201021184-191

(primary aldosteronism)(secondary
hypertension)
(screening test)(plasma aldosterone concentration)(plasma
renin activity)(ARR)(aldosterone to renin ratio)30 ng/dl per ng/ml/hour
(confirmatory tests)1.(oral sodium loading test), 2.
(intravenous saline infusion test), 3.Fludrocortisone(Fludrocortisone suppression
test), 4.Captopril test(subtypes)
(aldosterone-producing adenoma)(APA)(bilateral adrenal
hyperplasia)(BAH)(high resolution computed tomography)(HRCT)
(adrenal vein sampling)
(adrenalectomy)

(Resistant hypertension)
(Hypokalemia)
(Primary aldosteronism)
(Secondary hypertension)
(Aldosterone-producing adenoma)
(Bilateral adrenal hyperplasia)

(metabolic alkalosis)

(resistant hypertension)
(hypokalemia)

300690

(essential hypertension)
Conn1955
(primary

aldosteronism)1
Conn
(secondary hypertension)

185

aldosterone-producing adenoma or carcinoma)

(0.1%)

(prevalence)

(0.01~1.5%)

2,3

1981Hiramatsu

(plasma aldosterone concentration)(plasma renin activity)

(ARR) (aldosterone to renin ratio)
4

5,6

(aldosterone-producing adenoma)
5

dexamethasone2mg
(ng/dL)
(ng/mL/hour)ARR(ng/dL per

ng/mL/hour)(screening test)
(confirmatory test)

2~6 1961

5~13% 7-11
7,12

(1.0 ng/ml/hour)

1.

5,13,14

2008Mulatero

2.3.4.
205. (

15

160100)6.

1983~1993108

77.

20(3.5 meq/

(LVH) 10

20%

L)88%30%

ARRARR

43% (subtypes)

( c u t - o ff v a l u e ) 1 9 8 1

16

(bilateral adrenal hyperplasia)

HiramatsuARR75
20~75

35%60%

2041990Gordon

(primary (unilateral) adrenal

30199

hyperplasia)(2%)

9%

cinoma)(1%)(

20 ng/dL

(aldosterone-producing adrenocortical car-

WeinbergerFineberg199330

)(familial hyperal-

dosteronism type I (glucocorticoid-remediable

(sensitivity)90%(specificity)

(familial hyperaldosteronism type II) (2%)

aldosteronism))(1%)

(ectopic

91% 172005Mulatero30
15 ng/dL11ARR30

186

ARR
1.
2.3.
10

spironolactone
angiotensin

(ACE inhibitors)

angiotensin II(ARBs)-

10
()Fludrocortisone(Fludrocortisone
suppression test)

Fludrocortisone acetate0.1

mg2

6 ng/dL

23

-false-positive

10,11

angiotensin angiotensin II

12

dihydropyridine
false-negative

QT(QT dispersion)
24

-10,12

Fludrocortisone

angiotensin fosinopril

22

dihydropyridineamlodipine

()Captopril test

12

~ captopril 25 ~ 50 mg

captopril

()(oral sodium loading test)

30%

Captopril

218 mmol(12.8

test

25,26(accuracy)

false-positive

(creatinine)

false-negativeCaptopril test

18

200 mmol
33.3 nmol(12 g)

Captopril test

27

()(intravenous sa-

losartancaptopril

19

line infusion test)

28

(overnight)

(posture change test)

10 ng/dL

2~4

5~10 ng/dL

50%

5 ng/dL

8,20,21

22

187

8,38

(HRCT)

(MRI)

(contralateral)

10

(lateralization)38

290.5

()

(adrenalectomy)

(macronodule)

30,31

5,11

(adrenal vein sampling)

87%71% 15

131I-6--iodomethyl-19-norcho-

95%

lesterol (NP-59) scintigraphy

100%39

NP-59

40

32,33NP-59
scintigraphy1.5

1(microadeno-

mas)

34

35

2009NP-59 SPECT/CT

1 ~ 6

(laparoscopic

unilateral adrenalectomy)

36

19911220073

535

25

52.3

NP-59 scintigraphy
37

73.3%

(adrenal vein)

22.3(cure rate)
100%182 31 138
16109 17 82
540%(14/35)
60%

(orifice)

4125

(cortisol)

52%

188

35

37
60%
(90%)
42
(multifactorial)
(duration)
spironolactone

43
33 ~ 65 %

189

5~13%
80

30 ng/dL per ng/ml/hour

15 ng/dL

spironolactone

3.0 mmol/L

(hypoaldosteronism)
44

(mineralocorticoid re-

ceptor antagonist) spironolactone

12.5 ~ 25
400
7

spironolactone
25 ~ 50
spironolactone

amiloridetriamterene
spironolactone10eplerenone
(selective miner-

alocorticoid receptor antagonist)

spironolactone11,45

spironolactone
eplerenone

1.Conn JW. Primary aldosteronism, a new clinical syndrome. J

Lab Clin Med 1955; 45: 3-7.
2. Tucker RM, Labarthe DR. frequency of surgical treatment
for hypertension in adults at the Mayo Clinic from 1973 to
1975. Mayo Clin Proc 1977; 52: 549-55.
3. Anderson GH, Blakeman N, Streeten DHP. The effect of
age on prevalence of secondary forms of hypertension in
4429 consecutively referred patients. J Hypertens 1994; 12:
609-15.
4. Hiramatsu K, Yamada T, Yukimura Y, et al. A screening test
to identify aldosterone-producing adenoma by measuring
plasma rennin activity. Results in hypertensive patients. Arch
Intern Med 1981; 141: 1589-93.
5. Mulatero P, Stowasser M, Loh KC, et al. Increased diagnosis
of primary aldosteronism, including surgically correctable
forms, in centers from five continents. J Clin Endocrinol
Metab 2004; 89: 1045-50.
6. Seiler L, Rump LC, Schulte-Monting J, et al. Diagnosis
of primary aldosteronism: value of different screening
parameters and influence of antihypertensive medication.
Eur J Endocrinol 2004; 150: 329-37.
7. Young WF. Primary aldosteronism: renaissance of a

190

syndrome. Clin Endocrinol 2007; 66: 607-18.

8. Lim PO, Dow E, Prennan G, et al. High prevalence of
primary aldosteronism in the Tayside hypertension clinic
population. J Hum Hypertens 2000; 14: 311-5.
9. Young WF. Minireview: primary aldosteronism - changing
concepts in diagnosis and treatment. Endocrinology 2003;
144: 2208-13.
10.Brown CA, Bouldin MJ, Blackston JW, Duddleston DN,
Shepherd JM, Hicks GS. Hyperaldosteronism: The internist's
hypertensive disease. Am J Med Sci 2002; 324: 227-31.
11. Mulatero P, Dluhy RG, Giacchetti G, et al. Diagnosis of
primary aldosteronism: from screening to subtype differentiation. Trends Endocrinol Metab 2005; 16: 114-9.
12.Mulatero P, Rabbia F, Milan A, et al. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.
Hypertension 2002; 40: 897-902.
13.Schwartz GL, Turner ST. Screening for primary aldosteronism in essential hypertension: diagnostic accuracy of
the ratio of plasma aldosterone concentration to plasma rennin activity. Clin Chem 2005; 51: 386-94.
14. Williams JS, Williams GH, Raji A, et al. Prevalence of
primary hyperaldosteronism in mild to moderate hypertension without hypokalemia. J Hum Hypertens 2006; 20:
129-36.
15.Mulatero P, Bertello C, Rossato D, et al. Roles of clinical
criteria, computed tomography scan, and adrenal vein
sampling in differential diagnosis of primary aldosteronism
subtypes. J Clin Endocrinol Metab 2008; 93: 1366-71.
16.
2005; 32: 528-36
17.Weinberger MH, Fineberg NS. The diagnosis of primary
aldosteronism and separation of two major subtypes. Arch
Intern Med 1993; 153: 2125-9.
18.Young WF, Klee GG. Primary aldosteronism. Diagnostic
evaluation. Endocrinol Metab Clin North Am 1988; 17:
367-95.
19.Young WF, Hogan MJ, Klee GG, Grant CS, van Heerden JA.
Primary aldosteronism: diagnosis and treatment. Mayo Clin
Proc 1990; 65: 96-110.
20.Holland OB, Brown H, Kuhnert L, Fairchild C, Risk M,
Gomez-Sanchez CE. Further evaluation of saline infusion for
the diagnosis of primary aldosteronism. Hypertension 1984;
6: 717-23.
21.Arteaga E, Klein R, Biglieri EG. Use of the saline infusion
test to diagnose the cause of primary aldosteronism. Am J
Med 1985; 79: 722-8.
22.Mulatero P, Milan A, Fallo F, et al. Comparison of conrmatory tests for the diagnosis of primary aldosteronism. J
Clin Endocrinol Metab 2006; 91: 2618-23.
23.Stowasser M, Gordon RD. Primary aldosteronism - careful
investigation is essential and rewarding. Mol Cell Endocrinol
2004; 217: 33-9.
24.Lim PO, Farquharson CA, Shiels P, Jung RT, Struthers
AD, MacDonald TM. Adverse cardiac effects of salt with
fludrocortisone in hypertension. Hypertension 2001; 37:
856-61.
25.Agharazii M, Douville P, Grose JH, Lebel M. Captopril

suppression versus salt loading in confirming Primary

aldosteronism. Hypertens 2001; 37: 1440-3.
26.Racine MC, Douville P, Lebel M. Functional tests for
primary aldosteronism: value of captopril suppression. Curr
Hypertens Rep 2002; 4: 245-9.
27.Gian PR, Anna B, Giampaolo B, et al. Comparison of
the captopril and the saline infusion test for excluding
aldosterone-producing adenoma. Hypertens 2007; 50:
424-31.
28.Wu VC, Chang HW, Liu KL, et al. Primary aldosteronism:
Diagnostic accuracy of the losartan and captopril tests. Am J
Hypertens 2009; 22: 821-7.
29.Yan QZ, Li HZ, Pan DL. Causes of delaying diagnosis of
primary hyperaldosteronism with adrenal adenoma and
strategy therefore. Zhonghua Yi Xue Za Zhi 2006; 86:
3002-4.
30.Magill SB, Raff H, Shaker JL, et al. Comparison of
adrenal vein sampling and computed tomography in the
differentiation of primary aldosteronism. J Clin Endocrinol
Metab 2001; 86: 1066-71.
31.Harper R, Ferrett CG, McKnight JA, et al. Accuracy of CT
scanning and adrenal vein sampling in the pre-operative
localization of aldosterone-secreting adrenal adenomas. Q J
Med 1999; 92: 643-50.
32.Hogan MJ, McRae J, Schambelan M, Biglieri EG. Location
of aldosterone-producing adenomas with 131I-19-iodocholesterol. N Engl J Med 1976; 294: 410-4.
33.Nomura K, Kusakabe K, Maki M, Ito Y, Aiba M, Demura H.
Iodomethylnorcholesterol uptake in an aldosteronoma shown
by dexamethasone suppresswion scintigraphy: relationship
to adenoma size and functional activity. J Clin Endocrinol
Metab 1990; 71: 825-30.
34.Mansoor GA, Malchoff CD, Arici MH, Karimeddini MK,
Whalen GF. Unilateral adrenal hyperplasia causing primary
aldosteronism: limitations of I-131 norcholesterol scanning.
Am J Hypertens 2002; 15: 459-64.
35.Funder JW, Carey RM, Fardella C, et al. Case detection,
diagnosis, and treatment of patients with primary aldosteronism: An endocrine society clinical practice guideline. J
Clin Endocrinol Metab 2008; 93: 3266-81.
36.Yen RF, Wu VC, Liu KL, et al. 131I-6--Iodomethyl-19norcholesterol SPECT/CT for primary aldosteronism patients
with inconclusive adrenal venous sampling and CT results. J
Nucl Med 2009; 50: 1631-7.
37.Lee PH, Wu CJ, Chen YC, Chen HH. Aldosterone-producing
adenoma: clinical presentation, diagnosis and outcomes of
surgery in northern Taiwan. Acta Nephrologica 2009; 23:
143-8.
38.Gordon RD. Primary aldosteronism. J Endocrinol Invest
1995; 18: 495-511.
39.Young WF, Stanson AW, Thompson GB, Grant CS, Farley
DR, van Heerden JA. Role for adrenal venous sampling in
primary aldosteronism. Surgery 2004; 136: 1227-35.
40.Sheaves R, Goldin J, Reznek RH, et al. Relative value of
computed tomography scanning and venous sampling in
establishing the cause of primary hyperaldosteronism. Eur J
Endocrinol 1996; 134: 308-13.

41.Lombardi CP, Raffaelli M, De Crea C, Rufini V, Treglia

G, Bellantone R. Noninvasive adrenal imaging in hyperaldosteronism: is it accurate for correctly identifying
patients who should be selected for surgery? Langenbecks
Arch Surg 2007; 392: 623-8.
42.Wu VC, Chueh SC, Chang HW, et al. Association of kidney
function with residual hypertension after treatment of
aldosterone-producing adenoma. Am J kidney dis 2009; 54:
665-73.

191

43.
2004; 17: 9-21
44.Mattsson C, Young WF. Primary aldosteronism: diagnostic
and treatment strategies. Nat Clin Pract Nephrol 2006; 2:
198-208.
45.Young WF. Primary aldosteronism - treatment options.
Growth Horm IGF Res 2003; 13 (Suppl A): S102-8.

Diagnosis and Treatment of Primary Aldosteronism

Huang-Yang Tseng, Yi-Chou Chen1, Chih-Jen Wu1, and Po-Chuan Wang

Department of Internal Medicine, Hsinchu Mackay Memorial Hospital;

Division of Nephrology, Department of Internal Medicine, Taipei Mackay Memorial Hospital

Primary aldosteronism is the most common form of secondary hypertension. We got more information about
this disease in recent years. We could use aldosterone to renin ratio (ARR) above 30 ng/dL per ng/ml/hour as
screening test and conrmatory tests (oral sodium loading test, intravenous saline infusion test, udrocortisone
suppression test or captopril test) in diagnosis, and we could also differentially diagnose the two major subtypes
of primary aldosteronism, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) by high
resolution computed tomography (HRCT) and even adrenal vein sampling. APA could be cured by adrenalectomy,
but BAH was treated medically. In hypertensive management, by reviewing of the diagnosis and treatment of
primary aldosteronism in this literature, clinicians should pay much more attention to and find possible occult
primary aldosteronism and thus aggressive surgical intervention or medical treatment is indicated. ( J Intern Med
Taiwan 2010; 21: 184-191 )