Impact of New Quick Gold Nanoparticle-Based Cortisol Assay During Adrenal Vein Sampling for Primary Aldosteronism

Abstract

Context:

Adrenal vein sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism (PA), but accurate placement of the sampling catheter is technically challenging. Intraprocedural cortisol measurement can confirm the catheter's position, thereby increasing the AVS success rate.

Objective and Methods:

We developed a quick cortisol assay (QCA) that uses immunochromatography and gold nanoparticles and can be performed either semiquantitatively or quantitatively. The assay was evaluated in two studies. In a single-center study, PA patients were assigned to undergo AVS incorporating the semiquantitative QCA (n = 30), the quantitative QCA (n = 30), or without the QCA (n = 30), and the rates of successful AVS were determined. In a prospective multicenter randomized, controlled study, the success rates of AVS performed with (n = 148) or without (n = 145) the semiquantitative QCA were determined.

Results:

Cortisol concentrations were measured during AVS in 6 minutes or less in the radiology suite, without additional technical assistance, and significantly correlated with a conventional reference assay (R² = 0.994; P < .001). In the single-center study, the differences in the AVS success rates associated with semiquantitative and quantitative QCAs were not significant (both 93%); however, the success rates were significantly higher than the rate of successful AVS performed without using the QCA (63%; P < .001). The success rate of AVS performed in the multicenter study was 94% for the semiquantitative QCA, which was significantly higher than the rate for the patients without QCA (60%; P < .001).

Conclusions:

Our novel QCA was rapidly and easily performed at the point of care and improved the rate of successful AVS.

Primary aldosteronism (PA) is a common cause of secondary hypertension, occurring in 5–10% of all hypertensive patients (1–4). The rate of cardiovascular events in PA patients has been reported to be higher than in patients with essential hypertension (5, 6). There are two major subtypes of PA: unilateral and bilateral. Unilateral PA is curable by surgery, whereas bilateral PA should be treated by a mineralocorticoid receptor antagonist. The ability to accurately and efficiently differentiate PA subtypes is crucial to treatment planning. Computed tomography (CT) scanning has been reported to lack sensitivity and specificity (4, 7, 8), and only adrenal vein sampling (AVS) can reliably distinguish between the two subtypes. Successful AVS can be confirmed by determining the ratio of the concentration of adrenal cortisol to the concentration of inferior vena cava (IVC) cortisol. Although various ratios are considered to indicate success, and range from 1.1 to 5, a ratio of 2 or 3 is widely used, especially for non-ACTH stimulated AVS (9–14).

The collection of adequate samples from adrenal veins is technically challenging because of anatomic variations in the veins and/or dilution of the blood samples. Indeed, the AVS success rates for collecting adequate samples have ranged from 30 to 98% (9, 15). The average success rate has only been 31%, even at national referral centers in the German Conn's Registry (9).

Several studies have reported that an intraprocedural cortisol assay (IPCA) improved the rates of successful AVS (9, 14, 16–21); however, the assay methods were somewhat complicated, required additional assistance from laboratory technicians, and with a few exceptions, required more than 20 minutes to complete. In this report, we describe our novel quick cortisol assay (QCA), which is based on immunochromatography using gold nanoparticles (U.S. Patent No. 8927219; Japan Patent No.5590651), and we report on our clinical evaluation of the QCA for successful AVS.

Subjects and Methods

Quick cortisol assay

We developed a novel gold-nanoparticle-based immunochromatographic QCA, which enabled us to measure plasma cortisol concentrations quantitatively within 6 minutes and semiquantitatively within 5 minutes. The assay uses a competitive format where the gold-labeled cortisol and the analyte (cortisol in sample) compete for the limited number of binding sites on immobilized anticortisol antibody located in the test line. The intensity of the red color of the test line is almost inversely proportional to the cortisol concentration; ie, the color intensity decreases with increasing cortisol concentration (Figure 1A). The control line always appears colored if the gold conjugate is active (Figure 1A). This QCA used a rat monoclonal antibody against cortisol (CRT1G6; Fujikura Kasei Co., Ltd.). This technology was transferred and is commercially available. The QCA strip (Quick Cortisol Kit Q-CTZ-1000; Trust Medical Corporation) and the densitometer (Immunochromato-Reader ICA-1000; Hamamatsu Photonics) were used in the study. The entire assay system, including a small centrifuge, only requires a small amount of counter space and is easily transportable.

Figure 1.

A, The standard curve for the quantitative QCA. QCA using diluted samples also conformed to the same assay curve. B, Comparison of quantitative QCA and a conventional cortisol assay. A total of 90 samples, which were collected from the IVC and the right and left adrenal veins by AVS performed in 30 patients in the single-center study, were analyzed by quantitative QCA and the ECLIA, and the two assays show similar results. The correlation between cortisol levels ranging from 55 to 43 040 nmol/L that were determined by QCA and the conventional reference assay was excellent (R = 0.994; P < .001). C, Bland-Altman plot showing the differences between the QCA and a conventional cortisol assay.

QCA procedure (Supplemental Figure 1, A and B)

The procedure consists of the following steps:

1. 1. 

   A blood sample (1 mL) is collected in a small tube, and after centrifugation at 5200 × g (10 000 rpm) for 1 minute, 100 μL of plasma specimen is used for the test.

2. 2. 

   Plasma (100 μL) is placed in the well over the immunochromatographic paper strip.

3. 3. 

   For semiquantitative assessment of AVS, a semiquantitative QCA (Supplemental Figure 1A), which takes 5 minutes, can be performed and assessed by eye, with the following results: the test line on the immunochromatographic paper is visible if the cortisol concentration is low (<276 nmol/L), slightly visible if the cortisol concentration is between 276 and 828 nmol/L, and remains invisible if the cortisol concentration is high (>828 nmol/L).

4. 4. 

   To perform a quantitative QCA, the cortisol concentration is measured using a densitometer to quantify the color intensity of the test line.

Clinical studies

The single-center study was performed at Kanazawa University Hospital (K) (Kanazawa, Japan) from December 2010 to February 2012. The multicenter study was performed at seven medical centers, including Kanazawa University Hospital (K; Kanazawa, Japan), Houju Memorial Hospital (H; Nomi, Japan), Sanda Municipal Hospital (S; Sanda, Japan), Akashi Medical Center (A; Akashi, Japan), Ishikawa Prefectural Hospital (I; Kanazawa, Japan), Saiseikai Ishikawa Hospital (SI; Kanazawa, Japan), and Takaoka Municipal Hospital (T; Takaoka, Japan), from March 2012 to March 2015. The ethics committees of the participating centers approved the study protocols (UMIN000007440), and written informed consent was obtained from all the patients.

Study patients

We studied 383 patients with PA (181 men; mean age, 55 years) whose diagnosis was based on the criteria of the Japan Endocrine Society (22). Cortisol levels in all patients were suppressed by dexamethasone treatment (1.0 mg). The single-center study enrolled 90 patients (38 men; mean age, 54 years), and the multicenter study enrolled 293 patients (143 men; mean age, 56 years).

AVS procedures

A preinterventional multidetector CT scan of the adrenal glands (2-mm slice thickness) was performed for diagnosis and to map the adrenal veins. AVS was performed without ACTH stimulation, via the right femoral vein, using 6-F catheters (GA-UW/A6F S70S for the right adrenal veins, and GA-UW/A6F S65S for the left adrenal veins; Gadelius Medical K.K.). If an adrenal vein could not be located or if the catheter could not engage the orifice of the vein, additional catheters of different shapes, including a 5-F shepherd hook catheter or 5-F cobra-shaped catheter (Hanako Medical Co) were used.

Blood samples from the IVC were taken before the catheter was advanced into the adrenal vein. To sample from the left adrenal vein, a 3-F catheter (Gadelius Medical K.K.) was carefully advanced into the central adrenal vein through the 6-F catheter using a coaxial technique. To sample from the right adrenal vein, the adrenal vein was directly approached from the IVC. The position of the catheter was confirmed using digital subtraction venography plus manually injected contrast medium. A total of 5 mL of adrenal venous blood was obtained by intermittent gentle suction on the left and free drainage on the right adrenal vein. After blood sampling, contrast-enhanced venous imaging was again performed to verify that the catheter tip had remained in a suitable position.

Reference standard

To determine whether the AVS had been successful, plasma cortisol levels of samples from the adrenal veins and IVC were measured using a conventional enhanced chemiluminescence immunoassay (ECLIA; Roche Diagnostics). A sample was considered to be diagnostic if the ratio of the cortisol level of the adrenal vein to the cortisol level of the IVC was >2 (9, 12–14). The AVS was considered to be successful if diagnostic samples were obtained from both the right and left adrenal veins.

Single-center clinical study

Ninety PA patients (38 males; mean age, 54 years) were randomly assigned to undergo AVS evaluated by the new QCA performed semiquantitatively (n = 30), quantitatively (n = 30), and without QCA (control patients, n = 30) at the K center. The cortisol levels of all AVS samples were subsequently measured by the reference standard (ECLIA). AVS was performed by four radiologists (J.S., T.M., W.K., and T.A.), who were blinded to the types of evaluations used for the samples obtained from the three groups, until the initial sample was obtained from each patient. The AVS success rates of J.S., T.M., W.K., and T.A. before the study were 64% (9 of 14), 64% (7 of 11), 60% (6 of 10), and 60% (6 of 10), respectively (see Table 2). The differences between success rates were not significant. Samples tested by the semiquantitative QCA were provisionally considered to be diagnostic if the test line on the immunochromatographic paper remained invisible in the sample from the adrenal veins and visible in the sample from the IVC (Supplemental Figure 1B). If the test line was invisible or slightly visible in the IVC sample, it was diluted 2-fold and re-evaluated by semiquantitative QCA. Samples tested by quantitative QCA were considered to be diagnostic if the ratio of the adrenal vein cortisol level to the IVC cortisol level was >2. Provisional AVS success in the control patients was determined by angiographic findings only. If the test lines did not remain completely invisible in the samples from adrenal veins that were tested by the semiquantitative QCA or inadequate ratios were found in samples tested by the quantitative QCA, additional AVS samples were collected. If the observer could not decide whether there was or was not a visible test line from an adrenal vein sample tested by the semiquantitative QCA, additional AVS samples were collected for testing. For patients undergoing three attempts at sample collection without apparent success, AVS was provisionally considered to be unsuccessful. Finally, the cortisol levels of all samples were determined by the reference assay, in order to evaluate the provisional QCA assessments.

Table 2.

Success Rate of AVS for Patients Tested by Semiquantitative QCA and Quantitative QCA and for Untested Controls in the Single-Center Study

	Semiquantitative QCA Group	Quantitative QCA Group	Control Group	Before Introduction of QCA
Success rate	28/30 (93%)a	28/30 (93%)a	19/30 (63%)	Total, 28/45 (62%); J.S., 9/14 (64%); T.M., 7/11 (64%); W.K., 6/10 (60%); T.A., 6/10 (60%)
Rate of sample recollection	11/30 (37%)	9/30 (30%)

^a

P < .001 vs control group.

Multicenter clinical study

The impact of the new semiquantitative QCA on AVS was evaluated at seven medical centers. Before the implementation of the QCA, the mean success rate of AVS at three centers (K, H, and S) over a 4-year period was 54% (see Table 4). AVS had not been performed at T for 4 years and at I for 3 years (see Table 4). AVS had never been performed at A and SI before the introduction of the QCA (see Table 4). AVS was performed at K, H, T, I, and SI by radiologists who had learned AVS skills at K. At S and A, a cardiologist with experience in percutaneous coronary intervention but not AVS performed AVS. The 293 patients with PA were registered on the database in Kanazawa University and randomly assigned to undergo AVS with (n = 148) or without (control patients, n = 145) semiquantitative QCA. The randomization was stratified according to each individual center. Successful AVS was determined, as previously described by the single-center study protocol.

Table 4.

Rates of Successful AVS for Patients Tested by Semiquantitative QCA and Untested Control Patients at Seven Centers

	QCA Group	Control Group	Before Introduction of QCA
Total	139/148 (93)a,c	87/145 (60)	34/63 (54)
K	33/35 (94)a,c	22/34 (65)	28/45 (62) for 2 y
H	30/32 (94)a,c	20/31 (65)	5/10 (50) for 4 y
S	26/28 (93)a,c	16/28 (57)	1/8 (13) for 2 y
T	22/24 (92)b	16/26 (61)	None for 4 y
I	13/14 (93)b	6/12 (50)	None for 3 y
A	8/8 (100)b	4/7 (57)	None
SI	7/7 (100)b	3/7 (43)	None

Data are expressed as number of patients with successful AVS/total number tested (percentage).

^a

P < .001 vs control group.

^b

P < .05 vs control group.

^c

P < .001 vs before the introduction of QCA.

Statistical analysis

Subject background factors and frequencies of the reference values/levels before the start of the study were compiled according to groups. With regard to the metric values, summarized statistics (mean, standard deviation, maximum, minimum, and median) were calculated according to study groups. The possibility of distribution and summarized statistics being compared between groups was investigated with two tests for the classification data: Wilcoxon's two-sample test (rank sum test) for the order data, and a two-sample t test for the metric data. The success rates of AVS were calculated, and the values were compared with the χ² test.

Results

Accuracy of the plasma cortisol levels determined by the new QCA

The standard curve for the new QCA performed in the quantitative format is shown in Figure 1A. A precision study of the quantitative QCA revealed that the intra-assay and interassay variations were <10% each. A total of 90 samples, which were collected from the IVC and right and left adrenal veins during 30 AVS procedures, were tested by the quantitative QCA and the reference assay in the single-center study. The two assays were found to yield similar results (Figure 1B). The correlation between the cortisol levels ranging from 55 to 43 040 nmol/L that were determined by QCA and the conventional reference assay was excellent (R² = 0.9944; P < .001). A Bland-Altman plot showed that for cortisol levels <16 554 nmol/L, the differences between the two assays were small (Figure 1C). In the upper part of the range, a larger error was acceptable because the main purpose of an IPCA is to collect diagnostic samples.

Semiquantitative QCA

Semiquantitative results were available in 5 minutes. Supplemental Figure 1B shows an example of the results seen when the QCA is performed in the semiquantitative format during AVS. The test line was visible from an IVC sample with a cortisol concentration of 8.4 μg/dL, as measured by the reference standard. The test lines of samples from the right adrenal vein, left adrenal vein (distal), and left adrenal vein (proximal) with cortisol concentrations of 8285, 12 504, and 2144 nmol/L, respectively, as measured by the reference standard, remained invisible. A test line of a sample with a cortisol concentration of 657 nmol/L by the reference standard was slightly visible (Supplemental Figure 1B).

Single-center clinical study

There were no significant differences for age, gender distribution, systolic and diastolic blood pressure, serum potassium level, plasma renin activity, and plasma aldosterone level between the patients randomized to undergo testing by the semiquantitative QCA, the quantitative QCA, and no testing (Table 1). The rates of successful AVS for the patients tested by the semiquantitative and quantitative QCA were both 93% (28 of 30), which were significantly higher than for the controls (63%, 19 of 30; P < .001) (Table 2). The respective rates of collecting additional samples from an individual patient were 37% (11 of 30) and 30% (9 of 30) for the patients tested by the semiquantitative QCA and the quantitative QCA, which was not significant. Successful quantitative QCA measurement of the cortisol levels from adrenal vein samples often required diluting the samples 10-fold or 100-fold. Vessel anomalies were the main causes of AVS failures in both groups of patients tested by the QCA.

Table 1.

Characteristics of Patients in the Single-Center Study Randomized to Control (No Testing), Quantitative QCA, and Semiquantitative QCA

	Semiquantitative QCA	Quantitative QCA	Control	P Value
n	30	30	30
Age, y	55 ± 9	54 ± 10	54 ± 12	ns
Sex (male/female), n	14/16	11/19	13/17
Systolic BP, mm Hg	142 ± 23	152 ± 19	145 ± 17	ns
Diastolic BP, mm Hg	86 ± 13	96 ± 16	90 ± 10	ns
Serum potassium, mEq/L	3.9 ± 0.3	3.8 ± 0.3	3.8 ± 0.5	ns
PRA, ng/mL/h	0.4 ± 0.4	0.3 ± 0.2	0.3 ± 0.3	ns
PAC, pg/mL	147 ± 81	129 ± 69	165 ± 94	ns
ARR	597 ± 551	563 ± 504	707 ± 606	ns

Abbreviations: BP, blood pressure; PRA, plasma renin activity; PAC, plasma aldosterone concentration; ARR, PAC to PRA ratio; ns, no statistical significance between groups. Data are expressed as mean ± SD, unless specified otherwise.

Multicenter clinical study

The differences between age, gender distribution, systolic and diastolic blood pressure, serum potassium level, plasma renin activity, and plasma aldosterone level of the patients randomized to undergo semiquantitative new QCA testing or not undergo testing (control patients) were not significant (Table 3). The total rate of successful AVS for the patients tested by semiquantitative QCA was 94% (139 of 148), which was significantly higher than the AVS success rate of the control patients (60%, 87 of 145; P < .001) (Table 4). The number of times for catheter placement in right and left adrenal veins during AVS is shown in Table 5. There was no significant difference in the number of times of catheter placement between right and left adrenal veins. The rate of unsuccessful AVS in right adrenal veins was significantly higher than in left adrenal veins. Two right adrenal veins could not be located. In six right adrenal veins, the catheter could not engage the orifice because of a short common trunk with an accessory hepatic vein. One unsuccessful AVS in the left adrenal vein was due to misjudgment.

Table 3.

Characteristics of Patients in the Multicenter Study Randomized to Those Tested by Semiquantitative QCA and Those Not Tested (Controls)

	Semiquantitative QCA	Controls	P Value
n	148	145
Age, y	55 ± 11	57 ± 10	ns
Sex (male/female), n	72/76	71/74
Systolic BP, mm Hg	156 ± 19	157 ± 21	ns
Diastolic BP, mm Hg	96 ± 11	95 ± 17	ns
Serum potassium, mEq/L	3.9 ± 0.8	3.8 ± 0.6	ns
PRA, ng/mL/h	0.4 ± 1.0	0.3 ± 0.4	ns
PAC, pg/mL	161 ± 89	159 ± 99	ns
ARR	681 ± 455	852 ± 932	ns

Abbreviations: BP, blood pressure; PRA, plasma renin activity; PAC, plasma aldosterone concentration; ARR, PAC to PRA ratio; ns, no statistical significance between groups. Data are expressed as mean ± SD.

Table 5.

Number of Times of Catheter Placement During AVS in Semiquantitative QCA Group

Catheter Placement	Right Adrenal Vein				Left Adrenal Vein
	1st	2nd	3rd	Failure	1st	2nd	3rd	Failure
No. of patients (%)	89 (60)	27 (18)	24 (17)	8 (5)a	91 (61)	27 (18)	29 (20)	1 (1)

Total number of patients = 148.

^a

P < 0.001 vs left adrenal vein.

Discussion

The results of this study demonstrated that the newly developed QCA system was able to provide quantitative results for plasma cortisol levels within 6 minutes and semiquantitative results within 5 minutes in the clinical setting. In addition, this assay led to higher rates of successful AVS.

AVS is essential for differentiating between subtypes of PA; however, it is a technically challenging procedure. Several methods have been proposed to increase the rate of successful AVS, which include a quantitative IPCA (9, 23). Reardon et al (19) reported that IPCA improved the success rate of obtaining diagnostic samples. The feedback provided by the IPCA allowed the operator to salvage inadequate AVS. The first IPCA was a competitive fluorescence polarization assay that had been modified to decrease the incubation time from 16 to 6 minutes using the TDx reagent system (16). The total measurement time of a single sample was 10 minutes, which included 2 minutes for centrifugation. In other studies, the mean assay times ranged from 10 to 22 minutes and involved somewhat complicated assay procedures. Therefore, most of the methods could not be completed in the catheterization laboratory.

Our new QCA was faster and easier to perform than the previous IPCAs and could be performed at the point of care and easily repeated. The measurement time for our QCA was within 6 minutes, and the additional assistance of laboratory technicians was not required. If catheter repositioning was not needed because of inadequate initial samples, the procedure time for AVS was not increased by the QCA, compared with the time needed for the control patients, which enabled us to perform a randomized controlled trial. The results of the single-center study demonstrated that QCA performed either semiquantitatively or quantitatively led to similar increases in the rates of successful AVS. There were also no differences in the rates of collecting additional samples between the semiquantitative and quantitative assay formats. The quantitative QCA is considered to be more accurate than the semiquantitative format. However, the successful quantitative QCA measurement of high cortisol levels in the adrenal veins required a small amount of time and effort for diluting the samples. Because estimating the proper dilution for obtaining usable results is difficult, many test strips were needed, which was expensive. The price for a single QCA strip is $22. The semiquantitative assay did not require special expensive equipment, such as a densitometer and computer. Therefore, the semiquantitative assay was considered to be sufficient for confirming that the sampling catheter was in an adequate position and thus allowed us to perform a multicenter study.

Our randomized controlled multicenter study demonstrated that the QCA led to an increased rate of successful AVS. None of the previous reports on the IPCA were based on randomized, controlled studies (9, 14, 16–21). With the exception of one study, the other studies were single-center studies. In addition, many factors other than the IPCA might have affected the rate of AVS success, such as the CT system, the skill of the radiologist, features of the catheters used to collect samples, and standardization of the AVS protocol (9, 23). The AVS protocol other than IPCA in this study was originally used at the Kanzawa University Hospital, and the previous AVS success rate at this center was 62%, which was not different from the 65% rate seen for the control patients in this study (Table 4). At the H and S centers, the AVS success rates before this study were 50 and 13%, respectively, which was significantly lower than the 65 and 57% rates for the respective control patients in this study. This finding suggests that, as Young and Stanson (23) reported, only standardization of the AVS protocol other than IPCA can improve the success rate. However, our standardization of the AVS protocol without the addition of the QCA did not lead to increases in AVS success rates to greater than 90%. Notably, a high AVS success rate of 93% was achieved for the patients whose samples were tested by the QCA at the H and S centers (Table 4), which previously had had low AVS success rates. Therefore, the semiquantitative QCA led to increased AVS success rates at centers with initially low AVS success rates. Betz et al have also reported that IPCAs were useful at centers with low AVS success rates (18). Our QCA was also useful at three centers with little or no experience performing AVS (T, I, and SI in Table 4), where the AVS success rates were low in the control group in this study. The person performing AVS at center A and S was a cardiologist with experience in percutaneous coronary intervention but had not previously performed AVS. He performed AVS with a high success rate using our QCA. Vonend (9) and Young and Stanson (23) concluded that because it is technically challenging, AVS should be limited to a few dedicated AVS experts working in specialized centers. However, there are not many specialized centers performing AVS worldwide. Our novel QCA may lead to more centers that are capable of successfully performing this procedure. The identification of increased numbers of patients with surgically curable PA will benefit both patients and physicians (24) and lead to more cost-effective treatments (25).

Most centers around the world use ACTH during AVS (13). Actually, we performed ACTH-stimulated AVS using semiquantitative QCA for 64 PA patients. Blood samples were diluted 6.7-fold and tested. If the test line on the strip remained invisible in the sample from the adrenal veins, samples were provisionally considered to be diagnostic because the adrenal cortisol level was >5546 nmol/L (ie, the ratio of the adrenal vein cortisol level to the IVC cortisol level was at least >5 after ACTH stimulation). The AVS success rate was 100% (data not shown). The use of ACTH and our QCA during AVS might be the best procedure for increasing the AVS success rate. However, the use of ACTH is controversial. Some authors have reported that ACTH stimulation increases the rate of successful AVS (26) but decreases the accuracy of the diagnosis of PA subtype (27), whereas others have reported that a major problem with non-ACTH-stimulated AVS is a stress reaction in the patient, which may affect assessments of the successful AVS and the accuracy of the diagnosis of PA subtype (28).

In our multicenter study, 20 of 293 (6.8%) patients had a cortisol level of >552 nmol/L in a sample from the IVC at the start of AVS, and their mean cortisol level in a peripheral vein sample taken at another time was 329 nmol/L. The patients were stressed during AVS. This stress reaction has been reported to resolve over a 15 minutes period from the start of the AVS procedure (28). Our point-of-care cortisol assay might be useful for confirming that the patient's stress reaction is resolving and lead to later sampling and more accurate results in non-ACTH stimulated AVS.

We developed another strip where the test line remains invisible or clearly visible if the cortisol level is >1655 nmol/L or <414 nmol/L, respectively. This type of strip may be useful for a positive diagnosis using the criterion of a ratio of adrenal vein cortisol level to the IVC cortisol level of >3. Therefore, QCA strips can be designed to accommodate the diagnostic criteria.

In conclusion, we developed a novel QCA that can determine plasma cortisol levels easily, accurately, and quickly at the point of care, without any additional technical assistance. Results of our randomized, controlled multicenter study demonstrated that use of the QCA will lead to increased rates of successful AVS.

Acknowledgments

No grants or fellowships supported the writing of this paper.

Disclosure Summary: T.Y., K.I., and Y.Taka. receive royalties for the technology transfer of this quick cortisol assay (U.S. Patent No. 8927219; Japan Patent No. 5590651) from the Trust Medical Corporation (Kobe, Japan). Our novel quick cortisol assays are now commercially available. The other authors have nothing to disclose.

Abbreviations

 
• A

  Akashi Medical Center

 
• AVS

  adrenal vein sampling

 
• CT

  computed tomography

 
• ECLIA

  enhanced chemiluminescence immunoassay

 
• H

  Houju Memorial Hospital

 
• I

  Ishikawa Prefectural Hospital

 
• IPCA

  intraprocedural cortisol assay

 
• IVC

  inferior vena cava

 
• K

  Kanazawa University Hospital

 
• PA

  primary aldosteronism

 
• QCA

  quick cortisol assay

 
• S

  Sanda Municipal Hospital

 
• SI

  Saiseikai Ishikawa Hospital

 
• T

  Takaoka Municipal Hospital.