Renin Activity Ratio Research Articles

Are plasma renin activity and aldosterone levels useful as a screening test to differentiate between unilateral and bilateral renal artery stenosis in hypertensive patients?

To evaluate the serum aldosterone (Ald)/plasmatic renin activity (PRA) ratio as a surrogate marker of renin-angiotensin-aldosterone system status in unilateral (Uni)- and bilateral (Bi)-renal artery stenosis (RAS). Seven hundred and eight hypertensive patients (HTP) were studied. Intermediate and high pretest risk of RAS was detected in 66 HTP who subsequently underwent renal gadolinium-enhanced magnetic resonance and arteriography. After application of exclusion criteria 51 HTP remained: 16 with Uni-RAS, 16 with Bi-RAS and 19 essential hypertensives with normal arteries. Nineteen normotensive individuals were also studied. Ald and PRA were determined before and after stenosis resolution by balloon angioplasty and stent implantation. Ald/PRA (ng/dl per (ng/ml per h(-1))) was markedly high in Bi-RAS (5.92 +/- 2.30, P < 0.001), and markedly low in Uni-RAS (0.38 +/- 0.17, P < 0.001) versus essential hypertensives (1.52 +/- 2.02). Multilevel likelihood ratios for Bi-RAS were positive for Ald/PRA higher than 3.6, negative for Ald/PRA lower than 0.2, and neutral for Ald/PRA at least 0.2 and 3.6 or less. ROC analysis identified Ald/PRA lower than 0.5 and Ald/PRA higher than 3.7 to have the best sensitivity and specificity to detect Uni-RAS and Bi-RAS, respectively. In Uni-RAS, but not in Bi-RAS, postinterventional PRA was significantly lower than basal PRA. In Uni-RAS and Bi-RAS, postinterventional Ald was approximately 30% and approximately three times lower than basal Ald, respectively. In essential hypertensives, PRA and Ald showed no changes in the same period. In the population studied, Ald, PRA and Ald/PRA were significantly different among essential hypertensives, and HTP with Uni-RAS or Bi-RAS. Studies with a higher number of patients will allow exploration of the usefulness of pharmacologic aldosterone blockade in Bi-RAS, and to assess the relevance of Ald/PRA to differentiate Uni-RAS from Bi-RAS.

Diagnosis of primary aldosteronism: Comparison of post-captopril active renin concentration and plasma renin activity

A common pharmacologic test for the diagnosis of primary aldosteronism (PA) is the administration of captopril to determine whether an abnormal plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio(ARR) persists, although active renin concentration (ARC) may offer advantages with regard to processing and standardization. A prospective, head-to-head study was conducted between Feb 2008 and Dec 2008. One hundred and fourteen patients enrolled and received captopril to aid in the diagnosis of PA in the TAIPAI intervention. Fifty-one patients were diagnosed with PA. Post-captopril ARC was significantly correlated with PRA. The area under the receiver operating characteristic curve of the post-captopril ARR was not different in PRA vs ARC measurements. When post-captopril ARC-based ARR (ARR(ARC))>35.5 as the cut-off value, we obtained sensitivity of 75.0% and specificity of 86.4% to differentiate PA from essential hypertension. The correlation of individual PRA and ARC after administration of captopril was excellent; especially at the lower PRA levels. Post-captopril ARR(ARC) values used to diagnose PA are not different from post-captopril PRA-based (ARR(PRA)) values in patients without kidney, liver and heart failures. Primary aldosteronism can be diagnosed with a post-captopril cut-off value of ARR(ARC)>35.5 pmol/ng.

Genetic Analyses of the ChimericCYP11B1/CYP11B2Gene in a Korean Family with Glucocorticoid-Remediable Aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2.

Severe life-threatening hypokalemia in a cat with suspected distal renal tubular acidosis

Description of the clinical presentation and management of a critically ill cat with profound hypokalemia associated with a suspicion of distal renal tubular acidosis (DRTA) and secondary hyperaldosteronism. A cat was presented with severe generalized weakness and acute ventilatory failure associated with severe hypokalemia. The acid-base analysis and complete analytical profile of the urine confirmed the presence of a normal anion-gap metabolic acidosis with a urine pH of 7, a disorder consistent with DRTA. The high plasma renin activity, high aldosterone concentration, and low normal plasma aldosterone concentration/plasma renin activity ratio suggested secondary hyperaldosteronism. The management of the patient in the ICU was successful. No identifiable cause could be determined as a cause for the DRTA, so the disorder was assumed to be the primary problem. DRTA is a rare disorder occasionally reported in the veterinary literature; it is especially rare in cats. Complete diagnostic evaluation was necessary to identify the reported disorders as the cause of the clinical presentation. To the author's knowledge, this is the first case reporting DRTA, and a simultaneously documented mineralocorticoid response, as a cause of a life-threatening hypokalemia.

Some considerations about evolution of idiopathic primary aldosteronism

The prevalence of primary aldosteronism has increased since many patients who were previously considered as being affected by low renin essential hypertension are actually satisfying the new diagnostic criteria using plasma aldosterone/ plasma renin activity (PRA) ratio. Many of these cases could be classified as subclinical hyperaldosteronism, having normal aldosterone and low PRA, or in alternative the normal range of aldosterone should be revised. Idiopathic hyperaldosteronism can, in many cases, be considered as an evolutive disease: it can be hypothesized that the biochemical picture can be preceded by essential hypertension and that, after several years, primary aldosteronism can evolve back to essential hypertension due to age-related reduced vascular and adrenal sensitivity to angiotensin II. This effect is also evident after longterm treatment with aldosterone receptors blockers and therefore it possible that aldosterone-receptors blockers are able to normalize the sensitivity of glomerulosa to angiotensin II even after long-term withdrawal. The use of aldosterone receptors blockers prevents cardiovascular complications due to local aldosterone effect at the level of endothelium and mononuclear leukocytes; therefore, these drugs should be also considered for therapy of patients with hypertension. It is not excluded that aldosterone receptor blockers could prevent the onset of idiopathic hyperaldosteronism and its complications in patients with hypertension without primary hyperaldosteronism. From all these considerations it follows that the concept of normal range of aldosterone should be revised and the use of aldosterone receptor blockers should be revisited.

Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

BackgroundPrimary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.Methods and designIn this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR) as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT) as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL) who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin.ConclusionScreening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.

Prevalência do hiperaldosteronismo primário em uma liga de hipertensão arterial sistêmica

Until recently, primary hyperaldosteronism was considered a rare cause of secondary hypertension. However, in recent years, many studies have suggested that this disease can affect up to 20% of hypertensive individuals.To determine the prevalence of primary hyperaldosteronism in hypertensive patients treated at the hypertension league of a university hospital.Serum aldosterone and plasma renin activity levels were measured in 105 patients while they were undergoing standard antihypertensive treatment, with the exception of those using betablockers and spironolactone, in fasting condition and after rest in the supine position for 20 minutes. Those with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test and, after the confirmation of the autonomy of aldosterone secretion, a computed tomography of the adrenals was performed. The results are presented as percentages and means and standard deviations.Of the 105 patients, 6.54% presented refractory hypertension. Nine presented an aldosterone/plasma renin activity ratio > 25 (8.5% of the total). Of these, 08 were submitted to the saline suppression test and 01 (with refractory hypertension) had the diagnosis of primary hyperaldosteronism confirmed (0.96% of the total). A computed tomography of the adrenals was performed, which showed normal results.The prevalence of primary hyperaldosteronism in the studied sample was 0.96% of the total. However, when only the patients with refractory hypertension were evaluated, the prevalence was 14.3%.

Resistant hypertension and hyperaldosteronism

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.

Screening for Primary Aldosteronism in a Cohort of Brazilian Patients With Resistant Hypertension

The objective was to estimate the prevalence of plasma aldosterone concentration:plasma renin activity ratio >30 ng/dL:ng/mL/h in patients with resistant hypertension and to describe the computed tomography findings of adrenal glands in those with elevated ratios. In a cross-sectional design, 492 patients were enrolled. All patients with plasma aldosterone concentration:plasma renin activity ratio >or=30 ng/dL:ng/mL/h (n=77) underwent abdominal computed tomography. Patients with an adrenal image of possible aldosterone-producing adenoma underwent a saline-loading test. The prevalence of elevated plasma aldosterone concentration:plasma renin activity ratio was 15.7% (95% confidence interval, 12.6-19.2). Twelve patients showed adrenal abnormalities on computed tomography. The level of renin was low in 50% of the sample. Results indicate a low prevalence of aldosterone-producing adenoma. Our evidence points out the importance of confirming the hypothesis that essential hypertension, low-renin hypertension, and idiopathic hyperaldosteronism could be the same disease, but at different neurohormonal stages, and aldosterone-producing adenoma may be yet another disease.

Increased carotid intima–media thickness in hypertensive patients with a high aldosterone/plasma renin activity ratio and elevated aldosterone plasma concentration

aNeurology Department, Spain bClinical and Experimental Vascular Risk Unit, University Hospital Virgen del Rocio, Seville, Spain Correspondence to Professor Dr Pablo Stiefel, MD, PhD, Unidad Clínico Experimental de riesgo Vascular (UCERV), University Hospital Virgen del Rocio, Avda Manuel Siurot s/n, 41013 Seville, Spain Tel: +34 955012266; e-mail: [email protected]

Increased carotid intima–media thickness in hypertensive patients with a high aldosterone/plasma renin activity ratio and elevated aldosterone plasma concentration

Increased carotid intima–media thickness in hypertensive patients with a high aldosterone/plasma renin activity ratio and elevated aldosterone plasma concentration

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin 2 in Experimental Heart Failure

Adrenomedullin 2 (AM2) is a novel member of the calcitonin gene-related peptide family that is thought to play a regulatory role in circulatory homeostasis under normal physiological conditions. The effects of AM2 in heart failure have not been investigated previously. Two incremental doses of human AM2 (10 and 100 ng[kg.min] for 90 minutes each) were given by intravenous infusion to 8 sheep with pacing-induced heart failure. Compared with time-matched control infusions, AM2 produced dose-dependent increases in left ventricular dP/dt(max) (control 1168+/-138 mm Hg/s versus AM2 high-dose 1402+/-130 mm Hg/s; P<0.01) and cardiac output (2.09+/-0.66 L/min versus 3.81+/-0.30 L/min; P<0.001) and reductions in calculated total peripheral resistance (40+/-6 mm Hg(L.min) versus 21+/-4 mm Hg(L.min); P<0.001), mean arterial pressure (74.4+/-2.4 mm Hg versus 66.2+/-2.5 mm Hg; P<0.001), and left atrial pressure (23.3+/-1.0 mm Hg versus 18.8+/-1.3 mm Hg; P<0.001). AM2 administration also induced significant elevations in plasma cAMP (P<0.01) in association with rises in atrial (P<0.05) and brain (P<0.01) natriuretic peptides and plasma renin activity (P<0.01). Despite the increase in renin activity, plasma aldosterone levels were not significantly altered, whereas the aldosterone/plasma renin activity ratio was reduced (P=0.08). Plasma vasopressin, endothelin-1, and catecholamines levels were also unchanged by AM2. Renal effects of AM2 included increased excretion of sodium (P<0.05), cAMP (P<0.01), and creatinine (P<0.05), with augmented creatinine clearance (P<0.05), and a trend for urine output to rise (P=0.068). These results indicate that AM2 administration has favorable effects on cardiovascular, endocrine, and renal indexes in heart failure and identify the peptide as a potential therapeutic target in this disease.

Plasma and urine aldosterone to plasma renin activity ratio in the diagnosis of primary aldosteronism

To establish the best cut-off value of the aldosterone (ALD)/plasma renin activity (PRA) ratio when screening patients for primary aldosteronism. One hundred and six patients with primary aldosteronism and 100 essential hypertensive patients were investigated in rigorous standardized conditions. The ALD/PRA cut-off values were calculated from both the plasma and urine ALD/PRA ratio and analyzed by receiver operating characteristic (ROC) curve. In patients with PRA below 0.2 ng/ml/h [our radioimmunoassay detection limit], values were calculated both with PRA levels set at 0.2 ng/ml/h ('adjusted') and with PRA levels detected ('unadjusted') in the assay. ROC analysis on the ALD/PRA ratio indicated that the best performance was obtained when the plasma ALD (ng/dl)/PRA ratio was used in comparison with that observed in the urine ALD (microg/day)/PRA ratio. In patients with primary aldosteronism, as a whole group, the cut-off value of 69 corresponded to the best compromise value between sensitivity (96%) and specificity (85%), with and without PRA adjustment. In patients with aldosterone-producing adenoma, the cut-off to obtain 100% sensitivity with high specificity (85%) proved to be 69, with and without PRA adjustment. In patients with bilateral adrenal hyperplasia, both with and without PRA adjustment, the best compromise between sensitivity (94%) and specificity (86%) was a cut-off value of 71. The best cut-off to identify patients with primary aldosteronism, corresponding to 69, was obtained by using the plasma ALD/PRA ratio. Adjustment of PRA to 0.2 ng/ml/h does not interfere with calculation of the plasma ALD/PRA ratio cut-off.

Body Mass Index Predicts Plasma Aldosterone Concentrations in Overweight-Obese Primary Hypertensive Patients

Body mass index (BMI) shows a direct correlation with plasma aldosterone concentration (PAC) and urinary aldosterone excretion in normotensive individuals; whether the same applies to hypertensive patients is unknown. Our objective was to determine if BMI predicts PAC and the PAC/plasma renin activity ratio [aldosterone renin ratio (ARR)] in hypertensive patients, and if this affects the identification of primary aldosteronism (PA). This was a prospective evaluation of consecutive hypertensive patients referred nationwide to specialized hypertension centers. Sitting PAC, plasma renin activity, and the ARR, baseline and after 50 mg captopril orally with concomitant assessment of parameters, including BMI and daily sodium intake, were calculated. Complete biochemical data and a definite diagnosis were obtained in 1125 consecutive patients. Of them 999 had primary (essential) hypertension (PH) and 126 (11.2%) PA caused by an aldosterone-producing adenoma in 54 (4.8%). BMI independently predicted PAC (beta = 0.153; P < 0.0001) in PH, particularly in the overweight-obese, but not in the PA group. Covariance analysis and formal comparison of the raw, and the BMI-, sex-, and sodium intake-adjusted ARR with receiver operator characteristic curves, showed no significant improvement for the discrimination of aldosterone-producing adenoma from PH patients with covariate-adjusted ARR. BMI correlated with PAC independent of age, sex, and sodium intake in PH, but not in PA patients. This association of BMI is particularly evident in overweight-obese PH patients, and suggests a pathophysiological link between visceral adiposity and aldosterone secretion. However, it does not impact on the diagnostic accuracy of the ARR for discriminating PA from PH patients.

Diagnostic evaluation of plasma aldosterone concentration to plasma renin activity ratio in primary aldosteronism

Using the plasma aldosterone concentration to plasma renin activity ratio (PAC/PRA ratio) as the screening test of choice for primary aldosteronism in hypertensive patients, we studied the clinical characteristics and the diagnostic value of PAC/PRA ratio in primary aldosteronism. The plasma aldosterone concentration (PAC) and plasma renin activity (PRA) levels were measured by radioimmunoassay in 902 hypertensive patients from out-patient clinics or hospitals. One hundred and twenty-six suspected primary aldosteronism patients whose PAC/PRA ratio was > 25 ng/dL/ng/mL/hr had a lamellar computed tomography (CT) scan in the adrenal gland and follow-up visits. The proportion of primary aldosteronism in hypertensive patients was 14% (126/902). There were 54 patients with unilateral or bilateral hyperplasia and 25 patients with adenoma according to the CT scan. 39% (49/126) of the patients with primary aldosteronism had hypokalemia. Twenty-five patients received surgical treatment. The efficacy and cure rates were 100% (25/25) and 48% (12/25), respectively. The effective rate of aldactone and the single-drug cure rate were 89% (48/54) and 24% (13/54), respectively. Primary aldosteronism affects over 10% of hypertensive patients in China. The PAC/PRA ratio can be considered as a routine screening test in hypertensives, especially resistant hypertensive patients and a high PAC/PRA ratio is an invaluable index in primary aldosteronism diagnosis.

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.

Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism

The clinical presentations of the patient with pheochromocytoma -- a rare endocrine neoplasm -- include adrenal incidentaloma, hypertensive paroxysms, sustained apparent polygenic hypertension, hypertension in pregnancy, and hypertensive crisis induced by anesthesia. Although when undiagnosed a pheochromocytoma can be lethal, it can usually be cured with surgery. Biochemical documentation with measurements of fractionated metanephrines and catecholamines should precede imaging studies. Abdomen and pelvis computed imaging is usually the first imaging test. Careful preoperative pharmacologic preparation is important for a successful surgical outcome. Adrenal pheochromocytomas can usually be removed laparoscopically, whereas, catecholamine-secreting paragangliomas typically require an open approach. All first degree relatives of pheochromocytoma patients should have biochemical testing. In addition, molecular genetic testing for germline mutations should be considered in most patients with adrenal pheochromocytoma and in all patients with paraganglioma. Primary aldosteronism is a relatively common form of secondary hypertension -- affecting 5 to 10% of all patients with hypertension. A plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio should be obtained in patients with hypertension and hypokalemia, resistant hypertension, adrenal incidentaloma and hypertension, onset of hypertension at a young age (e.g., < 20 years of age), severe hypertension (e.g., > or =160 mm Hg systolic or > or =100 mm Hg diastolic), or whenever the clinician is considering other forms of secondary hypertension. The PAC/PRA ratio is a case finding test and a positive result should be confirmed with aldosterone suppression testing with either oral or intravenous sodium loading. The treatment goals for patients with primary aldosteronism are to prevent the morbidity and mortality associated with hypertension, hypokalemia, and cardiovascular damage. Both the subtype of primary aldosteronism and patient preference should dictate the treatment approach.

A possible association between primary aldosteronism and a lower β-cell function

Primary aldosteronism (PA) is the most common secondary cause of hypertension and recently has been implicated as a cause of impaired glucose tolerance. We investigated the glucose insulin sensitivity and insulin secretion in patients with idiopathic primary aldosteronism. Thirty PA patients and 60 essential hypertensive (EH) patients as controls were included, matched (1: 2) by their body mass index (BMI) (29.9 +/- 4.3 versus 29.8 +/- 5.8 m/kg), age (53.7 +/- 9.4 versus 59.9 +/- 8.6 years old) and gender (male/female: 8/22 versus 17/43). In all patients, we measured insulin, total cholesterol, triglycerides, C-peptide and fasting glucose levels. Homeostasis model assessment for insulin resistance (HOMA-IR) and HOMA of pancreatic beta-cell function (HOMA-betaF) indexes were calculated. We also evaluated the response to spironolactone in 19 PA patients. PA patients had higher levels of glucose (5.2 +/- 0.7 versus 4.9 +/- 0.7 mmol/l; P = 0.017). Insulin levels (10.7 +/- 6.5 versus 11.5 +/- 5.8 uUI/ml, P = 0.525) and HOMA-IR (2.51 +/- 1.59 versus 2.45 +/- 1.29 uUI/ml x mmol/l, P = 0.854) were similar in both groups. HOMA-betaF index (138.9 +/- 89.8 versus 179.8 +/- 100.2%, P = 0.049) and C-peptide (0.83 +/- 0.63 versus 1.56 +/- 0.84 ng/dl, P = 0.0001) were lower in PA patients. Potassium was normal in both groups. Negative correlations between serum aldosterone/plasma renin activity (SA/PRA) ratio and HOMA-betaF, and between C-peptide and SA levels were found in all patients. After the spironolactone treatment, we found an increase of C-peptide and insulin levels without changes in HOMA-IR or HOMA-betaF. Our results showed differences in glucose metabolism between PA patients and those with hypertension suggesting that these findings could probably be determined by a lower beta-cell function influenced by aldosterone. These findings highlight the importance of aldosterone in glucose metabolism.

Spontaneous Resolution of Idiopathic Aldosteronism After Long-Term Treatment With Potassium Canrenoate

To the Editor: Primary aldosteronism (PA) is the most common form of secondary hypertension. The prevalence of PA is raised from 1% to 3% to 10% to 15% because of the introduction of the upright plasma aldosterone/plasma renin activity ratio (APR) as screening procedure.1 The pathogenesis of idiopathic PA (IPA), which accounts for 50% of the cases of PA, is still not clear, and several factors have been involved, such as hypersensitivity to angiotensin II or to other stimulating factors or aberrant receptors in the glomerulosa. IPA is usually treated with aldosterone receptor blockers, such as spironolactone, potassium canrenoate (KC), canrenone, or eplerenone, which have, respectively, a high (spironolactone), low (KC and canrenone), or quite absent (eplerenone) antiandrogen activity. The dose of these drugs can be progressively reduced to the lowest amount able to keep normal both blood pressure (BP) and serum potassium. In a previous study,2 we reevaluated 15 patients with IPA 1 month after withdrawal of therapy with KC after 3 to 24 years of treatment. One month after withdrawal, APR was increased only …

Primary Aldosteronism in Diabetic Subjects With Resistant Hypertension

Despite the high prevalence of hypertension in patients with type 2 diabetes, the prevalence of primary aldosteronism in this population has not been determined. One hundred subjects with type 2 diabetes and resistant hypertension, defined as blood pressure > 140/90 mmHg despite the use of > or = 3 antihypertensive agents, were screened for primary aldosteronism. Screening was performed by measuring the plasma aldosterone (PAC)-to-plasma renin activity (PRA) ratio. Subjects with a PAC-to-PRA ratio > 30 ng x ml(-1) x h(-1) underwent confirmatory salt load testing. Diagnostic criteria included 24-h urine aldosterone > or = 12 microg during the 3rd day of the oral salt load or a PAC > or = 5 ng/dl after the 4-h intravenous saline load. Thirty-four subjects had a PAC-to-PRA ratio >30 ng x ml(-1) x h(-1). Fourteen subjects (14% [95% CI 7.2-20.8]) had a confirmed diagnosis of primary aldosteronism. Ninety-three patients were African Americans. There were no differences in age, glycemic control, and number of antihypertensive drugs between subjects with and without primary aldosteronism. Subjects with primary aldosteronism had lower serum potassium (3.7 +/- 0.4 vs. 4.0 +/- 0.4 mmol/l, P = 0.012), higher PAC (15.6 +/- 8 vs. 9.1 +/- 6 ng/dl, P = 0.0016), and higher PAC-to-PRA ratio (98 +/- 74 vs. 21 +/- 30 x ml(-1) x h(-1), P < 0.001) than patients without primary aldosteronism. Primary aldosteronism is common in diabetic patients with resistant hypertension, with a prevalence of 14%. Our results indicate that diabetic subjects with poorly controlled hypertension who are taking > or = 3 antihypertensive drugs should be screened for primary aldosteronism.