Subjects and study design
This retrospective cross-sectional single-center study was approved by the ethics committee of Kobe University Hospital, and written informed consent was obtained from all subjects (IRB #1351). We enrolled 83 consecutive patients with PCC, SCS, and NFA who were diagnosed and hospitalized in Kobe University Hospital between 2008 and 2014. We confirmed that all of these subjects had both PRA and PAC evaluated. Among them, patients who had received medication that can affect the renin-angiotensin aldosterone system, including aldosterone receptor blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and b-adrenergic blockers (n =16), were excluded. The diagnosis of PCC was based on the Endocrine Society Guideline [11], which focused on increased uMN or uNMN levels, tumor demonstration by imaging test, and positive 123I- metaiodobenzylguanidine (MIBG) scintigraphy. In all cases of PCC, the final diagnosis was histologically confirmed after surgery. The diagnosis of SCS and NFA was performed based on each guideline [12, 13].
Hormone assays
The PRA, PAC, and plasma CA levels were measured in the morning after overnight fasting in the supine position. After 24-h urinary excretion of fractionated MNs and CAs, all subjects were instructed to abstain from caffeinated foods and drinks for at least 48 h. PRA, PAC, and plasma CA levels were measured by high-performance liquid chromatography (HPLC) (LSI Medience Corporation, Tokyo, Japan), enzyme immunoassay (BML, Inc., Tokyo, Japan), and radioimmunoassay (LSI Medience Corporation, Tokyo, Japan), respectively. The intra- and inter assay coefficients of variations for each hormone assay were as follows: PRA, <10% and <15%; PAC, <7.8% and <10.6%; plasma Ad, <4.08% and <2.23%; NA, <9.34% and <2.27%; and DA, <8.96% and <2.89%. uMN and CA levels were measured by HPLC (LSI Medience Corporation, Tokyo, Japan). The intra- and inter assay coefficients of variations for each hormone assay were as follows: urinary Ad, <6.21% and <6.35%; urinary NA, <4.09% and <3.82%; urinary DA, <5.32% and <4.46%; uMN, <1.4% and <6.2%; and uNMN, <0.7% and <5.3%.
Statistical Analysis
Data were appropriately expressed as mean ± standard deviation or median (interquartile range). These data were logarithmically transformed to normality before statistical analysis. We defined PCC as a control, and compared to SCS and NFA. Statistical comparisons among patients with PCC, SCS, and NFA were made using the Kruskal-Wallis test with post hoc Bonferroni’s test or χ2 test followed by Tukey’s honestly significant difference test, as appropriate. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value in the diagnosis of PCC. P-values <0.05 were considered statistically significant. Statistical analyses were performed using with SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL).
Subjects and study design
This retrospective cross-sectional single-center study was approved by the ethics committee of Kobe University Hospital, and written informed consent was obtained from all subjects (IRB #1351). We enrolled 83 consecutive patients with PCC, SCS, and NFA who were diagnosed and hospitalized in Kobe University Hospital between 2008 and 2014. We confirmed that all of these subjects had both PRA and PAC evaluated. Among them, patients who had received medication that can affect the renin-angiotensin aldosterone system, including aldosterone receptor blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), and b-adrenergic blockers (n =16), were excluded. The diagnosis of PCC was based on the Endocrine Society Guideline [11], which focused on increased uMN or uNMN levels, tumor demonstration by imaging test, and positive 123I- metaiodobenzylguanidine (MIBG) scintigraphy. In all cases of PCC, the final diagnosis was histologically confirmed after surgery. The diagnosis of SCS and NFA was performed based on each guideline [12, 13].
Hormone assays
The PRA, PAC, and plasma CA levels were measured in the morning after overnight fasting in the supine position. After 24-h urinary excretion of fractionated MNs and CAs, all subjects were instructed to abstain from caffeinated foods and drinks for at least 48 h. PRA, PAC, and plasma CA levels were measured by high-performance liquid chromatography (HPLC) (LSI Medience Corporation, Tokyo, Japan), enzyme immunoassay (BML, Inc., Tokyo, Japan), and radioimmunoassay (LSI Medience Corporation, Tokyo, Japan), respectively. The intra- and inter assay coefficients of variations for each hormone assay were as follows: PRA, <10% and <15%; PAC, <7.8% and <10.6%; plasma Ad, <4.08% and <2.23%; NA, <9.34% and <2.27%; and DA, <8.96% and <2.89%. uMN and CA levels were measured by HPLC (LSI Medience Corporation, Tokyo, Japan). The intra- and inter assay coefficients of variations for each hormone assay were as follows: urinary Ad, <6.21% and <6.35%; urinary NA, <4.09% and <3.82%; urinary DA, <5.32% and <4.46%; uMN, <1.4% and <6.2%; and uNMN, <0.7% and <5.3%.
Statistical Analysis
Data were appropriately expressed as mean ± standard deviation or median (interquartile range). These data were logarithmically transformed to normality before statistical analysis. We defined PCC as a control, and compared to SCS and NFA. Statistical comparisons among patients with PCC, SCS, and NFA were made using the Kruskal-Wallis test with post hoc Bonferroni’s test or χ2 test followed by Tukey’s honestly significant difference test, as appropriate. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value in the diagnosis of PCC. P-values <0.05 were considered statistically significant. Statistical analyses were performed using with SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL).