Molecular Diagnosis And Prognostic Evaluation Of Unilateral Primary Aldehydes

H-SCORE OF ALDOSTERONE SYNTHASE IN THE HISTOPATHOLOGICAL DIAGNOSIS OF UNILATERAL PRIMARY ALDOSTERONISMObjective: To assess the diagnostic performance of the H-score of11β-Hydroxylase(CYP11B1)and Aldosterone Synthase(CYP11B2)in the histopathological diagnosis of unilateral primary aldosteronism(UPA).Methods: We retrospectively evaluated 85 cases of aldosterone producing adenoma(APA)and 11 cases of unilateral adrenal hyperplasia(UAH),and use a total of 125 cases of adrenocortical tumor(ACT)such as cortisol-producing adenoma(CPA)and adrenocortical carcinoma(ACC)as control.Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies.The staining was quantified by McCarty’s H-score system.The diagnostic performance was assessed by the receiver operating characteristic curve(ROC).Result: The CYP11B2 staining could effectively localize the site responsible for aldosterone secretion in UPA and to subtype differentiate it histopathologically.The positive rate of CYP11B2 is 92.6% in APA and90.9% in UAH.The H-score of CYP11B2 in the APA group is significantly higher than other ACT groups.The H-score of CYP11B1 is highest in the CPA group and lowest in the ACC group.The area under ROC(AUC)of an increased H-score of CYP11B2(>65)for the diagnosis of APA was0.971(95% CI 0.937-0.990).The AUC of an increased H-score of CYP11B1(>204)for the diagnosis of CPA was 0.725(95% CI0.658-0.786).The AUC of a decreased H-score of CYP11B1(<85)for the diagnosis of ACC was 0.960(95% CI 0.923-0.983).Further subgroup analysis attained similar results.Conclusions: H-score of CYP11B2 are reliable tools for the histopathological diagnosis of UPA.Besides,H-score of CYP11B1 offers some value in the histopathological subtyping of functional benign ACT and malignant ACT.GENETIC MUTATION SEQUENCING IN THE HISTOPATHOLOGICAL DIAGNOSIS OF ALDOSTERONE PRODUCING ADENOMAObjective: To investigated the genetic mutation rate and the clinical,biochemical and immunohistological charcteritics of patients with aldosterone producing adenoma(APA)in a Chinese cohort.Method: The clinical and biochemical datas of 206 patients with APA who received unilateral adrenalectomy and achievied complete biochemical success after surgety were collected.Sanger sequencing were used to identify mutation in the hot-point of KCNJ5,CACNA1 D,ATP1A1,ATP2B3 and CTNNB1 gene.The tumor specimen were stained by11β-Hydroxylase(CYP11B1)and Aldosterone Synthase(CYP11B2)and the staining were quantified by Mc Carty’s H-score system.Results: Mutation were identified in 166 out of 206(80.6%)cases of APA,of which 158 cases were KCNJ5 mutation,2 ATP1A1 mutation,5ATP2B3 mutation,1 CTNNB1 mutation.Compared with those without gene mutation,APA with gene mutation were younger,more frequently female,has a shorter duration of hypertension,a lower BMI,a higher systolic and diastolic blood pressure.Meanwhile,those with gene mutation has a lower serum potassium,a higher aldosterone to rennin ratio and a higher plasma concentration of aldosterone(PAC)after saline infusion test.Subgroup analysis revealed that,compared with those with ATPase (ATP1A1 and ATP2B3)mutation,APA with KCNJ5 mutation were younger,has a shorter duration of hypertension,a higher systolic blood pressure,a higher PAC after saline infusion test,a higher tumor diameter and a lower rate of left ventricular hypertrophy.The H-score of CYP11B1 were significantly higher [160.0(127.5,193.5)vs.80.0(27.5,152.3),p=0.020]and the H-score of CYP11B2 were significantly lower [155.0(123.0,190.0)vs.240.0(140.0,270.0),p < 0.001] in APA with KCNJ5 mutation than those with ATPase mutation.Conclusion: The mutation rate is as high as 80.6% in Chinese patients with APA and the type of genetic mutation is closely correlated with the clinical,biochemical and immunohistological phenotype.DEVELOPMENT AND VALIDATION OF A NOMOGRAM-BASED PREOPERATIVE SCORE FOR PREDICTING HYPERTENSION REMISSION IN UNILATERAL PRIMARY ALDOSTERONISMObjective: To develop and validate a nomogram-based preoperative score(NBPS)for clinical outcome-prediction in unilateral primary aldosteronism(UPA).Methods: Data of consecutive patients with UPA achieving complete biochemical success after unilateral adrenalectomy were collected from 3international hypertension referral center between April 6,2014,and February 22,2020.The patients of the Chongqing cohort(Chinese,N=150)were utilized as the training cohort and the patients from Munich and Torino cohort(whites,N=165)were employed as the validating cohort.Univariate and multivariate logistic regression analysis were performed to identify predictors of hypertension remission and the predictors independently associated with hypertension remission were incorporated into the nomogram.Receiver operating characteristic curve(ROC)analysis were used to compare the predictive performance of NBPS and two previously developed outcome-prediction scores,Aldosteronoma Resolution Score(ARS)and Primary Aldosteronism Surgical Outcome(PASO)Score.Results: Ninety-seven out of 150 cases(64%)achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165(34.5%)in the validating cohort.A nomogram was established by incorporating sex,duration of hypertension,aldosterone/rennin ratio(ARR)and target organ damage(TOD).The nomogram achieved good concordance indexes of 0.842(95%CI,0.776-0.898)and 0.833(95% CI0.767-0.886)in predicting complete clinical success in the training and validating cohorts,respectively.The area under the ROC curve(AUC)of NBPS for predicting hypertension remission was 0.853(0.786-0.905),which was superior to those of ARS [0.745(0.667-0.812),P=0.019 ] and PASO score [0.747(0.670-0.815),P=0.012].The optimal cut-off for NBPS to predict hypertension remission was ≥11.5,with a sensitivity of 85.6%(77.0%-91.9%)and a specificity of 71.7%(57.7%-83.2%),respectively.Conclusion: In patients with UPA,the NBPS is useful for predicting hypertension remission after unilateral adrenalectomy.