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Cited by 121Traumatic Brain Injury and Neurovascular DisturbancesPituitary Gland Disorders and TreatmentsTraumatic Brain Injury Research

Chapter 1: pathophysiology of hypopituitarism in the setting of brain injury

Open access
Dusick, Joshua R., Wang, Christina, Cohan, Pejman, Swerdloff, Ronald, Kelly, Daniel F.·2012·Pituitary
DOI 10.1007/s11102-008-0130-6PMC PMC4170072
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Abstract

The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. Chronic anterior hypopituitarism, although reversible in some patients, persists in 25–40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined. Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood.

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Crossref · 10.1007/s11102-008-0130-6

Cites

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Claims the paper makes

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  • Findingcitation

    Acute secondary adrenal insufficiency in traumatic brain injury is typically reversible.

    “Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Cohan P, Wang C, McArthur DL et al (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358–2366. doi: 10.1097/01.CCM.0000181735.51183.A7 source

      Not checked in the free run.

  • Findingcitation

    Acute secondary adrenal insufficiency in traumatic brain injury is associated with lower systemic blood pressure.

    “Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Cohan P, Wang C, McArthur DL et al (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358–2366. doi: 10.1097/01.CCM.0000181735.51183.A7 source

      Not checked in the free run.

  • Findingown data

    Acute secondary adrenal insufficiency occurs in up to 50% of intubated traumatic brain injury victims within 10 days of injury.

    “in our prior study of acute adrenal insufficiency which occurred in 50% of intu-bated TBI subjects within 10 days of injury”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Cohan P, Wang C, McArthur DL et al (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358–2366. doi: 10.1097/01.CCM.0000181735.51183.A7 source

      Not checked in the free run.

  • Findingown data

    In the authors' study, no association was seen between long-term hypopituitarism and acute hypotension, hypoxia, anemia or intracranial hypertension.

    “Interestingly, in our study, no association was seen between long-term hypopituitarism and acute hypotension, hypoxia, anemia or intracranial hypertension.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Bavisetty S, Bavisetty S, McArthur DL et al (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62 (in press) source

      Not checked in the free run.

  • Findingown data

    In the authors' study of 70 traumatic brain injury patients with long-term follow-up, the degree of brain injury as defined by acute CT is the strongest predictor of subsequent hypopituitarism.

    “our recently published study of 70 TBI patients with long-term follow-up suggests that the degree of brain injury as defined by acute CT (presence of diffuse brain swelling and evacuated intracerebral hematoma or multiple contusions, in particular) is the strongest predictor of subsequent hypopituitarism [43].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Bavisetty S, Bavisetty S, McArthur DL et al (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62 (in press) source

      Not checked in the free run.

  • May combine two claims. 24
  • Classified as probably not a substantial claim. 3

  • May combine two claims.

    Findingown data

    All patients with major chronic hormonal deficits in the authors' series had severe parenchymal brain injury, including 87% with diffuse brain swelling.

    “All patients with major chronic hormonal deficits in our series had severe parenchymal brain injury including 87% with diffuse brain swelling.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Bavisetty S, Bavisetty S, McArthur DL et al (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62 (in press) source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In the authors' study of acute secondary adrenal insufficiency, severity of injury as measured by injury severity score, younger age, ischemic factors and medication effects all had an impact on acute cortisol and ACTH levels.

    “In our study of acute secondary adrenal insufficiency we found that severity of injury, as measured by the injury severity score, younger age, ischemic factors and medication effects all had an impact on acute cortisol and ACTH levels [35].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Cohan P, Wang C, McArthur DL et al (2005) Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med 33:2358–2366. doi: 10.1097/01.CCM.0000181735.51183.A7 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The adrenal, thyroid and posterior pituitary axes show greater resilience, while the somatotroph and gonadotroph axes show relative vulnerability after traumatic brain injury.

    “indicate a greater resilience of the adrenal, thyroid and posterior pituitary axes and a relative vulnerability of the somatotroph and gonadotroph axes”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Most pituitary hormones have important cerebral effects that influence brain development, normal brain function, and effective brain repair and recovery.

    “most of the pituitary hormones have been shown to have important cerebral effects that impact not only brain development, but also allow normal brain function and are integral for effective brain repair and recovery.”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [47] D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13:227–255. doi: 10.1007/BF02740625 source

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    • cites [48] Hana V, Prazny M, Marek J, Skrha J, Justova V (2002) Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement. Eur J Endocrinol 147:333–337. doi: 10.1530/eje.0.1470333 source

      Not checked in the free run.

    • cites [49] Napoli R, Guardasole V, Angelini V et al (2003) Acute effects of growth hormone on vascular function in human subjects. J Clin Endocrinol Metab 88:2817–2820. doi: 10.1210/jc.2003-030144 source

      Not checked in the free run.

    • cites [50] Saatman KE, Contreras PC, Smith DH et al (1997) Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp Neurol 147:418–427. doi: 10.1006/exnr.1997.6629 source

      Not checked in the free run.

    • cites [51] Scheepens A, Sirimanne ES, Breier BH, Clark RG, Gluckman PD, Williams CE (2001) Growth hormone as a neuronal rescue factor during recovery from CNS injury. Neuroscience 104:677–687. doi: 10.1016/S0306-4522(01)00109-9 source

      Not checked in the free run.

    • cites [52] Scheepens A, Williams CE, Breier BH, Guan J, Gluckman PD (2000) A role for the somatotropic axis in neural development, injury and disease. J Pediatr Endocrinol Metab 13(Suppl 6):1483–1491 source

      Not checked in the free run.

    • cites [53] Silha JV, Krsek M, Hana V et al (2005) The effects of growth hormone status on circulating levels of vascular growth factors. Clin Endocrinol (Oxf) 63:79–86. doi: 10.1111/j.1365-2265.2005.02303.x source

      Not checked in the free run.

    • cites [54] Ye P, D’Ercole AJ (1999) Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury. Endocrinology 140:3063–3072. doi: 10.1210/en.140.7.3063 source

      Not checked in the free run.

    • cites [55] Ye P, Li L, Richards RG, DiAugustine RP, D’Ercole AJ (2002) Myelination is altered in insulin-like growth factor-I null mutant mice. J Neurosci 22:6041–6051 source

      Not checked in the free run.

    • cites [56] Zhong J, Deng J, Phan J et al (2005) Insulin-like growth factor-I protects granule neurons from apoptosis and improves ataxia in weaver mice. J Neurosci Res 80:481–490. doi: 10.1002/jnr.20490 source

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    Premisecitation

    Insulin-like growth factor 1 is important in myelination, re-myelination, prevention of demyelination, and protection of oligodendrocytes from tumor necrosis factor-α induced apoptosis.

    “IGF-1 appears to be an important factor in myelination, re-myelination, prevention of demyelination and protection of oligodendrocytes from tumor necrosis factor-α induced apoptosis [47–56].”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [47] D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13:227–255. doi: 10.1007/BF02740625 source

      Not checked in the free run.

    • cites [48] Hana V, Prazny M, Marek J, Skrha J, Justova V (2002) Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement. Eur J Endocrinol 147:333–337. doi: 10.1530/eje.0.1470333 source

      Not checked in the free run.

    • cites [49] Napoli R, Guardasole V, Angelini V et al (2003) Acute effects of growth hormone on vascular function in human subjects. J Clin Endocrinol Metab 88:2817–2820. doi: 10.1210/jc.2003-030144 source

      Not checked in the free run.

    • cites [50] Saatman KE, Contreras PC, Smith DH et al (1997) Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp Neurol 147:418–427. doi: 10.1006/exnr.1997.6629 source

      Not checked in the free run.

    • cites [51] Scheepens A, Sirimanne ES, Breier BH, Clark RG, Gluckman PD, Williams CE (2001) Growth hormone as a neuronal rescue factor during recovery from CNS injury. Neuroscience 104:677–687. doi: 10.1016/S0306-4522(01)00109-9 source

      Not checked in the free run.

    • cites [52] Scheepens A, Williams CE, Breier BH, Guan J, Gluckman PD (2000) A role for the somatotropic axis in neural development, injury and disease. J Pediatr Endocrinol Metab 13(Suppl 6):1483–1491 source

      Not checked in the free run.

    • cites [53] Silha JV, Krsek M, Hana V et al (2005) The effects of growth hormone status on circulating levels of vascular growth factors. Clin Endocrinol (Oxf) 63:79–86. doi: 10.1111/j.1365-2265.2005.02303.x source

      Not checked in the free run.

    • cites [54] Ye P, D’Ercole AJ (1999) Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury. Endocrinology 140:3063–3072. doi: 10.1210/en.140.7.3063 source

      Not checked in the free run.

    • cites [55] Ye P, Li L, Richards RG, DiAugustine RP, D’Ercole AJ (2002) Myelination is altered in insulin-like growth factor-I null mutant mice. J Neurosci 22:6041–6051 source

      Not checked in the free run.

    • cites [56] Zhong J, Deng J, Phan J et al (2005) Insulin-like growth factor-I protects granule neurons from apoptosis and improves ataxia in weaver mice. J Neurosci Res 80:481–490. doi: 10.1002/jnr.20490 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Growth hormone is directly involved in vascular reactivity, vascular tone and central nervous system repair processes after hypoxic injury.

    “GH has been shown to be directly involved in vascular reactivity, vascular tone and CNS repair processes after hypoxic injury”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [47] D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13:227–255. doi: 10.1007/BF02740625 source

      Not checked in the free run.

    • cites [48] Hana V, Prazny M, Marek J, Skrha J, Justova V (2002) Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement. Eur J Endocrinol 147:333–337. doi: 10.1530/eje.0.1470333 source

      Not checked in the free run.

    • cites [49] Napoli R, Guardasole V, Angelini V et al (2003) Acute effects of growth hormone on vascular function in human subjects. J Clin Endocrinol Metab 88:2817–2820. doi: 10.1210/jc.2003-030144 source

      Not checked in the free run.

    • cites [50] Saatman KE, Contreras PC, Smith DH et al (1997) Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp Neurol 147:418–427. doi: 10.1006/exnr.1997.6629 source

      Not checked in the free run.

    • cites [51] Scheepens A, Sirimanne ES, Breier BH, Clark RG, Gluckman PD, Williams CE (2001) Growth hormone as a neuronal rescue factor during recovery from CNS injury. Neuroscience 104:677–687. doi: 10.1016/S0306-4522(01)00109-9 source

      Not checked in the free run.

    • cites [52] Scheepens A, Williams CE, Breier BH, Guan J, Gluckman PD (2000) A role for the somatotropic axis in neural development, injury and disease. J Pediatr Endocrinol Metab 13(Suppl 6):1483–1491 source

      Not checked in the free run.

    • cites [53] Silha JV, Krsek M, Hana V et al (2005) The effects of growth hormone status on circulating levels of vascular growth factors. Clin Endocrinol (Oxf) 63:79–86. doi: 10.1111/j.1365-2265.2005.02303.x source

      Not checked in the free run.

    • cites [54] Ye P, D’Ercole AJ (1999) Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury. Endocrinology 140:3063–3072. doi: 10.1210/en.140.7.3063 source

      Not checked in the free run.

    • cites [55] Ye P, Li L, Richards RG, DiAugustine RP, D’Ercole AJ (2002) Myelination is altered in insulin-like growth factor-I null mutant mice. J Neurosci 22:6041–6051 source

      Not checked in the free run.

    • cites [56] Zhong J, Deng J, Phan J et al (2005) Insulin-like growth factor-I protects granule neurons from apoptosis and improves ataxia in weaver mice. J Neurosci Res 80:481–490. doi: 10.1002/jnr.20490 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both growth hormone and insulin-like growth factor 1 receptors are widely present in the brain.

    “it is now clear that there are both GH and insulinlike growth factor (IGF-1) receptors widely present in the brain.”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [47] D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13:227–255. doi: 10.1007/BF02740625 source

      Not checked in the free run.

    • cites [48] Hana V, Prazny M, Marek J, Skrha J, Justova V (2002) Reduced microvascular perfusion and reactivity in adult GH deficient patients is restored by GH replacement. Eur J Endocrinol 147:333–337. doi: 10.1530/eje.0.1470333 source

      Not checked in the free run.

    • cites [49] Napoli R, Guardasole V, Angelini V et al (2003) Acute effects of growth hormone on vascular function in human subjects. J Clin Endocrinol Metab 88:2817–2820. doi: 10.1210/jc.2003-030144 source

      Not checked in the free run.

    • cites [50] Saatman KE, Contreras PC, Smith DH et al (1997) Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp Neurol 147:418–427. doi: 10.1006/exnr.1997.6629 source

      Not checked in the free run.

    • cites [51] Scheepens A, Sirimanne ES, Breier BH, Clark RG, Gluckman PD, Williams CE (2001) Growth hormone as a neuronal rescue factor during recovery from CNS injury. Neuroscience 104:677–687. doi: 10.1016/S0306-4522(01)00109-9 source

      Not checked in the free run.

    • cites [52] Scheepens A, Williams CE, Breier BH, Guan J, Gluckman PD (2000) A role for the somatotropic axis in neural development, injury and disease. J Pediatr Endocrinol Metab 13(Suppl 6):1483–1491 source

      Not checked in the free run.

    • cites [53] Silha JV, Krsek M, Hana V et al (2005) The effects of growth hormone status on circulating levels of vascular growth factors. Clin Endocrinol (Oxf) 63:79–86. doi: 10.1111/j.1365-2265.2005.02303.x source

      Not checked in the free run.

    • cites [54] Ye P, D’Ercole AJ (1999) Insulin-like growth factor I protects oligodendrocytes from tumor necrosis factor-alpha-induced injury. Endocrinology 140:3063–3072. doi: 10.1210/en.140.7.3063 source

      Not checked in the free run.

    • cites [55] Ye P, Li L, Richards RG, DiAugustine RP, D’Ercole AJ (2002) Myelination is altered in insulin-like growth factor-I null mutant mice. J Neurosci 22:6041–6051 source

      Not checked in the free run.

    • cites [56] Zhong J, Deng J, Phan J et al (2005) Insulin-like growth factor-I protects granule neurons from apoptosis and improves ataxia in weaver mice. J Neurosci Res 80:481–490. doi: 10.1002/jnr.20490 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The pituitary gland is confined within the bony sella and is tethered to the hypothalamus by the infundibulum.

    “The pituitary gland, typically weighing less than one gram and measuring approximately 8 mm by 10 mm, is located within the sella turcica in the skull base. It is separated from the suprasellar cistern by the diaphragma sella and is tethered to the hypopthalamus by the infundibulum which inserts on its superior surface [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Rhoton AL Jr (2002) The sellar region. Neurosurgery 51:S335–S374. doi: 10.1097/00006123-200208000-00007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The short hypophyseal portal vessels supply less than 30% of the anterior gland, predominantly in the medial portion including the pars intermedia.

    “The short hypophyseal portal vessels arise from branches of the intracavernous internal carotid artery, the inferior hypophyseal arteries, which enter the sella from below the diaphragma sella and supply the anterior gland with less than 30% of its vascular supply, predominantly in the medial portion of the gland including the pars intermedia [58–60].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [58] Adams JH, Daniel PM, Prichard MM (1966) The long-term effect of transection of the pituitary stalk on the volume of the pituitary gland on the adult goat. Acta Endocrinol (Copenh) 51:377–390 source

      Not checked in the free run.

    • cites [59] Daniel PM (1963) The pituitary gland and its blood supply. Sci Basis Med Annu Rev 84:83–98

      Not checked in the free run.

    • cites [60] Gorczyca W, Hardy J (1987) Arterial supply of the human anterior pituitary gland. Neurosurgery 20:369–378. doi: 10.1097/00006123-198703000-00003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These factors individually and in varying combinations likely determine which hormonal axes are affected, the severity of abnormality, and whether deficits are reversible or permanent.

    “It is likely that these factors individually and in varying combinations determine which hormonal axes are affected, the severity of abnormality and whether such deficits are reversible or permanent.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Because of its confinement within the bony sella and tethering to the hypothalamus, the anterior and posterior pituitary may be susceptible to mechanical trauma at the moment of impact.

    “Given the pituitary glands confinement within the bony sella and overlying diaphragma sella, and its tethering to the hypothalamus by the infundibulum, it has been hypothesized that the anterior and posterior gland may be susceptible to mechanical trauma at the moment of impact.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Fractures through the skull base and sella turcica, as well as rotational and shearing injuries of the brain stem and hypothalamic-pituitary axis, may directly injure the gland, infundibulum and/or hypothalamus.

    “Fractures through the skull base and sella turcica as well as rotational and shearing injuries of the brain stem and hypothalamic-pituitary axis may directly injure the gland, infundibulum and/or hypothalamus.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [10] Chesnut RM, Marshall LF, Klauber MR et al (1993) The role of secondary brain injury in determining outcome from severe head injury. J Trauma 34:216–222. doi: 10.1097/00005373-199302000-00006 source

      Not checked in the free run.

    • cites [39] Kelly DF, 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 93:743–752 source

      Not checked in the free run.

    • cites [59] Daniel PM (1963) The pituitary gland and its blood supply. Sci Basis Med Annu Rev 84:83–98

      Not checked in the free run.

    • cites [61] Ceballos R (1966) Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 3:185–198

      Not checked in the free run.

    • cites [62] Daniel PM, Prichard MM, Treip CS (1959) Traumatic infarction of the anterior lobe of the pituitary gland. Lancet 2:927–931. doi: 10.1016/S0140-6736(59)91583-1 source

      Not checked in the free run.

    • cites [63] Kornblum RN, Fisher RS (1969) Pituitary lesions in craniocerebral injuries. Arch Pathol 88:242–248

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The infarction pattern in these autopsy cases followed the blood supply of the long hypophyseal portal veins, while tissue in the short portal vein territory survived.

    “In these cases, the infarction pattern was in the blood supply pattern of the long hypophyseal portal veins while tissue in the vascular territory of the short portal veins survived.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [61] Ceballos R (1966) Pituitary changes in head trauma (analysis of 102 consecutive cases of head injury). Ala J Med Sci 3:185–198

      Not checked in the free run.

    • cites [63] Kornblum RN, Fisher RS (1969) Pituitary lesions in craniocerebral injuries. Arch Pathol 88:242–248

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the acute phase after traumatic brain injury, pituitary glands are significantly enlarged compared with healthy controls, and many also show hemorrhage, infarction, signal abnormalities and/or partial stalk transsection.

    “In the acute phase, the pituitary glands of TBI patients are significantly enlarged as compared with normal healthy control subjects and many also demonstrate other abnormalities such as hemorrhage, infarction, signal abnormalities and/or partial stalk transsection [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] 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 34:468–475. doi: 10.1007/s00134-007-0902-x source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The cellular distribution of somatotrophs and gonadotrophs is consistent with the area irrigated by the long hypophyseal portal vessels, so infarction of the lateral and peripheral region of the gland would mostly affect these axes.

    “This cellular distribution is consistent with the area of irrigation of the long hypophyseal portal vessels. An infarction of this lateral and peripheral region of the gland will mostly affect somatotrophs and gonadotrophs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Somatotrophs are located primarily in the lateral wings of the anterior pituitary, while gonadotrophs are scattered throughout the pars distalis and are the major cell group in the pars tuberalis.

    “The somatotrophs are located primarily in the lateral wings of the anterior pituitary and the gonadotrophs are scattered throughout the pars distalis and are the major cell group in the pars tuberalis [69].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Asa S, Kovacs K, Melmed S (1995) The hypothalamic-pituitary axis. In: Melmed S (ed) The pituitary. Blackwell Science Inc., Cambridge, pp 3–44

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Corticotrophs are found predominantly in the central mucoid wedge and pars intermedia, while thyrotrophs tend to cluster in the anteromedial portion of the gland.

    “The corticotrophs, found predominantly in the central mucoid wedge and pars intermedia, and the thyrotrophs, tending to cluster in the anteromedial portion of the gland, are thus in the less susceptible short hypophyseal portal territory.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Asa S, Kovacs K, Melmed S (1995) The hypothalamic-pituitary axis. In: Melmed S (ed) The pituitary. Blackwell Science Inc., Cambridge, pp 3–44

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the chronic phase after traumatic brain injury, patients often show pituitary volume loss or empty sella, followed by abnormal pituitary gland signal heterogeneity, perfusion deficits and/or lack of posterior pituitary signal.

    “In the chronic phase, patients often demonstrate pituitary volume loss or empty sella, followed by abnormal pituitary gland signal heterogeneity, perfusion deficits and/or lack of posterior pituitary signal [68].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] 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 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The reversibility of acute adrenal insufficiency and the rarity of chronic adrenal insufficiency suggest that other factors may be relevant in the acute setting.

    “This reversibility of acute adrenal insufficiency and the fact that chronic adrenal insufficiency is so uncommon suggests that other factors (as discussed below) may be relevant in the acute setting.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Severe injury is not necessarily a prerequisite for development of chronic pituitary failure; several studies have demonstrated chronic endocrinopathy after milder traumatic brain injury.

    “a severe injury is not necessarily a prerequisite for development of chronic pituitary failure. Several studies have demonstrated chronic endocrinopathy after milder TBI [28, 29, 39, 45].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [28] Benvenga S, Campenni A, Ruggeri RM, Trimarchi F (2000) Clinical review 113: hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 85:1353–1361. doi: 10.1210/jc.85.4.1353 source

      Not checked in the free run.

    • cites [29] Edwards OM, Clark JD (1986) Post-traumatic hypopituitarism. Six cases and a review of the literature. Medicine (Baltimore) 65:281–290. doi: 10.1097/00005792-198609000-00001 source

      Not checked in the free run.

    • cites [39] Kelly DF, 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 93:743–752 source

      Not checked in the free run.

    • cites [45] 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 21:685–696. doi: 10.1089/0897715041269713 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effects of high-dose pentobarbital and propofol on adrenal function are more lasting but still reversible and dose-dependent.

    “the effect of the metabolic suppressive agents high-dose pentobarbital and propofol were more lasting but still reversible and dose-dependent [74–83].”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [74] Absalom A, Pledger D, Kong A (1999) Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 54:861–867. doi: 10.1046/j.1365-2044.1999.01003.x source

      Not checked in the free run.

    • cites [75] Aitkenhead AR, Pepperman ML, Willatts SM et al (1989) Comparison of propofol and midazolam for sedation in critically ill patients. Lancet 2:704–709. doi: 10.1016/S0140-6736(89)90770-8 source

      Not checked in the free run.

    • cites [76] Brooks SM, Werk EE, Ackerman SJ, Sullivan I, Thrasher K (1972) Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. N Engl J Med 286:1125–1128 source

      Not checked in the free run.

    • cites [77] Crozier TA, Beck D, Schlaeger M, Wuttke W, Kettler D (1987) Endocrinological changes following etomidate, midazolam, or methohexital for minor surgery. Anesthesiology 66:628–635. doi: 10.1097/00000542-198705000-00006 source

      Not checked in the free run.

    • cites [78] Fellows IW, Bastow MD, Byrne AJ, Allison SP (1983) Adrenocortical suppression in multiply injured patients: a complication of etomidate treatment. Br Med J (Clin Res ed) 287:1835–1837 source

      Not checked in the free run.

    • cites [79] Hoen S, Asehnoune K, Brailly-Tabard S et al (2002) Cortisol response to corticotrophin stimulation in trauma patients: influence of hemorrhagic shock. Anesthesiology 97:807–813. doi: 10.1097/00000542-200210000-00010 source

      Not checked in the free run.

    • cites [80] Malerba G, Romano-Girard F, Cravoisy A et al (2005) Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 31:388–392. doi: 10.1007/s00134-004-2550-8 source

      Not checked in the free run.

    • cites [81] Newman LH, McDonald JC, Wallace PG, Ledingham IM (1987) Propofol infusion for sedation in intensive care. Anaesthesia 42:929–937. doi: 10.1111/j.1365-2044.1987.tb05362.x source

      Not checked in the free run.

    • cites [82] Schenarts CL, Burton JH, Riker RR (2001) Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med 8:1–7. doi: 10.1111/j.1553-2712.2001.tb00537.x source

      Not checked in the free run.

    • cites [83] Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D (1984) Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 310:1415–1421 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Acute hypopituitarism after traumatic brain injury appears to be a transient and reversible effect largely related to metabolic suppressive agents or etomidate and did not lead to overt chronic adrenal deficiency.

    “Therefore, this acute hypopituitarism appeared to be a transient and reversible effect largely related to metabolic suppressive agents or etomidate and did not lead to overt chronic adrenal deficiency.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The site of injury causing pituitary hormonal dysfunction after traumatic brain injury varies and can include the hypothalamus, infundibulum, and pituitary gland.

    “Based on prior autopsy studies of fatal head injuries and imaging studies of TBI survivors, it appears the site of injury leading to pituitary hormonal dysfunction is variable and may include the hypothalamus, infundibulum and pituitary gland itself.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Post-traumatic brain injury pituitary dysfunction is related to transient medication effects.

    “Although the mechanism of post-TBI pituitary dysfunction remains incompletely understood, evidence suggests this is a multi-factorial process related to: (1) the primary brain injury event itself; (2) secondary insults such as hypotension, hypoxia and raised intracranial pressure; (3) the transient stress of critical illness; and (4) transient medication effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    This hormonal dysfunction can affect early and late recovery and ultimately influence long-term neurobehavioral function and quality of life.

    “This hormonal dysfunction can impact the early and late recovery process, ultimately effecting longterm neurobehavioral function and quality of life.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These factors, individually and in different combinations, determine which hormonal axes are affected, the severity of the abnormality, and whether the deficits are reversible or permanent.

    “It is likely that these factors individually and in varying combinations determine which hormonal axes are affected, the severity of abnormality and whether such deficits are reversible or permanent.”
    Quote in the paperSubstantial claim
26 of 26

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The exact pathophysiology of pituitary dysfunction after TBI is not well understood, but multiple pathological mechanisms have been proposed.

    “The exact pathophysiology of pituitary dysfunction after TBI is not well understood, but multiple pathological mechanisms have been proposed, including compression of the pituitary gland, hypothalamic nuclei, or interruption of the long hypophyseal portal vessels by edema; direct mechanical trauma to the pituitary gland, stalk, and/or hypothalamus; increased ICP; hemorrhage; skull fracture; or any”

    From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [133]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • GCS score of 13 is classified as both mild and moderate TBI

    Minor

    The paper assigns a Glasgow Coma Scale score of 13 to both the mild and moderate TBI categories, so the stated ranges overlap.

  • Reference publication year precedes the year in its title

    Minor

    Reference 8 lists a paper about TBI incidence in 2006 as published in 2003, before the year it purports to cover.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Cyran E (1918) Hypophysenschadigung durch Schadelbasisfraktur. Dtsch Med Wochenschr 44:1261

Cited by

Sorted by citations

Related

Authors
Dusick, J. R., Wang, C., Cohan, P., Swerdloff, R., & Kelly, D. F.
Affiliations
  • University of California, Los Angeles (US)
  • The Lundquist Institute (US)
  • Saint John's Health Center (US)
Corresponding author
Kelly, Daniel F.
ORCID
Venue
Pituitary
Publisher
Springer Science and Business Media LLC
Published
2008-05-15
Volume
15
Issue
1
Pages
2-9
ISSN
  • 1386-341X (ISSN-L)
  • 1573-7403
DOI
10.1007/s11102-008-0130-6
PMC
PMC4170072
OpenAlex
W2210815217
Semantic Scholar
2e74496d8082e16b7594d7ea441d3a531a19c74d
Cited by
121
References
107
Citations by year
2026: 5 · 2025: 3 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 5 · 2019: 19 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 5 · 2013: 5 · 2012: 3
FWCI
0.59
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Pituitary (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR000124)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, hypopituitarism, hypothalamic-pituitary dysfunction, secondary brain injury, adrenal insufficiency, medication effects, intracranial pressure, hypoxia, hypotension, cerebral blood flow
MeSH terms
Brain Injuries, Humans, Hypopituitarism

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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