构建库欣综合征术前疾病状态评估体系与11β-HSD2功能研究
发布时间：2018-08-21 10:42
【摘要】：目的：第一部分,本研究通过深入分析糖皮质激素增多对机体的影响及库欣综合征复杂的临床症状及体征,创新性地构建库欣综合征术前疾病状态评估体系,为库欣患者围手术期的诊疗提供客观依据,减少围手术期并发症的发生；第二部分,通过分析不同类型库欣综合征患者尿液中游离皮质醇(UFF)与游离皮质酮(UFE)的比值,反应体内11β羟基类固醇脱氢酶(11β-HSD2)的功能水平,进一步揭示ACTH非依赖性综合征库欣患者低血钾的发病机制。 材料和方法：第一部分,分析皮质醇增多对机体影响所产生的各种症状、体征和实验室检查异常形成条目,将条目归纳为皮肤、眼睛、中枢神经系统、骨骼和肌肉系统、新陈代谢及内分泌系统、心血管系统、免疫系统、性腺系统8大项,每个条目赋予相应的分数,初步构建库欣综合征疾病状态的评估量表。实验一,通过792例库欣综合征患者进行库欣综合征疾病状态评估量表的验证性因子分析；实验二,运用评估量表对86例库欣综合征患者和45肾上腺无功能腺瘤患者进行评估分析,通过Cronbach's a和皮尔森相关系数分析等统计方法验证量表内部条目一致性以及相关性,同时通过ROC曲线分析方法对量表评分进行等级划分。第二部分,运用液相色谱联合串联质谱分析(LC-MS/MS)方法对以下4组研究对象24小时尿液中游离皮质醇(UFF)和皮质酮(UFE)的含量进行测算,A组(n=6),异位ACTH综合征患者；B组(n=6),血钾正常肾上腺库欣腺瘤患者；C组(n=5),低血钾肾上腺库欣腺瘤患者；D组(n=6),正常人；运用χ2检验对4组研究对象的UFF+UFE总量以及UFF/UFE比值进行组间比较分析。 结果：第一部分,初步构建的库欣综合征疾病状态评估量表经实验一验证分析后,删除皮肤不易愈合、骨坏死、儿童发育迟缓3个载荷量差的条目,最终形成的评估量表包括共29个条目,6个条目测量皮肤系统表征,2个条目测量眼睛,2个条目测量中枢神经系统,2个条目测量骨骼和肌肉,8个条目测量新陈代谢及内分泌系统,3个条目测量心血管系统,2个条目测量免疫系统,4个条目测量性腺功能异常：总分值115分,量表结构的一致性和相关性良好；ROC曲线评估得分61分以下为轻中度,61分以上为重度患者。第二部分,通过LC-MS/MS对4组研究对象UFF以及UFE定量分析得出：A组UFF+UFE为2787.33±819.58ng/ml, UFF/UFE为2.98±0.35；B组UFF+UFE为688.67±163.46ng/ml, UFF/UFE为1.03±0.42；C组UFF+UFE为697.40±120.28ng/ml, UFF/UFE为2.24±0.37；D组UFF+UFE为70.18±26.67ng/ml, UFF/UFE为0.42±0.20；B组合C组UFF+UFE无统计差异,但C组UFF/UFE比值显著高于B组(P0.001),提示C组低血钾肾上腺库欣腺瘤患者存在11β-HSD2酶功能缺陷。 结论：第一部分,本研究构建的库欣综合征疾病状态评估量表结构效度、条目一致性及相关性均良好,能够应用于临床对需进行外科治疗的库欣综合征患者进行术前疾病状态评估,并根据得分划分轻中重等级,指导围手术期治疗；第二部分,部分ACTH非依赖性库欣综合征患者由于自身体内11β-HSD2酶功能缺陷,无法有效地将有活性的皮质醇(cortisol)转化为无活性的皮质酮(cortisone)出现典型低血钾等盐皮质激素过多表现。
[Abstract]:Objective: In the first part of this study, through in-depth analysis of the effects of increased glucocorticoids on the body and the complex clinical symptoms and signs of Cushing's syndrome, we innovatively constructed a preoperative disease assessment system for Cushing's syndrome, to provide objective basis for the perioperative diagnosis and treatment of Cushing's patients, and to reduce the incidence of perioperative complications. In the second part, the ratio of urinary free cortisol (UFF) to free corticosterone (UFE) in patients with different types of Cushing's syndrome was analyzed to reflect the functional level of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2) in vivo, and to further reveal the pathogenesis of hypokalemia in Cushing's patients with ACTH-independent syndrome.
Materials and Methods: In the first part, the symptoms, signs and abnormal laboratory examinations of the effects of increased cortisol on the body were analyzed. The items were classified as skin, eyes, central nervous system, skeletal and muscular system, metabolism and endocrine system, cardiovascular system, immune system and gonad system. Objective To construct a disease status assessment scale for Cushing's syndrome with corresponding scores. In experiment 1, 792 patients with Cushing's syndrome were assessed with confirmatory factor analysis of the disease status assessment scale for Cushing's syndrome; in experiment 2, 86 patients with Cushing's syndrome and 45 patients with adrenal nonfunctional adenoma were assessed with the assessment scale. The results were analyzed by Cronbach's A and Pearson's correlation coefficient analysis to verify the consistency and correlation of the internal items of the scale, and the rating of the scale was graded by ROC curve analysis. In the second part, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the 24-hour urine samples of the following four groups of subjects. Free cortisol (UFF) and corticosterone (UFE) were measured in group A (n = 6), ectopic ACTH syndrome; group B (n = 6), normal potassium adrenal Cushing adenoma; group C (n = 5), hypokalemic adrenal Cushing adenoma; group D (n = 6), normal subjects; total UFF + UFE and UFF / UFE ratio were measured by_2 test. Comparative analysis.
RESULTS: In the first part, after the validation and analysis of the preliminary constructed disease status assessment scale for Cushing's syndrome, three items with poor load were deleted, including skin non-healing, osteonecrosis and child growth retardation. The final assessment scale consisted of 29 items, 6 items to measure skin system characterization, 2 items to measure eyes and 2 items to measure children's growth retardation. Central nervous system was measured, 2 items were used to measure skeleton and muscle, 8 items were used to measure metabolism and endocrine system, 3 items were used to measure cardiovascular system, 2 items were used to measure immune system, 4 items were used to measure gonadal dysfunction: the total score was 115 points, the consistency and correlation of the scale structure were good; the ROC curve score was 61 points below. In the second part, the quantitative analysis of UFF and UFE in four groups by LC-MS/MS showed that UFF+UFE in group A was 2787.33+819.58ng/ml, UFF/UFE was 2.98+0.35, UFF+UFE in group B was 688.67+163.46ng/ml, UFF/UFE was 1.03+0.42, UFF+UFE in group C was 697.40+120.28ng/ml and UFF/UFE was 2.24+0.37. UFE was 70.18 65507
Conclusion: In the first part, the structure validity, item consistency and correlation of the disease status assessment scale for Cushing's syndrome constructed in this study are good. It can be used to evaluate the preoperative disease status of patients with Cushing's syndrome who need surgical treatment in clinic, and according to the score, it can be divided into different grades to guide the perioperative treatment. In part, some ACTH-independent Cushing's syndrome patients can not effectively convert active cortisol into inactive cortisone due to their own 11-beta-HSD2 enzyme dysfunction, resulting in typical hypokalemia and hypercortisone.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R699.3
本文编号：2195452
[Abstract]:Objective: In the first part of this study, through in-depth analysis of the effects of increased glucocorticoids on the body and the complex clinical symptoms and signs of Cushing's syndrome, we innovatively constructed a preoperative disease assessment system for Cushing's syndrome, to provide objective basis for the perioperative diagnosis and treatment of Cushing's patients, and to reduce the incidence of perioperative complications. In the second part, the ratio of urinary free cortisol (UFF) to free corticosterone (UFE) in patients with different types of Cushing's syndrome was analyzed to reflect the functional level of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD2) in vivo, and to further reveal the pathogenesis of hypokalemia in Cushing's patients with ACTH-independent syndrome.
Materials and Methods: In the first part, the symptoms, signs and abnormal laboratory examinations of the effects of increased cortisol on the body were analyzed. The items were classified as skin, eyes, central nervous system, skeletal and muscular system, metabolism and endocrine system, cardiovascular system, immune system and gonad system. Objective To construct a disease status assessment scale for Cushing's syndrome with corresponding scores. In experiment 1, 792 patients with Cushing's syndrome were assessed with confirmatory factor analysis of the disease status assessment scale for Cushing's syndrome; in experiment 2, 86 patients with Cushing's syndrome and 45 patients with adrenal nonfunctional adenoma were assessed with the assessment scale. The results were analyzed by Cronbach's A and Pearson's correlation coefficient analysis to verify the consistency and correlation of the internal items of the scale, and the rating of the scale was graded by ROC curve analysis. In the second part, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the 24-hour urine samples of the following four groups of subjects. Free cortisol (UFF) and corticosterone (UFE) were measured in group A (n = 6), ectopic ACTH syndrome; group B (n = 6), normal potassium adrenal Cushing adenoma; group C (n = 5), hypokalemic adrenal Cushing adenoma; group D (n = 6), normal subjects; total UFF + UFE and UFF / UFE ratio were measured by_2 test. Comparative analysis.
RESULTS: In the first part, after the validation and analysis of the preliminary constructed disease status assessment scale for Cushing's syndrome, three items with poor load were deleted, including skin non-healing, osteonecrosis and child growth retardation. The final assessment scale consisted of 29 items, 6 items to measure skin system characterization, 2 items to measure eyes and 2 items to measure children's growth retardation. Central nervous system was measured, 2 items were used to measure skeleton and muscle, 8 items were used to measure metabolism and endocrine system, 3 items were used to measure cardiovascular system, 2 items were used to measure immune system, 4 items were used to measure gonadal dysfunction: the total score was 115 points, the consistency and correlation of the scale structure were good; the ROC curve score was 61 points below. In the second part, the quantitative analysis of UFF and UFE in four groups by LC-MS/MS showed that UFF+UFE in group A was 2787.33+819.58ng/ml, UFF/UFE was 2.98+0.35, UFF+UFE in group B was 688.67+163.46ng/ml, UFF/UFE was 1.03+0.42, UFF+UFE in group C was 697.40+120.28ng/ml and UFF/UFE was 2.24+0.37. UFE was 70.18 65507
Conclusion: In the first part, the structure validity, item consistency and correlation of the disease status assessment scale for Cushing's syndrome constructed in this study are good. It can be used to evaluate the preoperative disease status of patients with Cushing's syndrome who need surgical treatment in clinic, and according to the score, it can be divided into different grades to guide the perioperative treatment. In part, some ACTH-independent Cushing's syndrome patients can not effectively convert active cortisol into inactive cortisone due to their own 11-beta-HSD2 enzyme dysfunction, resulting in typical hypokalemia and hypercortisone.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R699.3
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相关期刊论文 前2条
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2 张超;徐燕;陈平雁;;探索性因子分析与验证性因子分析在量表研究中的比较与应用[J];南方医科大学学报;2007年11期
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