Pituitary dysfunction due to sports-related traumatic brain injury
After traumatic brain injury was accepted as an important etiologic factor of pituitary dysfunction (PD), awareness of risk of developing PD following sports-related traumatic brain injury (SR-TBI) has also increased. However there are not many studies investigating PD following SR-TBIs yet. We aimed to summarize the data reported so far and to discuss screening algorithms and treatment strategies.
Recent data on pituitary dysfunction after SR-TBIs is reviewed on basis of diagnosis, clinical perspectives, therapy, screening and possible prevention strategies.
Pituitary dysfunction is reported to occur in a range of 15–46.6% following SR-TBIs depending on the study design. Growth hormone is the most commonly reported pituitary hormone deficiency in athletes. Pituitary hormone deficiencies may occur during acute phase after head trauma, may improve with time or new deficiencies may develop during follow-up. Central adrenal insufficiency is the only and most critical impairment that requires urgent detection and replacement during acute phase. Decision on replacement of growth hormone and gonadal deficiencies should be individualized. Moreover these two hormones are abused by many athletes and a therapeutic use exemption from the league’s drug policy may be required.
Even mild and forgotten SR-TBIs may cause PD that may have distressing consequences in some cases if remain undiagnosed. More studies are needed to elucidate epidemiology and pathophysiology of PD after SR-TBIs. Also studies to establish screening algorithms for PD as well as strategies for prevention of SR-TBIs are urgently required.
KeywordsSports-related traumatic brain injury Pituitary dysfunction Growth hormone deficiency Central hypogonadism
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Cryan E (1918) Pituitary damage due to skull base fracture. Dtsch Med Wochenschr 44:1261Google Scholar
- 4.McCrea M, Hammeke T, Olsen G, Leo P, Guskiewicz K (2004) Unreported concussion in high school football players: implications for prevention. Clin J Sport Med 14(1):13–17Google Scholar
- 5.Delaney JS, Lacroix VJ, Leclerc S, Johnston KM (2002) Concussions among university football and soccer players. Clin J Sport Med 12(6):331–338Google Scholar
- 6.Coronado VG, Haileyesus T, Cheng TA, Bell JM, Haarbauer-Krupa J, Lionbarger MR, Flores-Herrera J, McGuire LC, Gilchrist J (2015) Trends in Sports- and Recreation-Related Traumatic Brain Injuries Treated in US Emergency Departments: The National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) 2001–2012. J Head Trauma Rehabil 30(3):185–197. https://doi.org/10.1097/HTR.0000000000000156 Google Scholar
- 7.Zazryn TR, Finch CF, McCrory P (2003) A 16 year study of injuries to professional kickboxers in the state of Victoria, Australia. Br J Sports Med 37(5):448–451Google Scholar
- 11.Casson IR, Siegel O, Sham R, Campbell EA, Tarlau M, DiDomenico A (1984) Brain damage in modern boxers. JAMA 251(20):2663–2667Google Scholar
- 12.Tanriverdi F, Unluhizarci K, Kocyigit I, Tuna IS, Karaca Z, Durak AC, Selcuklu A, Casanueva FF, Kelestimur F (2008) Brief communication: pituitary volume and function in competing and retired male boxers. Ann Intern Med 148(11):827–831Google Scholar
- 15.Ives JC, Alderman M, Stred SE (2007) Hypopituitarism after multiple concussions: a retrospective case study in an adolescent male. J Athl Train 42(3):431–439Google Scholar
- 18.Kelly DF, Chaloner C, Evans D, Mathews A, Cohan P, Wang C, Swerdloff R, Sim MS, Lee J, Wright MJ, Kernan C, Barkhoudarian G, Yuen KC, Guskiewicz K (2014) Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study. J Neurotrauma 31(13):1161–1171. https://doi.org/10.1089/neu.2013.3212 Google Scholar
- 20.Gábor L, Kovács PT, Éva Rimanóczy G, Pánics (2016) Katalin Bánáti, Miklós Góth: Growth hormone deficiency and central hypogonadism in retired professional football players. Endocr Oncol Metab 2:234–240Google Scholar
- 27.Wolman L (1956) Pituitary necrosis in raised intracranial pressure. J Pathol 72(2):575–586Google Scholar
- 28.Harper CG, Doyle D, Adams JH, Graham DI (1986) Analysis of abnormalities in pituitary gland in non-missile head injury: study of 100 consecutive cases. J Clin Pathol 39(7):769–773Google Scholar
- 30.Tanriverdi F, De Bellis A, Ulutabanca H, Bizzarro A, Sinisi AA, Bellastella G, Paglionico A, Dalla Mora V, Selcuklu L, Unluhizarci A, Casanueva K, Kelestimur FF (2013) A five year prospective investigation of anterior pituitary function after traumatic brain injury: is hypopituitarism long-term after head trauma associated with autoimmunity? J Neurotrauma 30(16):1426–1433. https://doi.org/10.1089/neu.2012.2752 Google Scholar
- 31.Tanriverdi F, De Bellis A, Battaglia M, Bellastella G, Bizzarro A, Sinisi AA, Bellastella A, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F (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(5):861–867. https://doi.org/10.1530/EJE-09-1024 Google Scholar
- 32.Tanriverdi F, Taheri S, Ulutabanca H, Caglayan AO, Ozkul Y, Dundar M, Selcuklu A, Unluhizarci K, Casanueva FF, Kelestimur F (2008) Apolipoprotein E3/E3 genotype decreases the risk of pituitary dysfunction after traumatic brain injury due to various causes: preliminary data. J Neurotrauma 25(9):1071–1077. https://doi.org/10.1089/neu.2007.0456 Google Scholar
- 36.Yu L, Boyle PA, Nag S, Leurgans S, Buchman AS, Wilson RS, Arvanitakis Z, Farfel JM, De Jager PL, Bennett DA, Schneider JA (2015) APOE and cerebral amyloid angiopathy in community-dwelling older persons. Neurobiol Aging 36(11):2946–2953. https://doi.org/10.1016/j.neurobiolaging.2015.08.008 Google Scholar
- 37.Nicoll JA, Roberts GW, Graham DI (1995) Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat Med 1(2):135–137Google Scholar
- 39.Uryu K, Chen XH, Martinez D, Browne KD, Johnson VE, Graham DI, Lee VM, Trojanowski JQ, Smith DH (2007) Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol 208(2):185–192. https://doi.org/10.1016/j.expneurol.2007.06.018 Google Scholar
- 40.Bogoslovsky T, Wilson D, Chen Y, Hanlon D, Gill J, Jeromin A, Song L, Moore C, Gong Y, Kenney K, Diaz-Arrastia R (2017) Increases of plasma levels of glial fibrillary acidic protein, tau, and amyloid beta up to 90 days after traumatic brain injury. J Neurotrauma 34(1):66–73. https://doi.org/10.1089/neu.2015.4333 Google Scholar
- 47.Tritos NA, Yuen KC, Kelly DF, Neuroendocrine A, Pituitary Scientific C (2015) American Association of Clinical Endocrinologists and American College of endocrinology disease state clinical review: a neuroendocrine approach to patients with traumatic brain injury. Endocr Pract 21(7):823–831. https://doi.org/10.4158/EP14567.DSCR Google Scholar
- 48.Tanriverdi F, Agha A, Aimaretti G, Casanueva FF, Kelestimur F, Klose M, Masel BE, Pereira AM, Popovic V, Schneider HJ (2011) Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism. J Endocrinol Invest 34(7):541–543. https://doi.org/10.3275/7805 Google Scholar
- 51.Cunningham SK, Moore A, McKenna TJ (1983) Normal cortisol response to corticotropin in patients with secondary adrenal failure. Arch Intern Med 143(12):2276–2279Google Scholar
- 52.Maiya B, Newcombe V, Nortje J, Bradley P, Bernard F, Chatfield D, Outtrim J, Hutchinson P, Matta B, Antoun N, Menon D (2008) Magnetic resonance imaging changes in the pituitary gland following acute traumatic brain injury. Intensive Care Med 34(3):468–475. https://doi.org/10.1007/s00134-007-0902-x Google Scholar
- 54.Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, Jordan BD (2005) Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery 57(4):719–726 (discussion 719–726)Google Scholar
- 55.Hunt SM, McKenna SP, Doward LC (1993) Preliminary report on the development of a disease-specific instrument for assessing quality of life of adults with growth hormone deficiency. Acta Endocrinol (Copenh) 128(Suppl 2):37–40Google Scholar
- 56.Tanriverdi F, Suer C, Yapislar H, Kocyigit I, Selcuklu A, Unluhizarci K, Casanueva FF, Kelestimur F (2013) Growth hormone deficiency due to sports-related head trauma is associated with impaired cognitive performance in amateur boxers and kickboxers as revealed by P300 auditory event-related potentials. Clin Endocrinol (Oxf) 78(5):730–737. https://doi.org/10.1111/cen.12037 Google Scholar
- 58.Fatih Tanriverdi IK, Unluhizarci K, Casanueva FF, Kelestimur F (2008) Body composition, serum IGF-I and leptin level changes in amateur boxers: retired boxers have risk factors for cardiovascular disorders. Obes Metabol 4(2):118–123Google Scholar
- 61.Juul A, Hjortskov N, Jepsen LT, Nielsen B, Halkjaer-Kristensen J, Vahl N, Jorgensen JO, Christiansen JS, Skakkebaek NE (1995) Growth hormone deficiency and hyperthermia during exercise: a controlled study of sixteen GH-deficient patients. J Clin Endocrinol Metab 80(11):3335–3340. https://doi.org/10.1210/jcem.80.11.7593447 Google Scholar
- 65.WADA (2018) Prohibited List January 2018Google Scholar
- 66.Gotherstrom G, Svensson J, Koranyi J, Alpsten M, Bosaeus I, Bengtsson B, Johannsson G (2001) A prospective study of 5 years of GH replacement therapy in GH-deficient adults: sustained effects on body composition, bone mass, and metabolic indices. J Clin Endocrinol Metab 86(10):4657–4665. https://doi.org/10.1210/jcem.86.10.7887 Google Scholar
- 70.Cenci MC, Soares DV, Spina LD, de Lima Oliveira Brasil RR, Lobo PM, Mansur VA, Gold J, Michmacher E, Vaisman M, Conceicao FL (2009) Effects of 5 years of growth hormone (GH) replacement therapy on cardiac parameters and physical performance in adults with GH deficiency. Pituitary 12(4):322–329. https://doi.org/10.1007/s11102-009-0182-2 Google Scholar
- 71.Nass R, Huber RM, Klauss V, Muller OA, Schopohl J, Strasburger CJ (1995) Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 80(2):552–557. https://doi.org/10.1210/jcem.80.2.7852519 Google Scholar
- 73.Meinhardt U, Nelson AE, Hansen JL, Birzniece V, Clifford D, Leung KC, Graham K, Ho KK (2010) The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial. Ann Intern Med 152(9):568–577. https://doi.org/10.7326/0003-4819-152-9-201005040-00007 Google Scholar
- 74.Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR (2008) Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med 148(10):747–758Google Scholar
- 75.Hermansen K, Bengtsen M, Kjaer M, Vestergaard P, Jorgensen JOL (2017) Impact of GH administration on athletic performance in healthy young adults: a systematic review and meta-analysis of placebo-controlled trials. Growth Hormon IGF Res 34:38–44. https://doi.org/10.1016/j.ghir.2017.05.005 Google Scholar
- 76.Centers for Disease C, Prevention (2011) Nonfatal traumatic brain injuries related to sports and recreation activities among persons aged </=19 years—United States, 2001–2009. MMWR Morb Mortal Wkly Rep 60(39):1337–1342Google Scholar
- 78.Neidecker J, Sethi NK, Taylor R, Monsell R, Muzzi D, Spizler B, Lovelace L, Ayoub E, Weinstein R, Estwanik J, Reyes P, Cantu RC, Jordan B, Goodman M, Stiller JW, Gelber J, Boltuch R, Coletta D, Gagliardi A, Gelfman S, Golden P, Rizzo N, Wallace P, Fields A, Inalsingh C (2018) Concussion management in combat sports: consensus statement from the Association of Ringside Physicians. Br J Sports Med. https://doi.org/10.1136/bjsports-2017-098799 Google Scholar