka B, Abraham CS, Kovacs J (2007) Abnormalities of pituitary function after traumatic brain injury in children. J Neurotrauma 24:119–127

    PubMed  Article  Google Scholar 

  27. 27.

    Poomthavorn P, Maixner W, Zacharin M (2008) Pituitary function in paediatric survivors of severe traumatic brain injury. Arch Dis Child 93:133–137

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Medic-Stojanoska M, Pekic S, Curic N, Djilas-Ivanovic D, Popovic V (2007) Evolving hypopituitarism as a consequence of traumatic brain injury (TBI) in childhood—call for attention. Endocrine 31:268–271

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Acerini CL, Tasker RC (2007) Endocrine sequelae of traumatic brain injury in childhood. Horm Res 68(Suppl 5):14–17

    PubMed  Article  Google Scholar 

  30. 30.

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

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Bolado GG, Estebanez M, Arizkeuren EM, Calcena AA, Esteves AR, Vela A, Rica I (2011) Assessment of pituitary function after traumatic brain injury in childhood. Abstract P2-d1-680: European Society for Pediatric Endocrinology (ESPE), Glasgow

  32. 32.

    Aleksijevic D, Zapletalova J, Krahulik D, Klaskova E, Widermann J, Mihal V (2011) Endocrine dysfunction after traumatic brain injury in children and adolescents (a single centre prospective study). Abstract P2-d1-732: European Society for Pediatric Endocrinology (ESPE), Glasgow

  33. 33.

    Hewitt J, Pitkin J, Corbin V, Maixner W, Zacharin M (2011) Endocrine sequelae of traumatic brain injury in children: a prospective study. Abstract P1-d3-347: European Society for Pediatric Endocrinology (ESPE), Glasgow

  34. 34.

    Agha A, Thompson CJ (2005) High risk of hypogonadism after traumatic brain injury: clinical implications. Pituitary 8:245–249

    PubMed  Article  Google Scholar 

  35. 35.

    Popii V, Baumann G (2004) Laboratory measurement of growth hormone. Clin Chim Acta 350:1–16

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Romshe CA, Zipf WB, Miser A, Miser J, Sotos JF, Newton WA (1984) Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature. J Pediatr 104:177–181

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    Blatt J, Bercu BB, Gillin JC, Mendelson WB, Poplack DG (1984) Reduced pulsatile growth hormone secretion in children after therapy for acute lymphoblastic leukemia. J Pediatr 104:182–186

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Rose SR, Municchi G (1999) Six-hour and four-hour nocturnal sampling for growth hormone. J Pediatr Endocrinol Metab 12:167–173

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    Bondanelli M, Ambrosio MR, Cavazzini L, Bertocchi A, Zatelli MC, Carli A 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

    PubMed  Article  Google Scholar 

  40. 40.

    Klose M, Juul A, Struck J, Morgenthaler NG, Kosteljanetz M, Feldt-Rasmussen U (2007) Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study. Clin Endocrinol (Oxf) 67:598–606

    Article  CAS  Google Scholar 

  41. 41.

    Schneider HJ, Schneider M, Saller B, Petersenn S, Uhr M, Husemann B et al (2006) Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol 154:259–265

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Bavisetty S, McArthur DL, Dusick JR, Wang C, Cohan P, Boscardin WJ et al (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62:1080–1093 (discussion 1093-4)

    PubMed  Article  Google Scholar 

  43. 43.

    Norwood KW, DeBoer MD, Gurka MJ, Kuperminc MN, Rogol AD, Blackman JA, Wamstad JB, Buck ML, Patrick PD (2010) Traumatic brain injury in children and adolescents: surveillance for pituitary dysfunction. Clin Pediatr 49:1044–1049

    Article  Google Scholar 

  44. 44.

    Behan LA, Agha A (2007) Endocrine consequences of adult traumatic brain injury. Horm Res 68(Suppl 5):18–21

    PubMed  Article  Google Scholar 

  45. 45.

    Grumbach MM (2002) The neuroendocrinology of human puberty revisited. Horm Res 57(Suppl 2):2–14

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Bourguignon JP, Gérard A, Purnelle G, Czajkowski V, Yamanaka C, Lemaître M, Rigo JM, Moonen G, Franchimont P (1997) Duality of glutamatergic and GABAergic control of pulsatile GnRH secretion by rat hypothalamic explants: II. Reduced NR2C- and GABAA-receptor-mediated inhibition at initiation of sexual maturation. J Neuroendocrinol 9(3):193–199

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB et al (2008) Corticotropin tests for hypothalamic–pituitary–adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 93:4245–4253

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    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) 117:80–86

    CAS  Google Scholar 

  49. 49.

    Faglia G, Bitensky L, Pinchera A, Ferrari C, Paracchi A, Beck-Peccoz P et al (1979) Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin. J Clin Endocrinol Metab 48:989–998

    PubMed  Article  CAS  Google Scholar 

  50. 50.

    Rose SR (2010) Improved diagnosis of mild hypothyroidism using time-of-day normal ranges for thyrotropin. J Pediatr 157:662–667

    PubMed  Article  CAS  Google Scholar 

  51. 51.

    Rose SR, Nisula BC (1989) Circadian variation of thyrotropin in childhood. J Clin Endocrinol Metab 68:1086–1090

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Rose SR (1995) Isolated central hypothyroidism in short stature. Pediatr Res 38:967–973

    PubMed  Article  CAS  Google Scholar 

  53. 53.

    Rose SR (2001) Cranial irradiation and central hypothyroidism. Trends Endocrinol Metab 12(3):97–104

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Casanueva FF, Leal A, Koltowska-Haggstrom M, Jonsson P, Goth MI (2005) Traumatic brain injury as a relevant cause of growth hormone deficiency in adults: a KIMS-based study. Arch Phys Med Rehabil 86:463–468

    PubMed  Article  Google Scholar 

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Acknowledgments

This review would not have been possible without the diligent efforts of our colleagues Anne-Marie Kaulfers, Samantha Blum, Tammy Weis, Linda Michaud, and Kathi Makoroff.

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Correspondence to Susan R. Rose.

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Rose, S.R., Auble, B.A. Endocrine changes after pediatric traumatic brain injury. Pituitary 15, 267–275 (2012). https://doi.org/10.1007/s11102-011-0360-x

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Keywords

  • Traumatic brain injury
  • Hypopituitarism
  • Precocious puberty
  • Hypogonadotropic hypogonadism
  • Central hypothyroidism
  • Growth hormone deficiency
  • Adrenal insufficiency
  • Hyperprolactinemia
  • Adult
  • Pediatric