Primary Aldosteronism Group Research Articles

Twenty-four hour urine aldosterone level predicts left ventricular hypertrophy in patients with primary aldosteronism and essential hypertension

Objectives: Primary aldosteronism (PA) is associated with inappropriate left ventricular hypertrophy (LVH) in relation to a given gender and body size. Currently, there is no ideal parameter to predict the presence of LVH or inappropriate LVH in patients with primary aldosteronism. We investigate the performance of 24 hour urinary aldosterone level, plasma renin activity and aldosterone-to-renin ratio on this task. Materials and methods: We performed echocardiography in 106 patients with primary aldosteronism and 31 subjects with essential hypertension (EH) in a tertiary teaching hospital. Plasma renin activity, aldosterone concentration and 24-hour urinary aldosterone level were measured. In order to identify LVH, we compared four parameters: 24-hour urinary aldosterone, plasma aldosterone concentration, plasma renin activity and plasma aldosterone-to-renin ratio urinary aldosterone. Results: In a correlation study of both groups, only 24-hour urinary aldosterone correlated with left ventricular mass index (LVMI) and additional LVMI among the four parameters. The multivariate analysis revealed that the urinary aldosterone level was an independent predictor for LVMI and additional LVMI. The receiver operating characteristic analysis to assess the ability of urinary aldosterone, plasma aldosterone concentration and plasma aldosterone-to-renin ratio to identify the presence of LVH (ROC AUC=0.701, 0.568, 0.656, respectively) and the presence of inappropriate LV mass index (defined as: measured LVMI to predicted LVMI ratio > 135%) (ROC area under curve = 0.61, 0.43, 0.493, respectively) revealed the better performance of 24-hour urinary aldosterone in the PA group. The same phenomenon was also noted in the EH group. Conclusion: In conclusion, 24-hour urinary aldosterone level performed better than plasma aldosterone or aldosterone-to-renin ratio to predict the presence of LVH and inappropriate LVMI in patients with primary aldosteronism.

GW24-e2371 The association between KCNJ5 gene polymorphism and primary aldosteronism

ObjectivesTo investigate the association of rs1221497 in KCNJ5 gene and primary aldosteronism (PA). KCNJ5 is a gene encoding a G-protein-coupled inwardly rectifying potassium.MethodsA total of 218 PA patients and 853...

GW24-e3533 Correlation between C171T mutation of KCNJ5 gene and hypokalemic in patients with primary aldosteronism

ObjectivesTo investigate the correlation between C171T mutation of the potassium inwardly-rectifying channel, subfamily J, member 5 (KCNJ5) gene, and the hypokalemic primary aldosteronism (PA).MethodsA total of 364 patients with PA...

Prevalence and clinical characteristics of primary aldosteronism in Japanese patients with type 2 diabetes mellitus and hypertension

The prevalence of primary aldosteronism (PA) is around 3-15% in patients with hypertension. Hypertension is a frequent complication of type 2 diabetes mellitus (DM) because of the close etiological relationship between these two diseases. However, the possibility of PA in patients with DM and hypertension is often overlooked and the prevalence of PA in patients with DM and hypertension in Japan is unknown. We enrolled 124 hospitalized patients with both DM and hypertension. PA was diagnosed according to the modified criteria for Japanese patients. We examined the prevalence of PA and compared clinical characteristics between patients with and without PA. In another analysis of 43 patients with a confirmed diagnosis of PA, we compared the characteristics of patients with and without DM. Overall, 14/124 patients with DM and hypertension (11.3%) were diagnosed with PA. Multivariate logistic regression showed that the duration of DM was significantly shorter in the PA group. Fisher's direct probability test revealed that history of hypertension before the diagnosis of DM was a significant factor in patients with PA. Treatment with an angiotensin II receptor blocker (ARB) did not affect the diagnosis of PA in these patients. Among 43 patients with PA, those with DM were significantly older and the delay to the diagnosis of PA was significantly longer compared with patients without DM. In conclusion, almost 10% of patients with DM and hypertension actually have PA. More extensive screening for PA is recommended in patients with DM and hypertension, regardless of the use of ARBs.

One-hour Upright Posture is an Ideal Position for Serum Aldosterone Concentration and Plasma Renin Activity Measuring on Primary Aldosteronism Screening

The serum aldosterone concentration (SAC) to plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the variation of ARR and compare the screening efficiency of it under different postures.37 patients with PA and 92 patients with EH were recruited in this study. Blood was sampled for measuring SAC and PRA under conditions of overnight recumbency, keeping upright posture for 1 h, 2 h and 4 h. The variation and screening efficiency of ARR under these conditions were compared according to repeated measured ANOVA and ROC curve analysis.In the EH group, ARR measured under recumbency posture was higher than those measured under keeping upright posture for 1 h and 2 h. In the PA group, there is no statistical difference for ARR between any 2 postures. AUCs of ARR measured under 4 conditions were 0.976, 0.995, 0.988, and 0.974 respectively. Cutoff values were ranging from 24.75 ng/dl per ng/ml/h under keeping upright for 2 h to 69.19 ng/dl per ng/ml/h under overnight recumbercy. ARR measured under keeping upright posture for 1 h produced the best characteristic of screening efficiency.Keeping upright posture for 1 h was the ideal position for ARR measuring and using a cutoff value of 35.90 ng/dl per ng/ml/h will have a sensitivity and specificity of 100.00% and 92.30% respectively.

Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups

The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the ≥ 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the ≥ 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years.

LONG-TERM CHANGES OF BLOOD PRESSURE AND LEFT VENTRICULAR (LV) GEOMETRY AFTER ADRENALECTOMY OR MEDICAL TREATMENT FOR PRIMARY ALDOSTERONISM: PP.18.185

Objective: To investigate the effects of surgical or medical treatment of primary aldosteronism (PA). Design and Methods: After a baseline Doppler echocardiography assessment (DEA) of LV geometry, 136 patients (age 50.7 ± 13 yrs) with confirmed PA entered a prospective follow-up study with serial DEA after adrenalectomy or medical treatment. Aldosterone producing adenoma (APA) and idiopathic hyper-aldosteronism (IHA) were diagnosed by the 4 corners criteria. Optimally treated primary hypertensive patients (PH) (n = 142) undergoing serial DEA served as controls. Results and Conclusions: Of the PA patients (age 50.7 ± 12.3 yrs, 46%F), 65% had APA and 35% had IHA. At baseline, they showed a high prevalence (52%) of inappropriate LV mass that was similar in the surgically- and the medically-treated group and fell (to 47%) after 3.05 yrs follow-up it. Treatment lowered blood pressure (BP) to almost identical values (136 ± 15/85 ± 8 mmHg) in all groups, but this required more drugs in the medically-treated PA than in the other 2 groups. A decrease of LV mass index (LVMI) was seen in PA and in PH patients; however, in the medically treated PA it did not achieve statistical significance (Table). The fall in LVMI occurred via a decrease of LV end diastolic diameter and volume in both PA groups (p < 0.01), and via a decrease of LV wall thickness in PH patients. This translated into a significant decrease of LV stroke volume and stroke work in PA, but not in PH patients. Hence, more drugs were required to achieve a similar fall of BP in the medically-treated than in the adrenalectomized PA patients., but notwithstanding this higher drugs usage, a significant decrease of LVMI occurred only in the latter patients. However, the remodeling of the LV around a smaller volume translated into a decrease of LV work both in adrenalectomized and in medically treated PA patients.

Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism

Adrenomedullin (AM) is located in the zona glomerulosa of the adrenal cortex and is considered to suppress aldosterone release. To determine the effect of AM in primary aldosteronism (PA), we infused AM (2.5 pmol kg(-1) min(-1)) for 27 h, followed by a 15-h recovery period, in a control group (essential hypertensives with plasma aldosterone levels <or=100 pg ml(-1), n=7) and in a PA group (n=5). The control group was also infused with vehicle. Hemodynamic, hormonal, oxidative and inflammatory responses were studied. AM infusion caused similar and steady decreases in blood pressure and several markers for arteriosclerosis (for example, pulse wave velocity) in both groups. Interestingly, AM infusion suppressed aldosterone release to values within the normal range in the PA group (300.0+/-58.4 to 111.6+/-13.5 pg ml(-1), P<0.01). In the control group, aldosterone release suppression was significant but limited (81.7+/-9.1 to 47.9+/-9.9 pg ml(-1), P<0.01). The adrenocorticotropic hormone-cortisol system was not changed by AM infusion. Brain natriuretic peptide was cumulatively increased by prolonged AM infusion in both groups, probably because of cardiac overload. AM did not affect oxidative markers. In addition, a mild but significant increase in C-reactive protein (CRP) mediated by interleukin-6 was observed during AM infusion in every participant, without exception. This pathway might participate in CRP elevation in cardiovascular disease. In summary, AM seems to have an essential role in the suppression of aldosterone release in PA. AM may be an important modulator in PA, and intermediate-term (3 h) AM infusion could be used as an alternative renin-stimulating/aldosterone-suppressing test for PA detection.

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.

Aldosterone and Metabolic Syndrome

The classic role of aldosterone is to regulate water and electrolyte balance and, therefore, blood pressure homeostasis.1 Apart from that, experimental studies have demonstrated that aldosterone induces structural and functional alterations in the heart, kidneys, and vessels with effects such as myocardial fibrosis, nephrosclerosis, vascular inflammation and remodeling, and disturbed fibrinolysis.2,3 This damage seems to be aldosterone mediated, and aldosterone blockade with mineralocorticoid receptor (MR) antagonists, such as spironolactone, may prevent the onset of these effects.4,5 On the other hand, it cannot completely be ruled out that potassium and high blood pressure also play additional key roles in this damage.6,7 This evidence has impressively been supported by clinical studies, such as the Randomized Aldactone Evaluation Study and the Eplerenone Post-Acute Myocardial Infarction Survival and Efficacy Study.8,9 For example, increased mortality in patients with chronic heart failure has been associated with elevated aldosterone plasma levels,10 and high circulating plasma aldosterone levels predict the clinical outcome in patients after myocardial infarction.11 Furthermore, primary aldosteronism (PA) has been demonstrated to enhance the risk of cardiovascular events12 and kidney disease.13 In summary, aldosterone is considered a cardiovascular risk factor, promoting disease processes such as cardiac fibrosis, nephrosclerosis, and arteriosclerosis,2,3,14 all of which are increased in patients with obesity and the metabolic syndrome.15,16 The term “metabolic syndrome” (MSyn) has evolved various definitions in recent times; most of the studies introduced here use slight modifications. Nevertheless, all of the definitions used have a common denominator, which is reflected in a definition by the American Heart Association/National Heart, Lung, and Blood Institute.17 According to this definition, the MSyn is considered as a constellation of interrelated risk factors of metabolic origin, including arterial hypertension, dyslipidemias, alterations in glucose homeostasis with type 2 diabetes mellitus, and abdominal …

Cardiovascular Outcomes in Patients With Primary Aldosteronism After Treatment

Experimental and human studies demonstrate that long-term exposure to elevated aldosterone levels results in cardiac and vascular damage. We investigated long-term cardiovascular outcomes in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with or without evidence of adrenal adenomas were prospectively followed up for a mean of 7.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with patients with essential hypertension and were treated to reach a blood pressure of less than 140/90 mm Hg. The main outcome measure was a combined cardiovascular end point comprising myocardial infarction, stroke, any type of revascularization procedure, and sustained arrhythmias. At baseline, the prevalence of cardiovascular events was greater in primary aldosteronism (35%) than in essential hypertension (11%) (odds ratio, 4.61; 95% confidence interval, 2.38-8.95; P< .001), with odds ratios of 4.93, 4.36, and 2.80 for sustained arrhythmias, cerebrovascular events, and coronary heart disease, respectively. Blood pressure during follow-up was comparable in the primary aldosteronism and essential hypertension groups. Ten patients in the primary aldosteronism group and 19 in the essential hypertension group reached the primary end point (P= .85). Cox analysis indicated that older age and longer duration of hypertension were factors independently associated with the cardiovascular end point. Cardiovascular outcome was comparable in patients with aldosteronism treated with adrenalectomy vs aldosterone antagonists (P= .71). Primary aldosteronism is associated with a cardiovascular complication rate out of proportion to blood pressure levels that benefits substantially from surgical and medical treatment in the long term.

Increased Arterial Wall Stiffness in Primary Aldosteronism in Comparison With Essential Hypertension

Aldosterone has been shown to substantially contribute to the accumulation of collagen fibers and growth factors in the arterial wall, which can increase wall stiffness. This study aimed at comparing arterial stiffness between patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls using carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI). Thirty-six patients with confirmed PA, 28 patients with EH, and 20 normotensive subjects were investigated by Sphygmocor applanation tonometer. The office blood pressure (BP) at the time of the measurement (PA 167+/-34/92+/-12 mm Hg; EH 166+/-19/91+/-10 mm Hg), age, body mass index (BMI), cholesterol, triglyceride, blood glucose levels were comparable between PA and EH groups. The patients with PA had significantly higher PWV than the EH patients and control subjects (9.8+/-2.6 m/sec v 7.5+/-1.0 m/sec v 5.9+/-0.7 m/sec, respectively; all mutual differences P<.001). The difference in PWV between PA and EH remained statistically significant also after the adjustment for all clinical variables including 24-h BP using multivariate analysis (P=.001). Arterial wall stiffness is independently increased in PA compared to EH. This could be caused by the deleterious effects of aldosterone excess (potentially modulated by hypernatremia) on the fibrosis and remodeling of the arterial wall.

Long-term Renal Outcomes in Patients With Primary Aldosteronism

Experimental animal studies indicate that exposure to increased aldosterone levels might result in renal damage, but the clinical evidence supporting this role of aldosterone is preliminary. To determine the long-term outcome of renal function in patients with primary aldosteronism after surgical or medical treatment. Prospective study conducted at an Italian university medical center among a consecutive sample of 50 patients who were diagnosed as having primary aldosteronism between January 1994 and December 2001 and who were followed up for a mean of 6.4 years after treatment with adrenalectomy or spironolactone. Patients with primary aldosteronism were compared with 100 patients with essential hypertension, matched for severity and duration of hypertension. All patients were treated with antihypertensive drugs to reach a target blood pressure of less than 140/90 mm Hg. Primary outcome measures were rates of change of glomerular filtration rate and albuminuria during follow-up. Detection of new-onset microalbuminuria and restoration of normal albumin excretion during follow-up were considered as secondary outcomes. At baseline, glomerular filtration rate and albuminuria were higher in patients with primary aldosteronism than those with essential hypertension. The mean blood pressure during the study was 136/81 mm Hg in the primary aldosteronism group and 137/81 mm Hg in the essential hypertension group. Glomerular filtration rate and albuminuria declined during the initial 6-month period in both groups, with a change that was significantly greater (P<.001 for both variables) in patients with primary aldosteronism. Subsequent rate of decline of glomerular filtration was comparable in the 2 groups, whereas albuminuria did not progress in the remainder of the follow-up. Restoration of normal albumin excretion from microalbuminuria was significantly more frequent in primary aldosteronism than in essential hypertension (P = .02). In the majority of patients in this study, primary aldosteronism was characterized by partially reversible renal dysfunction in which elevated albuminuria is a marker of a dynamic rather than structural renal defect.

Plasma Osteopontin Levels Are Higher in Patients With Primary Aldosteronism Than in Patients With Essential Hypertension

The incidence of cardiovascular events is higher in patients with primary aldosteronism (PA) than in patients with essential hypertension (EHT). Aldosterone has been shown to play an important role in the development of vascular inflammation and myocardial fibrosis in animal models. Elevated serum inflammatory cytokine is an independent cardiovascular risk factor in patients with EHT. In the present study, we compared levels of inflammatory cytokines between patients with PA and EHT. The study subjects were 15 patients with PA and 15 age-matched patients with EHT. Serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hsCRP), and plasma osteopontin (OPN) levels were measured by enzyme-linked immunosorbent assays. Systolic and diastolic blood pressure (BP) did not differ between the PA and EHT patient groups. Levels of serum IL-6 (P = .563), TNF-alpha (P = .480), and hsCRP (P = .870) did not differ between the two groups. In contrast, plasma OPN levels in patients with PA were significantly higher than those in patients with EHT (P < .0001). There was no relationship between BP and plasma OPN levels in patients with PA. The present study showed that plasma OPN levels were higher in patients with PA than in patients with EHT.

Impact of essential hypertension and primary aldosteronism on plasma brain natriuretic peptide concentration

Introduction. Brain natriuretic peptide (BNP) has important role in the diagnosis and management of heart failure. Data on the impact of blood pressure (BP) on BNP are controversial. In primary aldosteronism (PA), BNP production can be affected by both hypertension and specific endocrine mechanisms. This study was aimed at investigating the impact of hypertension and hyperaldosteronism on plasma BNP levels. Methods. Plasma BNP concentration, casual and 24‐h BP and echocardiographic indices were assessed in 40 patients with moderate to severe essential hypertension (EH), 40 BP‐matched patients with PA, and 40 age‐ and sex‐matched healthy controls. Results. BNP levels in PA and EH groups did not differ significantly and were higher compared with those in controls [median and interquartile range 26 (13–48) pg/ml, p = 0.01, and 23 (9–32) pg/ml, n.s., vs 14 (6–26) pg/ml in controls]. Remarkably elevated BNP was observed only in three PA and two EH patients, all having significant left ventricular (LV) hypertrophy. BNP levels in PA and EH groups correlated weakly with casual and 24‐h BP, interventricular septal thickness and LV mass index (LVMI). Diastolic BP and LVMI were identified as the strongest independent determinants of BNP (p = 0.002 and p = 0.01, respectively). Conclusions. Both PA and EH patients had modest and mutually comparable elevation of BNP, which was independently determined by diastolic BP and LVMI. Both subtypes of PA (aldosterone‐producing adenoma and bilateral adrenal hyperplasia) had similar effect on BNP production. Specific impact of hyperaldosteronism on BNP was not confirmed.

Diurnal blood pressure variation in pheochromocytoma, primary aldosteronism and Cushing's syndrome.

We examined circadian blood pressure (BP) variation (expressed as a relative night-time BP decline) in subjects with primary aldosteronism (78 patients), pheochromocytoma (n=45) and Cushing's syndrome (n=18). Subjects with aldosterone-producing adenoma (n=21) and pheochromocytoma (n=27) were also investigated after the tumour removal. In all, 65 patients with essential hypertension served as a control group. The night-time BP decline was significantly attenuated in all three forms of endocrine hypertension compared to the control group (primary aldosteronism P<0.0001, pheochromocytoma P<0.0001 for systolic and diastolic BP and Cushing's syndrome P<0.0001/<0.001 vs essential hypertension). In the case of pheochromocytoma, the absence of the night-time BP decrease was more prominent compared to the primary aldosteronism group (P=0.003/0.001) and for the diastolic BP also in comparison with the Cushing's syndrome group (P=0.03). Tumour removal led in both groups to the restoration of the previously altered circadian rhythm (aldosterone-producing adenoma: P=0.0005/0.0009; pheochromocytoma: P=0.001/0.0007). Our study demonstrates a blunted circadian BP variation in all forms of adrenal hypertension in comparison with essential hypertension. This reduction of the night-time BP decrease was more prominent in pheochromocytoma than in primary aldosteronism or Cushing's syndrome.

Acute Effects of Intravenous Sodium Chloride Load on Calcium Metabolism and on Parathyroid Function in Patients With Primary Aldosteronism Compared With Subjects With Essential Hypertension

To elucidate the mechanisms involved in increased parathyroid function in primary aldosteronism (PA), we evaluated the effects of an intravenous NaCl load on Ca metabolism and plasma level of intact parathyroid hormone (PTH) in patients with PA compared with that in patients with essential hypertension (EH). Sixteen PA patients and 16 EH patients who were well matched for age, gender, body mass index, renal function, and systolic (SBP) and diastolic blood pressure (DBP) were examined. In each subject, after 6 days of a controlled intake of Na, K, and Ca, isotonic saline was infused at a rate of 500 mL/h for 4 h. At baseline, in spite of similar BP values and urinary Na excretion (U NaV), urinary excretion of Ca (U CaV) and PTH were higher in the PA group than in the EH group. In both groups, the NaCl load caused a decrease of serum ionized Ca (Ca 2+) and an increase in PTH, U NaV, and U CaV. However, these changes were significantly greater in the PA group. The increased baseline U CaV in PA could be due to reduced reabsorption of sodium in aldosterone insensitive tubular sites, as a result of the “escape phenomenon.” The increased U CaV may explain the higher basal PTH in PA patients, which is needed for maintaining a normal Ca 2+. The greater changes in the Ca 2+/PTH profile elicited by the saline load in PA patients are apparently due to a higher calciuretic response following a more exaggerated natriuresis in PA.

Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension.

We determined functional and morphological changes of the heart by 2-dimensional and pulse Doppler echocardiography in 20 patients with primary aldosteronism and compared the results with those in 50 healthy normotensive subjects, 12 patients with Cushing's syndrome, 9 patients with pheochromocytoma, and 47 patients with essential hypertension. All hypertensive groups had greater left ventricular mass indexes than did the normotensive group (76.9 +/- 17.2 g/m2). Despite similar age distribution, blood pressure during antihypertensive treatment, and duration of hypertension, the primary aldosteronism group had a significantly greater left ventricular mass index (152.5 +/- 42.5 g/m2) than did the Cushing's syndrome (103.4 +/- 37.5 g/m2), pheochromocytoma (122.4 +/- 28.5 g/m2), and essential hypertension (101.4 +/- 32.8 g/m2) groups. The left ventricular posterior wall thickness and interventricular septal wall thickness were significantly greater in the hypertensive groups than in the normotensive group and also significantly greater in the primary aldosteronism group than in any of the other hypertensive groups. By contrast, there were no significant differences among the four hypertensive groups in any variable of systolic or diastolic function of the heart. The results suggest that left ventricular hypertrophy is more pronounced in patients with primary aldosteronism than in patients with other forms of hypertension. It is therefore important to echocardiographically evaluate cardiac hypertrophy as a risk factor of morbidity and mortality in patients with this low renin hypertension.

Normal sympathetic vasomotor and cardiac parasympathetic activities in patients with primary aldosteronism: assessment by spectral analysis

The role of the autonomic nervous system in hypertension due to mineralocorticoid excess remains unclear. To address this issue, we performed power spectral analysis of blood pressure (BP) and RR interval oscillations in 20 patients with primary aldosteronism (PA), 54 patients with essential hypertension (EH) and 45 normotensive (NT) subjects. Blood pressure and the degree of organ damage were similar between PA and EH groups. Age did not differ between the three groups. The Mayer wave power spectrum (MWP) of BP (approx. 0.1 Hz), an index of sympathetic vasomotor tone, was smaller in patients with PA than in patients with EH either while subjects were supine (systolic/diastolic; 3.9 ± 3.2 (SD)/1.5 ± 1.3 vs. 5.5 ± 4.2/2.1 ± 1.6 mmHg 2, P < 0.05 for both) or standing (7.6 ± 6.6/3.0 ± 3.0 vs. 17.7 ± 23.7/7.2 ± 8.3 mmHg 2, P < 0.05 for both). Supine respiratory-related power spectrum (RRP) of the RR interval (approx. 0.25 Hz), an index of cardiac parasympathetic tone, was greater in patients with PA than in patients with EH (545 ± 574 vs. 302 ± 464 ms 2, P < 0.01). The MWP of BP and the RRP of the RR interval were similar between patients with PA and NT subjects. Adrenalectomy reduced the 24-h mean BP (−18 mmHg for systolic BP, P < 0.001; −12 mmHg for diastolic BP, P < 0.01) and increased the 24-h mean heart rate (+8 bpm, P < 0.001). Furthermore, the diastolic MWP increased mildly (+32%, P < 0.05) and the RRP of the RR interval decreased dramatically (−75%, P < 0.01) following adrenalectomy. These results suggest that both vascular sympathetic and cardiac parasympathetic regulatory systems have minor roles in the maintenance of hypertension in patients with PA. The autonomic nervous system contributes more to the maintenance of BP following than prior to adrenalectomy. This information may be useful for the management of hypertension still persists after removal of adrenal adenoma.

Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma.

We studied the roles played by the renin-angiotensin system in inducing hypertension in nine patients with Cushing's syndrome (CS) resulting from adrenocortical adenoma, and compared them with those in patients with primary aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension (EH). In the CS group, each parameter, including serum potassium, plasma renin activity, plasma aldosterone, deoxycorticosterone and corticosterone concentrations, is within the normal range. However, plasma renin activity in the CS group was lower than that in the RVH group but higher than that in the PA group, and plasma aldosterone concentration was lower than that in each RVH or PA group. These findings indicated that the CS group had a different type of hypertension from that in either RVH or PA, in which the renin angiotensin system or mineralocorticoids play an important role in hypertension. Meanwhile, captopril (50 mg) administration either with or without indomethacin pretreatment decreased the mean blood pressure in the CS group, although captopril failed to change it in the PA group or in normal subjects. Furthermore, the pressor response to exogenous angiotensin II in the CS group was higher than that in the RVH or EH group, but was not different from that in the PA group. Thus, the hypertension in patients with CS due to adrenocortical adenoma appears to be mediated through a change in the renin-angiotensin system in the form of exaggerated pressor responses to angiotensin II.