The Screening And Confirmatory Test Of Primary Aldosteronism Are Re-evaluated

Objective: Primary aldosteronism(PA)is a common cause of secondary hypertension.Plasma aldosterone concentration(PAC)/ renin concentration(PRC)ratio(ARR)measurement by radioimmunoassay has been commonly used for screening of PA.However,there were few reports of the diagnostic accuracy of ARR measured by chemiluminescent immunoassay as screening tests for PA in China.Aim of the study was to investigate the diagnostic accuracy and the optimal cutoff of ARR determined by the automated chemiluminescent immunoassay in screening for PA.Methods: A total of 154 hypertensive patients and 83 healthy volunteers were recruited in the study.PAC and PRC in the supine position and after 2 hour upright posture were determined with the automated chemiluminescent immunoassay for hypertensive patients;meanwhile,PAC and PRC were determined in the upright posture for healthy volunteers.ARR was calculated for all subjects.The diagnoses of PA were definitively made according to clinical manifestations,confirmatory tests and pathologic results.The diagnostic performances of different cutoff of ARR were compared by ROC curves.Result: Fifty-three patients were diagnosed as primary aldosteronism,85 as essential hypertension and 16 patients as other endocrine hypertension.For hypertensive patients,the area under the ROC curves(AUCROC)of ARR in the supine position and after 2 hour upright posture were 0.962(95% CI: 0.933-0.990,P<0.01),0.980(95% CI: 0.962-0.998,P<0.01),respectively.The AUCROC of ARR was higher than PAC or PRC alone in the same position.The highest Youden’s index of ARR in the upright posture was 0.85,and the cutoff was 4.3(ng/d L)/(m U/L)accordingly(sensitivity 94%,specificity 91%).Conclusions: ARR in the upright position based on the automated chemiluminescent immunoassay yields a high screening efficiency.The optimal cutoff of ARR is 4.3(ng/d L)/(m U/L).Objective: The diagnosis of primary aldosteronism(PA)typically requires at least one confirmatory test.The fludrocortisone suppression test(FST)is regarded as the most reliable confirmatory test for PA.However,evidence from accuracy studies of the saline infusion test(SIT)and the captopril challenge test(CCT)has provided conflicting results.This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using FST as the reference standard.Methods: Five hundred and thirty-one hypertensive patients with high risk of PA were enrolled.Plasma aldosterone-renin ratio(ARR)was used for screening.Hypertensive patients tested positive at PA screening(ARR≥3.7 ng.dl-1/μIU.ml-1),one in every three consecutive patient tested negative(ARR<3.7 ng.dl-1/μIU.ml-1)and patients who tested negative but PA was strongly suspected proceeded to three confirmatory tests.Area under receiver operator characteristics curve(AUC),sensitivity and specificity were calculated.Results: Finally,135 patients diagnosed with PA and 101 patients diagnosed with essential hypertension who completed the three confirmatory tests were included for the diagnostic accuracy analysis.The AUC of the CCT and SIT were 0.96(95% CI 0.92 to 0.98)and 0.96(0.92 to 0.98),respectively,using post-test plasma aldosterone concentration(PAC)for diagnosis.However,the AUC of the CCT decreased to 0.71(0.65 to 0.77)when the PAC suppression percentage was used to diagnose PA.The optimal cutoff of PAC post-CCT was set at 11 ng/dl,resulting in a sensitivity of 0.90(0.84 to 0.95)and a specificity of 0.90(0.83 to 0.95),which were not significantly different from those of SIT(with PAC post-SIT set at 8 ng/dl,sensitivity: 0.85(0.78 to 0.91),P=0.192;specificity: 0.92(0.85 to 0.97),P=0.551).Conclusion: Both CCT and SIT are accurate alternatives to the more complex FST.Because CCT is safe and much easier to perform,it may serve as a more feasible alternative.When interpreting the results of CCT,PAC post-CCT is highly recommended.Objective: Steroid 11 beta-hydroxylase deficiency(11β-OHD)caused by the CYP11B1 gene mutations is an autosomal recessive hereditary defect and one of the causes of congenital adrenal hyperplasia(CAH).This study was to report a classic 11β-OHD patient with a novel CYP11B1 mutation,and to describe the genetic characteristics.Methods: The suspected diagnosis was made according to the clinical manifestations,laboratory tests and imaging data.DNA of mononuclear cells were extracted from the peripheral blood of proband and his parents.The second generation sequencing and the Sanger sequencing were subsequently performed to analyze the genomic DNA of the CYP11B1 gene.Results: The proband displayed typical clinical features of 11β-OHD,such as stunted growth,precocious puberty,hyporeninemic hypokalemic hypertension and high ACTH levels with bilateral adrenal gland hyperplasia.A novel missense homozygous substitution A950 T in exon 5 of CYP11B1 gene was discovered by DNA sequencing of the proband,resulting in an amino acid change from aspartic acid to valine at position 317(D317V),which has not been previously described in patients with 11β-OHD.In addition,a heterozygous alteration R384 X was found in exon 7 that results in a premature stop codon,causing the formation of a truncated protein without biological activity,which was reported for the second time in the world.The Sanger sequencing showed that his parents were healthy and respectively carried a novel mutation c.950A>T(D317V)and a rare mutation c.1150C>T(R384X).Conclusion: we identify a novel CYP11B1 compound heterozygous mutations: a novel mutation c.950A>T(D317V)and a recently described non-sense novel mutation c.1150C>T(R384X)in a Chinese CAH patient due to classic 11β-OHD.This study expands the spectrum of mutations in CYP11B1 causing to 11β-OHD.