Characteristic Analysis And Diagnostic Strategies Of Patients With "grey Zone" Diagnosed By Saline Stress Test For Primary Aldosteronism

Objective: To explore the clinical,biochemical and molecular characteristics of patients with primary aldosteronism(PA)after saline infusion test(SIT)with a plasma aldosterone concentration(PAC)between5~10 ng/dl(PA indeterminate after SIT).Methods: The clinical and biochemical datas of 280 patients who received SIT were collected.According to the post-SIT PAC,the patients were divided into three groups: post-SIT PAC<5 ng/dl(unlikely PA),post-SIT PAC 5~10 ng/dl(very probable PA),and post-SIT PA?10 ng/dl(PA indeterminate).Sanger sequencing were used to identify mutation in the hot-point of KCNJ5,CACNA1 D,ATP1A1,ATP2B3 and CTNNB1 gene in patients with a post-SIT PAC between 5~10 ng/dl who were confirmed APA by pathological biopsy after unilateral adrenalectomy.The tumor specimens were stained by 11?-Hydroxylase(CYP11B1)and Aldosterone Synthase(CYP11B2).Results: There were 88 patients post-SIT <5 ng/dl,65 patients post-SIT 5~10 ng/dl and 127 patients post-SIT PAC?10 ng/dl,respectively.The clinical biochemical characteristics of the three groups showed that thesystolic blood pressure(SBP),diastolic blood pressure(DBP),serum potassium,baseline PAC,renin concentration(PRC)and aldosterone/renin ratio(ARR)of the post-SIT PAC group ranged from 5 to 10 ng/dl between the post-SIT PAC group <5 ng/dl and the post-SIT PAC group ?10 ng/dl.Three confirmatory tests revealed that the post-SIT?CCT and FST PAC of subjects with indeterminate SIT was between the post-SIT PAC<5ng/dl group and the post-SIT PAC?10ng/dl group.Of the 65 subjects with indeterminate results,9 were diagnosed as APA,12 subjects as bilateral adrenal hyperplasia(BAH)and 44 cases as unclassified.Compared to patients with definite diagnosis,subjects post-SIT 5~10 ng/dl showed higher proportion of undetermined types [68%(44/65)vs.17%(22/127)]and lower proportion of APA[14%(9/65)vs.66%(83/127)],while the BAH remained similar[18%(12/65)vs.17%(22/127)].In the patients with indeterminate SIT after three confirmatory tests,it was found significant differences in CCT-related indicators(P<0.05).Genetic detection was conducted 6 out of 9 subjects with indeterminate SIT.Mutation were identified in 2 out of 6(30%)cases of APA,which cases were all KCNJ5 mutation.There were no mutation in ATP1A1,ATP2B3,CTNNB1.Immunohistochemical staining was performed using anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies in 5 tumor specimens.The staining intensity of CYP11B2 of APA with post-SIT PAC 5~10 ng/dl was higher than negative control(non-hyperfunctioning adenoma,NHFA)and lowerthan positive control(post-SIT PAC ?10).Conclusion: A post-SIT PAC between 5~10 ng/dl is considered as indeterminate which cannot definitively diagnose or exclude PA.Combination of confirmatory tests may help reduce the misdiagnosis of unilateral primary aldosteronism(UPA).Objective: To assess the diagnostic performance of saline infusion test(SIT)and a combination of confircaptopril challenge test(CCT).Methods: A total of 787 hypertensive patients with high risk of primary aldosteronism(PA)admitted to the First Affiliated Hospital of Chongqing Medical University were included in the study.A post-SIT plasma aldosterone concentration(PAC)of 5~10 ng/dl is considered indeterminate.Subjects with indeterminate SIT then subsequently underwent the fludrocortisone suppression test(FST)and CCT.Using FST as the reference standard,diagnostic parameters including area under the receiver-operator characteristic curves(AUC),sensitivity(Sen)and specificity(Spe)were calculated,and the diagnostic efficacy of combination diagnosis and single diagnostic test were compared.Results: 65 subjects were diagnosed as clinically undetermined cases after receiving SIT.Single indicator analysis showed that the AUC of patients with indeterminate results post-CCT PAC was 0.789(0.670-0.880),which was significantly higher than other single clinical indicators.Compared to SIT alone,a combination of SIT and CCT showed higher AUC [0.91(0.87,0.94)vs.0.87(0.83,0.91),P=0.041] and an increased sensitivity for the diagnosis of PA [0.91(0.86,0.95)vs.0.83(0.76,0.89),P=0.028],while they have no difference in specificity Among the 280 patients with hypertensive patients undergoing saline load test.The AUC of SIT for the diagnosis of PA was(95% CI 0.67-0.88);the AUC of combination of SIT and CCT for the diagnosis of PA was 0.79(95% CI0.67-0.88).Conclusion: Combination of SIT and CCT can improve the diagnostic accuracy of PA,especially in patients with indeterminate SIT to exclude the diagnosis of PA.