Post-traumatic Hypopituitarism Research Articles

Post-Traumatic Hypopituitarism

Abstract Purpose of Review Traumatic brain injury (TBI) frequently effects the integrity and function of the anterior and/or posterior pituitary gland. This review will cover the current understanding of post-trauma hypopituitarism (PTHP) including frequency, risk factors, screening, and treatment. Recent Findings There is continuingly increased data on frequency of hormone deficiencies over time. This has created a push for algorithms to guide screening. Oxytocin is emerging as a potential target for treatment, but data is mixed and no treatment has been tested. There is significantly increased data regarding the long-term effect of growth hormone (GH) deficiency on metabolism and on the liver, which is driving renewed recommendations for consideration of GH replacement. Summary Pituitary dysfunction after TBI is frequent and has significant impact on morbidity, mortality, and recovery. If recognized, basic treatment is straightforward, though many gaps remain in our knowledge. Future work should focus on ideal screening strategies and treatment optimization.

Cortisol Dynamics, Quality of Life, and Fatigue following Traumatic Brain Injury in Childhood

Introduction: Traumatic brain injury (TBI) is a leading cause of acquired neurological morbidity. The prevalence of post-traumatic hypopituitarism and associated morbidity after childhood TBI is unclear. Our study investigated long-term hypothalamus-pituitary-adrenal (HPA) axis function, in a prospective childhood TBI and control cohort, using measures of cortisol/cortisone secretion (physiological and stimulated), HPA axis feedback, and exploring associations with fatigue, depression, and quality of life (QoL) outcomes. Methods: All TBI participants had data concerning severity and mechanism of TBI. All groups had clinical assessment, pituitary/brain MRI, questionnaire measures of QoL, fatigue, depression, and salivary cortisone profiles including dexamethasone suppression test. In addition, participants with moderate/severe TBI had ethical approval for baseline endocrine blood tests, overnight 12-h venous sampling of cortisol and growth hormone, and stimulated HPA axis evaluation with an insulin tolerance test (ITT). Results: Seventy-two participants with moderate/severe (n = 31, age 19.8 ± 4.2 years) or mild TBI (n = 24, age 17.8 ± 5.1 years) and matched controls (n = 17, age 18.5 ± 5.5 years) took part. Time post-TBI was 6.8–10.8 years. Baseline endocrine tests confirmed normal thyroid and posterior pituitary function. One female with moderate/severe TBI had hypogonadism. Pituitary neuroimaging was normal in all participants. In 2/25 ITT and 9/22 overnight serum profiles, peak cortisol was Conclusion: Although not as prevalent as previously reported, HPA axis dysfunction does occur in survivors of childhood TBI, confirming the need for endocrine surveillance. However, in most of our paediatric TBI survivors assessed 7–11 years post-TBI, HPA function and circadian rhythmicity were preserved or had recovered. Chronic fatigue is a common concern post-TBI, but in the majority, it is not associated with frank HPA axis dysfunction. Morning salivary cortisone levels were higher in TBI survivors (who have a high prevalence of fatigue) compared to healthy controls, despite the recognised association of chronic fatigue with cortisol hyposecretion.

A DELAYED PRESENTATION OF POSTERIOR HYPOPITUITARISM FOLLOWING TRAUMATIC BRAIN INJURY – A CASE REPORT OF A 24 YEAR OLD ASIAN FEMALE.

Background: Cases of post traumatic hypopituitarism are rarely contemplated in the Indian subcontinent. However global literatures disclose that the incidence rate of hypopituitarism following traumatic brain injury is around 15-30%. Most hospitals do not routinely screen patients for pituitary dysfunction following traumatic brain injury due to the lack of proper protocol supporting the same. Hence large number of cases with varying pituitary abnormalities is procrastinated, which could have been otherwise beneted from early interventions. This case is a classic example of delayed exhibition of posterior hypopituitarism post traumatic brain injury, which has signicantly compromised the quality of life of the patient in later stage due to the failure of timely screening. Case Presentation:This is a case of 24 year old female who sustained a traumatic brain injury 3 years ago allegedly due to domestic abuse. The patient presented to the urology department with the complaints of polyuria, polydipsia, secondary amenorrhea, sleep disturbance and weight gain for 6-7 months. The patient was not under regular follow-up for the traumatic injury. On further evaluation, all the anterior pituitary hormones were found to be normal. We further investigated the case with biochemical investigations and an MRI of brain (plain and contrast) which showed a thickened enhancing pituitary stalk with absence of posterior pituitary bright spot with a normal anterior pituitary gland – suggestive of Central Diabetes Insipidus. Upon initiation with Desmopressin, the patient showed signicant symptomatic improvement. Conclusion:One of the most common complications of traumatic brain injury is hypopituitarism. Early screening for hypopituitarism in such cases will help us intervene early and improve the quality of life of the patients.

Hormonal Deficiency in Patients with Acute Traumatic Brain Injury: A Prospective Study

Background :Traumatic brain injury (TBI) has become a major public health concern in developing and developed countries as it affects productivity and economy. The incidence, prevalence, and scope of survival and recovery from acute and chronic post-traumatic pituitary dysfunction (PTPD) have not been comprehensively assessed. Post-traumatic hypopituitarism accounts for 7.2% of all hypopituitarism cases. The identification of patients with acute brain injury who are at risk of hormonal deficiency and the provision of appropriate interventions can reduce morbidity associated with TBI. Study objectives • Assess the proportion of patients with severe head injury (Glasgow coma scale [GCS] score of < 9) who are at risk of reduced thyroidstimulating hormone (TSH), free T3 (FT3), free T4 (FT4), and serum cortisol levels within the first week after trauma. • Develop the Acute TBI Hormone Assessment Score (ATBIHAS), which is a 12-point scoring system comprising clinical and radiological parameters, and evaluate its correlation with hormone reduction during the acute phase of trauma, specifically on the fourth day. • Investigate whether the ATBIHAS can be used to quantify the percentage of hormonal reduction on the fourth day after trauma. • Evaluate the correlation between GCS score and hormonal reduction on the fourth day after trauma. Methods : This prospective observational study was conducted at the Neurosurgical Department of Rajiv Gandhi Government General Hospital, Chennai, India. In total, 30 patients with severe head injury who underwent brain computed tomography (CT) scan after the initial resuscitation and within the first 24 h after presentation were included in the analysis. Clinical Georg Thieme Verlag KG, P.O. Box 30 11 20, 70451 Stuttgart, Germany Manuscript submitted to Editorial Office of Central European Neurosurgery For Peer Review data were collected, and brain CT scan findings were recorded in the proforma. Moreover, information about sphenoidal hemosinus, frontal contusion, temporal contusion, edema, infarct, midline shift, and bony calvarial fracture was recorded. The ATBIHAS, a 12-point scoring system comprising clinical and radiological features and surgical procedures for the current scenario, was developed. This tool can assess pituitary stalk injury and hypothalamic pituitary axis disruption. All participants underwent the thyroid profile test, which comprised TSH, FT3, FT4, and serum cortisol levels. Samples were collected between 7:00 and 9:00 am on the day after the patient was successfully resuscitated. This time period was selected to prevent diurnal variations in hormone levels. The test was repeated between 7:00 and 9:00 am on the fourth day of admission. Data about all hormonal levels and their variations on the fourth day were assessed and compared with the ATBIHAS. This study was approved by the institutional ethics committee. Results: Among the participants, 27 were men and 3 women. Approximately 33.3% and 6.7% were aged 20–29 and 50–59 years, respectively. Hormonal reduction between the first and fourth days after trauma significantly differed (P < 0.001). The incidence rates of hormonal reduction after the fourth day of trauma were 90% for TSH, FT4, and serum cortisol and 93% for free T3. The ATBIHAS was found to be positively correlated with reduced TSH, FT3 and FT4, and serum cortisol levels. A higher score indicated a greater percentage of hormone reduction on the fourth day after trauma. However, there was no significant correlation between the GCS score as well as the ATBIHAS and TSH, FT3, FT4, and serum cortisol reduction (P > 0.05). Conclusion: Approximately > 90% of patients with severe head injury are at risk for TSH, FT3, FT4, and serum cortisol reduction within the first week after trauma. Moreover, there is a significant linear correlation between ATBIHAS and hormonal levels during the acute phase of trauma, specifically on the fourth day. Hence, the ATBIHAS ca

Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward.

Neuroendocrine dysfunction can occur as a consequence of traumatic brain injury (TBI), and disruptions to the hypothalamic-pituitary axis can be especially consequential to children. The purpose of our review is to summarize current literature relevant to studying sex differences in pediatric post-traumatic hypopituitarism (PTHP). Our understanding of incidence, time course, and impact is constrained by studies which are primarily small, are disadvantaged by significant methodological challenges, and have investigated limited temporal windows. Because hormonal changes underpin the basis of growth and development, the timing of injury and PTHP testing with respect to pubertal stage gains particular importance. Reciprocal relationships among neuroendocrine function, TBI, adverse childhood events, and physiological, psychological and cognitive sequelae are underconsidered influencers of sexually dimorphic outcomes. In light of the tremendous heterogeneity in this body of literature, we conclude with the common path upon which we must collectively arrive in order to make progress in understanding PTHP.

Prevalence of hypopituitarism and quality of life in survivors of post-traumatic brain injury.

BackgroundHypopituitarism is a recognized sequela of traumatic brain injury (TBI) and may worsen the quality of life (QoL) in survivors.AimsTo assess the prevalence of post‐traumatic hypopituitarism (PTHP) and growth hormone deficiency (GHD), and determine their correlation with QoL.MethodsSurvivors of moderate to severe TBI were recruited from two Algerian centres. At 3 and 12 months, pituitary function was evaluated using insulin tolerance test (ITT), QoL by growth hormone deficiency in adults’ questionnaire (QoL‐AGHDA), and 36‐item short‐form (SF‐36) health survey.ResultsOf 133 (M: 128; F: 5) patients aged 18‐65 years, PTHP and GHD were present at 3 and 12 months in 59 (44.4%) and 23 (17.29%), 41/116 (35.3%) and 18 (15.5%). Thirteen patients with GHD at 3 months tested normally at 12 months, while 9 had become GHD at 12 months. At 3 and 12 months, peak cortisol was < 500 nmol/L) in 39 (29.3%) and 29 (25%) patients, but <300 nmol/L in only five and seven. Prevalence for gonadotrophin deficiency was 6.8/8.6%, hypo‐ and hyperprolactinaemia 6.8/3.8% and 5.2/8.6%, and thyrotrophin deficiency 1.5/0.9%. Mean scores for QoL‐AGHDA were higher in patients with PTHP at 3 and 12 months: 7.07 vs 3.62 (P = .001) and in patients with GHD at 12 months: 8.72 vs 4.09 (P = .015). Mean SF‐36 scores were significantly lower for PTHP at 3 months.ConclusionPrevalence of PTHP and GHD changes with time. AGHDA measures QoL in GHD more specifically than SF‐36. Full pituitary evaluation and QoL‐AGHDA 12 months after TBI are recommended.

Traumatic brain injuries induced pituitary dysfunction: a call for algorithms.

Traumatic brain injury affects many people each year, resulting in a serious burden of devastating health consequences. Motor-vehicle and work-related accidents, falls, assaults, as well as sport activities are the most common causes of traumatic brain injuries. Consequently, they may lead to permanent or transient pituitary insufficiency that causes adverse changes in body composition, worrisome metabolic function, reduced bone density, and a significant decrease in one’s quality of life. The prevalence of post-traumatic hypopituitarism is difficult to determine, and the exact mechanisms lying behind it remain unclear. Several probable hypotheses have been suggested. The diagnosis of pituitary dysfunction is very challenging both due to the common occurrence of brain injuries, the subtle character of clinical manifestations, the variable course of the disease, as well as the lack of proper diagnostic algorithms. Insufficiency of somatotropic axis is the most common abnormality, followed by presence of hypogonadism, hypothyroidism, hypocortisolism, and diabetes insipidus. The purpose of this review is to summarize the current state of knowledge about post-traumatic hypopituitarism. Moreover, based on available data and on our own clinical experience, we suggest an algorithm for the evaluation of post-traumatic hypopituitarism. In addition, well-designed studies are needed to further investigate the pathophysiology, epidemiology, and timing of pituitary dysfunction after a traumatic brain injury with the purpose of establishing appropriate standards of care.

A national survey of clinical practice of surveillance for post-traumatic brain injury hypopituitarism in the United Kingdom and Ireland

Background: Traumatic brain injury (TBI) is the most common cause of death and disability in young adults in industrialised countries. Post-TBI hypopituitarism (PTHP) is thought to occur in one-third of patients, however the natural history and predictive factors are not fully understood and as such guidelines for surveillance vary. The aim of this study was to assess the variations in current surveillance practices across the Neurosurgery Centres within the United Kingdom.Methods: A questionnaire was developed following discussions with an expert panel and distributed to members of the Society of British Neurosurgeons (SBNS), by email and printed copy, to survey surveillance practices for PTHP. The questionnaire primarily aimed to determine how commonly screening was performed and the clinical parameters used to guide these surveillance practices.Results: There were 45 responders representing Neurosurgery units in regions of England, Scotland and Ireland. The majority of participants (86.7%) considered PTHP to be a problem but only 25% (11/45) routinely screened for PTHP. There was wide variation in the criteria used to determine which patients were screened.Conclusions: Our survey suggests that few Neurosurgeons routinely screen for PTHP and those that do use a wide variation of clinical parameters to guide surveillance practice. A UK-wide prospective cohort study may help identify patients at risk of developing PTHP.

Growth Hormone Deficiency Following Traumatic Brain Injury.

Traumatic brain injury (TBI) is fairly common and annually affects millions of people worldwide. Post traumatic hypopituitarism (PTHP) has been increasingly recognized as an important and prevalent clinical entity. Growth hormone deficiency (GHD) is the most common pituitary hormone deficit in long-term survivors of TBI. The pathophysiology of GHD post TBI is thought to be multifactorial including primary and secondary mechanisms. An interplay of ischemia, cytotoxicity, and inflammation post TBI have been suggested, resulting in pituitary hormone deficits. Signs and symptoms of GHD can overlap with those of TBI and may delay rehabilitation/recovery if not recognized and treated. Screening for GHD is recommended in the chronic phase, at least six months to a year after TBI as GH may recover in those with GHD in the acute phase; conversely, it may manifest in those with a previously intact GH axis. Dynamic testing is the standard method to diagnose GHD in this population. GHD is associated with long-term poor medical outcomes. Treatment with recombinant human growth hormone (rhGH) seems to ameliorate some of these features. This review will discuss the frequency and pathophysiology of GHD post TBI, its clinical consequences, and the outcomes of treatment with GH replacement.

A case of refractory serum sodium disorders with severe multiple trauma

Abstract A 40-year-old man was admitted to the hospital with multiple injuries, including head injury and his laboratory results were significant for sodium abnormalities. Initially, hypernatremia was from increased sodium intake. Subsequently, hyponatremia developed that was unresponsive to sodium supplementation. Syndrome of inappropriate antidiuretic hormone secretion or cerebral salt wasting syndrome was suspected. Additional tests suggested post-traumatic hypopituitarism was responsible for the hyponatremia. Corticosteroid were given which normalized the serum sodium level, but the urine volume increased. Masked diabetes insipidus was suspected and desmopressin was given, stabilizing the serum sodium level. Recognizing the factors that cause sodium abnormalities in trauma patients can help lead to the correct diagnosis.

Traumatic brain injury and resultant pituitary dysfunction: insights from experimental animal models.

Traumatic brain injury (TBI) is a major worldwide cause of disability, often burdening young people with serious lifelong health problems. A frequent clinical complication is post-traumatic hypopituitarism (PTHP) manifesting in several hypothalamus-pituitary axes. The head trauma-induced mechanisms underlying PTHP remain largely unknown. Several hypotheses have been proposed including direct damage to the pituitary gland and hypothalamus, vascular events and autoimmunity. This review aims to provide a summary of the currently limited number of studies exploring hypothalamus-pituitary dysfunction in experimental animal TBI models. Although the impact of different forms of TBI on a number of hypothalamus-pituitary axes has been investigated, consequences for pituitary tissue and function have only scarcely been described. Moreover, mechanisms underlying the endocrine dysfunctions remain under explored. Studies on TBI-induced pituitary dysfunction are still scarce. More research is needed to acquire mechanistic insights into the pathophysiology of PTHP which may eventually open up the horizon toward better treatments, including pituitary-regenerative approaches.

Hypopituitarism post traumatic brain injury (TBI): review.

Post-traumatic hypopituitarism (PTHP) is an important and relatively common complication of TBI (traumatic brain injury). A number of studies have shown that this clinical phenomenon can occur soon after TBI (acute) or later in the chronic phase. Patients with moderate to severe TBI are at a particular risk of developing PTHP. In the acute setting, it is important to monitor patients for hypoadrenalism as this confers a high risk for morbidity and even mortality. The gonadotrophin, growth hormone and TSH deficiencies are better defined in the chronic phase. Untreated PTHP can lead to delayed recovery, impaired rehabilitation and persistent neuropsychiatric symptoms. This review will discuss the frequency and natural history of PTHP and its clinical implications and propose a pathway for investigation and management of this still under-recognised entity.

Clinical picture and the treatment of TBI-induced hypopituitarism.

Traumatic brain injury (TBI) is an important public health problem with an increasing incidence in the last years. Relatively few cases are fatal; most individuals will survive and, in the long-term, the sequalae of TBI will include neuroendocrine dysfunctions with a much higher frequency than previously suspected. Patients who develop hypopituitarism after TBI present manifestations due to the number of deficient hormones, severity of hormonal deficiency, and the duration of hypopituitarism without diagnosis and treatment. The clinical spectrum of hypopituitarism is very large and many signs and symptoms of TBI survivors such as fatigue, concentration difficulties, depressive symptoms are nonspecific and overlap with symptoms of post-traumatic stress disorder and variably severe hypopituitarism related to brain damage remaining undiagnosed. This can explain why the diagnosis of hypopituitarism is often missed or delayed after this condition with potentially serious and hazardous consequences for the affected patients. Moreover, clinical experience cumulatively suggests that TBI-associated hypopituitarism is associated with poor recovery and worse outcome, since post-traumatic hypopituitarism is independently associated with cognitive impairment, poor quality of life, abnormal body composition, and adverse metabolic profile. In the present review, the current data related to clinical consequences of pituitary dysfunction after TBI in adult patients and therapeutic approaches are reported.

Pituitary pathology in traumatic brain injury: a review.

Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors, hypopituitarism is a common complication. Pituitary dysfunction occurs in approximately 20-40% of patients diagnosed with moderate and severe traumatic brain injury giving rise to growth hormone deficiency, hypogonadism, hypothyroidism, hypocortisolism, and central diabetes insipidus. Varying degrees of hypopituitarism have been identified in patients during both the acute and chronic phase. Anterior pituitary hormone deficiency has been shown to cause morbidity and increase mortality in TBI patients, already encumbered by other complications. Hypopituitarism after childhood traumatic brain injury may cause treatable morbidity in those survivors. Prospective studies indicate that the incidence rate of hypopituitarism may be ten-fold higher than assumed; factors altering reports include case definition, geographic location, variable hospital coding, and lost notes. While the precise pathophysiology of post traumatic hypopituitarism has not yet been elucidated, it has been hypothesized that, apart from the primary mechanical event, secondary insults such as hypotension, hypoxia, increased intracranial pressure, as well as changes in cerebral flow and metabolism may contribute to hypothalamic-pituitary damage. A number of mechanisms have been proposed to clarify the causes of primary mechanical events giving rise to ischemic adenohypophysial infarction and the ensuing development of hypopituitarism. Future research should focus more on experimental and clinical studies to elucidate the exact mechanisms behind post-traumatic pituitary damage. The use of preventive medical measures to limit possible damage in the pituitary gland and hypothalamic pituitary axis in order to maintain or re-establish near normal physiologic functions are crucial to minimize the effects of TBI.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function.

It is estimated that approximately 69million individuals worldwide will sustain a TBI each year, which accounts for substantial morbidity and mortality in both children and adults. TBI may lead to significant neuroendocrine changes, if the delicate pituitary is ruptured. In this review, we focus on the anterior pituitary hormonal changes in the acute post-TBI period and we present the evidence supporting the need for screening of anterior pituitary function in the early post-TBI time along with current suggestions regarding the endocrine assessment and management of these patients. Original systematic articles with prospective and/or retrospective design studies of acute TBI were included, as were review articles and case series. Although TBI may motivate an acute increase of stress hormones, it may also generate a wide spectrum of anterior pituitary hormonal deficiencies. The frequency of post-traumatic anterior hypopituitarism (PTHP) varies according to the severity, the type of trauma, the time elapsed since injury, the study population, and the methodology used to diagnose pituitary hormone deficiency. Early neuroendocrine abnormalities may be transient, but additional late ones may also appear during the course of rehabilitation. Acute hypocortisolism should be diagnosed and managed promptly, as it can be life-threatening, but currently there is no evidence to support treatment of acute GH, thyroid hormones or gonadotropins deficiencies. However, a more comprehensive assessment of anterior pituitary function should be undertaken both in the early and in the post-acute phase, since ongoing hormone deficiencies may adversely affect the recovery and quality of life of these patients.

The frequency and the diagnosis of pituitary dysfunction after traumatic brain injury.

Clinical research studies over the last 15years have reported a significant burden of hypopituitarism in survivors of traumatic brain injury (TBI). However, debate still exists about the true prevalence of hypopituitarism after head injury. We have reviewed the literature describing the frequency of post-traumatic hypopituitarism and discuss the factors which may explain the variable frequency of the reported deficits in clinical studies including research methodology and the natural history of the disease. Pituitary hormone perturbations in the acute phase following injury are frequent but are difficult to attribute to traumatic pituitary damage due to physiological hormonal changes in acute illness, the confounding effect of medications, other co-morbidities and lack of appropriate control subjects. Nevertheless, a small number of studies have emphasised the clinical importance of acute, dynamic disturbance of the hypothalamic-pituitary-adrenal axis. There is a much larger evidence base examining the frequency of hypopituitarism in the chronic, recovery phase following head injury. These studies report a very broad prevalence of long-term pituitary hormone dysfunction in survivors of TBI. However, systematic review suggests the prevalence to be between 27 and 31%. Survivors of head injury are at risk of pituitary hormone dysfunction and we suggest an approach to the diagnosis of post-traumatic hypopituitarism in routine clinical practice.

Post-traumatic hypopituitarism - a case report

Post-traumatic hypopituitarism - a case report

Post-Traumatic Hypopituitarism—Who Should Be Screened, When, and How?

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.

Chronic endocrine consequences of traumatic brain injury - what is the evidence?

Traumatic brain injury (TBI) is a major public health problem with potentially debilitating consequences for the individual. Hypopituitarism after TBI has received increasing attention over the past decade; development of the condition as a consequence of TBI was previously hardly mentioned in textbooks on the subject. Hypopituitarism has been reported in more than 25% of patients with TBI and is now thought to be one of the most important causes of treatable morbidity in TBI survivors. However, most clinicians dealing with neuroendocrine diseases and TBI generally do not see such a high incidence of hypopituitarism. This disproportion is not clearly explained, but recent data indicate that diagnostic testing, which is designed for high-risk populations and not for a cohort of patients with, for example, de novo isolated growth hormone deficiency (the predominant finding in TBI), might have overestimated the true risk and disease burden of hypopituitarism. In this Opinion article, we discuss current recommendations for post-traumatic hypopituitarism in light of recent evidence.