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.     

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.     

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

In order to gain further insight into hypopituitarism, that ensues moderate to severe traumatic brain injury (TBI), a group of experts actively working in the field gathered to exchange recent data and concepts. The objective arising from the meeting was to enhance the awareness of both medical specialists and health care administrators on the problem, whose prevalence is higher than previously thought. Guidelines for the diagnosis and management of TBI-mediated hypopituitarism were produced.     

Hypopituitarism induced by traumatic brain injury in the transition phase

Traumatic brain injury (TBI) has been associated with hypopituitarism in general and GH deficiency (GHD) in particular; the consequences of this on growth and development are likely to be critical in children and adolescents in the so-called "transition phase". In order to verify the consequences of TBI on pituitary function in the transition phase, we studied a population of adolescents and young adults 3 and 12 months after brain injury [no. = 23, 9 females, 14 males; age: 16-25 yr; body mass index (BMI): 21.9 +/- 0.6 kg/m2]. At 3 months, hypopituitarism was present in 34.6%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 21.7%, respectively. Diabetes insipidus (DI) was present in 8.6% patients and mild hyperprolactinemia in 4.3%. At 12 months, hypopituitarism was present in 30.3%. Total, multiple and isolated deficits were present in 8.6, 4.3 and 17.4%, respectively. DI was present in 4.3% of patients and mild hyperprolactinemia in 4.3%. Total hypopituitarism was always confirmed at retesting. Multiple and isolated hypopituitarism were confirmed in 0/1 and 2/5, respectively. Two/23 patients showed isolated hypopituitarism at 12 months only; 1 patient with isolated at 3 months showed multiple hypopituitarism at retesting. GHD and secondary hypogonadism were the most common acquired pituitary deficits. These results show the high risk of TBI-induced hypopituitarism also in the transition age. Thus it is recommended that pediatric endocrinologists follow-up pituitary function of children and adolescents after brain injuries.     

Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation

Pituitary dysfunction is now well recognised after traumatic brain injury (TBI) in adults; however, little except anecdotal evidence is known about this potential complication in childhood and adolescence. Histopathological evidence exists for both hypothalamic and pituitary damage, but few data specific to children have been published. We review the available paediatric data, which shows that after both mild and severe TBI, hypopituitarism may occur, with GH and gonadotrophin deficiencies appearing to be most common. Precocious puberty has also been documented. Road-traffic accidents, falls, sport and child abuse are the most common aetiological factors for paediatric TBI. There are no published data on the incidence or prevalence, neither within a population of children with TBI, of hypopituitarism, nor on its natural history or response to hormone replacement. We urge paediatric endocrinologists, in collaboration with adult endocrinologists, to perform formal prospective research studies in patients suffering from TBI to clarify these questions.     

Hypopituitarism after acute brain injury

Acute brain injury has many causes, but the most common is trauma. There are 1.5–2.0 million traumatic brain injuries (TBI) in the United States yearly, with an associated cost exceeding $10 billion. TBI is the most common cause of death and disability in young adults less than 35 years of age. The consequences of TBI can be severe, including disability in motor function, speech, cognition, and psychosocial and emotional skills. Recently, clinical studies have documented the occurrence of pituitary dysfunction after TBI and another cause of acute brain injury, subarachnoid hemorrhage (SAH). These studies have consistently demonstrated a 30–40% occurrence of pituitary dysfunction involving at least one anterior pituitary hormone following a moderate to severe TBI or SAH. Growth hormone (GH) deficiency is the most common pituitary hormone disorder, occurring in approximately 20% of patients when multiple tests of GH deficiency are used. Within 7–21 days of acute brain injury, adrenal insufficiency is the primary concern. Pituitary function can fluctuate over the first year after TBI, but it is well established by 1 year. Studies are ongoing to assess the effects of hormone replacement on motor function and cognition in TBI patients. Any subject with a moderate to severe acute brain injury should be screened for pituitary dysfunction.     

重型颅脑损伤的预后影响因素分析

目的研究影响重型颅脑损伤（TBI）患者预后的相关因素,建立简便、可靠、临床操作性强的TBI患者预后模型,提高重型颅脑损伤的治疗水平。方法回顾性分析236例重型TBI患者的临床资料。将脑疝、CT环池形态、患者年龄、GCS及手术方式作为观察指标,采用χ2检验及多因素Logistic回归分析。患者出院时进行预后分组,采用GCS分级标准,Ⅰ～Ⅱ级患者视为预后不良,Ⅲ～Ⅴ级患者视为预后良好。结果 236例重型TBI患者预后不良129例（54.66%）,其中死亡81例（34.32%）;预后良好107例（45.34%）。影响患者预后的因素依次为脑疝、CT环池形态、患者年龄、GCS。最优预后模型方程为In（P/1-P）=1.232×脑疝＋1.176×环池形态＋1.154×年龄-1.064×GCS＋0.012。结论建立了重型TBI患者预后模型。脑疝、CT环池形态、患者年龄、GCS对重型TBI患者的预后有显著影响,尤其是存在脑疝及环池严重受压者预后不良几率增高。     

重型颅脑损伤治疗的研究进展

重型颅脑损伤是神经外科临床常见的危重症之一,其病情复杂,治疗难度较大,病死率高,其治疗主要采取综合的方法。多年来,经国内外神经外科专家的不断探索和研究,对重型颅脑损伤的治疗取得了巨大的成果,但仍存在很大难点和不确定的因素,故其治疗方法仍是神经外科领域目前的研究课题。该文主要就近年来国内外重型颅脑损伤治疗的研究进展进行综述。     

急性重度脑外伤患者自主神经功能变化的研究

为探讨急性重度脑外伤（ASTBI）患者是否存在自主神经（ANS）功能障碍及其临床意义,对30例ASIBI患者（ASTBI组,GCS评分≤8分）于入院1周内进行24小时心率变异性（HRV）检测,动态心电图分析系统自动计算HRV各项指标（包括时域、频域和非线性分析）,绘制HRV直方图、散点图,并与31例正常人（对照组）进行比较。结果 ASTBI组HRV多数指标均明显降低（P＜0．05－0．001）;HRV直方图、散点图;均有特 征性改变,存活者和死亡者的HRV时域分析、频域分析各项指标比较有统计学意义。认为HRV能定量、全面、直观地反映ASTBI患者交感神经和迷走神经的功能状态;ASTBI患者存在明显的ANS功能障碍;ANS功能障碍与病情严重性呈正相关,且常直接影响预后。     

Posterior pituitary dysfunction following traumatic brain injury: review

Pituitary - Neurohypophysial dysfunction is common in the first days following traumatic brain injury (TBI), manifesting as dysnatremia in approximately 1 in 4 patients. Both hyponatremia and...     

Anterior pituitary dysfunction following traumatic brain injury (TBI)

Traumatic brain injury (TBI) is the commonest cause of death and disability in young adults living in industrialized countries. Several recent studies have convincingly shown that anterior hypopituitarism is a common complication of head trauma with a prevalence of at least 25% among long-term survivors. This is a much higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. These findings raise important questions about the potential contribution of PTHP to the high physical and neuropsychiatric morbidity seen in this group of patients. In this review, we examine the published reports on the neuroendocrine abnormalities in TBI patients and highlight new data that give novel insights into the natural history of this disorder. We discuss the potential contribution of PTHP to recovery and rehabilitation after injury and the need for the identification and the appropriate and timely management of hormone deficiencies to optimize patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.     

大鼠创伤性脑损伤后肠黏膜屏障的应激性变化

目的探讨创伤性脑损伤后大鼠肠黏膜屏障的应激性变化及其发生的形态学基础。方法雄性Wistar大鼠64只,均分为创伤性脑损伤组和假手术对照组,再分别按术后6、12、24和48 h时相点分为4个亚组(n=8);偶氮显色法鲎实验定量测定门静脉血内毒素水平;荧光显微镜检测肠系膜淋巴结、肝、脾、胰、肺和肾组织匀浆中标记的大肠杆菌移位率;观察肠黏膜组织病理及扫描和透射电镜下超微结构的变化。数据采用t检验。结果损伤后6 h,脑损伤但大鼠内毒素水平即开始升高,为(0.382±0.014)Eu/ml,12 h为(0.466±0.018)Eu/ml,24 h达高峰,至(0.478±0.029)Eu/ml,此后回落, 48 h为(0.412±0.036)Eu/ml,仍未降至正常,与对照组各时相点内毒素水平(0.102±0.007、0.114±0.021、0.112±0.018、0.108±0.011)比较,差异有统计学意义(P值均<0.05);多脏器荧光标记检出大肠杆菌的大鼠数均比对照组明显升高(P<0.05);光学显微镜下脑损伤组大鼠肠黏膜上皮细胞受损;透射电镜下可见细胞间紧密连接较对照组增宽。结论大鼠创伤性脑损伤后早期肠黏膜屏障功能即受损,肠黏膜通透性增高,细胞间紧密连接增宽可能是其形态学基础。     

重型颅脑损伤中枢性呼吸衰竭机械通气时机的分析

目的探讨机械通气时机对重型颅脑损伤并中枢性呼吸衰竭患者呼吸功能恢复和预后的影响。方法48例重型颅脑损伤接受呼吸机通气治疗患者,比较在出现潜在的呼吸衰竭前和后,使用机械通气治疗前后血气分析指标、呼吸办学指标的变化及治疗后一个月的生存率及格拉斯哥预后评分（GOS）。结果两组患者血气分析指标和呼吸力学指标均有不同程度的改善。早期机械通气治疗组的机械通气时间（4．5±2．5）天,短于晚期治疗组（8．6±4．7）天,脱机率为70．8％,一个月后生存率为75％,GOS评分优于晚期治疗组。结论早期机械通气治疗可尽早改善重型颅脑损伤患者的低氧血症、降低病死率、改善预后。     

重症监测技术在重型创伤性颅脑损伤的应用

重型创伤性颅脑损伤（STBI）是神经外科领域和现代社会共同面临的难题,是儿童和年轻人死亡的主要原因。随着重症监测技术的发展,STBI患者的预后有了显著的改善。本文从临床实践结合国内外的研究进展,描述颅内压监测（ICP）、颈静脉球静脉血氧饱和度（SjvO2）、脑组织氧分压（PbtO2）、脑微量透析（CMD）、经颅多普勒超声（TCD）、电生理监测、近红外光谱（NIRS）和大脑温度等重症监测技术在STBI的应用,为临床上根据患者的不同病情选择合适的监测技术提供参考,以期更好地改善STBI患者的预后。     

Hypopituitarism following radiotherapy

Deficiencies in anterior pituitary hormones secretion ranging from subtle to complete occur following radiation damage to the hypothalamic-pituitary (h-p) axis, the severity and frequency of which correlate with the total radiation dose delivered to the h-p axis and the length of follow up. Selective radiosensitivity of the neuroendocrine axes, with the GH axis being the most vulnerable, accounts for the high frequency of GH deficiency, which usually occurs in isolation following irradiation of the h-p axis with doses less than 30 Gy. With higher radiation doses (30-50 Gy), however, the frequency of GH insufficiency substantially increases and can be as high as 50-100%. Compensatory hyperstimulation of a partially damaged h-p axis may restore normality of spontaneous GH secretion in the context of reduced but normal stimulated responses; at its extreme, endogenous hyperstimulation may limit further stimulation by insulin-induced hypoglycaemia resulting in subnormal GH responses despite normality of spontaneous GH secretion in adults. In children, failure of the hyperstimulated partially damaged h-p axis to meet the increased demands for GH during growth and puberty may explain what has previously been described as radiation-induced GH neurosecretory dysfunction and, unlike in adults, the ITT remains the gold standard for assessing h-p functional reserve. Thyroid-stimulating hormone (TSH) and ACTH deficiency occur after intensive irradiation only (>50 Gy) with a long-term cumulative frequency of 3-6%. Abnormalities in gonadotrophin secretion are dose-dependent; precocious puberty can occur after radiation dose less than 30 Gy in girls only, and in both sexes equally with a radiation dose of 30-50 Gy. Gonadotrophin deficiency occurs infrequently and is usually a long-term complication following a minimum radiation dose of 30 Gy. Hyperprolactinemia, due to hypothalamic damage leading to reduced dopamine release, has been described in both sexes and all ages but is mostly seen in young women after intensive irradiation and is usually subclinical. A much higher incidence of gonadotrophin, ACTH and TSH deficiencies (30-60% after 10 years) occur after more intensive irradiation (>60 Gy) used for nasopharyngeal carcinomas and tumors of the skull base, and following conventional irradiation (30-50 Gy) for pituitary tumors. The frequency of hypopituitarism following stereotactic radiotherapy for pituitary tumors is mostly seen after long-term follow up and is similar to that following conventional irradiation. Radiation-induced anterior pituitary hormone deficiencies are irreversible and progressive. Regular testing is mandatory to ensure timely diagnosis and early hormone replacement therapy.     

强化胰岛素治疗在重型颅脑损伤中的临床应用价值探讨

目的：探讨强化胰岛素治疗（intensive insulin therapy,IIT）在重型颅脑损伤（severe traumatic brain injury,sTBI）中的临床应用价值。方法对200例sTBI患者（GCS评分3～8分）,入院后随机分为IIT组100例及常规胰岛素治疗（conventional insulin treatment ,CIT）组100例。 IIT组血糖（blood glucose,BG）控制在3.9～6.1 mmol／L,CIT组血糖控制在8.3～10.1 mmol／L。患者入院后即开始采用持续静脉泵入胰岛素对血糖进行控制,记录两组患者平均血糖水平、胰岛素用量、低血糖发生率,于伤后6个月时根据GOS评估法判断疗效（分为良好、中残、重残、植物生存和死亡）。结果治疗期IIT组BG低于CIT组（ P＜0.01）,低BG发生率、单位时间胰岛素用量均高于CIT组（ P＜0.05或P＜0.01）。伤后6个月,两组在良好、中残、重残、植物生存和死亡例数比较差异无统计学意义（ P＞0.05）。结论强化胰岛素治疗并不能改善sTBI的预后,且增加了低BG发生率,血糖控制在8.3～10.1 mmol／L是比较理想的水平。     

氧化应激在大鼠创伤性脑损伤后应激性肝损害中的作用

目的:探讨氧化应激(OS)在大鼠创伤性脑损伤(TBI)后应激性肝损害(HSI)中的作用.方法:用改良Allen法建立TBI模型.40只健康Wister大鼠随机分为5组,正常对照组、颅脑致伤后6、12、24、48 h时相组.酶学法检测血清ATL和AST水平,ABC-ELISA法测定血清TNF-α水平.硫代巴比妥酸法测定MDA水平变化,化学发光法测定SOD水平变化.光镜及电镜下观察肝脏组织学改变.结果:颅脑致伤后12 h,各组血ALT和AST、TNF-α水平及肝组织MDA明显增加,肝组织SOD显著减少,与对照组比较差异均显著(252.92±56.29 vs 41.17±7.88;283.12±45.28vs 45.22±6.57;1138.27±212.02 vs 210.56±28.22;15.21±0.36 vs 6.14±0.25;78.13±3.12vs 135.58±5.58,P<0.01或0.05);TBI各组光镜和电镜可观察到肝组织不同程度受损.结论:TBI后早期可出现HSI,OS可能参与了其发病过程.     

Calponin and caldesmon cellular domains in reacting microvessels following traumatic brain injury

Calponin (Cp) and caldesmon (Cd) are actin-binding proteins involved in the regulation of smooth muscle (SM) tone during blood vessel contraction. While in vitro studies have reported modifications of these proteins during vessel contractility, their role in vivo remains unclear. Traumatic brain injury (TBI) causes disruption of cerebral microvascular tone, leading to sustained contractility in reacting microvessels and cerebral hypoperfusion. This study aimed to determine the spatial and temporal expressions of Cp and Cd in rat cerebral cortical and hippocampal microvessels post-TBI. Reacting microvessels were analyzed in control, 4, 24, and 48 h post-injury. Single and double immunocytochemical techniques together with semiquantitative analyses revealed a Cp upregulation in SM at all time frames post-TBI; with the protein migrating from SM cytosol to the vicinity of the cell membrane. Similarly, Cd immunoreactivity significantly increased in both SM and endothelial cells (En). However, while Cp and Cd in SM remained elevated, their levels in En returned to normal at 48 h post-TBI. The results suggest that Cp and Cd levels increase while compartmentalizing to specific subcellular domains. These changes are temporally associated with modifications in the cytoskeleton and contractile apparatus of SM and En during blood vessel contractility. Furthermore, these changes may underlie the state of sustained contractility and hypoperfusion observed in reacting microvessels after TBI.