Primary aldosteronism, a common entity? the myth persists.
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Primary aldosterone excess or hyperaldosteronism is an important cause of hypertension which, when associated with an aldosterone secreting adenoma, is amenable to surgical cure. The biochemical hallmarks of the condition are a relative excess of aldosterone production with suppression of plasma levels of renin (a proxy for angiotensin II, the major trophic substance regulating aldosterone secretion). This combination of a high aldosterone and a low renin is however more commonly associated with 'nodular hyperplasia' of the adrenal glands, a condition not improved by surgery and variably responsive to the effects of the mineralocorticoid antagonist, spironolactone. Until recently the prevalence of either form of secondary hypertension has been thought to be low such that few clinicians 'hunted' for it in the absence of hypokalaemia (the traditional clue for the syndrome). This view has been challenged, firstly by the realisation that no more than 50% of such patients will have a low plasma potassium and secondly by the assumption that a 'normal' plasma aldosterone is in fact inappropriately elevated if the renin level is low. A single measurement of the ratio of aldosterone to renin levels is claimed to be highly predictive of patients who will have primary aldosterone excess. This paper examines the logic behind such claims and presents evidence from the literature that an abnormal ratio is simply a different description of the low renin state and that such patients do not necessarily have mineralocorticoid hypertension. Most patients 'discovered' by this test will have what many call low-renin hypertension, a condition not amenable to specific therapy. Claims that they are peculiarly sensitive to the hypotensive effects of spironolactone have not been tested in controlled trials. The test would however be expected to pick up those individuals with true Conn's syndrome but such patients remain too few in number to justify widespread use of an expensive screening test. (+info)
Primary aldosteronism in normokalemic patients with adrenal incidentalomas.
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OBJECTIVE: Since primary aldosteronism has been reported in asymptomatic incidental adrenal masses (adrenal incidentalomas, AI), the aim of our study was to detect primary aldosteronism in normokalemic patients with AI and to verify whether a raised plasma aldosterone (ALD)/plasma renin activity (PRA) ratio may be useful for diagnosis. DESIGN: One-hundred and twenty-five normokalemic patients with solid AI (90 hypertensives and 35 normotensives) and 82 essential hypertensives (EH) were studied. Upright ALD and PRA determination was performed in all cases while patients with abnormal ALD/PRA ratios were submitted to confirmatory tests (saline infusion and captopril tests) for diagnosis of primary aldosteronism. METHODS: ALD and PRA were measured by specific radioimmunoassays. RESULTS: PRA values in AI hypertensives (1.05+/-0.13 ng/ml/h) were lower than in AI normotensives (1.14+/-0.14 ng/ml/h, P<0.05) and in EH (1.68+/-0.15 ng/ml/h, P<0.0001). The ALD/PRA ratio in AI hypertensives (46.4+/-5.1) was higher than in AI normotensives (30.7+/-5.8, P<0.03) and in EH (33.2+/-3.5). Four patients with EH and 2 AI normotensive patients had elevated ALD/PRA ratios but normal responses to the suppressive tests, thus excluding diagnosis of primary aldosteronism. Eight patients with AI and hypertension had a high ALD/PRA ratio, and 7 of these were further studied: in 5 patients diagnosis of primary aldosteronism was well-established by dynamic tests, adrenal vein sampling or by surgery. CONCLUSIONS: Primary aldosteronism in normokalemic patients with incidentally discovered adrenal masses was detected in 4 of all cases and in at least 5.5% of those with hypertension. Consequently, these patients, particularly if hypertensive, need to be routinely studied to exclude this hormonal disease. Evaluation of the ALD/PRA ratio seems to be a simple and reliable test for diagnosis. (+info)
Discriminating factors for recurrent hypertension in patients with primary aldosteronism after adrenalectomy.
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Patients with primary aldosteronism show relatively high rates of hypertension after adrenalectomy, but the risk factors for postoperative hypertension remain unclear. Forty-six patients with primary aldosteronism (PA) who had undergone adrenalectomy between 1976 and 1998 were enrolled in this study. Follow-up information including blood pressure (BP) and cardiovascular complications was collected by means of correspondence or telephone contact. At discharge BP was normalized in 34 patients (72%); hypertension persisted in the remaining 12 patients, but BP control was significantly improved. The patients who remained hypertensive at discharge had longer durations of hypertension than did those with normalized BP. After an average follow-up period of 12.2 years, 16 of 34 BP-normalized patients (47%) had recurrent hypertension. Age at adrenalectomy, preoperative serum creatinine level and systolic blood pressure at discharge were significantly higher in patients with recurrent hypertension than in those without it. A multivariate logistic regression analysis revealed that only the level of serum creatinine was independently associated with the incidence of recurrent hypertension. Patients with serum creatinine of 0.9 mg/dl or greater had significantly higher rates of recurrent hypertension than those with lower values of serum creatinine. Cardiovascular complications occurred in 5 patients prior to the surgery and in 2 patients during the follow-up period. Although the severity of renal involvement is subclinical, renal damage may play an important role in the development of hypertension during a long period after adrenalectomy in patients with PA. (+info)
Diagnostic value of the post-captopril test in primary aldosteronism.
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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. (+info)
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.
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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. (+info)
Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism.
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Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K+, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all P< or =0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7+/-1.8 versus 45.5+/-2.0 g/m(2.7); P=0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI(s); -12.02+/-5.84% versus 6.06+/-3.08%; P=0.012) and posterior wall (-11.13+/-6.42% versus 8.63+/-9.62%; P=0.012). A regression analysis showed that CVI(s) was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for approximately 36% of CVI(s) variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval. (+info)
Clinical and gene mutation studies on a Chinese pedigree with glucocorticoid-remediable aldosteronism.
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OBJECTIVE: To report the clinical characteristics, biochemical profiles, diagnosis and treatment of one Chinese pedigree with glucocorticoid-remediable aldosteronism (GRA) and to study its molecular mechanism. METHODS: Plasma and urinary aldosterone, cortisol and plasma renin activities were dynamically tested and diagnostic therapy with dexamethasone was undergone in 3 affected subjects. Long-distance PCR as well as DNA sequencing were applied to detect the fusion gene in this pedigree. RESULTS: In this GRA pedigree, there were 4 affected subjects who had hypertension, hypokalemia and low basic and provoked renin activity. Three patients were given dexamethasone treatment, and had a significant decrease in plasma aldosterone concentrations (PACs) (from 192 +/- 9 ng/L to 87 +/- 7ng/L, P < 0.05) after 5 days. Among them, one patient (II -3) responded quite satisfactorily to the therapy, with serum K(+) rising from baseline value of 2.5 to 2.9, 3.8 and 4.15 mEq/L on the 10th, 28th and 35th days after treatment respectively. Three weeks later, his blood pressure decreased from its original level of 146.3 +/- 1 0.7/94.6 +/- 5.3 mm Hg to 138.3 +/- 3.1/87.3 +/- 6.1 mm Hg (P < 0.05). The other 2 members (III -2 and III -4) showed modest improvement although their PACs decreased significantly. Using long-distance PCR, we found a 3.9 kb band in all 4 affected individuals, which was absent in 5 unaffected members from this pedigree or 8 patients with aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). By DNA sequence analysis, we found that the breakpoint of "unequal crossing-over" is both within intron 2 of the 11beta-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2). CONCLUSIONS: The excess of mineralocorticoid in patients with GRA can be inhibited by exogenous glucocorticoids. The fusion gene resulting from unequal crossing-over between the 11beta-hydroxylase gene and the aldosterone synthase gene is the pathogenesis of this Chinese GRA pedigree. (+info)
Mineralocorticoid and angiotensin receptor antagonism during hyperaldosteronemia.
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Elevated aldosterone levels induce a spironolactone-inhibitable decrease in cardiac sarcolemmal Na+-K+ pump function. Because pump inhibition has been shown to contribute to myocyte hypertrophy, restoration of Na+-K+ pump function may represent a possible mechanism for the cardioprotective action of mineralocorticoid receptor (MR) blockade. The present study examines whether treatment with the angiotensin type 1 receptor antagonist losartan, with either spironolactone or eplerenone, has additive effects on sarcolemmal Na+-K+ pump activity in hyperaldosteronemia. New Zealand White rabbits were divided into 7 different groups: controls, aldosterone alone, aldosterone plus spironolactone, aldosterone plus eplerenone, aldosterone plus losartan, aldosterone plus losartan and spironolactone, and aldosterone plus losartan and eplerenone. After 7 days, myocytes were isolated by enzymatic digestion. Electrogenic Na+-K+ pump current (I(p)), arising from the 3:2 Na+:K+ exchange ratio, was measured by the whole-cell patch clamp technique. Elevated aldosterone levels lowered I(p); treatment with losartan reversed aldosterone-induced reduced pump function, as did MR blockade. Coadministration of spironolactone or eplerenone with losartan enhanced the losartan effect on pump function to a level similar to that measured in rabbits given losartan alone in the absence of hyperaldosteronemia. In conclusion, hyperaldosteronemia induces a decrease in I(p) at near physiological levels of intracellular Na+ concentration. Treatment with losartan reverses this aldosterone-induced decrease in pump function, and coadministration with MR antagonists produces an additive effect on pump function, consistent with a beneficial effect of MR blockade in patients with hypertension and congestive heart failure treated with angiotensin type 1 receptor antagonists. (+info)