The Clinical Classification And Basic Research Of Primary Aldosteronism

Part 1 The clinical classification of primary aldosteronismPart 1.1 The clinical value of bilateral adrenal venous sampling in the differential diagnosis of primary aldosteronism 【Objective】To evaluate the accuracy and clinical value of adrenal venous sampling(AVS)in the differential diagnosis of primary aldosteronism(PA).【Methods】418 PA patients confirmed by saline infusion test were included in the study.According to pathology and follow up,179 patients were diagnosed as APA,86 as UAH and 153 as IHA.All patients underwent adrenal CT scan,posture test and AVS.ROC analysis was used to compare the sensitivity and specificity of four different AVS index in the differential diagnosis of PA.【Results】The accuracy of AVS to diagnose unilateral PA is 93.3%,much higher than adrenal CT scan(66.7%)and posture test(61.3%).As for different AVS index,Ald/Cor(A:U)was the best marker in the diagnosis of unilateral PA.The optimal is 2.3,which displayed sensitivity of 95.1% and specificity of 90.2%,positive predictive value(PPV)of 94.4% and negative predictive(NPV)of 91.4%.When Ald/Cor(A:U)>10,the specificity and PPV were 100%.【Conclusion】AVS is more accurate and more reliable than adrenal CT scan and posture test in determining the unilateral and bilateral PA.Part 1.2 Diagnostic values of ACTH stimulation test in determining the subtypes of primary aldosteronism 【Objective】To evaluate the diagnostic value of ACTH stimulation test under 1mg dexamethasone suppression(DST)in the differential diagnosis of PA.【Methods】95 patients with PA were included.According to AVS and histopathology,39 patients was diagnosed as IHA,37 as APA and 19 as UAH.ACTH stimulation test and 1mg DST were performed in all patients.ROC analysis was used to compare the sensitivity and specificity of each time point during ACTH stimulation test to distinguish unilateral from bilateral PA.【Results】During ACTH stimulation test,aldosterone levels in APA and UAH were similar(P>0.05),but higher than those in IHA(P<0.001).Furthermore,stimulated aldosterone levels of unilateral PA were significantly higher those of bilateral PA.ROC analysis showed that aldosterone levels after ACTH stimulation were effective for determining the unilateral and bilateral PA.The diagnostic accuracy was highest at 120 min after ACTH stimulation test,the optimal cutoff value is 77.90ng/dL,with sensitivity of 76.8% and specificity of 87.2%,positive predictive value(PPV)of 89.6% and negative predictive(NPV)of 72.3%.【Conclusion】As a noninvasive method,ACTH stimulation test under 1mg DST with high sensitivity and specificity is useful to determine the subtype of PA,especially in unilateral and bilateral PA.Part 2 Efficacy and Safety of spironolactone in mono therapy versus low dose spironolactone in combined therapy for the treatment of idiopathic hyperaldosteronism 【Objective】The aim of this study was to compare the efficacy and safety of spironolactone in mono-therapy versus low dose spironolactone in combined-therapy for the treatment of idiopathic hyperaldosteronism(IHA).【Methods】This was a prospective and randomized study.After 2-week wash out period,48 patients confirmed IHA were assigned to either spironolactone mono-therapy group and low dose spironolactone combined-therapy group.All patients underwent adrenal venous sampling and showed no lateralization.The primary outcome was the percentage of patients with BP<140/90 mmHg at 16 weeks.Other observation was the occurrence of gynecomastia,renal insufficiency and hyperkalemia.【Results】At 16 weeks,the patients’ BP were normalized in 17 out of 24 patients(70.8%)in mono-therapy group and in 24 out of 25 patients(95.8%)in combined-therapy group(P<0.05).There was no hyperkalemia in each group.2 patients and 5 patients in mono-therapy group were observed renal insufficiency and gynecomastia,respectively.No patients in combined-therapy group presented with renal insufficiency or gynecomastia.【Conclusion】Low dose spironolactone combined-therapy group is more effective to control BP and hypokalemia without increase the occurrence of renal insufficiency or gynecomastia.Part 3 Somatic KCNJ5 mutation in aldosterone-producing adenoma and unilateral hyperplasia by whole exome sequencing 【Objective】Whole exome sequencing was used to screen the KCNJ5 mutation of APA and UAH,and further to discuss the clinical features and pathogenesis of two phenotype of unilateral PA.【Methods】140 PA patients were included in the study.According to pathology and follow up,91 were diagnosed as APA and 49 as UAH.We identified KCNJ5 mutations by whole exome sequencing to compare the somatic mutation rates of APA and UAH.Furthermore,we compared the clinical features with and without KCNJ5 mutations and to analyze the phenotype and genotype.【 Results 】 Among the 140 patients,115 were identified with KCNJ5 somatic mutations(82.1%),including 3 previously reported(57 with p.G151 R,53 with p.L168 R and 5 with p.E145Q).We found 79(86.8%)somatic KCNJ5 mutations in APAs and 36(73.5%)in UAHs,which was no significant difference between these two groups.KCNJ5 mutations were more prevalent in female patients and were younger,with shorter duration of hypertension,lower renin activity and higher post-saline aldosterone levels.We also compared the clinical features of G151 and L168 R,patients with L168 R were younger and were significantly more prevalent in females,of which the probably pathogenesis was unknown.【Conclusion】Somatic KCNJ5 mutations are more popular in Chinese patients with PA.Patients in APAs and UAHs share similar KCNJ5 mutations and further study should be conducted to investigate the relation between genotype and phenotype.