Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How?
Open accessAbstract
Traumatic brain injury (TBI) remains a major, global public health concern. Over the last 15 years, a significant body of evidence has emerged demonstrating that post-traumatic hypopituitarism (PTHP) is a common and clinically significant consequence of TBI. Non-specific symptomology and the lack of an agreed approach to screening for PTHP has led to significant under-diagnosis of this debilitating disease. In this review, we will discuss the frequency and clinical significance of acute and chronic PTHP as described in the current literature highlighting the evidence base for screening and hormone replacement in these patients. We will also offer a pragmatic approach to identifying relevant anterior pituitary dysfunction after TBI and a follow-up strategy for those patients. Specific controversies and remaining unanswered questions will be addressed.
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Written from the paper’s full text.
TL;DR
Post-traumatic hypopituitarism (PTHP) is a common and clinically significant complication of moderate-to-severe traumatic brain injury (TBI), but it remains underdiagnosed because symptoms are nonspecific and screening approaches are not standardized. This review summarizes the evidence and offers a pragmatic approach to screening and hormone replacement, focusing on acute ACTH-cortisol deficiency and later assessment of adrenal, thyroid, gonadal, and GH axes.
Key findings
- TBI incidence is estimated at 134–618 persons per 100,000 per year, with highest incidence in adult men; a meta-analysis of 19 studies reported a pooled PTHP prevalence of 27%.
- GH deficiency appears to be the commonest pituitary hormone deficiency when patients are tested 6 months or more after TBI; acute-phase abnormalities are most clinically significant for ACTH-cortisol deficiency and salt/water imbalance, with one acute study reporting ACTH deficiency in 78% and diabetes insipidus in 51%.
- Acute cortisol below 300 nmol/l is suggestive of adrenal insufficiency and glucocorticoid treatment should be instituted; levels of 300–500 nmol/l should be interpreted in clinical context.
- The authors recommend screening patients with moderate or severe TBI, not routinely screening mild TBI unless specific symptoms suggest hypopituitarism, and considering selected “complicated” mild TBI cases; chronic assessment is usually at 3–6 months, with GH assessment deferred until 1 year post-TBI.
Methods
- Narrative review of the current literature on acute and chronic PTHP after TBI, including a summary table of main studies assessing PTHP frequency.
- The review synthesizes evidence on epidemiology, pathophysiology, clinical significance, screening candidates, and timing of endocrine assessment.
- It proposes a pragmatic screening and management algorithm, including serial morning cortisol in the acute phase and dynamic testing such as the corticotrophin test for chronic adrenal assessment.
Limitations
- The paper states that data for mild TBI and hypopituitarism are limited, the relationship between TBI severity and PTHP remains controversial, and there is currently no evidence to support treating acute GH, thyroid hormone, gonadotropin deficiencies, or hyperprolactinemia.
- The paper states that randomized clinical trials examining GH replacement in post-traumatic GH deficiency are needed.
- Evident from the text: as a narrative review, no systematic search strategy, quality appraisal, or pooled analysis is described; reported PTHP frequencies vary due to patient selection, timing of testing, and methodological heterogeneity, and screening recommendations for complicated mild TBI have considerable resource implications.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
8 of 37 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
- Premisecitation
PTHP is correlated with decreased exercise capacity.
“as well as decreased exercise capacity (30)”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [30] Mossberg, 2008, Aerobic capacity and growth hormone deficiency after traumatic brain injury, J Clin Endocrinol Metab source
The Results report significantly lower peak oxygen consumption in patients with traumatic brain injury and GH insufficiency or deficiency than in those with a normal GH response. This supports an association with reduced exercise capacity for post-traumatic GH dysfunction, but the study does not establish the claim for post-traumatic hypopituitarism (PTHP) generally. (LLM, conf=0.86)
Experimental — accuracy not yet measured
- Premisecitation
In one well-executed study, the frequency of PTHP after simple mild TBI was found to be very low.
“In one well-executed study, the frequency of PTHP after simple mild TBI was found to be very low (22).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [22] van der Eerden, 2010, Should anterior pituitary function be tested during follow-up of all patients presenting at the emergency department because of traumatic brain injury?, Eur J Endocrinol source
The Abstract (p. 2) reports only one case of anterior pituitary dysfunction among 107 patients, including 77 with mild TBI; the Discussion (p. 9) says none of the 30 moderate/severe patients had dysfunction. This supports a very low frequency in the studied mild-TBI patients, but the paper does not report a separate frequency for “simple” or uncomplicated mild TBI. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
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).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [14] Agha, 2004, Anterior pituitary dysfunction in survivors of traumatic brain injury, J Clin Endocrinol Metab source
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
- Premisecitation
Early GH deficiency post TBI can be transient.
“Early GH deficiency post TBI can be transient (36).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [36] Agha, 2005, The natural history of post-traumatic hypopituitarism: implications for assessment and treatment, Am J Med source
- Premisecitation
Numerous retrospective and prospective studies show a high rate of PTHP among long-term survivors of TBI.
“However, over the last 15 years, there has been numerous retrospective and prospective studies showing a high rate of PTHP among long-term survivors of TBI (Table 1).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Table 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
PTHP contributes significantly to morbidity and possibly mortality in patients with moderate or severe TBI.
“Over the recent 15 years, numerous research studies have documented a high rate of pituitary gland dysfunction following moderate or severe TBI with evidence that post-traumatic hypopituitarism (PTHP) contributes significantly to the morbidity and possibly mortality in those patients (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Park, 2010, Anterior pituitary dysfunction in moderate-to-severe chronic traumatic brain injury patients and the influence on functional outcome, Brain Inj source
- Premisecitation
Data for mild TBI and hypopituitarism are limited.
“The data for mild TBI and hypopituitarism are limited (3).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] McKinlay, 2008, Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort, Brain Inj source
- Premisereasoning
The vast majority of the literature on TBI relates to patients who required hospital admission, typically with moderate or severe TBI.
“As a result, the vast majority of the literature on the subject relates to patients who required hospital admission, typically with moderate or severe TBI.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] McKinlay, 2008, Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort, Brain Inj source
- Premisecitation
Symptoms of hypopituitarism can be subtle.
“The symptoms of hypopituitarism can be subtle (18) and are summarized in Table 2.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Schneider, 2007, Hypopituitarism, Lancet source
- Premisecitation
In patients with moderate or severe TBI, Glasgow Coma Scale (GCS) scores do not seem to predict the risk of PTHP.
“In patients with moderate or severe TBI, the scores do not seem to predict the risk of PTHP (8) but it is important to emphasize that this scale is limited by significant inter-observer variability and that the GCS scores can fluctuate over time.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Schneider, 2007, Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage, JAMA source
- Premisecitation
Pooled data from 19 studies showed a prevalence of PTHP of 27%.
“In one meta-analysis, the pooled data from 19 studies showed a prevalence of 27% (8).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Schneider, 2007, Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage, JAMA source
- Interpretationnone given
Variations in the reported frequency of PTHP reflect patient selection, timing of testing, and methodological heterogeneity in the ascertainment of hypopituitarism.
“The variations in the reported frequency of PTHP reflect patient selection, timing of testing, and methodological heterogeneity in the ascertainment of hypopituitarism.”
Quote in the paperNot a substantial claim - Premisecitation
The most clinically significant abnormalities in the acute phase of TBI are ACTH-cortisol deficiency and salt and water imbalance.
“The most clinically significant abnormalities in the acute phase of TBI are ACTH-cortisol deficiency and salt and water imbalance (11, 17).”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Pituitary dysfunction occurs early after acute TBI.
“Prospective longitudinal studies have shown that pituitary dysfunction occurs early after acute TBI.”
Quote in the paperSubstantial claim - Premisecitation
Growth hormone (GH) deficiency appears to be the commonest pituitary hormone deficiency in those tested 6 months or more after TBI.
“Among the pituitary hormone deficiencies, growth hormone (GH) deficiency, as with other forms of hypopituitarism, appears to be the commonest deficiency in those who were tested 6 months or more following the event (Table 1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Table 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
An acute-phase cortisol level below 300 nmol/l is suggestive of adrenal insufficiency.
“An acute-phase cortisol level below 300 nmol/l is suggestive of adrenal insufficiency (34)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Cooper, 2003, Corticosteroid insufficiency in acutely ill patients, N Engl J Med source
- Interpretationreasoning
Screening for mild cases of TBI remains controversial.
“Screening for mild cases of TBI remains controversial.”
Quote in the paperSubstantial claim - Premisecitation
Anterior pituitary hormone deficiency has a negative impact on functional outcome at 6 months post TBI as assessed by mini-mental state exam and functional independence measure scores.
“Recent data seem to confirm that anterior pituitary hormone deficiency has a negative impact on functional outcome at 6 months post TBI as assessed by mini-mental state exam and functional independence measure scores (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Park, 2010, Anterior pituitary dysfunction in moderate-to-severe chronic traumatic brain injury patients and the influence on functional outcome, Brain Inj source
- Premisecitation
Long-term adult GH deficiency is associated with impaired cardiac function.
“impaired cardiac function (27)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Cittadini, 1994, Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement, Am J Physiol source
- Premisecitation
Schneider et al. demonstrated a high rate (16.8%) of PTHP following a mild TBI.
“Schneider et al. demonstrated a high rate (16.8%) of PTHP following a mild TBI (8)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Schneider, 2007, Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage, JAMA source
- Interpretationnone given
There is currently no evidence to support treatment of acute GH, thyroid hormone, or gonadotropin deficiencies, or hyperprolactinemia in the acute phase following TBI.
“There is currently no evidence to support the treatment of acute GH, thyroid hormones or gonadotropins deficiencies, or hyperprolactinemia in the acute phase following TBI.”
Quote in the paperNot a substantial claim - Premisecitation
Long-term adult GH deficiency is associated with decreased quality of life.
“Long-term adult GH deficiency is associated with decreased quality of life (24)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Cuneo, 1992, The growth hormone deficiency syndrome in adults, Clin Endocrinol source
- Interpretationreasoning
Assessment of the GH axis is more complex due to the need for dynamic testing which is often only available in specialist centers.
“Assessment of the GH axis is also more complex due to the need to perform dynamic testing which is often only available in specialist centers.”
Quote in the paperSubstantial claim - Interpretationreasoning
Screening every patient with TBI does not meet criteria for an appropriate screening tool due to high cost and complexity of testing.
“This approach does not meet the criteria for an appropriate screening tool due to the high cost and the complexity of testing which often requires dynamic and sometimes repeat assessments.”
Quote in the paperSubstantial claim - Interpretationreasoning
Screening every patient with TBI for PTHP is not feasible.
“Screening every patient with a TBI for PTHP is clearly not feasible.”
Quote in the paperSubstantial claim - Premisecitation
PTHP is correlated with neuropsychiatric complications.
“and neuropsychiatric complications (31).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [31] Olver, 1996, Outcome following traumatic brain injury: a comparison between 2 and 5 years after injury, Brain Inj source
- Interpretationnone given
Interpretation of acute-phase results is difficult.
“In addition, interpretation of the results in the acute phase is difficult.”
Quote in the paperNot a substantial claim - Premisecitation
Most endocrine abnormalities in mild TBI cases were not confirmed by second dynamic tests.
“although most of the endocrine abnormalities on mild TBI cases were not confirmed by second dynamic tests.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Schneider, 2007, Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage, JAMA source
- Premisecitation
Long-term adult GH deficiency is associated with reduced lean body mass.
“reduced lean body mass (25)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] Binnerts, 1992, Body composition in growth hormone deficient adults, Am J Clin Nutr source
- Premisecitation
Long-term adult GH deficiency is associated with reduced bone mineral density.
“reduced bone mineral density (26)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Kuzma, 2014, Impact of the growth hormone replacement on bone status in growth hormone deficient adults, Growth Horm IGF Res source
- May combine two claims. 12
- Classified as probably not a substantial claim. 1
May combine two claims.
PremisecitationSome 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).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [13] Schneider, 2006, Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury, Eur J Endocrinol source
- cites [14] Agha, 2004, Anterior pituitary dysfunction in survivors of traumatic brain injury, J Clin Endocrinol Metab source
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
May combine two claims.
PremisecitationData on the relationship between CT findings and PTHP are limited, with one study demonstrating a correlation between diffuse brain swelling and PTHP and another finding no such association.
“The data on this is limited with one study demonstrating a correlation between diffuse brain swelling and PTHP (19) and another finding no such association (14).”
Quote in the paperNot a substantial claim1 of 2 sources checkedMay combine two claims.
PremisecitationSome studies showed a significant association between mild TBI and hypopituitarism, while one large study showed a very low incidence of PTHP in mild TBI cases.
“While some studies showed a significant association (21), one excellent large study showed a very low incidence of PTHP in mild TBI cases (22).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [21] Tanriverdi, 2010, Pituitary function in subjects with mild traumatic brain injury: a review of literature and proposal of a screening strategy, Pituitary source
- cites [22] van der Eerden, 2010, Should anterior pituitary function be tested during follow-up of all patients presenting at the emergency department because of traumatic brain injury?, Eur J Endocrinol source
May combine two claims.
PremisecitationPTHP is correlated with unfavorable metabolic and body composition profiles and lower quality of life scores.
“Other studies have found a correlation between PTHP and unfavorable metabolic and body composition profiles with associated lower quality of life scores (28, 29)”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [28] Klose, 2007, Posttraumatic hypopituitarism is associated with an unfavorable body composition and lipid profile, and decreased quality of life 12 months after injury, J Clin Endocrinol Metab source
- cites [29] Mossberg, 2017, Functional changes after recombinant human growth hormone replacement in patients with chronic traumatic brain injury and abnormal growth hormone secretion journal of neurotrauma, J Neurotrauma source
The Introduction (page unavailable) reports that a prior study found decreased quality of life in TBI patients with growth hormone deficiency and also describes reduced muscle mass in people with growth hormone deficiency. It does not establish the claimed correlation between post-traumatic hypopituitarism, unfavorable metabolic and body-composition profiles, and lower quality-of-life scores; this study assessed changes after growth hormone replacement without a GH-sufficient TBI comparison group. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
Interpretationnone givenNon-specific symptomology and the lack of an agreed approach to screening for PTHP has led to significant under-diagnosis of PTHP.
“Non-specific symptomology and the lack of an agreed approach to screening for PTHP has led to significant under-diagnosis of this debilitating disease.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationPTHP can masquerade as post-concussional syndrome and can be overlooked, leading to delayed recovery and impaired rehabilitation.
“PTHP can masquerade as a post-concussional syndrome and can be overlooked leading to delayed recovery and impaired rehabilitation (5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] Ropper, 2007, Concussion, N Engl J Med source
May combine two claims.
Premisenone givenThe GCS is limited by significant inter-observer variability and scores can fluctuate over time.
“In patients with moderate or severe TBI, the scores do not seem to predict the risk of PTHP (8) but it is important to emphasize that this scale is limited by significant inter-observer variability and that the GCS scores can fluctuate over time.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationPost-traumatic hypopituitarism (PTHP) is a common and clinically significant consequence of traumatic brain injury (TBI).
“Over the last 15 years, a significant body of evidence has emerged demonstrating that post-traumatic hypopituitarism (PTHP) is a common and clinically significant consequence of TBI.”
- Also stated in: § Introduction · boosted
“Over the recent 15 years, numerous research studies have documented a high rate of pituitary gland dysfunction following moderate or severe TBI with evidence that post-traumatic hypopituitarism (PTHP) contributes significantly to the morbidity and possibly mortality in those patients (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Park, 2010, Anterior pituitary dysfunction in moderate-to-severe chronic traumatic brain injury patients and the influence on functional outcome, Brain Inj source
- Also stated in: § Introduction · boosted
May combine two claims.
InterpretationcitationVascular injury is likely the commonest mechanism of pituitary damage after TBI, as autopsy studies have demonstrated pituitary infarction in up to 43% of fatal TBI cases.
“It is likely that a vascular injury is the commonest mechanism as autopsy studies have demonstrated pituitary infarction in up to 43% of cases of fatal TBI (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Salehi, 2007, Histologic study of the human pituitary gland in acute traumatic brain injury, Brain Inj source
May combine two claims.
Interpretationnone givenDynamic tests of the adrenal axis (insulin stress test or corticotrophin test) are either inappropriate or unreliable in the acute setting of TBI.
“However, these dynamic tests are either inappropriate (the insulin stress test) or unreliable (the corticotrophin test) in the acute setting of TBI.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationFeatures that seem to confer increased risk of PTHP include diffuse axonal injury on brain imaging, prolonged ICU admission, basal skull fracture, and increasing age.
“Features that seem to confer an increased risk of PTHP include diffuse axonal injury on brain imaging, prolonged admission to ICU, basal skull fracture, and increasing age (32).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] Schneider, 2008, Predictors of anterior pituitary insufficiency after traumatic brain injury, Clin Endocrinol source
May combine two claims.
Interpretationnone givenPTHP is now recognized as a common, but often underdiagnosed, complication which may contribute significantly to morbidity and possibly mortality following moderate and severe TBI.
“PTHP is now recognized as a common, but often underdiagnosed, complication which may contribute significantly to the morbidity and possibly the mortality following moderate and severe TBI.”
Quote in the paperNot a substantial claim- Rests on an assumption: Early detection and treatment of PTHP improves clinical outcomes.
May combine two claims.
PremisecitationAcute-phase cortisol deficiency in TBI is potentially life threatening and is associated with increased morbidity and mortality.
“In patients with TBI, acute-phase cortisol deficiency is potentially life threatening and a number of studies have shown an association between increased morbidity and mortality in acute post-traumatic hypoadrenalism (11, 23).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [11] Hannon, 2013, Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality, J Clin Endocrinol Metab source
- cites [23] Cohan, 2005, Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study*, Crit Care Med source
The paper relies on this without support.
Early detection and treatment of PTHP improves clinical outcomes.
“Therefore, screening patients for PTHP should be an important part of the standard care provided following severe or moderate TBI.”
The paper relies on this without support.
Treatment of acute cortisol deficiency reduces mortality or morbidity in TBI patients.
“An acute-phase cortisol level below 300 nmol/l is suggestive of adrenal insufficiency (34) and treatment with glucocorticoids should be instituted (Figure 1).”
The paper relies on this without support.
Hormone replacement for chronic pituitary deficiencies improves outcomes.
“If a deficiency is detected, we recommend replacement as appropriate and repeating the assessment at 1 year as early deficiencies may recover (36).”
The paper relies on this without support.
Screening complicated mild TBI is beneficial.
“Therefore, selected cases of complicated mild TBI could also be offered screening but this will clearly have considerable resource implications.”
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Binnerts, A., Deurenberg, P., Swart, G., Wilson, J., & Lamberts, S. W. J. (1992) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/55.5.918 · Cited by 159 · cited 1× · see citing works
“Long-term adult GH deficiency is associated with decreased quality of life (24), reduced lean body mass (25), reduced bone mineral density (26), and impaired cardiac function (27).”
BackgroundImpaired cardiac performance in GH-deficient adults and its improvement after GH replacement
Cittadini, A., Cuocolo, A., Merola, B., Fazio, S., Sabatini, D., Nicolai, E., Colao, A., Longobardi, S., Lombardi, G., & Sacca, L. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.267.2.e219 · Cited by 154 · cited 1× · see citing works
“Long-term adult GH deficiency is associated with decreased quality of life (24), reduced lean body mass (25), reduced bone mineral density (26), and impaired cardiac function (27).”
BackgroundAgha, A., Tomlinson, J. W., Clark, P. M., Holder, G., & Stewart, P. M. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1131 · Cited by 141 · cited 1× · see citing works
“The choice of the dynamic test for adrenal reserves will depend on the preference of the endocrinologist but we prefer the corticotrophin test (Synacthen test) as a simple and reliable test (35).”
MethodSelf-citationPredictors of anterior pituitary insufficiency after traumatic brain injury
Schneider, M., Schneider, H. J., Yassouridis, A., Saller, B., Von Rosen, F., & Stalla, G. K. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.03020.x · Cited by 107 · cited 1× · see citing works
“Features that seem to confer an increased risk of PTHP include diffuse axonal injury on brain imaging, prolonged admission to ICU, basal skull fracture, and increasing age (32).”
BackgroundTanriverdi, F., Unluhizarci, K., & Kelestimur, F. (2010) · Pituitary · doi:10.1007/s11102-009-0215-x · Cited by 103 · see citing works
Histologic study of the human pituitary gland in acute traumatic brain injury
Salehi, F., Kovacs, K., Scheithauer, B. W., Pfeifer, E. A., & Cusimano, M. (2007) · Brain Injury · doi:10.1080/02699050701426956 · Cited by 96 · cited 1× · see citing works
“It is likely that a vascular injury is the commonest mechanism as autopsy studies have demonstrated pituitary infarction in up to 43% of cases of fatal TBI (20).”
BackgroundKlose, M., Watt, T., Brennum, J., & Feldt-Rasmussen, U. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0901 · Cited by 87 · cited 1× · see citing works
“Other studies have found a correlation between PTHP and unfavorable metabolic and body composition profiles with associated lower quality of life scores (28, 29) as well as decreased exercise capacity (30) and neuropsychiatric complications (31).”
BackgroundPituitary dysfunction after blast traumatic brain injury: The UK BIOSAP study
Baxter, D., Sharp, D. J., Feeney, C., Papadopoulou, D., Ham, T. E., Jilka, S., Hellyer, P. J., Patel, M. C., Bennett, A. N., Mistlin, A., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23958 · Cited by 81 · cited 2× · see citing works
“J Clin Endocrinol Metab (2007) 92(10):3861–8.”
Pituitary dysfunction following traumatic brain injury: clinical perspectives
Tanriverdi, F., & Kelestimur, F. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s65814 · Cited by 60 · cited 1× · see citing works
“However, it has been suggested that “complicated” cases labeled as mild TBI should also be included in the screening process (33).”
BackgroundLasting pituitary hormone deficiency after traumatic brain injury
Moreau, O. K., Yollin, E., Merlen, E., Daveluy, W., & Rousseaux, M. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2011.2048 · Cited by 59 · cited 1× · see citing works
“J Clin Endocrinol Metab (2004) 89(12):5987–92.”
van der Eerden, A. W., Twickler, M. T. B., Sweep, F. C. G. J., Beems, T., Hendricks, H. T., Hermus, A. R. M. M., & Vos, P. E. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0436 · Cited by 51 · cited 3× · see citing works
“In one well-executed study, the frequency of PTHP after simple mild TBI was found to be very low (22).”
BackgroundResultInfluentialPark, K. D., Kim, D. Y., Lee, J. K., Nam, H.-S., & Park, Y.-G. (2010) · Brain Injury · doi:10.3109/02699052.2010.506863 · Cited by 49 · cited 3× · see citing works
“” Over the recent 15 years, numerous research studies have documented a high rate of pituitary gland dysfunction following moderate or severe TBI with evidence that post-traumatic hypopituitarism (PTHP) contributes significantly to the morbidity and possibly mortality in those patients (4).”
BackgroundInfluentialMossberg, K. A., Durham, W. J., Zgaljardic, D. J., Gilkison, C. R., Danesi, C. P., Sheffield-Moore, M., Masel, B. E., & Urban, R. J. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4552 · Cited by 44 · cited 1× · see citing works
“Other studies have found a correlation between PTHP and unfavorable metabolic and body composition profiles with associated lower quality of life scores (28, 29) as well as decreased exercise capacity (30) and neuropsychiatric complications (31).”
BackgroundPersonnier, C., Crosnier, H., Meyer, P., Chevignard, M., Flechtner, I., Boddaert, N., Breton, S., Mignot, C., Dassa, Y., Souberbielle, J.-C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4129 · Cited by 43 · see citing works
Impact of the growth hormone replacement on bone status in growth hormone deficient adults
Kužma, M., Kužmová, Z., Zelinková, Z., Killinger, Z., Vaňuga, P., Lazurová, I., Tomková, S., & Payer, J. (2014) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2013.12.001 · Cited by 43 · see citing works
Aerobic capacity and growth hormone deficiency after traumatic brain injury
Mossberg, K. A., Masel, B. E., Gilkison, C. R., & Urban, R. J. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0368 · Cited by 43 · cited 1× · see citing works
“Other studies have found a correlation between PTHP and unfavorable metabolic and body composition profiles with associated lower quality of life scores (28, 29) as well as decreased exercise capacity (30) and neuropsychiatric complications (31).”
Background
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Cyran, 1918, Hypophysenschädigung durch Schädelbasisfraktur, Dtsch Med Wochenschr, 44, 1261
Cited by
Sorted by citations
A Tilted Axis: Maladaptive Inflammation and HPA Axis Dysfunction Contribute to Consequences of TBI
Tapp, Z. M., Godbout, J. P., & Kokiko‐Cochran, O. N. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00345 · Cited by 130 · see citing works
Neurorehabilitation of Traumatic Brain Injury (TBI): A Clinical Review
Oberholzer, M., & Müri, R. M. (2019) · Medical Sciences · doi:10.3390/medsci7030047 · Cited by 119 · see citing works
Wong, K. R., Mychasiuk, R., O'Brien, T. J., Shultz, S. R., McDonald, S. J., & Brady, R. D. (2020) · Bone Research · doi:10.1038/s41413-020-00119-9 · Cited by 65 · see citing works
Insights into non-classic and emerging causes of hypopituitarism
Prodam, F., Caputo, M., Mele, C., Marzullo, P., & Aimaretti, G. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00437-2 · Cited by 62 · see citing works
Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury
Mele, C., Pingue, V., Caputo, M., Zavattaro, M., Pagano, L., Prodam, F., Nardone, A., Aimaretti, G., & Marzullo, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052686 · Cited by 57 · see citing works
Traumatic brain injuries induced pituitary dysfunction: a call for algorithms
Gilis‐Januszewska, A., Kluczyński, Ł., & Hubalewska–Dydejczyk, A. (2020) · Endocrine Connections · doi:10.1530/ec-20-0117 · Cited by 58 · see citing works
“Next, they should be re-tested, to determine whether they have a persistent hypocortisolism [121, 122].”
BackgroundExtracranial complications after traumatic brain injury: targeting the brain and the body
Robba, C., Bonatti, G., Pelosi, P. P., & Citerio, G. (2020) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000707 · Cited by 49 · see citing works
“This chronic hypopituitarism often is under recognized in part because the symptoms are nonspecific and there is a lack of agreement on how best to screen for the disorder [78,79].”
BackgroundPsychopharmacology of traumatic brain injury
Polich, G. R., Iaccarino, M. A., & ZAFONTE, R. D. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64012-3.00015-0 · Cited by 42 · see citing works
Clinical picture and the treatment of TBI-induced hypopituitarism
Caputo, M., Mele, C., Prodam, F., Marzullo, P., & Aimaretti, G. (2019) · Pituitary · doi:10.1007/s11102-019-00956-w · Cited by 39 · see citing works
Dassa, Y., Crosnier, H., Chevignard, M., Viaud, M., Personnier, C., Flechtner, I., Meyer, P., Puget, S., Boddaert, N., Breton, S., et al. (2019) · European Journal of Endocrinology · doi:10.1530/eje-19-0034 · Cited by 34 · see citing works
Hypopituitarism post traumatic brain injury (TBI): review
Kgosidialwa, O., & Agha, A. (2019) · Irish Journal of Medical Science (1971 -) · doi:10.1007/s11845-019-02007-6 · Cited by 28 · see citing works
Self-citationAljboor, G. S. R., Tulemat, A., Al-Saedi, A. R., Rădoi, M. P., Toader, C., & Papacocea, T. M. (2024) · Neurosurgical Review · doi:10.1007/s10143-024-03088-3 · Cited by 26 · see citing works
The Outcome of Neurorehabilitation Efficacy and Management of Traumatic Brain Injury
Akira, M., Takata, Y., Tomotaka, U., Takaaki, K., Mori, K., & Miyamoto, C. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.870190 · Cited by 26 · see citing works
Post-Traumatic Hypopituitarism: A Neglected Consequence of Traumatic Brain Injury
Kałas, M., Miksiewicz, M., Kowalke, A., & Siemiński, M. (2023) · Neuroendocrinology · doi:10.1159/000529327 · Cited by 17 · see citing works
A neurosurgical approach to traumatic brain injury and post-traumatic hypopituitarism
Tan, C. L., & Hutchinson, P. J. (2018) · Pituitary · doi:10.1007/s11102-018-0925-z · Cited by 17 · see citing works
Yuen, K. C. J., Masel, B., Jaffee, M. S., O'Shanick, G., Wexler, T. L., Reifschneider, K., Urban, R. J., Hoang, S., Kelepouris, N., & Hoffman, A. R. (2022) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2022.101495 · Cited by 18 · see citing works
Braga, T. L., Pinto, S. R., dos Reis, S. R. R., Portilho, F. L., de Barros, A. O. D. S., Bernardes, E. S., dos Santos, S. N., Alencar, L. M. R., Ricci‐Júnior, E., & Santos‐Oliveira, R. (2019) · Pharmaceutical Research · doi:10.1007/s11095-019-2678-4 · Cited by 12 · see citing works
Fluid and electrolyte disorders following traumatic brain injury
Tomkins, M., Green, D., O’Reilly, M., & Sherlock, M. (2025) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2025.102014 · Cited by 11 · see citing works
Ebrahimi, F., Andereggen, L., & Christ, E. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-024-09888-8 · Cited by 8 · see citing works
An Approach to Traumatic Brain Injury-Related Hypopituitarism: Overcoming the Pediatric Challenges
Vlad, R. M., Albu, A. I., Nicolaescu, I. D., Dobritoiu, R., Carsote, M., Sandru, F., Albu, D., & Păcurar, D. (2023) · Diagnostics · doi:10.3390/diagnostics13020212 · Cited by 7 · see citing works
“That is why screening methods for pituitary dysfunction should be applied to patients who have suffered brain damage, not necessarily for those with mild forms of TBIs (unless they are admitted for suggestive symptomology), but for moderate to severe cases [16].”
BackgroundMethodInfluentialMild traumatic brain injury as a cause of adult growth hormone deficiency: Diagnosis and treatment
Herodes, M., Legaspi, A., & Garcia, J. M. (2023) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2023.101818 · Cited by 5 · see citing works
Rickels, E., Steudel, W., Repschläger, U., Schulte, C., Weißgärber, H., & Wende, D. (2023) · Deutsches Ärzteblatt International · doi:10.3238/arztebl.m2023.0046 · Cited by 7 · see citing works
Cárdenas, J. F., Kelepouris, N., Adiga, R., & Yuen, K. C. J. (2024) · BMC Medical Education · doi:10.1186/s12909-024-05027-8 · Cited by 4 · see citing works
“Since most TBIs are mild and do not result in hospital admission, the prevalence of TBI is likely underestimated [15, 16].”
BackgroundLoursac, R., Hager, J.-P., Capel, O., Ilie, M. D., Cotton, F., Vieira, T. D., Sonnery‐Cottet, B., Dine, G., & Raverot, G. (2022) · Annales d Endocrinologie · doi:10.1016/j.ando.2021.12.005 · Cited by 3 · see citing works
Traumatic Brain Injury-associated Hypopituitarism-A Case Report with Mini Review
Song, Y.-M. (2020) · 內科學誌 · doi:10.6314/jimt.202010_31(5).09 · Cited by 3 · see citing works
Varlamov, E. V., & Fleseriu, M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-99899-4.00019-6 · Cited by 4 · see citing works
Approach to the Patient With Traumatic Brain Injury–induced Pituitary Dysfunction
Keleştimur, F., Agha, A., Ioachimescu, A. G., McDonald, D., Karaca, Z., & Yuen, K. C. J. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag090 · Cited by 3 · see citing works
Self-citationMishra, V., Martinez, M., & Weppner, J. L. (2026) · Journal of Neurotrauma · doi:10.1177/08977151261434917 · Cited by 2 · see citing works
Penetrating brain injury with hypopituitarism
Appelbaum, R. D., Neri, K. E., Rebo, K. A., et al. (2022) · Trauma Case Reports · doi:10.1016/j.tcr.2022.100628 · Cited by 2 · see citing works
“A 2007 meta-analysis of 19 studies noted PTHP has a prevalence of 27% and is more common with moderate to severe TBI [2].”
BackgroundInfluentialA case of refractory serum sodium disorders with severe multiple trauma
Satoh, K., Furuya, T., Okuyama, M., & Nakae, H. (2019) · Personalized Medicine Universe · doi:10.1016/j.pmu.2019.06.001 · Cited by 2 · see citing works
Carolina Carmona, R., Pablo Villanueva, G., Huete, I., Cruz, J. P., Bravo, S., Guarda, F. J., & Nilo, F. (2020) · Revista médica de Chile · doi:10.4067/s0034-98872020001201796 · Cited by 3 · see citing works
Mele, C., Marchi, L. D., Pitino, R., Costantini, L., Cavigiolo, B., Caputo, M., Marzullo, P., & Aimaretti, G. (2025) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2025.102001 · Cited by 3 · see citing works
Adenohipófisis en la fase aguda del trauma craneoencefálico severo, estudio descriptivo
Tovar, A. P., Gonzalez, G. A., González, J. C. C., & Jiménez-Canizales, C. E. (2022) · Acta Colombiana de Cuidado Intensivo · doi:10.1016/j.acci.2022.08.001 · Cited by 1 · see citing works
Plavov, O., Martínez-Pérez, R., García-Ballestas, E., Agrawal, A., & Moscote‐Salazar, L. R. (2020) · British Journal of Neurosurgery · doi:10.1080/02688697.2020.1766664 · Cited by 1 · see citing works
Aron, D. C. (2019) · Springer eBooks · doi:10.1007/978-3-030-24593-1_17
Neuroendocrine, metabolic and hormonal conditions
McKay, O., & Jasey, N. N. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-65385-5.00032-9
Postsurgical and Posttraumatic Hyponatremia
Goel, A., & Verbalis, J. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-76097-3.00018-1
Hypopituitary syndrome with pituitary crisis in a patient with traumatic shock: A case report
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Growth Hormone Deficiency and Therapy During Aging
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Neuroendocrine dysfunction after TBI: A guide for the clinical neuropsychologist
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“24 Furthermore, the diverse patterns of hormone de fi ciency among patients call for tailored testing approaches, which makes the establishment of universal diagnostic standards quite challenging.”
Worldwide Distribution of OMCs
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Pituitary hormone abnormalities following military-related traumatic brain injuries
Herodes, M., & Garcia, J. M. (2026) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2026.101687
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P., S. K., Veetil, V. M., Sreekumar, T. K., P., M. V., Alapatt, J. P., Basheer, N., Mathew, J., Prakash, M. K., Joseph, A., & S., M. P. (2026) · Indian Journal of Neurotrauma · doi:10.1055/s-0046-1827494
嵩弥, 西., Nishiyama, K., Machiyama, A., Yamada, T., 光弘, 上., & 靖明, 水. (2026) · Nihon Kyukyu Igakukai Zasshi Journal of Japanese Association for Acute Medicine · doi:10.1002/jja2.13181
- Authors
- Quinn, M., & Agha, A.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- ORCID
- Quinn, Mark
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-02-02
- Volume
- 9
- Pages
- 8-8
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC5801312
- OpenAlex
- W2792730153
- Semantic Scholar
- 63ca1db888cf3bb537ca84bef5a3df31008c6eca
- Cited by
- 52
- References
- 39
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 3 · 2020: 8 · 2019: 9 · 2018: 1
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- post-traumatic hypopituitarism, traumatic brain injury, anterior pituitary dysfunction, screening, hormone replacement therapy, underdiagnosis, follow-up strategy
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