Screening For Primaryaldosteronism On And Off Interfering Medications

Objective:According to the current guidelines,before the primary aldosteronism(PA)screening test,ARR,the antihypertensive medications that affect the aldosterone/renin ratio(ARR)should be withdrawn or switched into no interfering medications(washout period).Therefore,this study aims to investigate whether not performing a drug washout(medication status)would affect the screening accuracy of ARR,especially the sensitivity.Methods:In this prospective study,patients under common antihypertensive medication therapy which including angiotensin converting enzyme inhibitors(ACEi),angiotensin Ⅱ receptor blockers(ARB),β blockers,Calcium channel blockers(CCB)and diuretics would be invited to enter the study.Patients performed ARR before and after washout and performed at least one confirmatory test to diagnose PA.αblockers and/or non dihydropyridine calcium channel blockers(CCB)are allowed as substitutes during wash out period,which lasts for 2-4 weeks.Evaluating the diagnostic accuracy of ARR during medication by the receiver operating characteristic curve(ROC),and calculating the sensitivity and specificity of different cut-off values of ARR before and after wash out.Results:A total of 513 subjects were included,of which 331 were met the inclusion criteria,including 206 patients with essential hypertension(EH)and 125 patients with PA.There was no significant difference in the area under ROC(AUC)between the medication group and wash out group(0.78 vs 0.84,p=0.07).The ARR cut-off value after wash out is 20 pg/μ IU,and the sensitivity and specificity were 0.82 and 0.66,respectively.When the cut-off value of ARR during the medication period dropped to 10 pg/μ IU,the sensitivity and specificity of this cut-off value were 0.86 and 0.58,respectively.This accuracy is very close to the accuracy when ARR cut-off value is 20 pg/μ IU,after wash out.Conclusion:Common antihypertensive medications affect PA screening,but the diagnose accuracy of ARR have less variation before and after wash out.ARR can be performed during antihypertensive medication,but the cut-off point should be lowered to 10 pg/μIU.Objective:Most guidelines recommend that antihypertensive drugs that significantly affect the aldosterone/renin ratio(ARR)should be withdrew before the confirmatory test of primary aldosteronism(PA),or use antihypertensive medications that have less effect on ARR instead(wash out).However,due to the cumbersome process,medication washout is often hard to complete in practice.The purpose of this study is to explore the impact of antihypertensive drugs on the diagnostic accuracy of captopril challenge test(CCT),and to propose the best cut-off value CCT under medication.Methods:This study performed in a prospective cohort.The subjects was the same cohort in the first chapeter.Patients underwent CCT once before and after drug washout,respectively.CCT or SIT after wash out was regard as the diagnosis evidence of PA.The washout period last for 2-4 weeks,medications was withdrew or using a-blockers and/or non-dihydropyridines(CCBs)as alternative drugs.ROC was used to evaluate the diagnostic performance of CCT was evaluated by ROC,and calculated the sensitivity and specificity of different cut-off value of CCT before and after drug washout.Results:A total of 531 subjects were included,including 341 subjects who met the research protocol,including 213 patients with essential hypertension(EH)and 128 patients with PA.When taking medications,the post-CCT PAC was 94.5(65.1-130)pg/ml,and the result of washout group was 91.2(61.7-134.0)pg/ml,and there was no statistical difference between them.The AUC of medication CCT is 0.82.after washout,when the post-CCT PAC cut-off is 110pg/ml,the sensitivity is 0.72,and the specificity is 0.91;during medication,the sensitivity of the same cut-off valuet is 0.62,and the specificity is 0.82,and have not statistically different to washout result.Conclusion:Common antihypertensive medications have less effect on the results of CCT,and post-CCT PAC have no significant statistical variation before and after washout.Taking medications during CCT have no effects on ites diagnostic efficiency;it is alloewed to performing CCT during medication without washout.Objective:In the aforementioned cohort,we found a case of familial hyperaldosteronism patient with a new mutation of KCNJ5.This study aims to explore the function of the new V99I mutation of KCNJ5 in FH-Ⅲtype.Methods:The clinical data,laboratory examination and imaging examination data of the index case and her mother were recorded.Clarity the type and location of gene mutations by generational sequencing,and summarize a genetic pedigree map according to the history of present illness.Constructing the morphological model of KCNJ5 and the new KCNJ5 mutation plasmid,transfect H295R cells.Exploring the expression level of aldosterone synthase CYP11B2 by Western Blot,and detecting the secretion level of aldosterone in the cell supernatant by mass spectrometry.Investigating the activation of CYP11B2 by the new mutation of KCNJ5 by Luciferase experiment Subactivity regulation.Results:The index case was a patient with PA,and her clinical features were late onset,blood pressure level Ⅱ hypertension without hypokalemia.Her adrenal CT showed unilateral adrenal enlargement;biochemical features showed bilateral dominant secretion,and was sensitive to MRA;The mutation type is KCNJ5 germline mutation,and her mother and son both have the same mutation(c295G>A,pVal99Ile),which is located at the intracellular rectifier potassium ion channel;Luciferase assay shows that the mutation can lead to increased activity of the CYP11B2 promoter in cells.Conclusion:The clinical features of the de novo FH-Ⅲ mutation(KCNJ5,c295G>A,pVal99Il)are late onset,grade Ⅱ hypertension or refractory hypertension,may be accompanied by hypokalemia,and are sensitive to spironolactone treatment.