1. Combination of ARR and PAC for a screening of PA Yui Shibayama, MD1, Norio Wada, MD, PhD1, Hironobu Umakoshi, MD2, Takamasa Ichijo, MD, PhD3, Yuichi Fujii, MD, PhD4, Kohei Kamemura, MD, PhD5, Tatsuya Kai, MD, PhD6, Ryuichi Sakamoto, MD, PhD7, Atsushi Ogo, MD, PhD7, Yuichi Matsuda, MD, PhD8 , Tomikazu Fukuoka, MD, PhD9, Mika Tsuiki, MD, PhD2, Tomoko Suzuki, PhD10, Mitsuhide Naruse, MD, PhD2 1Sapporo City General Hospital, 2Kyoto Medical Center, 3Saiseikai Yokohama Tobu Hospital, 4Hiroshima General Hospital of West Japan Railway Company, 5Akashi Medical Center, 6Saiseikai Tondabayashi Hospital, 7Kyushu Medical Center, 8Sanda City Hospital, 9Matsuyama Red Cross Hospital, 10Kitasato University School of Medicine

2. Introduction
For the screening test of primary aldosteronism (PA), aldosterone/renin ratio (ARR) has been utilized as the most reliable test.
However, the combination of very low plasma renin activity (PRA) and low plasma aldosterone concentration (PAC) may cause a false positive result.
To avoid this problem, some investigators recommended
a cut-off value of basal PAC as 100pg/ml or 150pg/ml
combined with an ARR for a screening test of PA.

3. Aim of this study In this study, we aimed to evaluate
the appropriate basal PAC value for detecting
unilateral subtype of PA combined with ARR.

4. Patients
The patients with PA who underwent AVS from 2006 to 2013 were enrolled in the West Japan adrenal vein sampling study (WAVES-J study),
a multi-center collaborative study in Japan.
We analyzed the basal PAC as a cut-off value for a screening test in 449 PA patients who fulfilled the basal ARR>200 and at least one positive confirmatory test.

5. Classification into the four PAC groups
Patients with basal ARR >200
and confirmed as PA (n=449)
Low PAC group (PAC ≦100pg/ml)
(n=54, 12%)
Normal PAC group
(PAC pg/ml)
(n=39, 9%)
High normal PAC group
(PAC pg/ml)
(n=81, 18%)
High PAC group
(PAC >150pg/ml)
(n=275, 61%)
SI>2 before ACTH stimulation (n=40)
SI>5 after ACTH stimulation (n=41)
SI>2 before ACTH stimulation (n=22)
SI>5 after ACTH stimulation (n=32)
SI>2 before ACTH stimulation (n=64)
SI>5 after ACTH stimulation (n=66)
SI>2 before ACTH stimulation (n=175)
SI>5 after ACTH stimulation (n=215)

6. Baseline characteristics of the four PAC groups
Low PAC group
(PAC ≦100pg/ml)
(n=54)
Normal PAC group
(PAC pg/ml)
(n=39)
High normal PAC group
(PAC pg/ml)
(n=81)
High PAC group
(PAC >150pg/ml)
(n=275)
Age (years)
58.6 a±7.8
59.1 a±8.8
55.3±10.9
52.5±11.6
Sex (men: women) (%)
16 (30%): 38 (70%) a
17 (44%): 22 (56%)
36 (44%): 45 (56%)
129 (47%): 146 (53%)
Systolic BP (mmHg)
139.8±16.0
147.2±22.8
141.7±19.1
145.6±19.7
Diastolic BP (mmHg)
84.1±11.0
87.7±15.8
83.9±13.4
87.8±14.3
Duration of HTN (years)
Medication score
5.5 b±7.3
50 b [25-75]
9.6±9.1
57 [50-100]
7.4±7.9
50 [50-100]
8.8±8.1
100 [50-125]
PRA (ng/ml/h)
0.2 b [ ]
0.3 [ ]
0.3 [ ]
PAC (pg/ml)
90 b [72-95]
110 b [ ]
134 b [ ]
228 [ ]
ARR
358 b [ ]
388 b [ ]
440 b [ ]
807 [ ]
Serum K (mEq/l)
3.9 a±0.3
3.9 a±0.4
3.5±0.6
eGFR (ml/min/1.73m2)
77.6±16.1
73.8±13.7
81.4±17.4
78.5±20.1
Adrenal nodule on CT (%)
27 b (50%)
23 (59%)
43 a (81%)
186 (67%)
a: significantly higher than High PAC group, b: significantly lower than High PAC group, p<0.05.

7. Percentages of the unilateral disease in the four PAC groups
After ACTH stimulation 
Low
PAC group
(n=41)
Normal
(n=32)
High normal PAC group
(n=66)
High
(n=215)
LI>2 (n=165)
12 (29%)
9 (28%)
18 (27%)
126 (59%) *
LI>2, CR<1 (n=115)
4 (10%)
5 (16%)
11 (17%)
95 (44%) *
LI>3 (n=116)
3 (7%)
3 (9%)
99 (46%) *
LI>3, CR<1 (n=89)
0 (0%)
2 (9%)
7 (11%)
80 (37%) *
LI>4 (n=101)
6 (9%)
90 (42%) *
LI>4, CR<1 (n=87)
1 (3%)
5 (8%)
81 (38%) *
*: significantly higher than other groups, p<0.05.

8. Percentages of patients with basal PAC less than each cut-off value
Percentages of detectable patients of the unilateral disease in each cut-off value of PAC and the patients with basal PAC less than each cut-off value
PAC
100pg/ml
(n=313)
120pg/ml
(n=281)
150pg/ml
(n=215)
Percentages of detectable patients of the unilateral disease in AVS after ACTH stimulation
LI>2 (n=165)
92.7%
87.3%
76.4%
LI>2, CR<1 (n=115)
96.5%
92.2%
82.7%
LI>3 (n=116)
97.4%
94.8%
85.3%
LI>3, CR<1 (n=89)
100%
97.8%
89.9%
LI>4 (n=101)
97.0%
95.0%
89.1%
LI>4, CR<1 (n=87)
98.9%
93.1%
Percentages of patients with basal PAC less than each cut-off value
12%
21%a
39%b
not significantly different than PAC 100pg/ml, p>0.05.
a: significantly higher than PAC 100pg/ml
b: significantly higher than PAC 120pg/ml, p<0.05.

9. Discussion decreasing the missing of the unilateral disease and
In order to emphasize the usefulness of the cut-off value of basal PAC combined with ARR for a screening test of PA, we have to consider a balance of the following two aspects,
decreasing the missing of the unilateral disease and
decreasing the confirmatory tests and AVS.
It is recommended that
the cut-off value of basal PAC (not exceeding 150pg/ml)
be adopted based on the clinical needs and
the capacity for confirmatory tests and AVS.
In contrast, the effectiveness of medical treatment for the cases with low PAC most of whom have the bilateral disease should be discussed.
be adopted based on and
in each center.

10. Conclusion
In screening for PA, we can find cases with unilateral subtype efficiently by adding basal PAC to ARR and can reduce excessive confirmatory tests and AVS.