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Disease State Evaluation System 11β-HSD2 Function Of Cushing's Syndrome Before Surgery And Construction

Posted on:2015-03-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:P G LianFull Text:PDF
GTID:1264330431972716Subject:Urology
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Objective; First part, cushing’s syndrome is complex disorder resulting from lengthy and inappropriate exposure to excessive concentrations of circulating free glucocorticoids. This study based on researching mechanisms involved in the side effects of glucocorticoids and symptoms and signs of cushing’s syndrome, to construct a preoperative disease state evaluation system of cushing’s syndrome。Second part, the conversion of cortisol, which binds avidly to the mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid function, is predominantly catalyzed by the11β-hydroxysteroid dehydrogenase type2(11β-HSD2). It was the objective of the present study to examine the impact of different forms of glucocorticoid excess on the cortisol/cortisone ratio and to reveal the mechanisms of hypokalemia in cushing’s syndrome patients.Metarial and method:Fist part, criterias from cortisol excess effect resulting variety of symptoms and signs and abnormal laboratory examinations,and criterias categorizes to8items include:eyes, central nervous system, skin, bone and muscle system, metabolic and endocrine systems, cardiovascular system, immune system and gonadal system, each criteria gives corresponding points, the preliminary assessment inventory of cushing’s syndrome disease states. Experiment one, using confirmatory factor analysis evaluates the construct validation of assessment inventory of Cushing’s syndrome disease states, through792cases of patients with Cushing’s syndrome; Experiment two, second validation of the assessment inventory of Cushing’s syndrome disease states.86patients with Cushing’s syndrome and45patients with adrenal non-functional adenoma enrolled, through Cronbach’s a and Pearson correlation coefficient analysis statistical methods, at the same time through the ROC curve analysis method for interval differentiate rating scaleSecond part,urinary free cortisol(UFF) and urinary free cortisone(UFE) were determined in6adults with ectopia ACTH syndrome (group A),6nomal level of serum potassium adults with hypercortisolism due to an adrenal tumor (group B),5hypokalemia adults with hypercortisolism due to an adrenal tumor (group C), and6healthy volunteers(group D), using high-performance liquid chromatography in combination with tandem mass spectrometry (LC-MS/MS).Result:First part,3criterias included disturbed wound healing,osteonecrosis,and children growth retardation were deleted from preliminary assessment inventory of cushing’s syndrome disease states after experimental verification analysis, eventually forming the assessment inventory of29criterias,6criterias measuring skin,2criterias measuring eyes,2criterias measuring the central nervous system,2criterias measuring the bones and muscles,8criterias measuring metabolic and endocrine system,3criterias measuring the cardiovascular system,2criterias measuring the immune system,4criterias measuring gonadal dysfunction, total value of115points.And the consistency and relevance evaluation of assessment inventory presented well,ROC curves indicated the evaluation score below61points for mild-to-moderate, above61points for severe cushing patients.Second part, UFF+UFE results of4groups (A.2787.33±819.58ng/ml, B.688.67±163.46ng/ml, C.697.40±120.28ng/ml, D.70.18±26.67ng/ml), UFF/UFE ratio of4groups (A.2.98±0.35,B.1.03±0.42,C.2.24±0.37,D.), the value of UFF+UFE was no statistical difference between B and C, the ratio of UFF/UFE of C was significant higher than B, that means11β-HSD deficiency in group C.Conclucions:First part, the study indicate that the assessment inventoryof cushing’s syndrome disease state is a valid and reliable clinical method to evaluate preoperative disease state in Cushing’s syndrome, mark off the classification.It may provide a tool for assessing the complex array of signs and symptoms in this condition, direct the surgeon therapy of CS.Second part,the result present that due to11β-HSD2deficiency, the active cortisol can not be transformed to inactive cortisone, some patient with ACTH-independent cushing’s syndrome manifest hypokalemia, like mineralocorticoid excess.
Keywords/Search Tags:cushing’s syndrome, evaluation system, confirmatory factor analysis, 11β-hydroxysteroid dehydrogenase, LC-MS/MS
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