重度颅脑创伤后垂体功能减退及其预测因子的探讨

Occurrence of hypopituitarism after severe craniocerebral trauma and its predictors

目的探究重度颅脑创伤后垂体功能减退发生情况及其预测因子。方法选取2020年1月至2022年5月山西医科大学第一医院急诊科收治的185例重度颅脑创伤患者,其中男108例,女77例;年龄(51.32±9.34)岁,范围18~79岁。颅脑创伤发生后3~7 d内进行垂体功能评估,统计重度颅脑创伤后垂体功能减退发生情况,根据是否发生垂体功能减退分为减退组(发生垂体功能减退)和未减退组(未发生垂体功能减退)。减退组41例,其中男26例,女15例,年龄(52.76±9.83)岁;未减退组144例,其中男82例,女62例,年龄(50.91±9.27)岁。比较减退组、未减退组临床资料,分析垂体功能减退发生的影响因素,基于相关影响因素构建Logistic预测模型,通过受试者工作特征(receiver operating characteristic,ROC)曲线评价该模型预测重度颅脑创伤后发生垂体功能减退的价值。结果本研究185例重度颅脑创伤患者垂体功能减退发生率为22.16%;减退组入院格拉斯哥昏迷量表(glasgow coma scale,GCS)评分低于未减退组[(6.36±1.04)&(7.48±0.59)分],高压氧治疗占比低于未减退组(21.95%&49.31%),颅内压增高占比高于未减退组(82.93%&49.31%),中线位移≥5 mm占比高于未减退组(78.05%&29.86%),颅底骨折占比高于未减退组(34.15%&17.36%),弥漫性脑水肿占比高于未减退组(19.51%比4.17%),血清脑源性神经细胞营养因子(brain derived neurophic factor,BDNF)高于未减退组[(6.35±1.29)&(4.51±1.06)ng/ml],神经元特异性烯醇化酶(neuronal-specific enolase,NSE)高于未减退组[(33.06±5.42)&(23.15±4.97)μg/L],血管内皮生长因子(vascular epithelial growth factor,VEGF)高于未减退组[(312.07±24.35)&(226.80±20.96)pg/ml],肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)高于未减退组[(281.24±38.91)&(186.55±35.72)ng/L](P值均<0.05);颅内压增高、中线位移≥5 mm、弥漫性脑水肿、血清BDNF、NSE、VEGF、TNF-α水平均为重度颅脑创伤后发生垂体功能减退的独立危险因素,入院GCS评分、高压氧治疗为保护因素(P<0.05)。根据影响因素构建Logistic预测模型为:Logit(P)=5.264-0.880×入院GCS评分+1.618×颅内压增高+1.941×中线位移≥5 mm+1.289×弥漫性脑水肿+1.306×BDNF+1.426×NSE+1.781×VEGF+1.615×TNF-α-0.758×高压氧治疗;该模型预测重度颅脑创伤后发生垂体功能减退的曲线下面积(area under the curve,AUC)为0.930(95%CI为0.883~0.962),预测敏感度、特异度分别为90.24%、89.19%。结论重度颅脑创伤后垂体功能减退发生率较高,颅内压增高、中线位移≥5 mm、弥漫性脑水肿、血清BDNF、NSE、VEGF、TNF-α水平均可作为垂体功能减退的预测因子。

Objective To investigate the occurrence and predictors of hypopituitarism after traumatic brain injury(TBI).Methods A prospective study was conducted on 185 patients with severe TBI in the Emergency Department of the First Hospital of Shanxi Medical University from Jan.2020 to May.2022,of whom 108 were male and 77 were female;age ranged from 18 to 79 years,mean(51.32±9.34)years.Pituitary function was assessed within 3-7 d after the onset of TBI,and the occurrence of hypopituitarism after severe TBI was counted.41 cases in the hypopituitarism group,26 males and 15 females,aged(52.76±9.83)years,were divided into the hypopituitarism group(hypopituitarism occurred)and the non-hypopituitarism group(hypopituitarism did not occur)according to whether hypopituitarism occurred.In the non-decompensated group,there were 144 cases,82 males and 62 females,aged(50.91±9.27)years.The clinical data of the decompensated and non-decompensated groups were compared,and the factors influencing the occurrence of hypopituitarism were analysed,and a logistic prediction model was constructed based on the relevant influencing factors.The value of this model in predicting the occurrence of hypopituitarism after severe TBI was evaluated by using the receiver operating characteristic(ROC)curve.Results The prevalence of hypopituitarism in the 185 patients with severe TBI in this study was 22.16%;the Glasgow coma scale(GCS)score on admission was lower in the decompensated group than in the non-decompensated group[(6.36±1.04)vs(7.48±0.59)],the percentage of hyperbaric oxygen therapy was lower than in the non-decompensated group(21.95%vs 49.31%),the percentage of intracranial pressure(82.93%vs 49.31%),midline displacement≥5 mm(78.05%vs 29.86%),skull base fracture(34.15%vs.17.36%),diffuse cerebral edema(19.51%vs 4.17%),and serum brain derived neurophic factor(BDNF).Brain derived neurophic factor(BDNF)was higher than that in the non-reduced group[(6.35±1.29)ng/ml vs(4.51±1.06)ng/ml],and neuronal-specific enolase(NSE)was higher than that in the non-reduced group[(33.06±5.42)μg/L vs(23.15±4.97)μg/L].(4.97)μg/L].Vascular epithelial growth factor(VEGF)was higher than that in the non-reduced group[(312.07±24.35)pg/ml vs(226.80±20.96)pg/ml],tumor necrosis factor-α(TNF-α)was higher than that in the non-reduced group[(281.24±38.91)ng/L vs(186.91)pg/ml],and tumor necrosis factor-α(TNF-α)was higher than that in the non-reduced group(186.55±35.72)ng/L(all P<0.05).Increased intracranial pressure,midline displacement≥5 mm,diffuse cerebral edema,serum BDNF,NSE,VEGF,and TNF-αlevels were all independent risk factors for the development of hypopituitarism after severe TBI,with admission GCS score and hyperbaric oxygen therapy as protective factors(P<0.05);a logistic prediction model was constructed based on the influencing factors as:Logit(P)=5.264-0.880×admission GCS score+1.618×increased intracranial pressure+1.941×midline displacement≥5 mm+1.289×diffuse cerebral edema+1.306×BDNF+1.426×NSE+1.781×VEGF+1.615×TNF-α-0.758×hyperbaric oxygen therapy;the model predicted the occurrence of severe TBI after the area under the curve(AUC)of hypopituitarism was 0.930(95%CI 0.883-0.962),with a predictive sensitivity and specificity of 90.24%and 89.19%,respectively.Conclusions The incidence of hypopituitarism is higher after severe TBI.Increased intracranial pressure,midline displacement≥5 mm,diffuse cerebral edema,serum BDNF,NSE,VEGF and TNF-αlevels are all used as predictors of hypopituitarism.