CoChat
Sign Up
Cited by 390Pituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth FactorsAdrenal Hormones and Disorders

Anterior Pituitary Dysfunction in Survivors of Traumatic Brain Injury

Agha, Amar, Rogers, Bairbre, Sherlock, Mark, O’Kelly, Patrick, Tormey, William, Phillips, Jack, Thompson, Christopher J.·2004·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2004-0511
Open this paper in CoChat — free account

Abstract

Recent data suggest that anterior pituitary dysfunction after traumatic brain injury (TBI) is common. We sought to confirm the results of earlier studies in a larger cohort of patients with dynamic testing of pituitary function. We studied 102 consecutive TBI survivors (85 males; median age 28, range 15-65 yr) who had survived severe or moderate TBI (initial Glasgow Coma Scale score 3-13) at a median of 17 months (range 6-36) post event. GH and ACTH reserves were initially assessed using the glucagon stimulation test (GST). Normative data on GH and cortisol responses to the GST were obtained from 31 matched healthy controls. Patients with subnormal GH or cortisol responses were further evaluated, using the insulin tolerance test (ITT) or arginine + GHRH test for GH assessment and the ITT or 250-microg short synacthen test for the assessment of ACTH reserve. Patients were considered to be GH or ACTH deficient if they failed both the GST and the second provocative test. Baseline thyroid function, prolactin, IGF-I, gonadotropins, testosterone, or estradiol was performed in all patients and compared with local reference ranges.In controls, normal response to the GST was a stimulated GH peak of greater than 5 microg/liter and cortisol peak greater than 450 nmol/liter (16 microg/dl). Eighteen TBI patients (17.6%) had GH response to the GST less than 5 microg/liter, 11 of whom also failed the ITT or the arginine + GHRH tests. GH-deficient patients had significantly higher body mass index (P = 0.003), and lower IGF-I concentrations (P < 0.001), than GH-sufficient patients. Twenty-three patients (22.5%) had cortisol responses to GST less than 450 nmol/liter, 13 of whom also failed the ITT or short synacthen test. GH or ACTH deficiencies were not related to age, Glasgow Coma Scale score, or the presence of other pituitary hormone abnormalities (P > 0.05). Twelve patients (11.8%) had gonadotropin and one (1%) had thyrotrophin deficiencies. Twelve patients (11.8%) had hyperprolactinemia. Twenty-nine patients (28.4%) had at least one anterior pituitary hormone deficiency. This is the largest study, to date, of hypopituitarism after TBI and confirms a high prevalence of undiagnosed anterior pituitary hormone abnormalities in survivors of TBI. Hypopituitarism is a treatable cause of morbidity after TBI. In addition to conventional pituitary hormone replacement, the potential of GH treatment to enhance recovery needs to be examined in a prospective study.

Integrity signals

Registry

Crossref · 10.1210/jc.2004-0511

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

1 of 24 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    It is not possible to be certain that the five patients who failed the GST but passed the SST have intact corticotrophic function because of well-reported false-pass results with the SST.

    “However, it is not possible to be certain that the five patients who failed the GST but passed the SST have intact corticotrophic function because of well-reported falsepass results with the latter test (45)(46)(47)(48).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [45] 45. Mukherjee JJ, de Castro JJ, Kaltsas G, Afshar F, Grossman AB, Wass JA, Besser GM 1997 A comparison of the insulin tolerance/glucagon test with the short ACTH test in the assessment of the hypothalamo-pituitary-adrenal axis in the early post-operative period after hypophysectomy. Clin Endocrinol (Oxf) 47:51-60 source
    • cites [46] 46. Thaler LM, Blevins LS 1998 The low dose (1-g) adrenocorticotropin stim- ulation test in the evaluation of patients with suspected central adrenal in- sufficiency. J Clin Endocrinol Metab 83:2726 -2729

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [47] 47. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR 2001 Longitu- dinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86:724 -731 source

      The Assays and Discussion passages (page numbers unavailable) concern testosterone measurement and hypogonadism in aging men, not GST, SST, or corticotrophic function. Searches for SST false-pass results and glucagon stimulation versus short Synacthen testing found no passage addressing the claim. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Findingown data

    In the same TBI cohort, 12 patients (11.8%) had gonadotropin deficiency.

    “Twelve patients (11.8%, 10 males) had gonadotropin deficiency, which was associated with hyperprolactinemia in four patients (three males).”
    • Also stated in: § Abstract · plain
      “Twelve patients (11.8%) had gonadotropin and one (1%) had thyrotrophin deficiencies.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the same TBI cohort, 13 patients (12.7%) were defined as ACTH deficient by failure of two provocative tests.

    “Diagnosing ACTH deficiency by failure of two provocative tests, 13 patients (12.7%) were defined as ACTH deficient.”
    • Also stated in: § Abstract · plain
      “13 of whom also failed the ITT or short synacthen test.”
    Quote in the paperSubstantial claim
  • Findingown data

    In the same TBI cohort, one patient (1%) had thyrotrophin deficiency.

    “TSH deficiency was present in one patient, who had panhypopituitarism (Fig. 2).”
    • Also stated in: § Abstract · plain
      “one (1%) had thyrotrophin deficiencies.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the same TBI cohort, 12 patients (11.8%) had hyperprolactinemia.

    “Hyperprolactinemia was present in 12 patients (one patient was on risperidone).”
    • Also stated in: § Abstract · plain
      “Twelve patients (11.8%) had hyperprolactinemia.”
    Quote in the paperNot a substantial claim
  • The quote only partly states this claim. 1
  • May combine two claims. 17
  • Classified as probably not a substantial claim. 9

  • The quote only partly states this claim.

    Findingown data

    In 102 consecutive TBI survivors (85 males; median age 28, range 15-65 yr) who had survived severe or moderate TBI (initial Glasgow Coma Scale score 3-13) at a median of 17 months (range 6-36) post event, 29 patients (28.4%) had at least one anterior pituitary hormone deficiency.

    “Twenty-nine patients (28.4%) had at least one anterior pituitary hormone deficiency.”
    • Also stated in: § Overall results · plain
      “Twenty-nine patients (28.4%) had at least one anterior pituitary hormone deficiency.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the same TBI cohort, 23 patients (22.5%) had isolated hormone deficiencies and 6 (5.9%) had multiple hormone deficiencies.

    “Twenty-three patients (22.5%) had isolated hormone deficiencies and six (5.9%) has mul- tiple hormone deficiencies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Hyperprolactinemia was not associated with age, GCS score, cerebral edema, or operative mass evacuation (P > 0.05 for each variable).

    “Multifactorial logistic regression analysis showed that hyperprolactinemia was not associated with age, GCS score, cerebral edema, or operative mass evacuation (P Ͼ 0.05 for each variable).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The TBI patients in this study who had subnormal GH responses to the GST did show biochemical and somatic features of GHD, in that they also had lower serum IGF-I levels and higher BMI than those with normal GH responses.

    “The TBI patients in this study who had subnormal GH responses to the GST did show biochemical and somatic features of GHD, in that they also had lower serum IGF-I levels and higher BMI than those with normal GH responses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The study cohort included 57 patients (55.9%) who recovered well after TBI (GOS score = 5), 33 (32.3%) with moderate disability (GOS score = 4), and 12 (11.8%) with severe disability (GOS score = 3).

    “Fifty-seven patients (55.9%) had recovered well after TBI (GOS score ϭ 5), 33 patients (32.3%) had moderate disability (GOS score ϭ 4), and 12 patients (11.8%) had severe disability (GOS score ϭ 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Gonadotropin deficiency was unrelated to hyperprolactinemia, gender, BMI, GCS score, CT scan appearance, cerebral edema, or mass evacuation (all P > 0.05).

    “but was unrelated to hyperprolactinemia (P ϭ 0.786), gender (P ϭ 0.375), BMI (P ϭ 0.728), GCS scores (P ϭ 0.561), CT scan appearance (P ϭ 0.064), cerebral edema (P ϭ 0.896), or mass evacuation (P ϭ 0.357).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among TBI patients who failed the GST, 7 of 18 passed either the ITT or arginine + GHRH test, showing discordance between these provocative tests of GH secretion.

    “Seven of the 18 patients who failed the GST passed either the ITT or arginine ϩ GHRH, showing some discordance between these provocative tests of GH secretion.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In multifactorial logistic regression, GH deficiency was not associated with age, gender, GCS score, CT scan appearance, cerebral edema, operative mass evacuation, gonadotropin deficiency, ACTH deficiency, or hyperprolactinemia (all P > 0.05).

    “GH deficiency to be associated with higher BMI (P ϭ 0.009) but unrelated to age (P ϭ 0.524), gender (P ϭ 0.225), GCS scores (P ϭ 0.314), CT scan appearance (P ϭ 0.589), cerebral edema (P ϭ 0.710), operative mass evacuation (P ϭ 0.579), the presence of gonadotropin (P ϭ 0.494) or ACTH (P ϭ 0.422) deficiencies, or hyperprolactinemia (P ϭ 0.752).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    ACTH deficiency was not significantly related to age, gender, BMI, GCS score, CT scan appearance, cerebral edema, operative mass evacuation, or gonadotropin deficiency (all P > 0.05), with borderline nonsignificance for hyperprolactinemia (P = 0.058).

    “ACTH deficiency was not significantly related to age (P ϭ 0.916), gender (P ϭ 0.952), BMI (P ϭ 0.170), GCS score (P ϭ 0.798), CT scan appearance (P ϭ 0.670), cerebral edema (P ϭ 0.543), operative mass evacuation (P ϭ 0.558), or gonadotropin deficiency (P ϭ 0.129); the association with hyperprolactinemia was of borderline nonsignificance (P ϭ 0.058).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Completed studies were performed in all patients, and no serious adverse reactions to any of the tests were observed.

    “Completed studies were performed in all patients.No serious adverse reactions to any of the tests were observed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    Thyrotrophs may be less susceptible to traumatic injury than the rest of the anterior lobe because they are located more medially in the protected territory of the short hypophyseal vessels, whereas the rest of the anterior lobe receives blood mainly from the more vulnerable long hypophyseal vessels.

    “Because the thyrotrophs are located more medially within the adenohypophysis in the protected territory of the short hypophyseal vessels (7, 52), they may be less susceptible to traumatic injury than the rest of the anterior lobe, which receives its blood supply predominantly from the more vulnerable long hypophyseal vessels (7).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] 7. Kelly DF, Gonzalo ITW, Cohan P, Berman N, Swerdloff R, Wang C 2000 Hypopituitarism following traumatic brain injury and aneurysmal subarach- noid hemorrhage: a preliminary report. J Neurosurg 93:743-752 source
    • cites [52] 52. Cuneo RC, Salomon F, Wiles CM, Hesp R, Sonksen PH 1991 Growth hor- mone treatment in growth hormone deficient adults II: effect on exercise performance. J Appl Physiol 70:695-700 source

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

    Interpretationnone given

    The study's data are broadly in agreement with earlier, smaller studies.

    “our data are broadly in agreement with earlier, smaller studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    GH deficiency is associated with reduced lean body mass, decreased exercise capacity, impaired cardiac function, reduction in bone mineral density, sleep disturbances, social isolation, reduced physical mobility, and reduced general well-being.

    “GH deficiency is associated with reduced lean body mass (53), decreased exercise capacity (54), impaired cardiac function (55), and reduction in bone mineral density (56), which may be of particular significance in immobilized patients, as well as sleep disturbances, social isolation, reduced physical mobility, and general well-being (57).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [53] 53. Merola B, Cittadini A, Colao A, Longobardi S, Fazio S, Sabatini D, Sacca L, Lombardi G 1993 Cardiac structure and functional abnormalities in adult patients with growth hormone deficiency. J Clin Endocrinol Metab 77:1658 - 1661 source
    • cites [54] 54. Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G 1999 Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopitu- itarism. J Clin Endocrinol Metab 84:1919 -1924

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [55] 55. Bjork S, Jonsson B, Westphal O, Levin J-E 1989 Quality of life of adults with growth hormone deficiency: a controlled study. Acta Paediatr Scand 356(Suppl):55-59 source

  • May combine two claims.

    Interpretationreasoning

    All these effects of hormone deficiencies can impair recovery and rehabilitation and may contribute to the significant morbidity associated with TBI.

    “All these effects can have the potential to impair recovery and rehabilitation and may contribute to the significant morbidity associated with TBI.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Testosterone deficiency in males leads to reduced lean body mass and reduced bone mineral density; estrogen deficiency in females predisposes them to premature osteoporosis.
    • Rests on an assumption: Deficiency in thyroid hormones leads to anergia, muscle weakness, and neuropsychiatric disorders.
    • Rests on an assumption: Glucocorticoid deficiency can be life threatening, particularly in acutely ill patients, and may impair recovery and rehabilitation in the post-TBI period due to lethargy, muscle fatigue, and poor exercise capacity.

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

    Interpretationown data

    Hyperprolactinemia may have been responsible for gonadotropin deficiency in the four patients with both conditions.

    “Four of the 12 patients with gonadotropin deficiency had hyperprolactinemia, which may have been responsible for this abnormality.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    The study's data are defensible because of the larger size of the cohort, the use of two separate dynamic tests of glucocorticoid secretion, and a rigorous definition for ACTH deficiency.

    “We would defend our data on the basis of the larger size of our cohort, the use of two separate dynamic tests of glucocorticoid secretion, and our rigorous definition for ACTH deficiency.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Pituitary insufficiency may have serious consequences and may aggravate the physical and neuropsychiatric morbidity observed after head injury.

    “Pituitary insufficiency may have serious consequences and may aggravate the physical and neuropsychiatric morbidity observed after head injury.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Testosterone deficiency in males leads to reduced lean body mass and reduced bone mineral density; estrogen deficiency in females predisposes them to premature osteoporosis.
    • Rests on an assumption: Deficiency in thyroid hormones leads to anergia, muscle weakness, and neuropsychiatric disorders.
    • Rests on an assumption: Glucocorticoid deficiency can be life threatening, particularly in acutely ill patients, and may impair recovery and rehabilitation in the post-TBI period due to lethargy, muscle fatigue, and poor exercise capacity.

  • May combine two claims.

    Interpretationcitation

    The study's results contrast with Kelly et al.'s finding of only one patient with blunted cortisol response to hypoglycemia, although Kelly et al. used the 95% confidence limit for the area under the curve for cortisol responses to define normality rather than the more conventional peak cortisol response.

    “Our results also contrast with those of Kelly et al. (7), who found only one patient with blunted cortisol response to hypoglycemia, although in this last study, the 95% confidence limit for the area under the curve for cortisol responses was used to define normality, rather than the more conventional peak cortisol response.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] 7. Kelly DF, Gonzalo ITW, Cohan P, Berman N, Swerdloff R, Wang C 2000 Hypopituitarism following traumatic brain injury and aneurysmal subarach- noid hemorrhage: a preliminary report. J Neurosurg 93:743-752 source

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

    Premisecitation

    Serum testosterone levels decline with age.

    “It is well recognized that serum testosterone levels decline with age (49).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] 49. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML 1989 Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med 70:145-160 source

  • May combine two claims.

    Premisecitation

    The GnRH test lacks both sensitivity and specificity and rarely adds helpful additional information for assessing gonadotrophic function.

    “We did not use the GnRH test for the assessment of gonadotrophic function because this test lacks both sensitivity and specificity and rarely adds any helpful additional information (35,36).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] 35. Rahim A, Toogood A, Shalet SM 1996 The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf) 45:557-562 source
    • cites [36] 36. Pfeifer M, Kanc K, Verhovec R, Kocijancic A 2001 Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men. Clin Endocrinol (Oxf) 54: 17-22 source

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

    Premisecitation

    The frequency of TSH deficiency relative to other anterior pituitary hormone abnormalities in pituitary disorders is variable.

    “The frequency of TSH deficiency with relation to other anterior pituitary hormone abnormalities, in pituitary disorders, is variable (50,51).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [50] 50. Asa S, Kovacs K, Melmed S 2002 Functional anatomy of the hypothalamic pituitary axis. In: Melmed S, ed. The pituitary. 2nd ed. Cambridge, UK: Black- well Science; 4 -44

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [51] 51. Binnerts A, Deurenberg P, Swart GR, Wilson JHP, Lamberts SWJ 1992 Body composition in growth hormone deficient adults. Am J Clin Nutr 55:918 -923 source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Identification of post-TBI hypopituitarism offers the potential to improve the chances of rehabilitation and enhance QoL because hypopituitarism may impair recovery from TBI and the benefit of replacement of hormone deficiencies is well established.

    “Because hypopituitarism may impair recovery from TBI and because the benefit of replacement of hormone deficiencies is well established, identification of post-TBI hypopituitarism offers the potential to improve the chances of rehabilitation and enhance QoL.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The benefit of replacement of hormone deficiencies is well established.

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

    Interpretationcitation

    Our results are more comparable with those of Lieberman et al. (8).

    “Our results are more comparable with those of Lieberman et al. (8)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lieberman et al. (8) 8. Lieberman SA, Oberoi AL, Gilkinson CR, Masel BE, Urban RJ 2001 Prev- alence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86:2752-2756

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

    Premisecitation

    Most patients with pituitary disease who pass the standard 250-g SST do well without glucocorticoid replacement.

    “It is important to acknowledge that most patients with pituitary disease who pass the standard 250-g SST do well without glucocorticoid replacement (29).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] 29. Trainer PJ, Besser GM 1995 Barts endocrine protocols. Edinburgh: Churchill Livingstone International; 6 -8
24 of 24

  • The paper relies on this without support.

    Anterior pituitary dysfunction after traumatic brain injury is common.

    “Recent data suggest that anterior pituitary dysfunction after traumatic brain injury (TBI) is common.”

  • The paper relies on this without support.

    Normal GH and cortisol responses to the glucagon stimulation test are not well established.

    “Because normal GH and cortisol responses to the GST are not well established, we performed the GST in 31 healthy subjects (22 males) who were matched for age, sex, and body mass index (BMI) to the patient population.”

  • The paper relies on this without support.

    This is the largest study to date of hypopituitarism after TBI.

    “This is the largest study, to date, of hypopituitarism after TBI and confirms a high prevalence of undiagnosed anterior pituitary hormone abnormalities in survivors of TBI.”

  • The paper relies on this without support.

    Hypopituitarism is a treatable cause of morbidity after TBI.

    “Hypopituitarism is a treatable cause of morbidity after TBI.”

  • The paper relies on this without support.

    Under stressed conditions, such as intercurrent illness, mild untreated ACTH deficiency may become life threatening.

    “However, under stressed conditions, such as intercurrent illness, mild untreated ACTH deficiency may become life threatening.”

  • The paper relies on this without support.

    No study in adults has compared the glucagon stimulation test with the arginine + GHRH test.

    “No study, in adults, has compared the GST with the arginine ϩ GHRH test.”

  • The authors state this as an assumption.

    The three patients without documented GCS scores were assumed to have a GCS of 13 or less because they were admitted to the intensive care unit.

    “The three remaining patients had no documented GCS scores but were admitted to the intensive care unit (ITU) and therefore were assumed to have a GCS of 13 or less.”

  • The paper relies on this without support.

    The GST has well-recognized false-fail results.

    “The discordance between the GST and ITT results in five of the 15 patients who failed the GST can be explained by the well-recognized false-fail results associated with the GST.”

  • The paper relies on this without support.

    Testosterone deficiency in males leads to reduced lean body mass and reduced bone mineral density; estrogen deficiency in females predisposes them to premature osteoporosis.

    “Testosterone deficiency in males leads to reduced lean body mass and reduced bone mineral density; estrogen deficiency in females predisposes them to premature osteoporosis.”

  • The paper relies on this without support.

    Deficiency in thyroid hormones leads to anergia, muscle weakness, and neuropsychiatric disorders.

    “Deficiency in thyroid hormones leads to anergia, muscle weakness, and neuropsychiatric disorders.”

  • The paper relies on this without support.

    The benefit of replacement of hormone deficiencies is well established.

    “Because hypopituitarism may impair recovery from TBI and because the benefit of replacement of hormone deficiencies is well established, identification of post-TBI hypopituitarism offers the potential to improve the chances of rehabilitation and enhance QoL.”

  • The paper relies on this without support.

    The study's patient sample was representative of survivors of TBI admitted to the study unit.

    “Although our patient sample was representative of survivors of TBI admitted to our unit, only a small number of our patients had long-term severe disability.”

  • The paper relies on this without support.

    Glucocorticoid deficiency can be life threatening, particularly in acutely ill patients, and may impair recovery and rehabilitation in the post-TBI period due to lethargy, muscle fatigue, and poor exercise capacity.

    “Glucocorticoid deficiency can be life threatening, particularly in acutely ill patients, and may impair recovery and rehabilitation in the post-TBI period due to lethargy, muscle fatigue, and poor exercise capacity.”
13 of 13

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?

  • TBI has previously been considered a rare cause of hypopituitarism, but an increased prevalence of neuroendocrine dysfunction in patients with TBI has been reported during the last 15 years in most retrospective and prospective studies.

    “TBI has previously been considered as a rare cause of hypopituitarism, but an increased prevalence of neuroendocrine dysfunction in patients with TBI has been reported during the last 15 years in most of the retrospective and prospective studies.”

    From Pituitary dysfunction following traumatic brain injury: clinical perspectives (2015) · cites this paper as [8]

    The Discussion (page not provided) says undiagnosed pituitary dysfunction is common after TBI and that this study broadly agrees with earlier, smaller studies. It does not establish that TBI was previously considered a rare cause, or that most retrospective and prospective studies over the preceding 15 years reported increased prevalence. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The somatotrophs and gonadotrophs, located in the area perfused by long hypophyseal portal vessels, are the most frequent hormonal deficiencies after TBI; however, in some studies ACTH deficiency is the most common or second most common hormonal deficiency after TBI.

    “The somatotrophs and gonadotrophs, which are located in the area of the pituitary perfused by long hypophyseal portal vessels, are the most frequent hormonal deficiencies after TBI (15, 18, 27, 29, 150, 160); however, in some studies ACTH deficiency (corticotrophs are located in the territory supplied by the short portal vessels) is the most common or second most common hormonal deficiency after”

    From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [29]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Some early pituitary abnormalities are transient and recover fully within days or weeks after TBI, while new pituitary hormone deficiency may become apparent in the post-acute phase.

    “Some of these early abnormalities are transient and recover fully within days or weeks after TBI while new pituitary hormone deficiency may become apparent in the post-acute phase (13, 14).”

    From Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How? (2018) · cites this paper as [14]

    The Discussion (page unavailable) says early hormone deficiencies may spontaneously recover, but describes their natural history as largely unknown; it does not establish full recovery within days or weeks. The Methods report testing survivors 6–36 months after injury, but the paper does not show that new deficiencies emerged in the post-acute phase. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The most robust data on incidence of PTHP are in patients with moderate or severe TBI.

    “The most robust data with regard to incidence of PTHP are in those patients with moderate or severe TBI (14).”

    From Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How? (2018) · cites this paper as [14]

    The Discussion (page unavailable) calls this the largest study to date of anterior pituitary function after TBI and says it studied a large group of moderate or severe TBI survivors. This supports the claim that substantial evidence comes from that group, but the paper reports prevalence among survivors, not incidence, and does not establish that these are the most robust data compared with data for mild TBI. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • In three included studies, confirmatory testing was applied if a screening test was positive.

    “however, in three studies, confirmatory testing was applied if a screening test was positive (29,30,255; Table 2).”

    From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [29]

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.

  • Table 1 shows fewer GST responses below 3 than reported

    Minor

    The first 11 patients in Table 1 have GST responses below 3 g/liter. Of the remaining seven shown here, only patient 15 is below 3; patient 16 is reported as exactly 3. The table therefore shows 12, not 13, responses below the stated threshold.

  • BMI subgroup means imply different cohort-wide means

    Minor

    The Table 2 BMI means imply an overall mean of about 24.45 kg/m2 across 102 patients. The Table 5 means imply about 25.70 kg/m2 for the same 102 patients; rounding cannot account for the difference.

  • Hyperprolactinemia count differs for gonadotropin-deficient patients

    Minor

    The text says four gonadotropin-deficient patients had hyperprolactinemia, whereas Table 5 lists three.

3 of 3

Cites

Flagged first, then by citations

2 of the 59 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [50]50. Asa S, Kovacs K, Melmed S 2002 Functional anatomy of the hypothalamic pituitary axis. In: Melmed S, ed. The pituitary. 2nd ed. Cambridge, UK: Black- well Science; 4 -44

Cited by

Sorted by citations

Related

Authors
Agha, A., Rogers, B., Sherlock, M., O’Kelly, P., Tormey, W., Phillips, J., & Thompson, C. J.
Affiliations
Beaumont Hospital (IE)
Corresponding author
Thompson, Christopher J.
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2004-10
Volume
89
Issue
10
Pages
4929-4936
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2004-0511
OpenAlex
W2077490225
Semantic Scholar
b57d05b038775cd07617187bad96eced97cfcfce
Cited by
390
References
59
Citations by year
2026: 5 · 2025: 6 · 2024: 14 · 2023: 6 · 2022: 7 · 2021: 11 · 2020: 15 · 2019: 17 · 2018: 16 · 2017: 15 · 2016: 17 · 2015: 28 · 2014: 15 · 2013: 20 · 2012: 23
FWCI
17.75
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
  • Pfizer
  • Royal College of Surgeons in Ireland
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
traumatic brain injury, anterior pituitary dysfunction, growth hormone deficiency, ACTH deficiency, glucagon stimulation test, insulin tolerance test, ACTH stimulation test, insulin-like growth factor I, body mass index, hyperprolactinemia, gonadotropin deficiency, thyrotropin deficiency, pituitary hormone replacement
MeSH terms
Adolescent, Adrenocorticotropic Hormone, Adult, Aged, Brain Injuries, Disability Evaluation, Female, Gonadotropins, Humans, Hydrocortisone, Hypopituitarism, Male, Middle Aged, Pituitary Diseases, Thyrotropin, Cohort Studies, Prevalence

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 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review