Diagnosis of primary aldosteronism: value of different screening parameters and influence of antihypertensive medication

OBJECTIVE: The aim of this study was to investigate the utility of different screening techniques for primary aldosteronism (PA), including serum aldosterone (SA), plasma renin activity (PRA) and the SA/PRA ratio in hypertensive patients of a tertiary-care centre. Furthermore, the influence of antihypertensive medication on SA and the SA/PRA ratio were studied. DESIGN: Clinical records of 425 hypertensive patients who had SA and PRA measurements over a 27-month period were analysed retrospectively. Eighty patients were excluded from further analysis because of incomplete data. The remaining 345 patients were classified into the following groups: patients with essential hypertension (EH) (n=260, 75.4%), patients with PA (n=49, 14.2%) and patients with secondary hypertension other than PA (n=36, 10.4%). Diagnosis of PA was made in accordance with established laboratory criteria (including measurements of SA, PRA, urinary excretion of aldosterone and metabolites, imaging techniques and response to treatment). RESULTS: Although mean serum potassium values were significantly lower (P<0.001) in the PA group compared with the EH group, 61% of PA subjects were normokalaemic (3.4-5.2 mmol/l). The SA/PRA ratio alone identified 94% of the patients with PA, but was false positive in 30% of the patients with EH. The SA/PRA ratio together with SA>150 g/ml increased the diagnostic accuracy, led to the correct identification of 84% of the patients with PA, and decreased the false-positive rate to 3%. A multivariate binary logistic regression analysis based on SA and PRA was performed, which identified PA with 90% sensitivity and 91% accuracy. The SA(2)/PRA or the SA(3)/PRA ratio was found useful for simplification of the regression analysis. Antihypertensive medication influenced SA, PRA and the SA/PRA ratio only in EH patients. In EH patients taking beta-adrenoceptor antagonists PRA tended to be lower, leading to a significantly higher SA/PRA ratio and therefore increasing the false-negative rate. CONCLUSION: To reduce false-positive results in screening for PA, and thereby avoid unnecessary and cost-intensive diagnostic procedures, SA should be taken into account in addition to the SA/PRA ratio as a second screening criterion. Alternatively, the SA(2)/PRA or the SA(3)/PRA ratio is more accurate screening tests than the SA/PRA ratio. Beta-blockers should be avoided whilst screening for PA.     

Determination of the aldosterone/renin ratio in 269 patients with adrenal incidentaloma.

To determine the prevalence of primary aldosteronism among patients with incidentally discovered adrenal adenomas ('incidentalomas') plasma concentrations of aldosterone (PA) and plasma renin activity (PRA) were determined in 269 patients (100 normotensives, 169 hypertensives) newly referred incidentaloma patients. Among the 100 normotensives a PA [ng/dl]/PRA [ng/ml.h]-ratio (A/R-R) >50 and a concomitant elevation of PA (>15 pg/ml) was initially seen in two cases but further investigations excluded the presence of primary aldosteronism in both patients suggesting a prevalence of primary aldosteronism of <1% among normotensive patients with adrenal incidentaloma. Among the 169 hypertensive incidentaloma patients 14 presented with both, an elevated PA [>15 pg/ml] and an A/R-R >50. Primary aldosteronism was confirmed in 6 of this cases resulting in a prevalence of primary aldosteronism among hypertensive incidentaloma patients of 4%. Although obtained in patients with a supposedly high pre-test probability of primary aldosteronism this percentage--while in keeping with the older literature--is surprisingly low given the recently reported large(r) prevalence of primary aldosteronism among hypertensives in general.     

Who should be screened for primary aldosteronism? A comprehensive review of current evidence

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone‐producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug‐resistant hypertension, hypertensive with spontaneous or diuretic‐induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first‐degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well‐established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.     

Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology

There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity (PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL x h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL x h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.     

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.     

High prevalence of primary aldosteronism in the Tayside hypertension clinic population

Primary aldosteronism (PA) was thought to be rare but recent evidence from Australia suggests that it may be more common. As this has important implications in terms of hypertension management, we undertook to screen for this treatable condition in our hypertension clinic. We obtained blood samples in sequential patients referred for assessment in our hypertension clinic in Tayside for plasma renin activity (PRA) and aldosterone. The aldosterone to PRA ratio (ARR) was used as an initial screening test to identify potential patients with PA. Those patients with an elevated ratio (> or =750) were admitted for the salt loading and fludrocortisone suppression test. These patients also underwent adrenal CT scanning, and in selected patients, adrenal scintigraphy. Between May 1995 and January 1997 (21 months), we screened a total of 495 patients. ARR was available in 465 (93.9%) patients. Out of that number, 77 (16. 6%) had an elevated ratio of > or =750, five of whom had an adrenal adenoma (one had previous adrenalectomy). Forty-five of these patients were admitted for the salt loading and fludrocortisone suppression test with 41 positive test results suggesting PA. One patient with a negative salt loading test result however had an adenoma proven on histology. A total of 43 cases of PA were identified, giving a minimum prevalence of 9.2% (43/465). Potentially the prevalence may be up to 15% assuming that the ARR has a sensitivity of 93% (42/45) in predicting PA. In conclusion, about one in 10 patients attending a hypertension clinic may have PA. This suggests that the prevalence of PA in Tayside is as high as that in the Australian hypertensive population, and this is likely to be true elsewhere, with obvious important implications for hypertension management.     

Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism

Theoretically, the relationship between plasma aldosterone (PA) and PRA in normal subjects under random conditions should differ from that in patients with primary hyperaldosteronism or primary adrenal failure, but should be similar to that in patients with secondary hyperaldosteronism or hyporeninemic hypoaldosteronism. PA, expressed as a function of PRA, the PA/PRA ratio, provides an index of adrenal sensitivity in normal subjects under routine conditions. The random PA/PRA ratios in patients with primary adrenal disorders did not overlap with those in normal subjects, patients with secondary adrenal disorders, hypertensive subjects, or other patients. A single elevated PA/PRA ratio, i.e. more than 920, associated with elevated PA in 4 patients or normal PA in 6 patients indicated primary hyperaldosteronism in 10 patients. However, 5 of 17 patients with chronic renal failure had elevated PA/PRA ratios, but did not have primary hyperaldosteronism. All 14 patients with secondary hyperaldosteronism had elevated PA associated with normal PA/PRA ratios. A single PA/PRA ratio of less than 28 associated with low PA in 18 patients and a normal PA in 1 patient indicated primary adrenal insufficiency, while a low PA associated with a normal PA/PRA ratio indicated hyporeninemic hypoaldosteronism in 7 patients. Fifty-nine patients with nonadrenal disorders other than renal failure had normal PA and PA/PRA ratios. Therefore, with the exception of patients with advanced renal failure, only a single blood sample is required to establish all diagnoses of disorders of the renin-angiotensin-aldosterone axis under random conditions.     

Unadjusted Plasma Renin Activity as a “First‐Look” Test to Decide Upon Further Investigations for Primary Aldosteronism

The authors sought to define the 95th percentile of plasma renin activity (PRA) in a sample of patients with confirmed primary aldosteronism (PA) prior to adjustment of medications as a practical “first‐look” test to identify those with very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR) was measured without adjustment of antihypertensive medications, with further workup as appropriate. Two groups were defined: patients with surgically “confirmed PA” (n=58) and patients with “high‐probability PA” (n=59), defined as having any of the following: computed tomography–confirmed adrenal adenoma plus lateralizing adrenal vein sampling (AVS) without surgery, high ARR and hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia and two had adrenal adenomas. There was no difference between the confirmed and high probability groups. In the absence of highly suspicious clinical features, patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation for PA.     

新疆乌鲁木齐地区原发性醛固酮增多症105例临床分析

目的分析原发性醛固酮增多症(PA)的临床表现、辅助检查及治疗情况。方法对1999年7月至2005年3月间连续确诊的105例患者的临床资料进行回顾性分析。结果89例患者中有低血钾者占85%,血浆立、卧位肾素活性处于正常低值,立、卧位醛固酮水平均增高。醛固酮和肾素活性比值(ARR)>25者占71%,ARR>50者占8%。81例行B超检查,99例行CT检查,20例行MRI检查,其阳性率分别为:51.9%,80.8%,85%。58例原发性醛固酮增多症患者行手术治疗,其中43例血压均恢复正常,15例仍需要药物继续控制血压。结论血浆肾素活性,血浆醛固酮水平,以及血浆醛固酮和肾素活性比值(ARR)是原发性醛固酮增多症的主要定性诊断方法。CT是原发性醛固酮增多症的主要定位诊断依据。外科手术是治疗原发性醛固酮增多症的重要方法。     

Hyperaldosteronism: the internist's hypertensive disease

Primary aldosteronism (PA) is a disorder typically characterized by resistant hypertension, hypokalemia, alkalosis and suppressed plasma renin activity, and excessive aldosterone production. A true estimate of the prevalence of the disorder is difficult to estimate because its detection is dependent on the awareness of the healthcare provider to the disorder, but it has generally been felt to be a rare occurrence. Its frequency of detection began to change when Hiramatsu suggested calculating the ratio of plasma aldosterone/plasma renin activity as a screening tool for the disorder. He found a ratio greater than 75 as a sensitive indicator for aldosterone-producing adenomas. Using the ratio, several investigators have found prevalence ranging from 3 to 9%. Two major classifications of PA exist: aldosterone-producing adrenal adenoma (APA) and zona glomerulosa hyperplasia (IHA). Distinguishing between these 2 entities is important clinically, because removal of a unilateral aldosterone-producing adenoma may result in correction of elevated blood pressure and hypokalemia. Thus, when evaluating hypertensive patients, PA should be suspected in those with moderate to severe hypertension or with hypertension refractory to standard treatment or in hypertensive patients with disease onset at an early age. The aldosterone-to-renin ratio is an easy, inexpensive, and rapid means of screening for the disorder. The ratio is the screening test of choice, but further confirmatory testing is required to clinch the diagnosis. Frequently employed confirmatory tests include urinary aldosterone excretion on a high-salt diet, aldosterone suppression after a saline infusion, and the fludrocortisone suppression test, which is considered the most sensitive confirmatory maneuver. Both high-resolution CT and MRI scans appear to have similar ability to differentiate between APA and IHA. As with essential hypertension, the goal of treatment is to prevent the long-term sequela of hypertension. The underlying pathology resulting in PA dictates the treatment strategy. The drug of choice is spironolactone. Surgical intervention should be entertained in those patients with PA in whom imaging studies suggest an adenoma.     

Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism

An increased plasma aldosterone concentration (PAC) with decreased plasma renin activity (PRA) is the abnormal endocrine finding in primary aldosteronism (PA). However, it remains unknown whether this profile is universal when blood samples are obtained in a random manner. We retrospectively evaluated the renin/aldosterone profile in 71 patients with PA due to unilateral adrenal adenoma. Blood samples were obtained randomly at an out-patient clinic and under standardized conditions during hospitalization before surgery. The frequency of PAC above 15 ng/dl, PRA below 0.5 ng angiotensin I/ml x h, and a PAC/PRA ratio greater than 35 was determined. These three variables showed a large intra- and interpatient variation. At least one measurement of PAC, PRA, and PAC/PRA ratio was in the normal range in 39%, 48%, and 31% of patients, respectively. Only 37% of patients always had the characteristic profile associated with PA. The mean values of PAC at the out-patient clinic were slightly, but significantly, lower than those in the hospital. These results clearly demonstrated that the renin/aldosterone profile in PA is not always abnormal due in part to conditions for blood sampling. We conclude that a single normal PAC, PRA, or PAC/PRA ratio does not excluded the diagnosis of PA in a hypertensive patient, but repeated measurements yields one or more abnormal parameters in the vast majority of patients. The PAC/PRA ratio is recommended to use as a screening, but other testing is required to arrive at the correct diagnosis.     

Detecting and treating primary aldosteronism: primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies, using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. Idiopathic bilateral adrenal hyperplasia (IHA) and aldosterone-producing adrenal adenoma (APA), are the leading causes of primary aldosteronism. Glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, familial hyperaldosteronism type II and carcinomas are rare causes of PA. Patients with hypertension and hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with medication-resistant hypertension should be screened for PA using the PAC/PRA ratio. If a high ratio is found, a sodium loading test or a captopril test is warranted to confirm the diagnosis. Adrenal gland imaging is important in subtype differentiation (APA vs IHA). Adrenal venous sampling should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA. Surgery is considered the treatment of choice for patients with APA, while bilateral hyperplasia subtypes are treated medically. Normalization of aldosterone levels or aldosterone receptor blockade are necessary to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage.     

Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.     

Diagnostic value of the post-captopril test in primary aldosteronism

Primary aldosteronism is a disorder with hypertension, hypokalemia, increased plasma aldosterone, and suppressed renin activity. A random plasma aldosterone/renin activity (PA/PRA) >65 (conventional units ratio [CUR] >30) has been proposed as a screening test. We have retrospectively determined the value of the post-captopril plasma aldosterone/renin activity (CAPT PA/PRA) test for the diagnosis of patients with primary aldosteronism whose PA/PRA was <65. We considered the CAPT PA/PRA test to be positive for primary aldosteronism if either the plasma aldosterone concentration did not drop below 0.33 nmol/L (12 ng/dL) or the ratio was >26 (CUR >12). We found 6 patients with a random PA/PRA of 21 to 60 (CUR 10 to 28), yet with an abnormal post-captopril test criteria for primary aldosteronism. Five had an abnormal saline suppression test, and all 6 were confirmed by a combination of diagnostic localization with computerized axial tomography, iodocholesterol scan, adrenal venous sampling, and/or surgery. Four had idiopathic adrenal hyperplasia, and 2 had an aldosterone-producing adenoma. One other patient had an abnormal random plasma aldosterone/renin activity ratio of 99 (CUR 46), a negative saline infusion study, and was determined to have essential hypertension. In summary, the CAPT PA/PRA, but not the random PA/PRA, correctly diagnosed 6 patients with primary aldosteronism in our institution. An additional patient with essential hypertension was incorrectly diagnosed as having primary aldosteronism by the PA/PRA test. We conclude that the simple addition of 25 mg of captopril, taken orally 2 hours before sampling, enhances the accuracy for diagnosing patients with primary aldosteronism.     

Clinical and biochemical characteristics of normotensive patients with primary aldosteronism: a comparison with hypertensive cases

Objective It is unknown why some patients with biochemical evidence of primary aldosteronism (PA) do not develop hypertension. We aimed to compare clinical and biochemical characteristics of normotensive and hypertensive patients with PA. Design and patients Retrospective comparison of 10 normotensive and 168 hypertensive patients with PA for office or ambulatory blood pressure, serum potassium, plasma aldosterone and renin concentrations; the aldosterone : renin ratio, and tumour size. Comparison of initial hormonal pattern and drop in blood pressure following adrenalectomy in five normotensive and nine hypertensive patients matched for age, sex and body mass index. Results The 10 normotensive patients were women and presented with hypokalemia or an adrenal mass. Age, plasma aldosterone and renin concentrations were similar in normotensive and hypertensive cases, but kalemia and body mass index were significantly lower in the normotensive patients. Mean tumour diameter was larger in the normotensive patients than in the hypertensive matched patients with an adenoma (P < 0·01). In normotensive patients, diastolic blood pressure and upright aldosterone correlated negatively with kalemia. Blood pressure was lowered similarly after adrenalectomy in five normotensive PA patients and in their matched hypertensive counterparts. Aldosterone synthase expression was detected in four out of five adrenal tumours. Conclusions Blood pressure may be normal in patients with well‐documented PA. The occurrence of hypokalemia, despite a normal blood pressure profile, suggests that protective mechanisms against hypertension are present in normotensive patients.     

Cross-classification of JNC VI blood pressure stages and risk groups in the Framingham Heart Study.

BACKGROUND: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are stratified into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (> or =1 associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). OBJECTIVE: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. METHODS: We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. RESULTS: In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group A, 59.3% were in group B, and 38.2% were in group C. In the high-normal or hypertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. CONCLUSIONS: These results provide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice.     

Association of hypotension with hyperreninemic hypoaldosteronism in the critically ill patient

Paradoxical suppression of plasma aldosterone (PA) despite increased plasma renin activity (PRA) has recently been noted in some critically ill patients. To determine the prevalence of this entity and to identify possible etiologic factors, we studied 100 consecutive patients admitted to a medical intensive care unit (ICU). Twenty-two of 100 ICU patients had hyperreninemia and inappropriately reduced PA concentrations, with a PA to PRA ratio less than the 98th percentile of the control population. Comparison of clinical data of these 22 patients with the other hyperreninemic ICU patients revealed no differences in electrolyte concentrations, nutrition, medications, or survival. However, persistent hypotension was much more frequent (91% v 53%). Thus, impaired aldosterone response to hyperreninemia has a high prevalence among critically ill patients and may be related to adrenal damage from persistent hypotension.     

Circadian rhythm of plasma renin activity in older normal and essential hypertensive men: relation with inactive renin, aldosterone, cortisol and REM sleep

The 24-h pattern of plasma renin activity (PRA), inactive renin (IR), plasma aldosterone (PA) and cortisol was studied in 13 normal men and 12 male patients with essential hypertension, all of whom were older than 55 years. Following gradual habituation over 4 days to the sleep laboratory and intravenous lines, blood samples were obtained every 2 h between 0900-2100 h and every 30 min between 2100-0900 h, during which sleep was also monitored. Plasma renin activity showed a circadian rhythm in both groups, but mean levels were lower in the hypertensive subjects (0.92 +/- 0.03 versus 1.41 +/- 0.06 ng/ml per h). The circadian rhythm of PRA in older men appeared to follow the same pattern described in younger individuals. Rapid eye movement (REM) sleep was associated with a small decrease in PRA, but this link was only evident in the normotensive group. Mean 24-h IR levels were also lower in the hypertensive group (7.26 +/- 0.18 versus 15.10 +/- 0.47 ng/ml per h) but were not affected by clock-time and generally showed no association with the 24-h PRA cycle. Mean 24-h PA was closely related to cortisol but not to PRA in both groups. Mean PA levels of the two groups were similar. Thus, the PA:PRA ratio was higher in the hypertensive group. The higher basal PA:PRA ratio in older hypertensives that emerged over the 24-h study period may reflect increased sensitivity of the adrenal gland to angiotensin II (ANG II) in hypertension of the elderly.     

Primary aldosteronism in patients with adrenal incidentaloma: Is screening appropriate for everyone?

Primary aldosteronism (PA) is a common form of secondary hypertension. Several guidelines recommend that patients with adrenal incidentaloma have a high probability of suffering from PA. We conducted a prospective study of 269 consecutive adults with adrenal incidentaloma to investigate the prevalence and clinical characteristics of PA. In total, 9 participants were detected with PA, suggesting a prevalence of 3.35% among the study population. PA participants had a higher blood pressure level by 14/20.8 mm Hg and a lower serum potassium level by 0.8 mmol/L (P < .05). Importantly, all patients with PA presented with concurrent indications (hypertension with or without hypokalemia) for screening of the disease, but they have not undergone relative screening by the referring physician, thus casting doubts about the appropriate implementation of current guidelines in real‐life practice. Intense efforts are needed to familiarize physicians with recommendations for PA to minimize undiagnosed cases and the detrimental sequelae of this endocrine form of hypertension.     

New diagnostic procedure for primary aldosteronism: adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker--application to a case of bilateral multiple adrenal microadenomas.

Formerly, the incidence of primary aldosteronism (PA) among patients with hypertension was believed to be less than 1%. However, recent studies have suggested a much higher incidence of 6.59%-14.4% among such patients. These findings suggest that many cases of PA caused by small aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA) have not been properly diagnosed. To make a more accurate diagnosis in such cases, we developed a new diagnostic procedure for localization of PA, namely, adrenal venous sampling under continuous infusion of adrenocorticotropic hormone (ACTH) and administration of angiotensin II receptor blocker (AVS with ACTH and ARB). Here, we confirm the efficacy of this procedure in the case of a 37-year-old male suspected of having PA. The anticipated diagnosis of PA was based on the presence of hypokalemia, low plasma renin activity (PRA), elevated plasma aldosterone concentration (PAC) and left adrenal mass. However, AVS with ACTH and ARB revealed the presence of bilateral multiple adrenal microadenomas. In the new AVS method, neither ACTH nor the renin-angiotensin system (RAS) exert any influence on the plasma aldosterone level, and a more accurate aldosterone secretary state and a more accurate assessment of the aldosterone secretion of both adrenal glands can be recognized than by conventional AVS. Use of this new method should enable identification of additional cases of APA among patients diagnosed with essential hypertension.