Abstract
Plasma aldosterone concentration (PAC) was routinely measured using radioimmunoassay (RIA); however, the RIA kit was discontinued in March 2021 in Japan. This study examined PAC conversion in adrenal venous sampling (AVS) and AVS criteria when measured using chemiluminescent enzyme immunoassay (CLEIA). PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) of 63 patients with primary aldosteronism was measured using RIA (Spac-S aldosterone kit; Fujirebio Inc.) and CLEIA (Lumipulse Presto Aldosterone; Fujirebio Inc.). PAC of 70 AVS samples was also measured using liquid chromatography-mass spectrometry (LC-MS/MS, ASKA Pharma Medical Co., Ltd.). PAC conversion formulas were determined for each AVS sample assay. PAC measured using CLEIA was significantly correlated with that measured using RIA (correlation coefficient = 0.971). The PAC conversion formula was PAC (CLEIA) = PAC (RIA) × 0.772 – 1,199 pg/mL. The PAC of 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. PAC measured using CLEIA was also correlated with that measured using LC-MS/MS, and the PAC conversion formula was PAC (CLEIA, pg/mL) = 0.97 × PAC (LC-MS/MS, pg/mL) + 211. The inter-assay coefficient of variability (CV) was 1.1–1.3% and intra-assay CV was 1.0–1.7%, measured using CLEIA. The PAC conversion formula for AVS samples was obtained using CLEIA and RIA, and the conversion formula was different from that for peripheral blood. PAC values measured by CLEIA showed preferable accuracy and high concordance with those measured by LC-MS/MS, even in AVS samples. The study outcomes are useful for interpreting AVS results using non-RIA measurement methods.
IN THE MEDICAL PRACTICE of primary aldosteronism (PA), the measurement of plasma aldosterone concentration (PAC) is a cornerstone and has long been measured by radioimmunoassay (RIA) [1]. This method has difficulties in the precision and rapidity of measurement and isotope handling [2]. Therefore, many hormone assay kits are shifting from RIA to non-RIA methods such as chemiluminescent enzyme immunoassay (CLEIA). PAC was measured by RIA using the Spac-S aldosterone kit (Fujirebio Inc., Tokyo, Japan) in Japan; however, the supply of this kit was discontinued at the end of March 2021. Since April 2021, PAC has been measured using CLEIA as an alternative to RIA [3].
Several CLEIA kits are currently available in Japan, all of which have been developed in principle to ensure metrological traceability to human serum for aldosterone analysis (NMIJ CRM 6402) and favorable correlation with liquid chromatography-mass spectrometry (LC-MS/MS) [4]. The Japan Endocrine Society’s 2021 clinical practice guideline for the diagnosis and management of PA also recommends the CLEIA method in clinical practice [3].
CLEIA, which yields standardized LC-MS/MS-compliant measurements, shows a lower PAC than RIA because of its very low cross-intersectionality with steroids and substances other than aldosterone [2]. The PA practice guidelines also provide conversion formulas for RIA and CLEIA for each of the various kits [3]. For example, when measured using Lumipulse Presto aldosterone (Fujirebio Inc., Tokyo, Japan), the CLEIA values equivalent to RIA 120 pg/mL and 60 pg/mL were 66.2 pg/mL and 15.1 pg/mL, respectively. Because of this difference between the RIA and CLEIA values, the screening criteria and criteria for confirmatory testing of PA have been revised in the guidelines.
These differences between RIA and CLEIA values have been studied using samples representing aldosterone concentrations in the peripheral blood. Samples obtained by adrenal venous sampling (AVS) have higher aldosterone concentrations than peripheral blood samples; thus, it is unclear whether the same conversion formula can be used.
AVS is necessary to determine whether the PA is unilateral or bilateral, and the lateralization index (LI), contralateral ratio (CR), and absolute PAC in the adrenal venous blood are used as indices to determine localization [3, 5-8]. Because all these indices are affected by the PAC measurement method, it is not clear what the cut-off value would be if measurements by non-RIA methods, such as CLEIA, were used. In some institutions, including our hospital, we have conducted segmental AVS (sAVS) by collecting blood samples from multiple tributary veins in each adrenal gland to detect the exact location of the PA causative lesions and have reported its usefulness [7-10]. In sAVS, the absolute PAC value in adrenal venous blood after adrenocorticotropic hormone loading is used to determine aldosterone excess, and 14,000 pg/mL has been used as the cut-off value [3, 5, 7]. We recently reported that assessment by absolute aldosterone and aldosterone/cortisol ratio (A/C ratio) in AVS has excellent predictive capacity for biochemical and clinical surgical outcomes [8]. However, these were verified based on the results of PAC measurements by RIA.
In the present study, we analyzed specimens obtained by AVS using RIA and CLEIA to determine the extent to which the results differed between the two methods and the conversion formula. In addition, we also measured some samples by LC-MS/MS and compared conversion formulas for “LC-MS/MS and RIA” and “LC-MS/MS and CLEIA.”
Materials and Methods
Ethics Statement
The study was approved by the institutional review boards of Yokohama Rosai Hospital (approval no. 25-36-4). The requirement for informed consent was waived because the data were anonymous, and the study was not interventional. The study adhered to the principles of the Declaration of Helsinki.
Clinical samples
A total of 415 stored adrenal venous blood samples from AVS (including sAVS) of 63 patients with PA diagnosed based on the Japan Endocrine Society’s clinical guideline [1, 3] were analyzed. Blood samples obtained using AVS were collected in serum collection tubes and centrifuged at 1,100–1,500 × g for 10–15 minutes. Then, 0.1 mL of serum was transferred to a tube for storage and stored in a –80°C freezer.
Measurement of PAC and cortisol
Serum PACs were measured using the CLEIA method (Lumipulse Presto Aldosterone; Fujirebio Inc., Tokyo, Japan), LC-MS/MS (ASKA Pharma Medical Co., Ltd., Kanagawa, Japan), or RIA method (Spac-S aldosterone kit; Fujirebio Inc., Tokyo, Japan) [4]. RIA measurements were performed when AVS was performed, and CLEIA and LC-MS/MS measurements were performed using frozen stocked samples. Lumipulse Presto Aldosterone is a two-site sandwich immunoassay that uses an anti-aldosterone mouse monoclonal antibody and an anti-metatype chicken antibody to recognize the aldosterone–aldosterone monoclonal antibody complex [11]. This kit is available only in Japan. The Spac-S aldosterone kit is a competitive immunoassay kit. Because the samples obtained by AVS were expected to have a high PAC, the measurements started with a 10-fold dilution, and those outside the measurement range were further diluted up to a maximum of 1,000-fold.
Serum cortisol concentrations were also measured when AVS was performed on the same samples using CLEIA (Access Cortisol; Beckman Coulter Inc., Brea, CA, USA), with confirmed validity and reliability.
Samples measured by LC-MS/MS method
LC-MS/MS measurements were performed on samples collected from the adrenal central veins, with sufficient remaining sample volume after measurement using the CLEIA method. As the number of samples that could be measured was limited owing to the cost, we decided to limit the number of samples to those in the range important for diagnosis (PAC (CLEIA) 1,500–30,000 pg/mL).
Statistical analyses
Based on the results obtained using RIA, CLEIA, and LC-MS/MS, the conversion formulas for PAC, A/C ratio, and LI between each method were determined. Because LI varies widely, we also determined a conversion formula for LI in a limited range that is important for diagnosis (LI (RIA) <10). Moreover, CLEIA equivalents, which correspond to the AVS criteria using conventional RIA [3, 5-8], were calculated. The inter-assay coefficients of variability (CV) were calculated using the same sample and measured twice daily for 5 days. Five consecutive days are not required. The intra-assay CV was calculated by performing 10 measurements on the same day using the same sample. The conversion formulas were determined by Passing–Bablok regression. Analyse-it v5.30.5 (Analyse-it Software, Ltd., Leeds, UK) was used for the analysis.
Results
Clinical characteristics of the participants
The clinical characteristics of the 63 patients included in the study are presented in Table 1. The median blood pressure on admission was 138/85 mmHg, and the patients were taking a median of one antihypertensive drug; the median plasma renin activity, PAC, and aldosterone-to-renin ratio were 0.3 ng/mL/h, 144 pg/mL, and 573, respectively. Surgical therapy was performed in 46 of the 63 patients.
Table 1
Characteristics of the participants
| Number of participants |
63 |
| Age (years) |
48 [42–56] |
| Sex (male/female) |
39/24 |
| BMI (kg/m2) |
24.9 [22.1–27.3] |
| Systolic blood pressure (mmHg) |
138 [125–147] |
| Diastolic blood pressure (mmHg) |
85 [76–92] |
| eGFR (mL/min/1.73 m2) |
84.2 [71.3–95.7] |
| Serum potassium (mEq/L) |
3.6 [3.2–3.9] |
| PAC (RIA; pg/mL) |
144 [115–268] |
| PRA (ng/mL/h) |
0.3 [0.2–0.5] |
| ARR |
573 [234–1,530] |
| Number of antihypertensive agents |
1 [1–2] |
| Treatment method (surgery/medication) |
46/17 |
Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; PAC, plasma aldosterone concentration; RIA, radioimmunoassay; PRA, plasma renin activity; ARR, PAC-to-PRA ratio
A statistical summary of the PAC values measured using CLEIA and RIA methods is shown in Table 2. The PAC of the 415 samples obtained by AVS was a mean of 23,957.5 pg/mL and a median of 9,823.3 pg/mL using CLEIA, and a mean of 30,910.5 pg/mL and a median of 14,600 pg/mL using RIA.
Table 2
Statistical summary of PAC values measured by CLEIA and RIA methods
|
CLEIA |
RIA |
| Number of samples |
415 |
415 |
| Mean |
23,957.5 |
30,910.5 |
| Standard deviation |
45,775.2 |
51,514.3 |
| 95% upper confidence boundary |
28,374.5 |
35,881.3 |
| 95% lower confidence boundary |
19,540.5 |
25,939.7 |
| Median |
9,823.3 |
14,600 |
| Maximum value |
374,445.8 |
365,000 |
| 75% quartile |
20,600.5 |
30,600 |
| 25% quartile |
3,659.8 |
5,980 |
| Minimum value |
314.4 |
691 |
Values represent PAC (pg/mL). Abbreviations: PAC, plasma aldosterone concentration; CLEIA, chemiluminescence enzyme immunoassay; RIA, radioimmunoassay
A comparison of PAC by CLEIA and RIA methods obtained by Passing–Bablok regression is shown in Fig. 1. The correlation coefficient between the two methods was 0.971, and the conversion formulas were PAC (CLEIA, pg/mL) = 0.772 × PAC (RIA, pg/mL) – 1,199 (Fig. 1A) and PAC (RIA, pg/mL) = 1.295 × PAC (CLEIA, pg/mL) + 1,553 (Fig. 1B).
Comparison of PAC/cortisol by CLEIA and RIA methods
The conversion formulas between the two assays for the A/C ratio, obtained by dividing the PAC by the cortisol value measured in the same sample, were PAC (CLEIA)/Cortisol = 0.79 × PAC (RIA)/Cortisol – 2.43 and PAC (RIA)/Cortisol = 1.27 × PAC (CLEIA)/Cortisol + 3.08, as shown in Fig. 2A and B, respectively.
Comparison of LI by CLEIA and RIA methods
The PAC of the bilateral adrenal central veins was measured using both RIA and CLEIA in 52 cases. The conversion formula for LI in 52 cases was LI (CLEIA) = 1.82 × LI (RIA) – 1.01 (Fig. 3A). There were 44 cases with LI (RIA) <10, which is considered to be an important range for diagnosis, and the conversion formula was as follows: LI (CLEIA) = 1.37 × LI (RIA) – 0.41 (Fig. 3B).
Comparison of PAC conversion formulas between CLEIA and LC-MS/MS and between RIA and LC-MS/MS methods
Seventy samples were used to analyze the conversion between the LC-MS/MS values and the other two methods. The statistical summary of PAC values for the 70 samples is shown in Table 3. The PAC conversion formulas between CLEIA and LC-MS/MS and between RIA and LC-MS/MS obtained by Passing–Bablok regression are shown in Fig. 4. The correlation coefficients between the two methods were 0.986 (CLEIA) and 0.939 (RIA), and the conversion formulas were PAC (CLEIA, pg/mL) = 0.965 × PAC (LC-MS/MS, pg/mL) + 211 (Fig. 4A) and PAC (RIA, pg/mL) = 1.325 × PAC (LC-MS/MS, pg/mL) + 1,478 (Fig. 4B).
Table 3
Statistical summary of PAC values measured by LC-MS/MS, CLEIA, and RIA methods, for comparison of PAC conversion formulas between CLEIA and LC-MS/MS and between RIA and LC-MS/MS methods
|
LC-MS/MS |
CLEIA |
RIA |
| Number of samples |
70 |
70 |
70 |
| Mean |
9,953.2 |
9,800.8 |
14,763.3 |
| Standard deviation |
6,738.7 |
6,341.2 |
8,851.4 |
| 95% upper confidence boundary |
11,560.0 |
11,312.8 |
16,873.8 |
| 95% lower confidence boundary |
8,346.4 |
8,288.8 |
12,652.7 |
| Median |
8,393.4 |
8,498.5 |
12,950 |
| Maximum value |
29,630 |
29,639.8 |
38,600 |
| 75% quartile |
13,712.5 |
14,790.2 |
21,325 |
| 25% quartile |
4,455.1 |
4,409.1 |
7,227.5 |
| Minimum value |
1,554.8 |
1,766.9 |
3,730 |
Values represent PAC (pg/mL). Abbreviations: PAC, plasma aldosterone concentration; LC-MS/MS, liquid chromatography-mass spectrometry; CLEIA, chemiluminescence enzyme immunoassay; RIA, radioimmunoassay
The inter-assay and intra-assay CVs were calculated using the CLEIA method on three samples at different concentrations, and the results are shown in Table 4. The inter-assay CVs were 1.1%, 1.2%, and 1.3% for the low- (Sample A), medium- (Sample B), and high-concentration (Sample C) samples, respectively. The intra-assay CVs were 1.0%, 1.7%, and 1.5% for the low- (Sample 1), medium- (Sample 2), and high-concentration (Sample 3) samples, respectively.
Table 4
Inter- and intra-assay coefficients of variability in CLEIA method
|
PAC (pg/mL) |
| Sample A |
Sample B |
Sample C |
| Day of measurement |
Day 1 |
3,927.7 |
13,235.8 |
66,785.0 |
| 3,909.7 |
12,972.9 |
66,118.3 |
| Day 2 |
3,863.5 |
13,160.4 |
64,371.0 |
| 3,845.4 |
13,108.7 |
66,270.4 |
| Day 3 |
3,925.1 |
12,988.8 |
66,389.5 |
| 3,835.2 |
13,068.5 |
67,101.9 |
| Day 4 |
3,851.6 |
13,191.6 |
64,528.8 |
| 3,896.0 |
12,826.8 |
64,591.9 |
| Day 5 |
3,889.8 |
13,521.5 |
65,811.0 |
| 3,948.7 |
12,710.7 |
65,188.7 |
| Average |
Day 1 |
3,918.7 |
13,104.4 |
66,451.7 |
| Day 2 |
3,854.5 |
13,134.6 |
65,320.7 |
| Day 3 |
3,880.2 |
13,028.7 |
66,745.7 |
| Day 4 |
3,873.8 |
13,009.2 |
64,560.4 |
| Day 5 |
3,919.3 |
13,116.1 |
65,499.9 |
| Inter-assay CV |
1.0% |
1.7% |
1.5% |
| |
|
PAC (pg/mL) |
| Sample 1 |
Sample 2 |
Sample 3 |
| No. of measurements |
1 |
3,784.9 |
12,710.0 |
68,450.3 |
| 2 |
3,873.2 |
12,874.6 |
66,996.5 |
| 3 |
3,846.9 |
12,611.4 |
65,745.1 |
| 4 |
3,817.9 |
12,897.9 |
67,295.3 |
| 5 |
3,806.9 |
12,467.3 |
66,221.3 |
| 6 |
3,747.9 |
12,732.5 |
66,730.1 |
| 7 |
3,801.6 |
12,460.8 |
65,842.7 |
| 8 |
3,803.5 |
12,687.4 |
66,080.3 |
| 9 |
3,727.0 |
12,577.9 |
66,417.7 |
| 10 |
3,827.6 |
12,711.0 |
65,538.3 |
| Average |
3,803.7 |
12,673.1 |
66,531.8 |
| Intra-assay CV |
1.1% |
1.2% |
1.3% |
Abbreviations: CV, coefficient of variability; PAC, plasma aldosterone concentration
Discussion
This study revealed that the conversion formulas, especially the intercepts, for RIA and CLEIA were different for samples obtained from AVS than for samples obtained from peripheral blood, using a large number of AVS samples. For AVS samples, the conversion formula was PAC (CLEIA, pg/mL) = 0.772 × PAC (RIA, pg/mL) – 1,199, which differed considerably from the peripheral blood sample conversion formula (PAC (CLEIA, pg/mL) = 0.852 × PAC (RIA, pg/mL) – 36.0) [3, 4]. When interpreting AVS results using non-RIA methods such as CLEIA, the conversion between RIA and non-RIA values specific to AVS should be considered in order to continue using conventional criteria based on RIA measurements.
A possible reason for the difference in conversion formulas between AVS and peripheral blood samples is that the sample is measured after dilution and then converted back to pre-dilution values by calculation. The intercept in the conversion formula is expected to increase by calculating the post-dilution values back to the pre-dilution values. Only the intercept was considerably different, whereas the slopes were relatively close between the conversion formulas for peripheral blood and AVS samples.
The correlations with the values measured using the LC-MS/MS method were also confirmed, though the number of samples was limited. The CLEIA method values had a slope close to 1.0 and an intercept close to 0 in the conversion formula (PAC (CLEIA, pg/mL) = 0.965 × PAC (LC-MS/MS, pg/mL) + 211) with the LC-MS/MS values. This indicated that the CLEIA and LC-MS/MS values were highly concordant in the concentration range measured in this study. The conversion formula between the LC-MS/MS and RIA values (PAC (RIA, pg/mL) = 1.325 × PAC (LC-MS/MS, pg/mL) + 1,478) was also considerably similar to the conversion formula between the CLEIA and RIA values (PAC (RIA, pg/mL) = 1.295 × PAC (CLEIA, pg/mL) + 1,553). Inter- and intra-assay CV calculations showed that the CLEIA method has favorable reproducibility of PAC values in the concentration range of AVS, which is comparable to peripheral blood data [2, 12]. These results indicate that the PAC values measured by the CLEIA method have excellent accuracy, even in the concentration range of AVS. We also believe that the conversion formula with the RIA method, calculated based on the CLEIA method in this study, is applicable to the LC-MS/MS method. Since standardizing aldosterone measurements worldwide using non-RIA methods is essential in order to eliminate discrepancies among facilities and regions, our study findings are significant because they reveal that such standardization, even for AVS samples, can be achieved using CLEIA and LC-MS/MS methods.
Based on the results of this study, comparisons of the criteria for AVS measured using the RIA and CLEIA methods are shown in Table 5. Some centers, including ours, have used an RIA value of 14,000 pg/mL as the cut-off for determining aldosterone excess in AVS; the equivalent value using the CLEIA method was 9,613 pg/mL when the conversion formula identified in our study was used, and it was 11,892 pg/mL when the peripheral blood conversion formula was used.
Table 5
Comparisons of criteria for AVS measured by RIA and CLEIA methods
|
RIA |
CLEIA |
| When using the conversion formula in peripheral blood samples |
When using the conversion formula based on the current results |
| PAC |
14,000 pg/mL |
11,892 pg/mL |
9,613 pg/mL |
| LI |
4.0 |
Not verified |
5.07 |
| CR |
1.0 |
Not verified |
Not verified |
Abbreviations: AVS, adrenal venous sampling; RIA, radioimmunoassay; CLEIA, chemiluminescent enzyme immunoassay; PAC, plasma aldosterone concentration; LI, lateralization index; CR, contralateral ratio
For the LI and CR, 4.0 and 1.0 are commonly used as cut-off values, respectively, for the criteria using RIA measurements. However, because of the large intercept in the conversion formula between the RIA and CLEIA methods for PAC, these ratios cannot be used for CLEIA measurements. Therefore, in this study, we present a conversion formula for the LI identified from the samples; a conversion formula for the CR could not be obtained because peripheral blood samples were not included in this study. Because of the presence of a large intercept, the conversion formula for the LI could not be expressed as a straight line; therefore, we identified the conversion formula by delimiting the range of values to approximate a straight line. Using the conversion formula identified by delimiting the range, LI (CLEIA), which corresponds to LI (RIA) = 4, was 5.07. It should be noted that this LI conversion was identified using the samples of the current study, and the results will differ depending on the sample used. This is because there is a large intercept in the conversion formulas for PAC, and the impact of the intercept is likely to vary depending on the size of the numerator and denominator values that compose the LI. For greater accuracy, another approach is to calculate the LI and CR after converting the PAC from non-RIA values to equivalent RIA values.
We recently published an article in which we reported that PAC values on the unresected side of the adrenal gland in AVS were associated with biochemical success after surgery [8]. In that article, both PAC values and PAC-to-cortisol ratios in the central adrenal vein or tributary vein of the unresected adrenal gland were associated with biochemical success at one year after surgery. The cut-off values of specificity ≥80% (the parameters of ≥80% of cases in which biochemical complete success was achieved were below this value) and sensitivity ≥80% (the parameters of ≥80% of cases in which biochemical complete success was not achieved were above this value) were calculated. The cut-off values of CLEIA converted from RIA based on the results of the present study are shown in Table 6. For example, 80% of the cases with complete postoperative biochemical success have a maximum PAC of 9,073 pg/mL or less in the adrenal tributary veins and a PAC of 5,535 pg/mL or less in the adrenal central vein on the unresected side using the CLEIA method. The results of the present study can be readily applied to AVS evaluation based on the predictive ability of intra-adrenal PAC values and PAC-to-cortisol ratios for postoperative outcomes.
Table 6
Cut-off values of aldosterone value of ≥80% for specificity and sensitivity each, considering that postoperative biochemical persistence of PA is positive
|
Specificity ≥80% |
Sensitivity ≥80% |
| RIA |
CLEIA |
RIA |
CLEIA |
| Maximum PAC in tributary veins of the unresected adrenal gland (pg/mL) |
13,300 |
9,073 |
7,950 |
4,941 |
| Maximum PAC/Cort ratio in tributary veins of the unresected adrenal gland |
18.48 |
12.11 |
12.77 |
7.62 |
| PAC in the central vein of the unresected adrenal gland (pg/mL) |
8,720 |
5,535 |
5,480 |
3,033 |
| PAC/Cort ratio in the central vein of the unresected adrenal gland |
11.95 |
6.97 |
9.51 |
5.05 |
The cut-off values of specificity ≥80% (parameters of ≥80% of cases in which biochemical complete success was achieved were below this value) and sensitivity ≥80% (parameters of ≥80% of cases in which biochemical complete success was not achieved were above this value) for RIA and CLEIA are shown in this table.
Abbreviations: PAC, plasma aldosterone concentration; Cort, cortisol; RIA, radioimmunoassay; CLEIA, chemiluminescent enzyme immunoassay; PA, primary aldosteronism
This study has several limitations. First, the lower limit of the PAC range to which the conversion formulas obtained in this study can be applied cannot be strictly determined. However, because dilution is likely the main cause of the difference in the conversion formulas, it may be reasonable to consider the threshold of PAC over which dilution is required as the boundary for the conversion formulas. Moreover, in AVS, a PAC value that is at the borderline of requiring dilution can be considered a low intra-adrenal PAC; therefore, the question of which conversion formula to apply is not critical. Second, it is unclear whether the same conversion formula can be applied to samples with different dilution rates. However, we believe that the range of values in which many samples were concentrated in this study is important for actual diagnosis, and that diagnosis is possible using the conversion formulas obtained in this study. Extremely high-value ranges with widely varying dilution rates are considered ranges that do not require precise conversion for AVS diagnosis (as they can be regarded as ranges of aldosterone hypersecretion with certainty even if precise conversion is not possible). Third, the RIA method is likely to lose accuracy if the measured values are in a low concentration range, even after dilution. Because RIA is a competitive method, the linearity of the calibration curve tends to be lost at low concentrations. Even within the measurement range, the correlation between RIA and CLEIA tends to change slightly in the slope between the low-concentration range and other ranges.
In conclusion, the conversion formula for aldosterone concentration from RIA values to CLEIA values (Lumipulse Presto Aldosterone; Fujirebio) was CLEIA = RIA × 0.772 – 1,199 for AVS samples, which is different from the conversion formula for peripheral blood. The PAC values measured using CLEIA had preferable accuracy and very high concordance with those measured using LC-MS/MS, even within the concentration range of AVS. When interpreting AVS results using CLEIA or LC-MS/MS methods, careful attention should be paid and the diagnostic criteria should be revised. We believe that our results will be useful in establishing new AVS reference values for PAC measurements using non-RIA methods.
Abbreviations
PA, primary aldosteronism; PAC, plasma aldosterone concentration; RIA, radioimmunoassay; CLEIA, chemiluminescent enzyme immunoassay; LC-MS/MS, liquid chromatography-mass spectrometry; AVS, adrenal venous sampling; LI, lateralization index; CR, contralateral ratio; sAVS, segmental AVS; A/C ratio, aldosterone/cortisol ratio; CV, coefficients of variability
Acknowledgments
We thank the staff at Yokohama Rosai Hospital for their valuable contributions to the appropriate management of patients and the collection of clinical data. We are also grateful to ASKA Pharma Medical Co., Ltd. for their cooperation in conducting accurate aldosterone measurements using the LC-MS/MS method.
Disclosure
This study was partly funded by Fujirebio Inc. (Tokyo, Japan) based on contracts.
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