構(gòu)建庫(kù)欣綜合征術(shù)前疾病狀態(tài)評(píng)估體系與11β-HSD2功能研究
發(fā)布時(shí)間：2018-08-21 10:42
【摘要】：目的：第一部分,本研究通過(guò)深入分析糖皮質(zhì)激素增多對(duì)機(jī)體的影響及庫(kù)欣綜合征復(fù)雜的臨床癥狀及體征,創(chuàng)新性地構(gòu)建庫(kù)欣綜合征術(shù)前疾病狀態(tài)評(píng)估體系,為庫(kù)欣患者圍手術(shù)期的診療提供客觀依據(jù),減少?lài)中g(shù)期并發(fā)癥的發(fā)生；第二部分,通過(guò)分析不同類(lèi)型庫(kù)欣綜合征患者尿液中游離皮質(zhì)醇(UFF)與游離皮質(zhì)酮(UFE)的比值,反應(yīng)體內(nèi)11β羥基類(lèi)固醇脫氫酶(11β-HSD2)的功能水平,進(jìn)一步揭示ACTH非依賴(lài)性綜合征庫(kù)欣患者低血鉀的發(fā)病機(jī)制。 材料和方法：第一部分,分析皮質(zhì)醇增多對(duì)機(jī)體影響所產(chǎn)生的各種癥狀、體征和實(shí)驗(yàn)室檢查異常形成條目,將條目歸納為皮膚、眼睛、中樞神經(jīng)系統(tǒng)、骨骼和肌肉系統(tǒng)、新陳代謝及內(nèi)分泌系統(tǒng)、心血管系統(tǒng)、免疫系統(tǒng)、性腺系統(tǒng)8大項(xiàng),每個(gè)條目賦予相應(yīng)的分?jǐn)?shù),初步構(gòu)建庫(kù)欣綜合征疾病狀態(tài)的評(píng)估量表。實(shí)驗(yàn)一,通過(guò)792例庫(kù)欣綜合征患者進(jìn)行庫(kù)欣綜合征疾病狀態(tài)評(píng)估量表的驗(yàn)證性因子分析；實(shí)驗(yàn)二,運(yùn)用評(píng)估量表對(duì)86例庫(kù)欣綜合征患者和45腎上腺無(wú)功能腺瘤患者進(jìn)行評(píng)估分析,通過(guò)Cronbach's a和皮爾森相關(guān)系數(shù)分析等統(tǒng)計(jì)方法驗(yàn)證量表內(nèi)部條目一致性以及相關(guān)性,同時(shí)通過(guò)ROC曲線(xiàn)分析方法對(duì)量表評(píng)分進(jìn)行等級(jí)劃分。第二部分,運(yùn)用液相色譜聯(lián)合串聯(lián)質(zhì)譜分析(LC-MS/MS)方法對(duì)以下4組研究對(duì)象24小時(shí)尿液中游離皮質(zhì)醇(UFF)和皮質(zhì)酮(UFE)的含量進(jìn)行測(cè)算,A組(n=6),異位ACTH綜合征患者；B組(n=6),血鉀正常腎上腺庫(kù)欣腺瘤患者；C組(n=5),低血鉀腎上腺庫(kù)欣腺瘤患者；D組(n=6),正常人；運(yùn)用χ2檢驗(yàn)對(duì)4組研究對(duì)象的UFF+UFE總量以及UFF/UFE比值進(jìn)行組間比較分析。 結(jié)果：第一部分,初步構(gòu)建的庫(kù)欣綜合征疾病狀態(tài)評(píng)估量表經(jīng)實(shí)驗(yàn)一驗(yàn)證分析后,刪除皮膚不易愈合、骨壞死、兒童發(fā)育遲緩3個(gè)載荷量差的條目,最終形成的評(píng)估量表包括共29個(gè)條目,6個(gè)條目測(cè)量皮膚系統(tǒng)表征,2個(gè)條目測(cè)量眼睛,2個(gè)條目測(cè)量中樞神經(jīng)系統(tǒng),2個(gè)條目測(cè)量骨骼和肌肉,8個(gè)條目測(cè)量新陳代謝及內(nèi)分泌系統(tǒng),3個(gè)條目測(cè)量心血管系統(tǒng),2個(gè)條目測(cè)量免疫系統(tǒng),4個(gè)條目測(cè)量性腺功能異常：總分值115分,量表結(jié)構(gòu)的一致性和相關(guān)性良好；ROC曲線(xiàn)評(píng)估得分61分以下為輕中度,61分以上為重度患者。第二部分,通過(guò)LC-MS/MS對(duì)4組研究對(duì)象UFF以及UFE定量分析得出：A組UFF+UFE為2787.33±819.58ng/ml, UFF/UFE為2.98±0.35；B組UFF+UFE為688.67±163.46ng/ml, UFF/UFE為1.03±0.42；C組UFF+UFE為697.40±120.28ng/ml, UFF/UFE為2.24±0.37；D組UFF+UFE為70.18±26.67ng/ml, UFF/UFE為0.42±0.20；B組合C組UFF+UFE無(wú)統(tǒng)計(jì)差異,但C組UFF/UFE比值顯著高于B組(P0.001),提示C組低血鉀腎上腺庫(kù)欣腺瘤患者存在11β-HSD2酶功能缺陷。 結(jié)論：第一部分,本研究構(gòu)建的庫(kù)欣綜合征疾病狀態(tài)評(píng)估量表結(jié)構(gòu)效度、條目一致性及相關(guān)性均良好,能夠應(yīng)用于臨床對(duì)需進(jìn)行外科治療的庫(kù)欣綜合征患者進(jìn)行術(shù)前疾病狀態(tài)評(píng)估,并根據(jù)得分劃分輕中重等級(jí),指導(dǎo)圍手術(shù)期治療；第二部分,部分ACTH非依賴(lài)性庫(kù)欣綜合征患者由于自身體內(nèi)11β-HSD2酶功能缺陷,無(wú)法有效地將有活性的皮質(zhì)醇(cortisol)轉(zhuǎn)化為無(wú)活性的皮質(zhì)酮(cortisone)出現(xiàn)典型低血鉀等鹽皮質(zhì)激素過(guò)多表現(xiàn)。
[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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R699.3
本文編號(hào)：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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R699.3
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
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