Hypopituitarism after traumatic brain injury

Traumatic brain injury (TBI) is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long-term cognitive, behavioural, psychological and social defects. Post-traumatic hypopituitarism (PTHP) was recognized more than 80 years ago, but it was thought to be a rare occurrence. Recently, clinical evidence has demonstrated that TBI may frequently cause hypothalamic-pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. Changes in pituitary hormone secretion may be observed during the acute phase post-TBI, representing part of the acute adaptive response to the injury. Moreover, diminished pituitary hormone secretion, caused by damage to the pituitary and/or hypothalamus, may occur at any time after TBI. PTHP is observed in about 40% of patients with a history of TBI, presenting as an isolated deficiency in most cases, and more rarely as complete pituitary failure. The most common alterations appear to be gonadotropin and somatotropin deficiency, followed by corticotropin and thyrotropin deficiency. Hyper- or hypoprolactinemia may also be present. Diabetes insipidus may be frequent in the early, acute phase post-TBI, but it is rarely permanent. Severity of TBI seems to be an important risk factor for developing PTHP; however, PTHP can also manifest after mild TBI. Accurate evaluation and long-term follow-up of all TBI patients are necessary in order to detect the occurrence of PTHP, regardless of clinical evidence for pituitary dysfunction. In order to improve outcome and quality of life of TBI patients, an adequate replacement therapy is of paramount importance.     

Recurrent hyponatremia after traumatic brain injury

Dysregulation of the neuroendocrine system is a frequent complication after traumatic brain injury (TBI). Symptoms of these hormonal abnormalities might be subtle and thus easily ignored. Hyponatremia usually indicates underlying disorders that disrupt fluid homeostasis. In most patients with TBI, hyponatremia is a feature of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion due to pituitary dysfunction after head injury. Usually TBI-associated hyponatremia is transient and reversible. We report the case of a 48-year-old man with TBI-associated hyponatremia with delayed recovery and recurrent hyponatremia precipitated by subsequent surgery. In this report, we emphasize the importance of identifying patients with slow recovery of the injured brain, which could complicate with SIADH and acute hyponatremia. Differentiating TBI-associated SIADH from other important causes of hyponatremia such as cerebral salt wasting, and hypocortisonism are also reviewed. Prevention of its recurrence by avoiding further risk is mandatory in managing patients with TBI.     

Endocrine changes after pediatric traumatic brain injury

Traumatic brain injury (TBI) is a very common occurrence in childhood, and can lead to devastating long term consequences. Recent research has focused on the potential endocrine consequences of TBI in adults. The research in children is less robust. This paper reviews current literature regarding TBI and possible hypothalamic and pituitary deficiencies in childhood. Acute endocrine changes are commonly found after TBI in pediatric patients, which can include changes in hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release. In the long term, both temporary and permanent alterations in pituitary function have been found. About 30% of children have hypopituitarism up to 5 years after injury. Growth hormone deficiency and disturbances in puberty are the most common, but children can also experience ACTH deficiency, diabetes insipidus, central hypothyroidism, and elevated prolactin. Every hormonal axis can be affected after TBI in children, although growth hormone deficiency and alterations in puberty are the most common. Because transient and permanent hypopituitarism is common after TBI, survivors should be screened serially for possible endocrine disturbances. These children should undergo routine surveillance at least 1 year after injury to ensure early detection of deficiencies in hormonal production in order to permit normal growth and development.     

Posterior pituitary dysfunction after traumatic brain injury

Disorders of water balance are well recognized after traumatic brain injury (TBI), but there are no reliable data on their true prevalence in post-TBI patients. We aimed to evaluate the prevalence of posterior pituitary dysfunction in a large cohort of survivors of TBI. One hundred two consecutive patients (85 males) who suffered severe or moderate TBI were evaluated for diabetes insipidus (DI) at a median of 17 months (range 6-36 months) after the event, using the 8-h water deprivation test (WDT). Their results were compared against normative data obtained from 27 matched, healthy controls. Patients' medical records were retrospectively reviewed for the presence of abnormalities of salt and water balance in the immediate post-TBI period. Twenty-two patients (21.6%) developed DI in the immediate post-TBI period (acute DI group), of whom five had abnormal WDT on later testing. In total, seven patients (6.9%) had abnormal WDT (permanent DI group), five of whom had partial DI. Patients in the acute and permanent DI groups were more likely to have more severe TBI, compared with the rest of the cohort (P < 0.05). In the immediate post-TBI period, 13 patients (12.9%) had syndrome of inappropriate secretion of antidiuretic hormone, which persisted in one patient, and one other patient developed cerebral salt wasting. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone were common in the immediate post-TBI period. Permanent DI was present in 6.9% of patients who survived severe or moderate TBI, which is higher than traditionally thought. Identification of patients with partial posttraumatic DI is important because appropriate treatment may reduce morbidity and optimize the potential for recovery.     

Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury

Pediatric traumatic brain injury (TBI) is a major cause of acquired cognitive dysfunction in children. Hippocampal Brain Derived Neurotrophic Factor (BDNF) is important for normal cognition. Little is known about the effects of TBI on BDNF levels in the developing hippocampus. We used controlled cortical impact (CCI) in the 17 day old rat pup to test the hypothesis that CCI would first increase rat hippocampal BDNF mRNA/protein levels relative to SHAM and Na?ve rats by post injury day (PID) 2 and then decrease BDNF mRNA/protein by PID14. Relative to SHAM, CCI did not change BDNF mRNA/protein levels in the injured hippocampus in the first 2 days after injury but did decrease BDNF protein at PID14. Surprisingly, BDNF mRNA decreased at PID 1, 3, 7 and 14, and BDNF protein decreased at PID 2, in SHAM and CCI hippocampi relative to Na?ve. In conclusion, TBI decreased BDNF protein in the injured rat pup hippocampus 14 days after injury. BDNF mRNA levels decreased in both CCI and SHAM hippocampi relative to Na?ve, suggesting that certain aspects of the experimental paradigm (such as craniotomy, anesthesia, and/or maternal separation) may decrease the expression of BDNF in the developing hippocampus. While BDNF is important for normal cognition, no inferences can be made regarding the cognitive impact of any of these factors. Such findings, however, suggest that meticulous attention to the experimental paradigm, and possible inclusion of a Na?ve group, is warranted in studies of BDNF expression in the developing brain after TBI.     

The history of pituitary dysfunction after traumatic brain injury

Pituitary - To estimate the total number of articles on traumatic brain injury (TBI)-related hypopituitarism and patients (including children and adolescents) with such disorder that were published...     

Predictors of anterior pituitary insufficiency after traumatic brain injury

Background Several studies have reported a high prevalence of hypopituitarism after traumatic brain injury (TBI). Risk stratification is a prerequisite for cost‐effective hormonal screening of these patients. However, it is still unclear which risk factors predispose patients to develop anterior hypopituitarism after TBI. Objective To assess clinical and radiological risk factors for post‐traumatic hypopituitarism. Patients and methods Seventy‐eight consecutive patients (52 men, 26 women; mean age 36·0 years, range 18–65 years) with mild, moderate or severe TBI were studied. Endocrine and clinical parameters were assessed 3 and 12 months after TBI. Results We found diffuse axonal injury, basal skull fracture and older age to be major risk factors of post‐traumatic hypopituitarism. Conclusions We have defined specific risk factors for the development of post‐traumatic hypopituitarism that are consistent with pathophysiological considerations. These findings might help to identify at‐risk patients.     

大鼠创伤性脑损伤后认知行为的变化

目的 建立直接手术损伤大鼠部分脑皮质及海马CA1区的创伤性脑损伤模型,并观察损伤后动物认知行为的改变情况.方法 将大鼠进行脑损伤建模后,于术后11～15 d和26～30 d采用Morris水迷宫的方法评价动物的认知行为变化后,灌杀动物取脑切片,HE染色及尼氏染色观察损伤范围;胶质纤维酸性蛋白(GFAP)免疫组织化学染色观察星型胶质细胞(AST)的活化及胶质瘢痕形成情况;术后5 d行Nestin及GFAP双重免疫荧光染色显示海马内干细胞的激活,并观察损伤边缘的干细胞迁移情况.结果 直接手术损伤部分脑皮质及海马CA1区后,造成了动物认知功能障碍,并且1个月时有自发的认知功能恢复;5 d时星型胶质细胞活化,1个月时胶质瘢痕的形成.结论 本实验采用的模型可成功造成动物认知行为的改变,为组织工程材料的移植治疗脑损伤提供了比较适用的研究模型.     

Evaluation of pituitary function after traumatic brain injury in childhood

Objectives Post‐traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. Design Retrospective exploratory study. Patients: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4–21·7 years) and median (range) interval since injury 4·3 years (1·4–7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. Measurements Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. Results No subject had short stature (mean height SD score +0·50, range −1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri‐pubertal boys (one with slow growth on follow‐up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm . Nine of twenty‐five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH‐stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. Conclusions No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.     

Aerobic capacity and growth hormone deficiency after traumatic brain injury

CONTEXT: GH deficiency occurs in approximately 20% of all individuals who suffer from a moderate to severe traumatic brain injury. OBJECTIVE: This study determined whether GH deficiency secondary to traumatic brain injury had an effect on aerobic capacity. DESIGN: Subjects were screened for GH deficiency by the glucagon stimulation test and performed a maximal treadmill exercise test. SETTING: Patients were studied in the postacute recovery phase after traumatic brain injury. PARTICIPANTS: Thirty-five individuals were studied. Groups were formed as follows: normal GH axis, greater than 8 ng/ml response (n = 12); insufficient, GH 3-8 ng/ml response (n = 11); and deficient, less than 3 ng/ml response (n = 12). INTERVENTION: There was no intervention. MAIN OUTCOME MEASURE: Aerobic capacity was assessed by measuring expired gases during a graded treadmill exercise test. One-way and two-way ANOVAs were carried out on all peak and submaximal cardiorespiratory variables, respectively. Appropriate post hoc comparisons followed as necessary. RESULTS: Significantly higher peak oxygen consumption was found in traumatic brain injury subjects with GH normal vs. GH insufficient and deficient [26.4 +/- 6.9, 20.8 +/- 4.6, and 19.7 +/- 5.0, respectively (P < 0.05)]. Submaximal oxygen consumption was significantly higher in the GH normal group. All other variables were statistically similar. CONCLUSIONS: This study shows that individuals with traumatic brain injury with normal GH secretion have below normal aerobic capacity and those patients who have GH insufficiency/deficiency are further deconditioned. Studies of GH replacement in these subjects should be conducted to assess whether GH therapy can improve cardiorespiratory fitness and prevent secondary disability.     

创伤性脑损伤大鼠脑组织基质金属蛋白酶的表达

目的研究创伤性脑损伤大鼠脑组织基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达规律及其参与创伤性脑水肿形成的作用机制。方法选择SD大鼠115只,随机分为假手术组(23只)和创伤组(92只),创伤组又分为6h,1、3和5天4个时间点,每个时间点的大鼠23只,建立大鼠创伤性脑损伤模型,采用免疫组织化学方法检测脑组织MMP-2和MMP-9的表达;并观察脑组织含水量、血脑屏障通透性、脑微血管分布密度及超微结构等变化。结果创伤组6h创伤灶周围脑组织中即开始出现MMP-2和MMP-9的表达,MMP-9表达水平在1天达高峰,MMP-2的表达则在5天达到较高水平,与假手术组比较,差异有显著性意义(P<0.01)。MMP-9表达与脑组织伊文思蓝含量的变化呈正相关;MMP-2在创伤后1、3和5天的表达与创伤灶周围微血管面积密度变化一致。结论MMP-2和MMP-9参与了创伤性脑损伤后血脑屏障破坏、脑水肿形成、炎性反应等过程,并在损伤修复中可能有重要作用。     

Hypopituitarism following traumatic brain injury.

Recent studies have demonstrated that hypopituitarism, and in particular growth hormone (GH) deficiency, is common among survivors of traumatic brain injury (TBI) tested several months or years following head trauma. In addition, it has been shown that post-traumatic neuroendocrine abnormalities occur early and with high frequency. These findings may have significant implications for the recovery and rehabilitation of patients with TBI. Although data emerging after 2000 demonstrate the relevance of the problem, in general there is a lack of awareness in the medical community about the incidence and clinical repercussions of the pathology. Most, but not all, head trauma associated with hypopituitarism is the result of motor accidents. The subjects at risk are those who have suffered moderate-to severe head trauma although mild intensity trauma may precede hypopituitarism also. Particular attention should be paid to this problem in children and adolescents. Onset of pituitary deficits can evolve over years following injury. For the assessment of the GH-IGF axis in TBI patients, plasma IGF-I concentrations, plus dynamic GH testing is indicated. Some degree of hypopituitarism is found in 35-40% of TBI patients. Among multiple pituitary deficits, the most common ones were GHD and gonadotrophin deficiency. In most series 10-15% presented with severe GHD and 15% with partial GHD after stimulating GH secretion confirming that the most common isolated deficit is GHD. Psychometric evaluation together with neurocognitive testing shows variability of disability and the possibility that untreated TBI induced hypopituitarism contributes to the chronic neurobehavioral problems seen in many head-injured patients warrants consideration. Preliminary data, from small pilot, open-label studies show that subjects treated with GH experience significant improvements in concentration, memory, depression, anxiety and fatigue. In conclusion, pituitary failure can occur even in minor head injuries and is poorly recognized.