Fludrocortisone Suppression Test Research Articles

Primary Aldosteronism: The Role of Confirmatory Tests

The high prevalence of primary aldosteronism among hypertensives justifies large scale screening by the aldosterone-renin ratio; however, this test is subject to several variables responsible for false-positive results. Functional tests to confirm autonomous aldosterone secretion are commonly used, with the fludrocortisone suppression test considered the gold standard, and saline infusion or captopril challenge, the most practical. However, each of these tests has sub-optimal sensitivity and specificity and none has been so far prospectively validated by comparing the results with the lateralization by adrenal vein sampling and the results of surgery. Their role in confirming the diagnosis of primary aldosteronism due to unilateral adenoma remains incompletely resolved.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension

Previous studies based on standard endocrine testing have generally shown a low prevalence of primary aldosteronism, a form of autonomous aldosterone secretion (AAS), in hypertensive individuals. The purpose of this case-control study was to evaluate whether use of appropriately defined controls and combined testing reveal previously undetected AAS in hypertensives. We investigated aldosterone secretion in 180 hypertensives with (n = 44) and without (n = 136) adrenal adenomas on computerized tomography (CT) and 72 matched nonhypertensive individuals with normal adrenal CT. Serum aldosterone and active renin were measured, and the aldosterone/active renin ratio was calculated before and after a modified fludrocortisone-suppression test (FST). In the latter, to eliminate any stimulatory effect of endogenous stress-induced adrenocorticotrophin hormone on aldosterone secretion, we administered 1 mg of dexamethasone on the last day of the classical FST fludrocortisone/dexamethasone suppression test (FDST). Using the 97·5 percentiles of serum aldosterone (74 pM L(-1)) and the aldosterone/renin ratio (32 pM L(-1) mU(-1) L(-1)) values obtained from the controls following the FDST, normal cut-off values indicative of adequate aldosterone suppression were established. Using the combination of these cut-offs, the estimated prevalence of AAS in patients with hypertension was 31%. Multiple linear regression analysis revealed a significant correlation between systolic and/or diastolic arterial blood pressure and the aldosterone value (P < 0·0001 and P < 0·01, respectively) and/or the aldosterone/renin ratio (P < 0·0001 and P < 0·01, respectively), which were obtained following the FDST. By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area

Objective. To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Design. Patient survey study. Setting and subjects. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. Main outcome measures. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Results. Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Conclusion. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

Re‐evaluation of the fludrocortisone test: duration, NaCl supplementation and cut‐off limits for aldosterone

Objective. Primary aldosteronism (PA) is the most common form of secondary hypertension. Thus, the aims of this study were: (1) to clarify whether the fludrocortisone suppression test (FST), which confirms autonomous aldosterone secretion, is reliable when carried out during a shorter period of time and (2) to confirm the importance of NaCl supplementation. The cut‐off limits already obtained for aldosterone in healthy subjects during the FST were applied in hypertensive patients with a high aldosterone to renin ratio (ARR). Material and methods. The healthy subjects were allocated to three groups. Fludrocortisone was administered 4 times daily over 4 days and sodium chloride was supplemented in 3 different doses. The result was applied in 24 hypertensive patients, in 24 healthy subjects (10 women (23–38 years old) and 14 men (23–58 years old)) and in 24 patients with hypertension and high ARR (16 women (45–74 years old) and 8 men (56–73 years old)). Blood pressure, aldosterone, renin, potassium and sodium were measured. Results. After three days of FST, there was a significant decrease in the serum level of aldosterone in the healthy subjects, regardless of high or low sodium chloride supplementation (p<0.001). The decrease in serum aldosterone was significantly less pronounced in patients with PA than in healthy subjects and hypertensive patients without PA (p<0.001). The 95th percentile of plasma aldosterone at the end of the test was 225 pmol/L. Conclusions. The FST can be shortened to 3 days and a daily 500 mg NaCl supplementation is sufficient. A cut‐off value for aldosterone of 225 pmol/L after 4 days with FST is appropriate.

Urinary Aldosterone to Creatinine Ratio in Cats before and after Suppression with Salt or Fludrocortisone Acetate

The endocrine diagnosis of primary hyperaldosteronism in cats currently is based on an increased plasma aldosterone to renin ratio, which has several disadvantages for use in veterinary practice. To establish a reference range for the urinary aldosterone to creatinine ratio (UACR) and to determine whether oral administration of either sodium chloride or fludrocortisone acetate is effective for use in a suppression test. Forty-two healthy cats from an animal shelter and 1 cat with primary hyperaldosteronism from a veterinary teaching hospital. Morning urine samples for determination of the basal UACR were collected from 42 healthy cats. For the suppression tests, urine samples for the UACR were collected after twice daily oral administration for 4 consecutive days of either sodium chloride, 0.25 g/kg body weight (n = 22) or fludrocortisone acetate, 0.05 mg/kg body weight (n = 15). The median basal UACR was 7.2 x 10(-9) (range, 1.8-52.3 x 10(-9)), with a calculated reference range of < 46.5 x 10(-9). Administration of sodium chloride resulted in adequate salt loading in 10 of 22 cats, but without significant reduction in the UACR. Administration of fludrocortisone resulted in a significant decrease in the UACR (median, 78%; range, 44-97%; P < .001) in healthy cats. In the cat with an aldosterone-producing adrenocortical carcinoma, the basal UACR and the UACR after fludrocortisone administration were 32 x 10(-9) and 36 x 10(-9), respectively. Using the UACR for an oral fludrocortisone suppression test may be useful for the diagnosis of primary hyperaldosteronism in cats.

Primary aldosteronism and aldosterone-associated hypertension

The field of primary aldosteronism (PA) and aldosterone-related hypertension has undergone rapid evolution. From a relatively rare curiosity PA has become a common problem particularly in selected hypertensive populations. Patients...

Screening and diagnosis of primary aldosteronism

Primary aldosteronism (PA) is the most common cause of mineralocorticoid hypertension. Different studies using the plasma aldosterone concentration (PAC)–plasma renin activity ratio (ARR ratio) for the screening of patients with hypertension, have shown a marked increase in the detection rate of PA. PA is commonly caused by an adrenal adenoma (APA) or idiopathic bilateral adrenal hyperplasia of the adrenal zona glomerulosa (IHA) and, in rare cases, by the inherited condition of glucocorticoid-remediable aldosteronism (GRA). The early diagnosis of PA is important, not only because the forms caused by adrenal adenoma are surgically curable, but also because correlation between the duration of PA and the development of cardiovascular complications has been reported. Patients with resistant and/or severe hypertension, patients with hypokalemia, those with a family history of hypertension and stroke at an early age, or patients with an adrenal incidentaloma should be screened for PA using the ARR ratio. Suspicion of PA owing to a pathological ratio requires confirmatory testing, including fludrocortisone suppression test, saline infusion and captopril challenge. Adrenal gland imaging is important in subtype differentiation (APA vs IHA), but adrenal venous sampling is the gold standard and should be used when other tests prove inconclusive. Genetic testing has facilitated detection of GRA.

Is There an Unrecognized Epidemic of Primary Aldosteronism? (Pro)

My answer is “no.” Although primary aldosteronism (PA) is likely more common than most experts believed in the 1960–1990 interval, it is not nearly as common as Dr Calhoun and other investigators report from 1990 until now. As many younger clinicians may not remember, this same issue arose soon after Dr Jerome Conn characterized this disease in 1955.1 Reporting on the prevalence of PA in his highly referred population of likely suspects, Dr Conn and coworkers’ estimates were as high as 20%.2 Subsequently, studies on unreferred patients supported a prevalence of <1%.3 The lower estimate was commonly accepted until Gordan and colleagues started screening for PA with the plasma aldosterone:renin ratio (ARR) first described in 19764 and expanded by Hiramatsu et al in 1981.5 In 1993, Gordon et al6 reported an elevated ARR in 20% of 199 patients, with 8.5% having an abnormal saline suppression test and 2.5% proven to have an aldosterone-producing adenoma. Since then, numerous series have been reported (Table). As seen in Table 1, the prevalence of an elevated ARR has varied from 5.5% to 39.0%. Part of the wide variation rises from the use of varying thresholds; more of the variation rises from inclusion of various types of patients. The latter point must be recognized, because most patients in these series were referred to specialized centers, just as Dr Conn’s high numbers were largely derived from a referred population. View this table: Prevalence of Autonomous Hyperaldosteronism and APAs in Patients Tested by ARR Two recently published series epitomize the vagaries of most series listed in the Table. The first is a study of 1125 recently diagnosed subjects with hypertension referred to 14 specialized hypertension clinics throughout Italy.27 Plasma renin activity and plasma aldosterone were measured at baseline and again 60 …

Captopril Test Can Give Misleading Results in Patients With Suspect Primary Aldosteronism

To the Editor: Primary aldosteronism (PA) has emerged as the most common form of secondary hypertension.1 The widespread use of the plasma aldosterone/plasma renin activity ratio as a screening test for both hypokalemic and normokaliemic hypertensive subjects has allowed the demonstration of a high prevalence of this disease, with PA accounting for up to 5% to 10% of all hypertensive patients.1,2 The diagnosis of PA is of particular importance for the clinician, because it has been demonstrated recently that patients with PA are more prone to cardiovascular and cerebrovascular complications, and to target organ damage compared with essential hypertensive subjects with similar risk profiles.3 A positive plasma aldosterone concentration/plasma renin activity ratio should always be followed by a suppression test to definitively confirm the diagnosis. The confirmatory diagnosis is usually made with a saline load test (SLT; oral or intravenous) or with the fludrocortisone suppression test (FST).1 Confirmation of the diagnosis of PA should subsequently undergo a …

Screening for primary aldosteronism

Normokalaemic manifestation of primary aldosteronism is a frequent cause of secondary hypertension. It occurs in approximately 5-12% of all patients with hypertension, primarily patients with severe and uncontrolled blood pressure. Main causes are bilateral adrenal hyperplasia (2/3 of cases) and aldosterone-producing adenoma (1/3 of cases). Screening is performed by measurement of the aldosterone/renin ratio, which is raised in affected patients. Suspicion of primary aldosteronism due to a pathological ratio requires confirmatory testing e.g. by saline infusion test or fludrocortisone suppression test. If the diagnosis is confirmed, the underlying cause of aldosterone excess needs to be identified because therapy differs. First, adrenal imaging (CT/MRI) is performed, which is followed by postural testing in cases with a unilateral lesion. Concordant results confirm the diagnosis of an aldosterone-producing adenoma and allow treatment to proceed to adrenalectomy. In cases of equivocal results or normal/bilaterally enlarged adrenal glands on imaging, adrenal venous sampling must be performed for subtype differentiation.

Comparison of Confirmatory Tests for the Diagnosis of Primary Aldosteronism

Primary aldosteronism (PA) is the most frequent form of secondary hypertension, accounting for up to 5-10% of all hypertensive patients, and the diagnosis of PA can present an important challenge for the clinician. After a positive screening test, the diagnosis is confirmed by a suppression test, often an iv saline load test (SLT) or a fludrocortisone suppression test (FST). The FST is considered by many to be the most reliable but is more complex and expensive. Our objective was to compare the specificity of SLT with FST for the diagnosis of PA. The study included 100 hypertensive patients referred to hypertension units with suspected PA after the screening test. All patients underwent FST and SLT. We assessed plasma aldosterone concentrations (PAC) before and after FST and SLT. After iv SLT, 10.4% of the PA patients were negative and 16.1% of patients with essential hypertension were positive after SLT; that is, a correct diagnosis with SLT was obtained in 88% of patients compared with FST. PAC after SLT and PAC after FST were highly correlated (P < 0.0001). Receiver operator characteristic curve analysis demonstrated that the best cutoff for PAC after SLT was 5 ng/dl. Patients with aldosterone-producing adenoma displayed a smaller reduction of PAC compared with patients with bilateral adrenal hyperplasia; a PAC after SLT greater than 6 ng/dl identified all patients eventually diagnosed as having aldosterone-producing adenoma. This study demonstrates that the iv SLT is a reasonably good alternative to the more expensive and complex FST for the diagnosis of PA after a positive screening test.

High frequency of primary hyperaldosteronism among hypertensive patients from a primary care area in Sweden

Objective. To search for primary hyperaldosteronism (PHA) among previously known hypertensive patients in primary care, using the aldosterone/renin ratio (ARR), and to evaluate clinical and biochemical characteristics in patients with high or normal ratio. Design. Patient survey study. Setting and subjects. The study population was recruited by written invitation among hypertensive patients in two primary care areas in Sweden. A total of 200 patients met the criteria and were included in the study. Main outcome measures. The ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was set to 100, as confirmed in 28 healthy subjects. Patients with increased ARR were considered for a confirmatory test, using the fludrocortisone suppression test. Results. Of 200 patients, 50 patients had ARR > 100; 26 patients were further evaluated by fludrocortisone suppression test. Seventeen of these patients had an incomplete aldosterone inhibition. Conclusion. In total 17 of 200 evaluated patients (8.5%) had an incomplete suppression with fludrocortisone. This confirms previous reports on a high frequency of PHA. No significant biochemical or clinical differences were found among hypertensive patients with PHA compared with the whole sample.

Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity

Familial hyperaldosteronism type II (FH-II) is characterized by the familial occurrence of primary aldosteronism; unlike FH-I, it is not glucocorticoid-remediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. Linkage to a 5-Mbp region of chromosome 7p22 was previously reported in an Australian family with eight affected members. Mutations in the exons or intron-exon boundaries of PRKAR1B (7p22, closely related to PRKAR1A, which is mutated in Carney complex) have been excluded in this family. To refine the region of linkage, and to seek evidence of linkage in a South American family and in three other Australian families with FH-II, using seven closely spaced markers at 7p22. To establish phenotypes (affected, uncertain or unaffected), blood pressure, plasma aldosterone and plasma renin (activity or concentration) were measured and the aldosterone: renin ratio (ARR) calculated. Individuals with consistently increased ARR underwent fludrocortisone suppression testing. The genotypes of the five pedigrees were analysed using seven closely spaced microsatellite markers at 7p22, and two-point and multipoint logarithm of odds (LOD) scores were calculated to assess linkage with FH-II. The combined multipoint LOD score for three families (the original Australian, the South American and a new Australian family) showing linkage at 7p22 was highly significant at 4.61 (theta = 0) for markers D7S462 and D7S517. A newly found recombination event in the first Australian family narrowed the area of linkage by 1.8 Mbp, permitting exclusion of approximately half the candidate genes in the originally reported locus. It was not possible to demonstrate linkage at the 7p22 region in the remaining two Australian families. This study provides further evidence for linkage of FH-II to 7p22, refines the locus, and supports the notion that FH-II may be genetically heterogeneous.

No association between primary aldosteronism and two CYP11B2 polymorphisms in a well-characterized Australian sample

Two aldosterone (aldo) synthase gene (CYP11B2) polymorphisms have been reported to be associated with undifferentiated hypertension (HT), low renin HT and HT due to primary aldosteronism (PAL); (i) a C-344T substitution at a steroidogenic factor-1 binding site in the promoter and (ii) a conversion involving transfer of intron 2 from 11β-hydroxylase (CYP11B1). However, other studies have reported no association or implicated the other allele. So far, reported studies examining these polymorphisms have been confined to European or Japanese hypertensive populations. Using similar laboratory and statistical methods, we compared frequencies of these polymorphisms in 107 predominantly white Caucasian Australian patients with PAL (confirmed by fludrocortisone suppression testing after screening using aldo/renin ratio), with those in 99 normotensive controls. No differences in frequency were found for either polymorphism, whether comparing controls to all with PAL or to those with aldo producing adenoma [n=18] or bilateral adrenal hyperplasia [n=71] (differentiated by adrenal venous sampling). The two polymorphisms were in linkage disequilibrium, as previously reported. Reported associations with HT in several different populations could be due to linkage disequilibrium of these alleles with important functional polymorphisms. The conflicting association data may be a result of the CYP11B2 variants being present on multiple different risk haplotypes. Alternatively, ethnic background might be an important determinant of allele distribution for these polymorphisms. Given the current study's sample size, a direct effect of these polymorphisms in a small subset of our patients is possible, but it excludes overall relative risks greater than 1.9-fold. (See Table 1)

Normokalemic Conn-syndrome: New Approaches in Diagnostics

The clinical features of primary aldosteronism with hypertension, hypokalemia, and metabolic alkalosis were first described by Conn in the mid fifties. The classical form of primary aldosteronism is a rare disease with prevalence rates of 0.1 to 0.5% within the hypertensive population. The normokalemic variant of primary aldosteronism seems much more frequent (5–13%). Although we still do not have a validated and standardized diagnostic protocol for this entity, recent studies have found the aldosterone-to-renin ratio to be a useful screening test. To increase diagnostic sensitivity and specificity of the ratio, aldosterone should be added as the second screening criterion (sensitivity and specificity about 90%). Commercial tests for measuring free plasma renin concentrations recently became available. Using renin concentration instead of renin activity increases diagnostic accuracy; therefore, the aldosterone-to-renin concentration ratio might present a more precise screening test. Apart from that, the influence of antihypertensive medications on hormonal values should be taken into account. Dynamic “confirmatory“ tests for autonomous aldosterone secretion have to follow a positive screening result. One simple confirmatory test is the salt-loading test, but the fludrocortisone suppression test, the captopril challenge test or the determination of urinary aldosterone-18-glucuronide and tetrahydroaldosterone can also be used. Further diagnostic evaluation, such as CT scan, postural-test and in case of discrepancy, adrenal vein catheterization to differentiate the most common forms of primary aldosteronism, aldosterone-producing adenomas, and idiopathic hyperaldosteronism should be performed in cases of proven primary aldosteronism. Since many patients with primary aldosteronism can be cured by operation, and failure to diagnose the disease often leads to significant end-organ damage, evaluating hypertensive patients with therapy-resistant hypertension for primary aldosteronism is important.

Primary aldosteronism—careful investigation is essential and rewarding

Once considered rare, primary aldosteronism (PAL) is now regarded as the commonest potentially curable and specifically treatable form of hypertension. At Greenslopes Hospital Hypertension Unit (GHHU), the decision in 1991 to screen all (and not just hypokalemic or resistant) hypertensives by aldosterone/renin ratio (ARR) testing led to a 10-fold increase in detection rate of PAL and four-fold increase in removal rate of aldosterone-producing adenomas (APAs). The GHHU/Princess Alexandra Hospital Hypertension Unit PAL series stands at 977 patients and 250 APAs removed with hypertension cured in 50–60% (remainder improved). Reliable detection requires that interfering medications are withdrawn (or their effects considered) before ARR measurement, and reliable methods (such as fludrocortisone suppression testing) to confirm PAL. Adrenal venous sampling is the only dependable way to differentiate APA from bilateral adrenal hyperplasia. Genetic testing has facilitated detection of glucocorticoid-remediable, familial PAL. Identification of mutations causing the more common familial variety described by GHHU in 1991 should further aid in detection of PAL.

High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients.

Wide testing of the aldosterone : renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone : renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldosteronism, hypertension responded to spironolactone (12.5-50 mg/day) or amiloride (2.5-10 mg/day). When performed with careful regard to confounding factors, measurement of the aldosterone : renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension.

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.

Primary aldosteronism: rare bird or common cause of secondary hypertension?

Wider application of the aldosterone/plasma renin activity ratio among hypertensives has facilitated the detection of primary aldosteronism at earlier stages of evolution (with most patients normokalemic), and found prevalence rates far greater than those previously reported. Reliable detection of patients with PAL requires that 1) the diagnosis is considered in all hypertensives; 2) blood samples are collected under standardized conditions of diet, posture, and time of day; 3) medications known to alter the ratio are avoided or their effects taken into account; 4) aldosterone and plasma renin activity are measured using consistently accurate assay techniques; and 5) reliable methods (such as fludrocortisone suppression testing) are used to confirm primary aldosteronism. Adrenal venous sampling is the only dependable way to differentiate aldosterone-producing adenoma from bilateral adrenal hyperplasia. As has occurred in familial hyperaldosteronism type I, the elucidation of genetic mutations causing other forms of primary aldosteronism should further facilitate detection of this potentially curable or specifically treatable variety of hypertension.

Primary aldosteronism: a practical approach to diagnosis and treatment.

Primary aldosteronism (PA) may account for as many as 10%-14% of hypertension cases. The plasma aldosterone concentration/plasma renin activity ratio is a simple screening test for PA that should be performed in all patients with refractory/severe hypertension, spontaneous or provoked (by diuretics) hypokalemia, or a requirement for excessive potassium supplementation to maintain normokalemia. PA can be confirmed by a fludrocortisone suppression test or 24-hour urine collection for aldosterone. Confirmatory testing should be followed by high-resolution computerized tomography of the adrenal glands to distinguish bilateral hyperplasia or an adenoma. A solitary tumor greater than 1 cm in size in a younger patient is an indication for surgery; all other (nondiagnostic) findings should be followed by bilateral adrenal venous sampling (if available) to identify a unilateral cause of PA. Treatment for a lateralizing positive study is surgical; spironolactone or another mineralocorticoid receptor antagonist is the treatment of choice for a nonlateralizing study. If adrenal venous sampling is not readily available, patients may be successfully treated pharmacologically.