Pituitary insufficiency after traumatic brain injury

doi:10.1016/j.jocn.2008.01.009

Journal of Clinical Neuroscience

Volume 16, Issue 2, February 2009, Pages 202-208

https://doi.org/10.1016/j.jocn.2008.01.009 Get rights and content

Abstract

After traumatic brain injury (TBI), patients present with psychological disorders that may be explained by post-traumatic pituitary insufficiency (PI). The goal of this study was to determine the relationship between hypopituitarism, neuropsychological changes and findings on CT scans after TBI. Hospital charts of 55 TBI patients were screened for age, Glasgow Coma Scale (GSC) score, hypoxia or hypotension. The first two CT scans were analyzed for hemorrhagic lesions. Basal levels of the following hormones were recorded: cortisol, prolactin, estradiol, testosterone, insulin-like growth factor 1 and free thyroxine. Hormonal stimulation tests were performed either if the basal hormone screening revealed an abnormality or if the patient answered “yes” to at least one question in the non-evaluated neuropsychological questionnaire. Overall, 14 out of 55 patients (25.4%) presented with PI; one of them with two hormonal deficits. Growth hormone deficit, hypothyroidism and hypocortisolism were found in one, one and two patients, respectively. Neuropsychological complaints were present in 67% of the patients and were associated with intracerebral hemorrhagic lesions and not PI. Neuropsychological complaints after TBI are more frequent than PI. Brain tissue damage is most important than PI in the development of psychological changes after TBI.

Introduction

Pituitary insufficiency (PI) after traumatic brain injury (TBI) has been known for almost a century and venous infarction following the distribution of the long hypophyseal portal veins is thought to be the underlying pathophysiological cause.[1], 2, 3 Recently Kelly et al. found hypopituitarism in about 25% of patients after TBI and this prompted renewed interest in the topic. Other investigators found hypopituitarism in 30% to 55% of patients after TBI and severe growth hormone deficits (GHD) in 15% to 20% of adult patients.4, 5, 6, 7, 8, 9, 10, 11, 12 In other studies, neuropsychological disorders, including fatigue, frustration and concentration deficits were identified in 42% of TBI patients.13, 14 GHD are thought to be the major cause of diverse post-traumatic physical and psychological complaints.11, 15 Most studies do not discriminate between pre-traumatic pituitary dysfunction and loss of brain tissue after TBI. The consensus guidelines on screening for hypopituitarism following TBI increased awareness of the risks of TBI-induced endocrinopathies among physicians.⁹ No prior studies have investigated the association between the incidence of post-traumatic pituitary dysfunction and CT structural cerebral damage with neurobehavioral dysfunction.⁹

This study was originally designed as a screening project to identify the frequency of PI in the post-traumatic population. The results, however, were surprising and went against current opinions on hypopituitarism after TBI.

Section snippets

Materials and methods

This cross-sectional study was designed as a retrospective chart review combined with prospective testing for PI. A search of the hospital’s database for the ICD-10 code “S06”, which represents TBI, identified 312 TBI patients, and of these, 267 hospital charts were available for review. TBI was correctly coded in 196 patients, whereas chronic subdural hematoma, spontaneous intracerebral hemorrhage and spinal trauma were the correct diagnoses in 50, 14 and 7 patients, respectively. Forty-one

The patients

The study comprised 53 patients, the majority male (64.1%), with an average (± SD) age of 45.2 ± 20.1 years and a median age of 45 years (Table 1). At the trauma scene, mild, moderate and severe TBI was present in 66%, 7% and 17% of patients, respectively. At the time of admission to the hospital, 17% of the patients presented with a GCS score of 13 to 15, but 61.2% patients had a GCS score of 8 or less. The change in GCS score between the trauma scene and admission to hospital was primarily due

Methodology

The present investigation was designed as a retrospective screening project where TBI patients were invited to participate in the study up to 4 years after trauma. A selection bias might have been associated with this study design. At follow-up, 93% of patients presented with a favourable outcome, defined as GOS scores of 4 and 5. Patients in nursing homes or long-term rehabilitation facilities were not willing or able to return the letter of invitation. As a result, only 32% of contacted

Conclusion

This screening project identified hypopituitarism in almost 25% of patients after trauma. Overall neuropsychological and QoL deficits were associated more frequently with hemorrhagic lesions on CT scans than with hypopituitarism.

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Cited by (49)

The rate of empty sella (ES) in traumatic brain injury: Links with endocrine profiles
2022, Cellular, Molecular, Physiological, and Behavioral Aspects of Traumatic Brain Injury
Empty sella is a frequent incidental finding during performance of brain radiological imaging for other reasons than looking for pituitary abnormalities. It is reported in approximately 2% to 38% of patients upon radiological examination, and it does not necessarily indicate presence of pituitary insufficiency or disease requiring treatment.
Empty sella can be primary or secondary to a specific pathological process and can be seen after traumatic brain injury. It has been suggested to be an indicator of post-traumatic hypopituitarism in some studies. Although post-traumatic hypopituitarism should not be confused with stress-related endocrine alterations especially in the acute and early post-acute phase, neither should severe hypopituitarism be overlooked as potentially lethal if left untreated in case of central adrenal insufficiency. Treatment indication in less severe cases may however also exist.
Growth hormone deficiency is the most common endocrine complication occurring after head trauma. The decision to treat post-traumatic pituitary insufficiency relies on a correct diagnosis of the various hormone insufficiencies, and the order of commencement of treatment of multiple hormones is usually adrenal, thyroid, sex hormones and finally growth hormone.
GH and Pituitary Hormone Alterations after Traumatic Brain Injury
2016, Progress in Molecular Biology and Translational Science
Citation Excerpt :
In a study from Germany, conducted on 55 patients with TBI in whom the GCS varied from 3 to 15, 24.5% of the patients had hypopituitarism. The GHRH stimulation test alone was used in the investigation of GHD and it was defined in only one patient.32 Berg et al. reported that 21% of the patients with moderate to severe TBI had hypopituitarism, of whom 1% had total, 2% had partial, and 18% had isolated hypopituitarism in a cross-sectional study including 246 patients.
Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI itself. Therefore, the diagnosis and treatment of unrecognized hypopituitarism due to TBI are very important not only to decrease morbidity and mortality due to hypopituitarism but also to alleviate the chronic sequelae caused by TBI.
Hypopituitarism following traumatic brain injury: diagnostic and therapeutic issues
2015, Annales d'Endocrinologie
Les traumatismes crâniens sont une cause fréquente de mortalité et de handicap, en particulier chez le sujet jeune. A côté des séquelles neurologiques et psychiatriques, un déficit hypophysaire peut également apparaître, à court ou long terme. La prévalence réelle de cette pathologie est difficile à évaluer en raison de l'hétérogénéité des études publiées et de la difficulté d'interpréter les résultats des tests hormonaux dans cette population particulière. Des facteurs prédictifs de survenue d'un déficit ont été proposés et permettent d'orienter le dépistage. Les mécanismes physiopathologiques à l'origine du déficit sont encore mal connus mais il semble que les atteintes d'origine vasculaire soient prédominantes. Les cellules souches hypophysaires sont probablement mises en jeu dans le processus de régénération tissulaire faisant suite au traumatisme. Ces mêmes cellules sont toutefois également impliquées dans des processus de tumorigenèse hypophysaire, ce qui en fait des acteurs essentiels dans la pathologie hypophysaire. Cet article reprend ainsi les données récentes de la littérature sur le déficit hypophysaire post-traumatique et met en lumière les biais et difficultés qui peuvent être rencontrés lors de son diagnostic.
Traumatic Brain Injury (TBI) is a well-known public health problem worldwide and is a leading cause of death and disability, particularly in young adults. Besides neurological and psychiatric issues, pituitary dysfunction can also occur after TBI, in the acute or chronic phase. The exact prevalence of post-traumatic hypopituitarism is difficult to assess due to the wide heterogeneity of published studies and bias in interpretation of hormonal test results in this specific population. Predictive factors for hypopituitarism have been proposed and are helpful for the screening. The pathophysiology of pituitary dysfunction after TBI is not well understood but the vascular hypothesis is privileged. Activation of pituitary stem/progenitor cells is probably involved in the recovery of pituitary functions. Those cells also play a role in the induction of pituitary tumors, highlighting their crucial place in pituitary conditions. This review updates the current data related to anterior pituitary dysfunction after TBI and discusses the bias and difficulties encountered in its diagnosis.
Hypopituitarism After Traumatic Brain Injury
2015, Endocrinology and Metabolism Clinics of North America
Citation Excerpt :
2) Postmortem studies have revealed a high prevalence of necrosis or hemorrhage into the pituitary gland, which suggests a direct traumatic injury to the pituitary gland as another possible mechanism.25 ( 3) Multiple secondary insults from hypotension, hypoxia, anemia, and brain swelling could also lead to an ischemic pituitary gland.26 ( 4) Another mechanism described as responsible for hypopituitarism due to vascular damage is the transection of the pituitary stalk, which potentially causes hypopituitarism because of infarction of the pituitary tissue.21,23
Alternative causes of hypopituitarism: Traumatic brain injury, cranial irradiation, and infections
2014, Handbook of Clinical Neurology
Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic–pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic–pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic–pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease.
Traumatic brain injury and anterior pituitary dysfunction. Regarding 33 cases: Evolution profile over a six-month period
2013, Neurochirurgie
To measure anterior pituitary dysfunction in traumatic brain injury (TBI) and assess the correlations between this disorder, clinical signs and brain lesions.
This was a prospective, longitudinal and analytic study conducted in the department of neurosurgery at the National Hospital of Niamey and the institute of radioisotopes of Niamey University between November 2009 and November 2010. All patients admitted for head trauma were included in the study. They were followed-up for 6 months and underwent clinical, hormonal and CT scan analysis. The hormonal studies targeted gonadotroph hormone, growth hormone (GH), corticotroph, lactotroph, and thyreotroph axes.
Thirty-three patients were included in the study. The sex ratio was 15.4:1. The mean age was 28.21 years. Glasgow coma scale score was between 7 and 12 in 52% of cases, with brain contusions in 54.5% of cases. In the acute phase, hypogonadism was reported in 64% of cases, and growth hormone deficiency in 58% of cases. Hormonal follow-up at three months showed GH deficiency in 48% of cases with an elevated luteinizing hormone (LH) in 42% of cases. At sixth months, a rise in LH was observed in 55% with GH deficiency in 52% of cases. Surgical procedures were performed in 21% of cases. At 6 months a post-concussion syndrome was observed in 48.48% of cases.
These pituitary dysfunctions are common and should be investigated into the management of TBI.
Mesurer les perturbations antéhypophysaires chez les traumatisés crâniens et analyser les corrélations entre ces troubles, les signes cliniques et les lésions encéphaliques.
Il s’agissait d’une étude prospective, analytique et longitudinale réalisée dans le service de neurochirurgie de l’hôpital national de Niamey et l’institut des radio-isotopes de l’université de Niamey entre novembre 2009 et novembre 2010. Étaient inclus les patients admis pour traumatisme crânien et suivis pendant au moins 6 mois avec un bilan clinique, hormonal et scannographique. Les dosages hormonaux concernaient les axes gonadotrope, somatotrope, corticotrope, lactotrope et thyréotrope.
Trente-trois patients étaient inclus dans l’étude. Le sex-ratio était de 15,4:1. La moyenne d’âge était de 28,21 ans. Le score de Glasgow variait entre 7 et 12 dans 52 % des cas. Il s’agissait de contusions cérébrales dans 54,5 % de cas. À la phase aiguë un hypogonadisme était rapporté dans 64 % des cas, et un déficit en GH dans 58 % des cas. Au 3^e mois, un déficit en GH était mesuré dans 48 % des cas avec une élévation de LH dans 42 % des cas. Au 6^e mois, une élévation de LH était constatée dans 55 % avec un déficit en GH dans 52 % des cas. La prise en charge était chirurgicale dans 21 % et à 6 mois un syndrome subjectif du traumatisé crânien était observé dans 48,48 % des cas.
Au décours des traumatismes crâniens, les perturbations hypophysaires sont fréquentes et devraient être intégrées dans leur prise en charge.

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Clinical StudyPituitary insufficiency after traumatic brain injury

Abstract

Introduction

Section snippets

Materials and methods

The patients

Methodology

Conclusion

Psychoneuroendocrinology

Lancet

Hypophysenschädigung durch Schädel-Basis-Fraktur

Deutsche Medizinische Wochenschrift

Traumatic infarction of the anterior lobe of the pituitary gland

Lancet

Pituitary lesions in craniocerebral injuries

Arch Pathol

Anterior pituitary dysfunction following traumatic brain injury (TBI)

Clin Endocrinol (Oxf)

Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury

Clin Endocrinol (Oxf)

Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI)

Growth Horm IGF Res

Occurrence of pituitary dysfunction following traumatic brain injury

J Neurotrauma

Hypopituitarism following traumatic brain injury (TBI): a guideline decalogue

J Endocrinol Invest

Consensus guidelines on screening for hypopituitarism following traumatic brain injury

Brain Inj

Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report

J Neurosurg

Hypopituitarism as a consequence of traumatic brain injury (TBI) and its possible relation with cognitive disabilities and mental distress

J Endocrinol Invest

Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury

Eur J Endocrinol

Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria

J Clin Endocrinol Metab

Functional outcome at 1 vs. 2 years after severe traumatic brain injury

Brain Inj

The diagnosis of head injury requires a classification based on computed axial tomography

J Neurotrauma

Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury

J Neurosurg

Cognitive and psychosocial outcome following moderate or severe traumatic brain injury

Brain Inj

Clinical Study
Pituitary insufficiency after traumatic brain injury