Anna Patalano

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

CONTEXT 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. OBJECTIVE 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). DESIGN This was a prospective evaluation of consecutive hypertensive patients referred nationwide to specialized hypertension centers. MAIN OUTCOME MEASURES 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. RESULTS 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. CONCLUSIONS 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.

Within-Patient Reproducibility of the Aldosterone:Renin Ratio in Primary Aldosteronism

The plasma aldosterone concentration:renin ratio (ARR) is widely used for the screening of primary aldosteronism, but its reproducibility is unknown. We, therefore, investigated the within-patient reproducibility of the ARR in a prospective multicenter study of consecutive hypertensive patients referred to specialized centers for hypertension in Italy. After the patients were carefully prepared from the pharmacological standpoint, the ARR was determined at baseline in 1136 patients and repeated after, on average, 4 weeks in the patients who had initially an ARR ≥40 and in 1 of every 4 of those with an ARR <40. The reproducibility of the ARR was assessed with Passing and Bablok and Deming regression, coefficient of reproducibility, and Bland-Altman and Mountain plots. Within-patient ARR comparison was available in 268 patients, of whom 49 had an aldosterone-producing adenoma, on the basis of the “4-corner criteria.” The ARR showed a highly significant within-patient correlation (r=0.69; P<0.0001) and reproducibility. Bland-Altman plot showed no proportional, magnitude-related, or absolute systematic error between the ARR; moreover, only 7% of the values, for example, slightly more than what could be expected by chance, fell out of the 95% CI for the between-test difference. The accuracy of each ARR for pinpointing aldosterone-producing adenoma patients was ≈80%. Thus, although it was performed under different conditions in a multicenter study, the ARR showed a good within-patient reproducibility. Hence, contrary to previously claimed poor reproducibility of the ARR, these data support its use for the screening of primary aldosteronism.

The aldosterone-renin ratio based on the plasma renin activity and the direct renin assay for diagnosing aldosterone-producing adenoma.

Background The screening for primary aldosteronism is based on the aldosterone–renin ratio calculated with the plasma renin activity (PRA) value as denominator. A direct measurement of active renin (DRA) is being used as an alternative to PRA, but its diagnostic performance remains unclear. Method We, therefore compared, head-to-head, the aldosterone–renin ratio based on PRA with that based on DRA, at baseline and after captopril administration, for identifying aldosterone-producing adenoma (APA) in 251 patients of the Primary Aldosteronism Prevalence in hYpertension Study (PAPY). The area under the receiver operator characteristics curves was used for estimating the accuracy of the aldosterone–renin ratio based on either renin assay for identifying APA and for the comparison between tests. Results The rate of primary aldosteronism was 13.2%; 6.4% of the patients had an APA and 6.8% idiopathic hyperaldosteronism; 218 (86.8%) had primary hypertension. The area under the receiver operator characteristics curve for identifying APA was higher than 0.50 for the aldosterone–renin ratio based on both renin values (0.870 ± 0.058 for DRA and 0.973 ± 0.028 for PRA) (P < 0.0001 for both) and did not differ significantly between the aldosterone–renin ratios calculated with either renin assay. For the aldosterone–renin ratio based on DRA, the optimal cutoff value for identifying APA was 27.3 ng/mIU, remarkably similar to that previously determined for the aldosterone–renin ratio based on PRA. Conclusion Thus, the aldosterone–renin ratio based on DRA is a valuable alternative to that based on PRA for detecting APA.

Aldosterone-Producing Adrenocortical Carcinoma

In 1955 Conn described the syndrome of primary hyperaldosteronism (PHA) [1], which has come to be known as “Conn’s Syndrome” [2]. PHA is a group of disorders in which aldosterone production is inappropriately high, relatively autonomous from the renin-angiotensin system, and nonsuppressible by sodium loading. Such inappropriate production of aldosterone causes cardiovascular damage, suppression of plasma renin, hypertension, sodium retention, and potassium excretion that if prolonged and severe may lead to hypokalemia. PHA is commonly caused by adenoma (35%), bilateral adrenal hyperplasia (60%), or (rarely) by aldosterone producing adrenocortical carcinoma (APAC) (<1%) (Table 27.1) [3]. The first APAC was reported in 1955 by Foye and Feichtmeir [4] shortly after Conn’s original report. Aldosterone hypersecretion in adrenocortical carcinoma (ACC) is rare with only 58 patients being reported in a recent review [5]. The reported numbers of APAC amongst ACCs vary significantly. In one large series of ACCs, only 2.5% had developed hyperaldosteronism [6]. In a single center analysis on ACCs, which were subjected to operative management at the Mayo Clnic, the portion of APACs was 11%. Conversely, it has been estimated that hyperaldosteronism is due to APAC in only 1% of patients with PHA [7].

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.