Screening For Primary Aldosteronism Research Articles

Minireview: primary aldosteronism--changing concepts in diagnosis and treatment.

Primary aldosteronism affects 5-13% of patients with hypertension. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with a plasma aldosterone concentration to plasma renin activity ratio. A high plasma aldosterone concentration to plasma renin activity ratio is a positive screening test result, a finding that warrants confirmatory testing. For those patients that want to pursue a surgical cure, the accurate distinction between the subtypes (unilateral vs. bilateral adrenal disease) of primary aldosteronism is a critical step. The subtype evaluation may require one or more tests, the first of which is imaging the adrenal glands with computed tomography, followed by selective use of adrenal venous sampling. Because of the deleterious cardiovascular effects of aldosterone, normalization of circulating aldosterone or aldosterone receptor blockade should be part of the management plan for all patients with primary aldosteronism. Unilateral laparoscopic adrenalectomy is an excellent treatment option for patients with unilateral aldosterone-producing adenoma. Bilateral idiopathic hyperaldosteronism should be treated medically. In addition, aldosterone-producing adenoma patients may be treated medically if the medical treatment includes mineralocorticoid receptor blockade.

Active renin concentration and the aldosterone/renin ratio in screening primary aldosteronism

The ratio of plasma aldosterone to renin level (aldo/renin ratio) is the preferred screening approach for distinguishing patients with essential hypertension (EHT) from those with primary aldosteronism (PAL). Until now, no reference values have been available for reporting the aldo/renin ratio using plasma active renin concentration (ng/L) instead of plasma renin activity (ng/ml/h). We studied 206 subjects who had either normal blood pressure (controls), EHT or PAL. Plasma active renin concentration was measured by immunoradiometric assay (Biorad, Renin III Generation). Plasma aldo was measured by RIA and expressed in SI units (pmol/L) and in traditional units (ng/dl). The table provides the mean ± SEM of plasma aldo values (pmol/L and ng/dl), plasma active renin concentrations (ng/L) and aldo/renin ratios (pmol/ng and ng/dl/ng/L). EHT patients usually have aldo/renin ratios below 100 (pmol/ng) or 3.6 (ng/dl/ng/L), whereas ratios for patients with PAL are above 140 (pmol/ng) or 5 (ng/dl/ng/L). Results that fall between 100 and 140 (3.6 and 5) suggest a need for repeat testing.

Screening for Primary Aldosteronism: Implications of an Increased Plasma Aldosterone/Renin Ratio

The value of the ratio of plasma aldosterone concentration (aldosterone) to plasma renin activity (renin) to identify patients at risk for primary aldosteronism is controversial. We determined the sensitivity, specificity, and predictive value of the ratio to identify combinations of renin and aldosterone compatible with primary aldosteronism. The ratio was calculated in 505 adults with essential hypertension (143 black women, 82 black men, 122 white women, and 158 white men). We used a conventional cutpoint for an increased ratio (i.e., 20 mL/dL x h). The primary combination of renin and aldosterone considered compatible with primary aldosteronism was increased aldosterone for the concomitant renin, defined as aldosterone in the highest quartile predicted by linear regression on renin. Renin was considered low if it was in the lowest quartile of the sample distribution. The sensitivity of the ratio to identify individuals with increased aldosterone for the concomitant renin was 66% (80% in blacks and 56% in whites; P = 0.009), and the specificity of the ratio was 67% (46% in blacks and 84% in whites; P <0.0001). In 36% of instances of an increased ratio, it was a measure of low renin alone without increased aldosterone for renin (32% in blacks and 45% in whites; P = 0.072). The positive predictive value of the ratio to identify individuals with increased aldosterone for the concomitant renin was 34% (49% in whites and 27% in blacks; P <0.002). The aldosterone/renin ratio lacks sensitivity and specificity and has only a modest predictive value for combinations of renin and aldosterone that are compatible with primary aldosteronism.

Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism.

Antihypertensive drugs influence the neurohumoral cardiovascular system and the concentration of hormones involved in blood pressure regulation. Little is known, however, about the extent to which various antihypertensive drugs influence cardiovascular hormone concentrations and thus disturb the differential diagnosis of hypertension in clinical practice. In this study we compare the impact of different antihypertensive medicaments on the renin-angiotensin-aldosterone system in patients with essential hypertension who are screened for primary aldosteronism. We analysed serum aldosterone (SAC) and plasma renin concentration (PRC) in 37 normotensive controls, 144 hypertensive patients with essential hypertension, and 19 patients with primary aldosteronism. Patients were on different treatment regimens such as single drug or combination therapy with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II subtype 1 (AT1) receptor antagonists, calcium channel blockers, spironolactone and no treatment. In patients with essential hypertension, beta-blocker therapy (n = 47) led to a highly significant suppression of renin, whereas serum levels of aldosterone were not significantly altered. ACE inhibitors and AT1 receptor antagonists (n = 55) decreased aldosterone levels only to a minor extent. Calcium channel blockers (n = 23) had no significant influence on SAC or PRC. In patients with primary aldosteronism treated with spironolactone (n = 8), renin escaped suppression and reached very high levels. Beta-blockers and aldosterone antagonists have the strongest impact on the renin-angiotensin system. The decrease in renin concentration by beta-blockers leads to an increase in the ratio of aldosterone to renin, and thus to false-positive results in patients with essential hypertension. Calcium channel blockers, and probably also ACE inhibitors and AT1 receptor antagonists alone or in combination, may be continued during screening for primary aldosteronism by determination of renin and aldosterone concentration.

Primary aldosteronism: management issues.

Since its initial description in 1955, primary aldosteronism was thought to be a rare cause of hypertension. However, improved screening methods show that primary aldosteronism is a common form of secondary hypertension. Diagnosis of this disorder results in improved or cured hypertension or targeted pharmacotherapy. Patients with hypertension and hypokalemia and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism. A random and ambulatory ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA) that is elevated and a PAC higher than a set cutoff is a positive screen for primary aldosteronism. An increased PAC/PRA ratio alone is not diagnostic of primary aldosteronism; primary aldosteronism must be confirmed by demonstrating inappropriate aldosterone secretion with either the intravenous saline suppression test or measurement of 24-hr urinary aldosterone while the patient is on a high-sodium diet. The two major subtypes of primary aldosteronism are unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA). Patients with APA are usually treated with unilateral adrenalectomy, and patients with IHA are treated medically. The subtype evaluation may require one or more tests, the first of which is imaging the adrenals with computerized tomography (CT). When a solitary unilateral macroadenoma (> 1 cm) and normal contralateral adrenal morphologic pattern are found on CT in a young patient with primary aldosteronism, unilateral laparoscopic adrenalectomy is a reasonable therapeutic option. However, in many cases, CT imaging may reveal normal-appearing adrenals or ambiguous findings. Adrenal venous sampling helps to resolve these clinical dilemmas.

Predictive value of the aldosterone-renin ratio in screening for primary aldosteronism

Predictive value of the aldosterone-renin ratio in screening for primary aldosteronism

Rastreamento, Comprovação e Diferenciação Laboratorial do Hiperaldosteronismo Primário

Hiperaldosteronismo primário (HAP), antes considerado uma causa rara de hipertensão, pode corresponder, em séries recentes, a 5-10% da população de hipertensos. Embora alguns considerem o HAP como a principal causa de hipertensão secundária, outros recomendam cautela na análise desta recente "epidemia". As manifestações clássicas do excesso de aldosterona não estão sempre presentes no HAP, determinando como base para o seu rastreamento a relação aldosterona: renina plasmática (ng/dl:ng/ml/h). Hipertensos com valor desta relação &gt; ou = 25 (e aldosterona &gt;14ng/dl) devem prosseguir numa avaliação que inclui testes de supressão da aldosterona plasmática ou urinária (infusão de salina, administração de fludrocortisona ou dieta hipersódica). A ausência de supressão caracteriza autonomia da secreção de aldosterona e HAP, cujas principais etiologias são o adenoma adrenal (APA) e a hiperplasia bilateral ou hiperaldosteronismo idiopático (HAI). A diferenciação entre APA e HAI - obrigatória para direcionar a intervenção terapêutica -, fundamenta-se na ausência de resposta da aldosterona aos testes de estímulo da renina (teste postural, diuréticos ou dieta hipossódica) no primeiro e na hiperresposta, no último. A complementação diagnóstica inclui a avaliação por TC e, se necessário, cateterismo venoso bilateral com dosagem de aldosterona dos efluentes adrenais para confirmar a origem de seu excesso.

Validity of the Aldosterone-Renin Ratio Used to Screen for Primary Aldosteronism

To determine whether the calculated ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA), a proposed screening test for primary aldosteronism, provides a renin-independent measure of circulating aldosterone that is suitable to judge whether PAC is inappropriately elevated relative to PRA. This study consisting of 221 black and 276 white subjects with previously diagnosed essential hypertension was conducted between 1996 and 2000. Antihypertensive drugs were withdrawn for at least 4 weeks; PAC and PRA were measured while subjects were supine and then seated after 30 minutes of ambulation. The seated measurements were repeated after 4 weeks of oral diuretic therapy with hydrochlorothiazide (25 mg/d). The variation in the aldosterone-renin ratio was strongly and inversely dependent on PRA (R2=0.71; P<.001). When subjects changed position from supine to seated, the increase in mean +/- SD PRA (from 1.18 +/- 1.06 to 1.31 +/- 1.19 ng x mL(-1) x h(-1); P<.001) was associated with an increase in the mean ratio (from 18.6 +/- 52.8 to 25.8 +/- 38.1 h x 10(2); P<.001), whereas the increase in mean +/- SD PRA in response to diuretic therapy (from 1.31 +/- 1.19 to 2.72 +/- 2.67 ng x mL(-1) x h(-1); P=.007) was associated with a decrease in the mean ratio (from 25.8 +/- 38.1 to 16.4 +/- 31.6 h 10(2); P<.001). In patients with previously diagnosed essential hypertension, calculation of the aldosterone-renin ratio does not provide a renin-independent measure of circulating aldosterone that is suitable for determining whether PAC is elevated relative to PRA. Because elevation of the aldosterone-renin ratio is predominantly an indicator of low PRA, its perceived value in screening for primary aldosteronism most likely derives from additional diagnostic tests being done in patients with low-renin hypertension.

Validity of the Aldosterone-Renin Ratio Used to Screen for Primary Aldosteronism

Validity of the Aldosterone-Renin Ratio Used to Screen for Primary Aldosteronism

Primary aldosteronism in a referral hypertension center

Primary aldosteronism (PA) is a potentially curable form of secondary hypertension, but is regarded as being relatively rare in unselected hypertensive populations. The prevalence and characteristics of PA were evaluated on 1046 subsequent hypertensive patients (pts) sent to a referral Hypertension Center between January 1st 1997 and December 31st 1999. Screening of PA was performed with the captopril test. Final diagnosis was based on lack of suppression of aldosterone upon acute volume expansion. Aldosteronoma (A) was defined as a unilateral adrenal nodule on CT scan with enhanced uptake at 131I-cholesterol scintigraphy. The diagnosis of idiopathic hyperaldosteronism (IHA) was based on evidence of bilateral adrenal hyperplasia on CT scan and enhanced bilateral uptake at scintigraphy. Sixty-six (6.3%) pts were finally diagnosed as having PA. In 16 (24.2%) of these pts, A was demonstrated by adrenal CT and scintigraphy, and the diagnosis histologically confirmed in the 10 cases so far submitted to surgery. In the remaining 50 (75.8%) pts IHA was diagnosed. The pts with PA had slightly higher systolic blood pressure values than those with essential hypertension (EH)(171.8±23.3 vs 166.9±14.1 mmHg, P<0.05 by t-test). Known duration of hypertension was greater in the pts with PA, although statistical significance was reached only in those with IHA (median (25°-75° percentile): EH 28 (6-60), IHA 60 (24-120), A 46 (5-87) mo; P=0.004 by ANOVA). At the time of the first visit, 30/66 (45.4%) pts with PA were treated with 2 or more drugs, compared with 152/931 (16.3%) pts with EH (χ2 33.117, P<0.0001); in the former group there were 23/50 (46%) cases of IHA and 9/16 (56.3%) cases of A (χ2 0.182, P=0.670). In the group of the untreated pts there were 536/931 (57.6%) cases of EH, 13/50 (26.0%) cases of IHA and 4/16 (25.0%) cases of A (χ2 25.260, P<0.0001). In these untreated pts hypertension was classified as mild to moderate (i.e., <180/104 mmHg) in 318/536 (59.5%) cases of EH, 8/13 (61.5%) cases of IHA and 3/4 (75.0%) cases of A (χ2 0.428, P=0.807). Serum potassium values were significantly lower in the pts with either IHA or A compared with those with EH (EH 4.0±0.3, IHA 3.6±0.3, A 3.3±0.5 mEq/l; P<0.0001 by ANOVA). However, 37/66 (56.1%) pts with PA had serum potassium values ≥3.6 mEq/l; in this group there were 33/50 (66.1%) cases of IHA and 7/16 (43.7%) cases of A (χ2 1.668, P=0.197). We conclude that: 1) PA is more frequent than traditionally thought; 2) it is not necessarily associated with severe and/or resistant hypertension; 3) IHA seems to be more prevalent than A; 4) hypokalemia is not a sensitive criterion for the screening of PA.

The captopril test for the screening of primary aldosteronism

Aldosterone-to-plasma renin activity ratio (ALDO/PRA) has been proposed as a screening test for primary aldosteronism (PA). However, remarkable overlap between values in patients (pts) with essential hypertension (EH) and pts with PA, particularly in the case of low-renin EH, curtails the accuracy of casual ALDO/PRA determinations for the screening PA in unselected hypertensive populations. The captopril test has been suggested as a useful means to increase the specificity and accuracy of ALDO/PRA for the identification of cases of PA. We formally compared the sensitivity and specificity of ALDO/PRA for the screening of PA before and after a single oral captopril dose in a group of 75 hypertensive pts, including 53 essential hypertensives with baseline PRA < 1ngAI/ml/h after 4 days of controlled Na intake (approximately 100 mmol/day) and 22 historical pts with PA (16 pts with idiopathic hyperaldosteronism (IHA) and 8 pts with unilateral aldosteronoma (A)). Lack of ALDO suppression following an intravenous saline load was used as a gold standard for the diagnosis of PA. The presence of A was confirmed in all of the 6 cases upon surgery; in the remaining 16 pts with PA, the diagnosis of IHA was based on evidence of bilateral adrenal hyperplasia on CT scan with enhanced radiotracer uptake at scintigraphy with 131I-cholesterol under dexamethasone suppression. All pts underwent 2 separate ALDO/PRA determinations in the seated position, at baseline and 90 min after captopril 50 mg per os. Diuretics, ACE-inhibitors and betablockers were withdrawn at least 4 weeks before the test, and substituted with doxazosin and/or calcium antagonists if necessary. On a different occasion, an intravenous saline load (2 l 0.9% NaCl in 4 hours) was carried out; lack of ALDO suppression was defined as ALDO > 7.5 ng/dl at the end of the saline load. Formal ROC curve analysis showed that the areas under the estimated curves for ALDO/PRA before (ALDO/PRAb) and after captopril (ALDO/PRAc) were significantly different (p=0.03). A value of 35 for ALDO/PRAb had 95.4% sensitivity but only 28.4% specificity for the identification of PA; the corresponding sensitivity and specificity values for ALDO/PRAc at the same cut-off were 100% and 68.0%, respectively. Specificity for the identification of A cases at the same cut-off point (100% sensitivity) was 28.3% for ALDO/PRAb and 68.0% for ALDO/PRAc. We conclude that a single determination of ALDO/PRA 90 min after 50 mg captopril is a better screening tool for PA compared with casual ALDO/PRA determinations.

Screening for primary aldosteronism without discontinuing hypertensive medications: Plasma aldosterone-renin ratio

The traditional workup for primary aldosteronism is cumbersome and requires discontinuing antihypertensive medications, which is inconvenient and potentially dangerous. A simple and accurate screening test that can be used without modifying medications is needed. The plasma aldosterone-renin ratio (ARR) is a valid screening assay for primary aldosteronism, but antihypertensives are usually discontinued before obtaining this ratio, limiting its utility. The present prospective study is designed to examine the validity of the ARR as a screening test for primary aldosteronism if the ratio is measured randomly while patients continue antihypertensive therapy. During the 18-month study period, 90 patients were referred to the hypertension clinic with poorly controlled hypertension. ARR was measured in random blood samples in all 90 patients while maintaining their prescribed antihypertensive medications. Those with elevated ARRs (> 100 ng/dL ÷ ng/mL/h) underwent further diagnostic workup, including adrenal computed tomography and/or magnetic resonance imaging and adrenal iodine 131 norcholesterol uptake scan. Fifteen patients (17%) had elevated ARRs greater than 100:1. Ten of 15 patients were found to have adrenal adenoma on diagnostic workup, and adenoma was later confirmed by histological examination after surgical removal in these 10 patients. Five patients were found to have adrenal hyperplasia; all 5 patients responded to antialdosterone treatment. Thus, all 15 patients had good control of blood pressure after surgery and/or antialdosterone medications. No patient showed a falsely elevated ARR. Data suggest that the ARR is a valid screening assay for primary aldosteronism in patients with poorly controlled blood pressure, and discontinuation of antihypertensive medications is not needed for this test.

Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore.

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

Screening for primary aldosteronism in hypertensive patients

Screening for primary aldosteronism in hypertensive patients

Positive screening for primary aldosteronism in blacks and whites with essential hypertension

Positive screening for primary aldosteronism in blacks and whites with essential hypertension

Screening for primary aldosteronism with a logistic multivariate discriminant analysis.

Primary aldosteronism (PA) is the most common endocrine cause of curable hypertension, but no single test unequivocally identifies it. Accordingly, we investigated the usefulness of a logistic multivariate discriminant analysis (MDA) approach for PA screening. Generation of a logistic MDA function based on retrospective analysis of biochemical tests in a large cohort of referred patients with/without confirmed Conn's adenoma (CA), followed by prospective validation of the model. We investigated 574 selected hypertensives: 206 (32 with and 174 without CA) retrospectively, 48 (with a 13% prevalence of CA) prospectively for the validation of the model, and 320 referred hypertensives (with a 3.4% prevalence of CA) similarly evaluated. Patients were referred to a specialised centre for hypertension (4th Clinica Medica--University of Padua) and to a department of Internal Medicine of a regional hospital (Reggio Emilia). In all patients we measured several demographic and biochemical variables and performed a captopril test. A stepwise analysis of variance, based on a model fitted with several different variables, identified baseline (sALDO) and captopril-suppressed plasma aldosterone (cALDO), supine plasma renin activity (sPRA) and K+ as the most informative. Therefore, two models of logistic MDA with sPRA, K+, and either sALDO (model A) or cALDO (model B) were developed and used. ROC analysis was also performed to assess the optimal cut-off values. The model B of MDA provided the best performance and identified CA with 100% sensitivity and 81% accuracy. When used prospectively it showed 100% sensitivity, both in the Padua (88% accuracy) and in the Reggio Emilia series (90% accuracy). However, at both institutions most patients with idiopathic hyperaldosteronism (IHA) were also detected. Thus, although developed from patients with confirmed Conn's adenoma, a strategy based on multivariate discriminant analysis can be used prospectively for accurate screening for primary aldosteronism. Furthermore, it was proven to be accurate and applicable to patients tested with similar modalities at a different institution. Although this approach did not provide a clear-cut discrimination of Conn's adenoma from idiopathic hyperaldosteronism, it may avoid unnecessary and costly further testing in patients with a low probability of primary aldosteronism.

J3 Evaluation of aldosterone/plasma renin activity ratio (ARR) in the screening of primary aldosteronism

J3 Evaluation of aldosterone/plasma renin activity ratio (ARR) in the screening of primary aldosteronism

Single oral administration of captopril may not bring an improvement in screening of primary aldosteronism.

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and 72 with essential hypertension (EHT) to differentiate the two disorders in the following conditions: after overnight recumbency (basal state) and after oral administration of captopril. Screening criteria were determined in order to pick up all of PA patients as positive. After the captopril administration, the specificity of a criterion based on the combination of PAC and PAC/PRA ratio was 93% and positive predictive value 79%. This criterion was superior to other conventional screening methods. However, higher specificity (97%) and positive predictive value (90%) were obtained from a combination criterion based on the basal PAC and PAC/PRA ratio. The single oral administration of captopril may not bring an improvement in the screening of PA.

Screening for primary aldosteronism: hypokalemia in hypertensive patients.

A serum potassium determination is usually recommended for new hypertensive patients as a screening test for primary aldosteronism and as a baseline for drug therapy. Since hypokalemia is not specific for aldosteronism, the authors assessed its use and limitations as a screening test in nine reported studies of 303 patients with aldosterone-producing adenomas (n = 252) or adrenal hyperplasia (n = 51). The optimal potassium cutoff level and the predictive ability of hypokalemia to detect aldosteronism were analyzed in a primary care setting with different diseases, test characteristics, and prevalences. Optimal screening for primary aldosteronism occurred at serum potassium less than 3.2 mEq/l in a primary care, low-prevalence population, and at higher potassium levels in higher-prevalence populations. Other screening tests, such as urinary aldosterone levels and plasma renin activity, showed lower individual test performance characteristics, but when combined were similar in performance to serum potassium measurement.

Is single oral administration of captopril beneficial in screening for primary aldosteronism?

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and in 72 with essential hypertension (EHT) to differentiate the two disorders during the following conditions on normal salt diet: after overnight recumbency (basal state) and 2 hours after oral administration of 25 mg of captopril. Screening criteria were determined so that all PA patients were diagnosed as positive, and their specificities were compared with those of other conventional screening methods for PA. After captopril administration, the specificity of a criterion based on a combination of PAC and PAC PRA ratio was 93% and positive predictive value was 79%. This criterion was superior to blood pressure response to angiotensin II analog infusion, PRA on salt depletion, and to PAC on salt loading. However, higher specificity (97%) and positive predictive value (90%) were obtained from a criterion based on a combination of basal PAC and PAC PRA ratio. Therefore, the use of a combination criterion based on PAC and PAC PRA ratio at basal state rather than after captopril administration may give a satisfactory result in the screening for PA.