Shinshu M ed J, 63⑶ :145〜156, 2015

The Ratio of Plasma Aldosterone Concentration to Potassium in
Adrenocorticotropin Stimulation Test is a Possible New Index for
Diagnosis of Aldosterone‑producing Adenoma in Patientswith Primary Aldosteronism
Hiroaki ISHII, Yuki KOBAYASHI, Yusuke SHIBATA, Takahiro MIYAKOSHI
Wakana MIYAKOSHI, Jun‑ichiro KITAHARA, Kousuke KATO, Naokazu YOKOTA
Yuko KAWAI and Mitsuhisa KOMATSU
Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine,
Shinshu University School of Medicine

Primary aldosteronism (PA)is the most common form of secondary hypertension, and is characterized byhigh plasma aldosterone concentration (PAC)and low plasma renin activity (PRA), refractory hypertension,and occasional hypokalemia. Reliable parameters are required to identify aldosterone‑producing adenoma(APA) in patients with PA, because APA is treatable with surgical resection if localization of aldosterone
hypersecretion can be determined by adrenal venous sampling (AVS).The purpose of this study is to summarize the results of AVS in our institute and to evaluate the diagnostic accuracy of various parameters withadrenocorticotropic hormone (ACTH)stimulation test in identifying probable APA among patients with PA.
Eighty‑one patients with PA were admitted to Shinshu UniversityHospital from April 2009 to March 2013,and
59 patients who underwent AVS were included in the study. PAC and aldosterone to potassium ratio (APR)
in ACTH stimulation tests were examined in 28 patients. Receiver operating characteristic (ROC) curve
analysis was used to evaluate diagnostic accuracy.The response of PAC to ACTH in the probable APA groupwas stronger than that in the others.In ROC curve analysis,the area under the curve(AUC)of APR (PAC/

potassium) for diagnosis of probable APA was 0.9840 with an optimal cutoﬀ value＞102.6 corresponding tosensitivity and speciﬁcity of 94.1% and 90.9 % for diagnosis of APA, respectively. This study indicated that
APR after the ACTH stimulation test may be a useful and accurate parameter in cases of PA.In cases with
APR 100 after ACTH stimulation,AVS is strongly recommended for localization of aldosterone hypersecretion. Shinshu Med J 63 : 145 ―156, 2015
(Received for publication December 8, 2014;accepted in revised form January 28, 2015)
Key words: primary aldosteronism, aldosterone‑producing adenoma, idiopathic hyperaldosteronism,
adrenal venous sampling
Abbreviations: APA, aldosterone‑producing adenoma ; APR, aldosterone potassium ratio ; ARR, aldosterone renin
ratio ;AUC,area under the curve;AVS,adrenal venous sampling ;CR,contralateral ratio ;IHA,idiopathic hyperaldosteronism ;LR, lateralized ratio ;PA, primary aldosteronism ;PAC, plasma aldosterone concentration ;PRA, plasma
renin activity;ROC, receiver operating characteristic

Corresponding author:Mitsuhisa Komatsu
Division of Diabetes, Endocrinology and M etabolism,
Department of Internal Medicine, Shinshu University
School of M edicine, 3‑1‑1 Asahi, M atsumoto, Nagano

Introduction
Primary aldosteronism (PA) is one of the most

390‑8621, Japan

common causes of secondary hypertension and it

E‑mail:mitsuk＠shinshu‑u.ac.jp

should be treated with either surgical or medical

No. 3, 2015

145

Ishii.Kobayashi.Shibata et al.

approaches depending on the etiology.PA was ﬁrst

various parameters in all patients diagnosed with

reported by Conn,who proposed a predominant role

PA in our hospital over a 4‑year period. Weof aldosterone hypersecretion in this syndrome .

conﬁrmed the importance of the adrenocor-

PA was initially considered to be uncommon,but its

ticotropic hormone (ACTH) stimulation test to

incidence has now been established to be approxi-

distinguish between APA and non‑APA , andmately 5%‑10% of all hypertensive patients.

found that the ratio of plasma aldosterone concen-

With the widespread use of diagnostic imaging,suchtration (PAC) to potassium (APR) in the ACTH

as abdominal ultrasonography and computed tomo-

stimulation test may be more useful for this pur-graphy (CT), the opportunities to ﬁnd adrenalpose.

tumor(s)by chance have increased. Some such “incidentalomas”are ﬁnally diagnosed as PA after
endocrinological tests. A recent study in Japan in-Patients and Analysis
Patients and methods

dicated that PA accounted for 5% of adrenal in-

We retrospectively analyzed clinical data fromcidentalomas .PA is often resistant to conventional

patients with PA over the past 4 years.From April

antihypertensive medication and causes cardiovas-

2009 to March 2013, we diagnosed 81 patients as

cular and renal complications compared with essen-having PA at Shinshu University Hospital, M at-tial hypertension

sumoto, Japan, according to the protocol of The. Therefore, it is necessary to

screen for PA in all hypertensive patients.

Japan Endocrine Society. In 59 out of 81 patients,

The aldosterone/renin ratio (ARR)is known to be

we performed AVS because they desired surgicalan excellent index for use in screening for PA .

treatment if necessary. The study protocol was

When ARR screening is positive,conﬁrmatory tests

approved by the Ethics Committee of Shinshu

are added, such as the oral sodium loading test,

University School of Medicine. The study was per-captopril challenge test, saline infusion test,

formed in accordance with the ethical principles of

ﬂudrocortisone suppression test, and upright pos-

the Declaration of Helsinki. M ost patients wereture with furosemide infusion test. The criteria forreferred from local hospitals or clinics for refrac-diagnosis of PA diﬀer between referral centers,andtory hypertension, or detailed examination ofas yet there is no global consensus. After provi-

adrenal incidentaloma or hypokalemia.

sional diagnosis of PA on conﬁrmatory tests, it is

PAC and plasma renin activity (PRA)were mea-

necessary to decide on an appropriate therapeutic

sured in the supine position in the morning.ARR ofstrategy.In this process,localization of aldosterone

200 pg/mL per ng/mL/h or more was considered

hypersecretion provides the most signiﬁcant infor-

positive on PA screening. With regard to deﬁnitive

mation for selecting among therapeutic options.PA

diagnosis of PA, the Japan Endocrine Society rec-can be roughly divided into two categories:aldos-

ommends performing

terone‑producing adenoma (APA) and idiopathic

conﬁrmatory tests. Therefore, we performed two

hyperaldosteronism (IHA). APA can be treateddistinct conﬁrmatory tests:a captopril loading test

surgically if the localization of aldosterone hyperse-

and furosemide infusion test with the patient in thecretion can be determined. At present, the adrenal

upright posture.In the captopril‑loading test,cases

venous sampling test (AVS) is the most usefulwere considered positive if ARR was over 200 pg/

means of determining the localization of aldoster-mL per ng/mL/h at 60 min or 90 min after adminis-

one hypersecretion. However, AVS is expensive,

tration of 50 mg of captopril. Furosemide (40 mg)

relatively invasive,and requires a great deal of skill

was infused intravenously,and we determined PRA

to perform ;therefore,new methods are required as

at 60 min and 120 min after infusion with the patientadjuncts for diagnosis of APA before AVS.

in the upright posture. The result was considered

In the present study, we systematically analyzed
146

at least two diﬀerent

positive when PRA was less than 2.0 ng/mL/h at
Shinshu Med J Vol.63

Aldosterone potassium ratio for APA

both time points. When both of these conﬁrmatory
tests were positive, PA was diagnosed. In addition

the bilateral adrenal veins.
Data analysis and statistical methods

to the conﬁrmatory tests,we performed the ACTH

We used the Mann‑Whitney U test for statisticalstimulation test in as many patients as possible

analyses of the ACTH test and furosemide infusion

because it has been reported to be useful as an

test results between the probable APA and otheradjunct for the diagnosis of PA . In the ACTH

patients. The results are given as means ± SEM.

stimulation test, blood samples were taken before

The diagnostic accuracy of various parameters wasand after 30 and 60 min injection of 0.25 mg ofassessed by receiver operating characteristic (ROC)

ACTH in the morning. We measured PAC andcurve analysis and from the area under the curve

plasma cortisol,and calculated the ratio of PAC to(AUC). The diﬀerences in AUC in the ROC curves

cortisol. In all 81 patients, 1 mg dexamethasone

between each parameter were examined using

suppression test was performed in order to rule out

M edCalc. In all analyses, P ＜0.05 was taken toautonomic cortisol hypersecretion or sub‑clinicalindicate statistical signiﬁcance.

Cushingʼs syndrome. Three patients had subclinicalResults

Cushingʼs syndrome concomitant with PA.
AVS was performed to determine the localization

Patientsʼbackgroundsof aldosterone hypersecretion. First, we obtained

We diagnosed 81 patients with PA over the 4‑

baseline samples from four points,i.e.,right and left

year study period.PAC,ARR,and urinary aldoster-adrenal veins and the anterior‑posterior inferior

one were markedly high and PRA was low in our

vena cava of the adrenal vein. Then, we injectedpatients with PA as expected. Among them 59

0.25 mg of ACTH intravenously and obtained blood

patients who underwent AVS were enrolled in thesamples from the same four sites 20 min later.

study. The characteristics and laboratory data of

Successful cannulation was conﬁrmed by the criter-these patients are shown in Table 1. The average

ia proposed by the Japan Endocrine Society.Unilat-

pre‑treatment blood pressure was 144/88 mmHg.

eral hypersecretion was determined with two

The average blood pressure was reduced to 131/82

parameters:lateralized ratio (LR)and contralater-from 144/88 mmHg one month after the treatment :al ratio (CR). LR was calculated by the values of

131/83 from 147/91 in the 33 patients treated with

PAC/cortisol from both sides.CR was calculated bymineralocorticoid receptor antagonists and 130/81

the following equation :CR ＝ (PAC/cortisol fromfrom 142/86 in the 29 with surgical operation.All of

opposite site) / (PAC/cortisol from anterior vena

the patients who received surgical resection hadcava).When CR was less than 1.0,it was consideredsuccessful dose reduction or discontinuation of anti-that aldosterone secretion from the opposite site of

hypertensive drugs. We performed potassium sup-the adrenal gland was profoundly suppressed. We

plementation in 30 cases in which the serum potas-

considered lateralization positive when LR was

sium level at the initial visit to our hospital was lessover 2.6 and CR was less than 1.0. Aldosterone

than 3 mEq/L with the goal of 3 mEq/L or more.

hypersecretion was deﬁned as PAC 14,000 pg/mL.

However, in 9 cases with severe aldosteronism,theWhen both aldosterone hypersecretion and LR＞2.6

plasma potassium level did not exceed 3 mEq/L.

were conﬁrmed, we considered it as “unilateral

The mean value of potassium in 59 patients was 3.4

aldosterone hypersecretion”, which clinically indi-

mEq/L.

cates APA (deﬁned as “probable APA” in thisAs shown in Fig. 1,AVS was attempted in 59 out

study).A diagnosis of bilateral aldosterone hyperse-of the 81 patients with PA,and the technical failure

cretion, which clinically suggested IHA (deﬁned asof AVS occurred in 2 patients.Thus AVS was were“
probable IHA”in this study) was made when the

successfully performed in 57 patients. As thepatients exhibited aldosterone hypersecretion fromremaining 22 patients intended to continue oral

No. 3, 2015

147

Ishii.Kobayashi.Shibata et al.
Table 1 Characteristics and Laboratory Data in 59 Patients with Primary Aldosteronism

Age (yr)
Sex (male:female)
Pre‑treatment systolic BP(mmHg)
Pre‑treatment diastolic BP(mmHg)
Post‑treatment systolic BP(mmHg)
Post‑treatment diastolic BP(mmHg)PAC (pg/mL)
PRA (ng/mL/hr)
ARR (pg/mL per ng/mL/hr)
Serum potassium (mEq/L)
Urinary aldosterone (μg/day)
HbA1c (%)

Mean±SEM
53.3±1.5
27:32

Localization of tumor
Right

22

144±3

Left

23

88±2

Bilateral

7

131±2

None

7

Number82±2377.8±49.6
0.14±0.02
2101±500
3.4±0.1
13.4±1.9
5.5±0.1

Size of tumor
Right
Left

Operation

14.0 mm
16.1 mm
Number26 (44 %)BP,blood pressure;PAC,plasma aldosterone concentration ;PRA,plasma renin activity;
ARR, aldosterone renin ratio

Fig. 1 Proportion of the patients. Overall classiﬁcation of the patients reviewed in the study.
PA, primary aldosteronism ;AVS, adrenal venous sampling ;APA, aldosterone‑producing adenoma ;IHA, idiopathic hyperaldosteronism ;ACTH, adrenocorticotropic hormone

antihypertensive therapy and did not wish to

receptor antagonists. The two patients in whom

undergo AVS, they were treated with aldosterone

AVS failed were also treated with aldosterone rece-

148

Shinshu Med J Vol.63

Aldosterone potassium ratio for APA

Fig. 2

Scattergram of lateralized ratio (A)and contralateral ratio (B) among 3 groups inpatients with PA successfully undergoing AVS.
APA, aldosterone‑producing adenoma ;IHA, idiopathic hyperaldosteronism

ptor antagonists. Based on the results of AVS, weclinically diagnosed 32 and 16 patients as “probable

APA.
ACTH stimulation test

APA” and “probable IHA”
, respectively. The

The ACTH stimulation test was performed in 28

remaining 9 patients showed marginal hypersecre-patients with PA (17 patients with probable APA,9tion of aldosterone, and did not satisfy the criteria

patients with probable IHA, and 2 patients withfor diagnosis of the laterality (Fig. 1).

ambiguous laterality)(Fig. 1). The ACTH stimula-Fig. 2 shows LR and CR in the 57 patients intion test data are shown in Table 2. We compared

whom AVS was successfully performed. The LR

the results of the ACTH stimulation test in between

was 2.6 in all except one of the probable APA

the probable APA patients and the combined

patients (Fig. 2A). Among the 32 patients withpatients with probable IHA and ambiguous later-probable APA,4 had CR＞1(Fig.2B),and 2 patients

ality.The latter group was referred to as “probable

did not agree to surgical resection.Thus,26 patients

non‑APA”.Serum potassium level was lower in thewere treated by surgery.Among the 26 patients,25

probable APA patients than in the probable non‑were histologically diagnosed as having adenomas

APA patients. There were signiﬁcant diﬀerences

and one was diagnosed as having hyperplasia. The

between the probable APA and the probable non‑

CR of the patient showing hyperplasia was exactly

APA patients with regard to PAC before and after

1.0 in AVS, suggesting suppression of aldosterone

30 and 60 min of ACTH stimulation.There were nosecretion from the opposite site of the adrenal glandsigniﬁcant diﬀerences in cortisol levels at any time

would be a valuable addition to clinical diagnosis ofpoint. The response of PAC to the ACTH stimula-

No. 3, 2015

149

Ishii.Kobayashi.Shibata et al.
Table 2 Adrenocorticotropin Stimulation Test
Number
PAC
PAC
PAC
K
of
0 min
30 min60 min(mmol/L)
patients(pg/mL) (pg/mL) (pg/mL)
Probable APA
Probable non‑APA(Probable IHA＋
Ambiguouslaterality)

COR(ng/dL)COR
30 min(ng/dL)COR
60 min(ng/dL)26.2±1.0

17

3.1±0.1438±81852±137 847±131 10.7±0.7 23.3±0.9114.0±0.1

118±10242±24267±239.8±1.2＜0.001＜0.001＜0.001＜0.001

0.466

P value(VS non APA)

22.0±1.0 25.9 ±1.1

0.466

0.906

Data are expressed as means ± SEM . PAC, plasma aldosterone concentration ; COR, plasma cortisol
concentration ;K, potassium ;APA, aldosterone‑producing adenoma ;IHA, idiopathic hyperaldosteronism

tion test in the probable APA group was stronger

signiﬁcance. In general, ACTH stimulation im-

than that in the probable non‑APA, however there

proved the ROC curves as shown in Fig.4.It should

were no signiﬁcant diﬀerences between the two

be noted that 30 min after stimulation might be agroups (Fig. 3A). In contrast, the PAC increment

better time point than 60 min after stimulation.The

from the basal level was robust in the probable

ROC curves, cutoﬀ values, sensitivities, and

APA group (Fig. 3B). As a high value of PAC/

speciﬁcities of various parameters are shown in Fig.

cortisol ratio after the ACTH stimulation test is

4A‑I. With a PAC

one of the hallmarks of PA ,we next analyzed the102.6, sensitivity was 94.1% and speciﬁcity waschanges in PAC/cortisol ratio as shown in Fig. 3C.

90.9 %. The AUC of this parameter reached 0.9840

As expected,the values were higher in the probable(95% CI :0.848‑1.00) (Fig. 4H). The AUC of APR

APA patients than in the probable non‑APA (Fig.

(PAC

3C). As the potassium levels were low and PACs

0.9733 (95% CI :0.831‑1.00) with an optimal cutoﬀ

were high in the probable APA patients,we expect-value＞97.7 corresponding

ed that the aldosterone potassium ratio (APR)

speciﬁcity of 94.1% and 90.9 % for diagnosis ofwould be a useful parameter in the diagnosis of

APA, respectively.

APA.Accordingly,we analyzed the changes in APR
in the ACTH stimulation test. APR was markedly
higher in the probable APA patients than in theprobable non‑APA (Fig. 3D).

/potassium ratio cutoﬀ of/potassium) for diagnosis of APA wasto sensitivity andDiscussion
In this study, we retrospectively analyzed thecharacteristic features of 59 patients with PA who

ROC curve analysis for diagnosis of APA

underwent AVS in our hospital over a 4‑year

We performed ROC curve analysis and calculated

period. PA is the most common etiology of secon-

the sensitivity and speciﬁcity of various parameters

dary hypertension, and APA, which is one of thein the diagnosis of APA in the patients with PA

subtypes of PA, is surgically treatable. Therefore,

cutoﬀvalue of 152 pg/mL,

there is a need for a simple and accessible method to

we obtained a sensitivity of 88.2% and speciﬁcityof

detect APA. In this study, we conﬁrmed the impor-

90.9 %. The AUC of PAC(Fig. 4).With a PAC

for diagnosis of APA

tance of the ACTH stimulation test before adopting

was 0.8984 (Fig. 4A). Among PAC (Fig. 4A‑C),

AVS to identify probable APA among patients with

PAC/cortisol (Fig. 4D‑F), and PAC/potassium

PA .In addition,we found that APR in the ACTH

(Fig. 4G‑I), PAC/potassium had the highest AUC

stimulation test was a potentially powerful andand PAC/cortisol was the lowest AUC,although thereliable parameter in the test. Among the various

diﬀerences in these AUCs did not reach statisticalparameters in the ACTH stimulation test, APR at

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Shinshu Med J Vol.63

Aldosterone potassium ratio for APA

Fig. 3

Changes in PAC/PAC(A),increments in PAC (B),PAC/COR ratio (C),and PAC/
potassium ratio (D)after ACTH injection in the probable APA group (continuous line)
and the probable non‑APA group (dashed line).
Data are shown as means ± SEM . : P ＜0.05, : P ＜0.01,: P ＜0.001 vs.
probable non‑APA group. ACTH, adrenocorticotropic hormone;PAC, plasma aldosterone concentration ;PAC ,PAC at 0 min ;△ PAC,absolute increases ofPAC from0 min, COR, cortisol

30 min after stimulation was suggested to be an

it is generally considered that APA patients show

excellent parameter to detect APA by ROC curve

an ACTH‑dependent aldosterone response,whereas

analysis.By consensus,the ratio of maximum PAC

IHA patients tend to have an angiotensin II‑depen-

to cortisol after ACTH stimulation is a well‑known

dent aldosterone response

parameter in the test.However,our results suggest-several lines of evidence have suggested that PAC

ed that PAC itself is more useful than the PAC toin the upright posture usually decreases in patients

cortisol ratio. In addition, APR may be a morewith APA, and increases in those with IHA

useful parameter for identifying APA. Obviously,

Biglieri reported that an upright posture is usefulaccumulation of larger numbers of cases is requiredfor diﬀerentiating between APA and IHA ,to conﬁrm our hypothesis that APR is an une-although there were some equivocal ﬁndings

quivocally useful parameter in comparison withbackground for these ﬁndings, it was reported that

PAC itself after the ACTH stimulation test.

adrenal sensitivity to angiotensin II was increased. Since the 1970s,.

.As

If we discuss ACTH responsiveness in detail,in IHA patients . In addition, angiotensin II was

there is a wide degree of heterogeneity of Connʼsreported to fail to stimulate aldosterone secretion in

adenoma responsiveness to ACTH

patients with APA . Meanwhile, Tunny et al. re-No. 3, 2015

. However,

151

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Shinshu Med J Vol.63

at 30 min ;COR

,PAC at 300 min ;PAC

,PAC at 60 min ;COR)(F), PAC
,cortisol at 0 min ;COR

/COR

, cortisol at 60 min ;AUC, area under curve;ACTH, adrenocorticotropic hormone;APA, aldosterone‑producing adenoma,PAC at 0 min ;PAC

Fig. 4 ROC curve analysis of various parameters in ACTH stimulation test.
/COR(B), PAC(C), PAC /cortisol(COR)(D), PAC)(E), PAC
/potassium (I)in the diagnosis of probable APA among patients with PA.

PAC,plasma aldosterone concentration ;PAC

A‑I, ROC curve of PAC(A), PAC/potassium (H), and PAC(G), PAC,cortisol/potassium

Ishii.Kobayashi.Shibata et al.

Aldosterone potassium ratio for APA

ported that 40% of APA patients had a response to

useful than the degree of increment in PAC .They

angiotensin II . In the present study, we assessedalso failed to obtain a favorable ROC curve of PAC

PAC response in the upright posture with the fur-before stimulation with ACTH. For example, withosemide infusion test substituting for angiotensin II

PAC

infusion to determine whether APA patients show

0.623, 47.8%, and 69.4%, respectively, in the theresponses to angiotensin II. These results indicateddiagnosis of APA in PA patients.This was probablythat there were signiﬁcant diﬀerences in the PAC

due to overnight suppression of ACTH with dex-

response between APA and IHA patients,but ROC

amethasone. Therefore, dexamethasone loading

curve analysis failed to show excellent sensitivity

may be unnecessary for diﬀerential diagnosis ofand speciﬁcity. In this study, we conﬁrmed the

APA from PA.

, the AUC, sensitivity, and speciﬁcity were

ﬁndings reported by Sonoyama et al.indicating that

We performed the rapid ACTH test without thethe ACTH stimulation test is useful for the diagno-

dexamethasone suppression test, but several days

sis of APA among patients with suspected PA .

after admission when endocrinological stabilization

Physiologically, aldosterone secretion from thehad been achieved.This is why pre‑stimulated PAC

adrenal cortex is regulated by several factors, in-was a relatively good marker to identify clinicalcluding angiotensin II, ACTH, and potassium.

APA in our study. Nevertheless, post‑stimulated

Therefore, we considered that the concentration of

PAC seems to be a more speciﬁc and sensitive

potassium might aﬀect the reactivity of the ACTH

parameter in ROC analysis. This issue should be

stimulation test ; in fact, it was lower in APA

conﬁrmed in future studies. With regard to thepatients than the IHA patients in the present study.

PAC/cortisol ratios before and after ACTH stimu-

This can be understood from the tendency toward

lation,we also performed the analysis using respec-

strong aldosterone hypersecretion in patients withtive peak values, and the sensitivity and speciﬁcity

APA. As potassium supplementation is performed

were essentially the same as the values calculated

for hypokalemia in some patients, the potassium

30 min or 60 min after stimulation.

concentration itself was not suﬃcient to distinguish

Several attempts have already been made to

between IHA and APA in our study,but it would be

localize unilateral aldosterone hypersecretion with-

one factor determining the PAC response. Further,out AVS : single‑photon emission CT with［

we assumed that the PAC response to the ACTH

‑metomidate positron emisiodocholesterol ,［ C］

stimulation test would be enhanced to a greater

sion tomography‑CT , clinical prediction score ,extent if hypokalemia had been corrected.Based on

and parathormone levels . Nevertheless, AVS is

this concept,we considered the ratio of aldosterone

currently considered the gold standard method toand potassium as an index.Accordingly,our results

identifythe lateralityof aldosterone hypersecretion.

suggested that APR may be a very useful indicator

Therefore, selection of appropriate patients forin the diagnosis of APA among patients with PA.

AVS by the ACTH stimulation test is plausible.

‑
I］

Dexamethasone treatment before the ACTH

The future possibilities of APR may be broader

stimulation test was initiallyproposed byKem et al.

than the spectrum explored in this study. Many

. Indeed, Sonoyama et al. performed dexameth-patients with suspected secondary hypertension had

asone pretreatment in their study . If the serum

already received antihypertensive drugs, including

ACTH levels in the morning are suppressed byangiotensin converting enzyme inhibitors,angioten-

pretreatment with 1 mg of dexamethasone over-sin II receptor blockers, aldosterone antagonists,

night,it is possible that the diﬀerence in PAC before

and beta‑blockers,which aﬀected screening for PA.

and after the ACTH stimulation test might become

In the next step, we will apply the ACTH stimula-more apparent. However, Sonoyama et al. foundtion test and evaluate APR under various condi-

that the PAC itself after stimulation was moretions.

No. 3, 2015

153

Ishii.Kobayashi.Shibata et al.

This study was performed in a single medical

reliable parameter in cases of suspected PA. Even

center and with retrospective analysis. One of thewhen CT does not reveal a tumor or swelling of the

drawbacks of our study was the limited number ofadrenal glands,we propose that the ACTH stimula-patients receiving the ACTH stimulation test.How-tion test should be performed in refractory hyper-

ever, this was not due to selection bias, but wastensive patients to identify APA.

simply due to the absence of the ACTH stimulation

Acknowledgments

test as a mandatoryexamination in suspected PA in
our hospital during the study period. To overcome

We are grateful for the excellent support by thethese limitations, it will be necessary to perform a

medical staﬀ in the Department of Radiology andprospective and multi‑center study to conﬁrm the

Urology of Shinshu University School of Medicine.

diagnostic accuracy and usefulness of APR in the

Disclosure Statement

clinical diagnosis of APA.
In conclusion, we conﬁrmed the usefulness of the
ACTH stimulation test in the diagnosis of APA,and

The authors have no potential conﬂicts of interest
associated with this research.

suggested that post‑ACTH APR may be a new andReferences
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