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Background Adrenal venous sampling (AVS) is the gold standard for the identification of unilateral primary aldosteronism (PA), but is technically difficult. The aim of our study was to assess whether intraprocedural cortisol measurement (IPCM) increases AVS success rate. Methods Twenty-five consecutive PA patients underwent cosyntropin-stimulated AVS. Cortisol was measured immediately in a first set of samples drawn from adrenal veins and inferior vena cava. The selectivity criterion was an adrenal vein-to-inferior vena cava cortisol ratio ≥5. If bilateral selectivity was not achieved in a first set of samples, a second set was obtained during the same radiological session. PA was judged as unilateral if the gradient of cortisol-corrected aldosterone between dominant and nondominant side was >3.5. Twenty-five consecutive PA patients who had previously been submitted to AVS without IPCM served as historical controls. Lateralizing patients who underwent unilateral adrenalectomy were followed for 2 years after surgery. Results Bilateral selectivity using IPCM was achieved in 19/25 patients in the first set of samples, and in an additional four cases in the second set (92% vs. 76%; P = 0.06). The final rate of bilateral selectivity was higher than that obtained in the historical series (23/25 vs. 16/25, P = 0.04), whereas bilateral selectivity in the first set of samples was not different from that achieved in the historical series. Nineteen lateralizing patients (13 of the present series, six of the historical series) were submitted to adrenalectomy, resulting in reversal of PA. Conclusions IPCM increases the success rate of AVS.

BACKGROUND: Liddle's syndrome (LS) is a monogenic form of hypertension simulating a mineralocorticoid excess, and is currently suspected in young hypokalemic hypertensives. The aims of the study were: (i) to evaluate the clinical phenotype of LS in a newly identified Italian family of Sicilian origin carrying a gain-of-function mutation of the β subunit of the epithelial sodium channel (ENaC) (P617L) previously reported by our group in an apparently unrelated Sicilian patient presenting the typical phenotype of LS including hypokalemia; (ii) to determine whether an unknown biological relationship exists between the newly identified family and the family of the proband previously reported. METHODS: Genetic analysis was performed in the present family, in the individual in which the βP617L mutation was first observed, and in his relatives. RESULTS: βP617L mutation was identified in the proband and in three maternal relatives. None of them showed hypokalemia. Mild to severe early onset hypertension and left ventricular hypertrophy were present in all of them. Analysis of mitochondrial DNA (mtDNA) and Y chromosome profiles in the present family and in the proband's family previously reported showed the absence of a relationship between them. The availability of only one carrier of the mutation in one of the two families meant that a genetic analysis able to assess a founder effect was not feasible. CONCLUSIONS: LS should be considered in all cases of early onset hypertension, independently of the plasma potassium concentration. The incidence of LS may be greater than is currently thought, because hypokalemia is not invariably present.

The prevalence of primary aldosteronism (PA) was assessed in a specialized hypertension center. Baseline and postcaptopril (50 mg orally) aldosterone to plasma renin activity ratio (A/R) as a screening tool were preliminarily tested in a sample including 22 patients with histories of PA and 53 patients with low-renin essential hypertension (EH). Sensitivity and specificity of A/Ror =35 were 95.4% and 28.3% at baseline, compared with 100% and 67.9% after captopril. Using postcaptopril A/Ror =35 and confirmation by acute saline loading, a PA prevalence of 6.3% was found among 1046 consecutive hypertensive patients with normal renal function. Of those 66 PA patients, 16 (24.2%) had a unilateral adenoma, whereas 50 (75.8%) had idiopathic hyperaldosteronism. At presentation, 45.4% of the PA and 16.3% of EH patients were treated with two or more antihypertensive drugs (chi(2) = 33.117, P.0001). However, among untreated patients (n = 553), the prevalence of mild-to-moderate hypertension (ie,180/110 mm Hg) was not different between patients with PA and those with EH (70.6% v 76.7%, chi(2) = 0.086, P =.770). Serum potassiumor =3.6 mEq/L was found in 60.6% of PA patients. In conclusion, we observed the following: 1) postcaptopril compared with baseline A/R is a better screening tool for PA; 2) PA is relatively frequent among hypertensive individuals; 3) PA is not necessarily associated with severe hypertension; and 4) hypokalemia is an insensitive screening criterion for PA.

Most patients with low renin essential hypertension are not qualitatively different from patients with idiopathic hyperaldosteronism, as in both conditions aldosterone secretion is not appropriately reduced. The aim of the study was to investigate allele and genotype frequencies of the −344C/T polymorphism, located in the promoter region of the aldosterone synthase gene, in 83 patients with idiopathic low renin hypertension characterized by an increased aldosterone to renin ratio, including both patients with low renin essential hypertension (n = 53) and subjects with idiopathic hyperaldosteronism (n = 30), compared with 78 patients with normal to high renin essential hypertension and 126 normotensive control subjects. The relationship of −344C/T genotypes to basal and post-captopril plasma aldosterone/plasma renin activity ratio was also examined in the entire hypertensive population. An increased frequency of the T allele and a relative excess of TT homozygosity over CC homozygosity were found in patients with idiopathic low renin hypertension in comparison with both normal to high renin hypertensives and normotensive controls. A higher post-captopril aldosterone to renin ratio was found in the hypertensives with TT genotype than in those with CC genotype, and TT+TC genotypes were associated with a smaller decrease in the aldosterone-to-renin ratio elicited by captopril administration. The present study suggests that the −344C/T polymorphism, or a functional variant in linkage disequilibrium with it, may play a role in the abnormal regulation of aldosterone secretion in idiopathic low renin hypertension.

Platelet-derived growth factor (PDGF) could play a role in both vascular hypertrophy and atherosclerotic disease associated with hypertension. To assess whether plasma PDGF level is increased in mild essential hypertension, we measured plasma PDGF concentration in 25 never-treated patients with uncomplicated mild essential hypertension and in 22 normotensive healthy subjects. To evaluate the contribution of platelets to plasma PDGF in the two groups, we also measured plasma beta-thromboglobulin (BTG). Measurement of PDGF was carried out through an enzyme-linked immunoadsorbent assay, which detects two PDGF dimers, namely PDGF-BB and PDGF-AB. Both plasma PDGF and BTG were higher in the hypertensive than in the normotensive subjects. The ratio of PDGF to BTG was similar in the two groups. Plasma PDGF was weakly correlated with plasma BTG in the normotensive subjects, whereas this relationship was lost in the hypertensive patients. Our results suggest that the increase in plasma PDGF (PDGF-AB + PDGF-BB) in never-treated essential hypertension is mainly due to platelet activation. The increased circulating level of PDGF could play a role in the vascular structural changes associated with 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[Na]V), urinary excretion of Ca (U[Ca]V) 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 (Ca2+) and an increase in PTH, U(Na)V, and U(Ca)V. However, these changes were significantly greater in the PA group. The increased baseline U(Ca)V 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(Ca)V may explain the higher basal PTH in PA patients, which is needed for maintaining a normal Ca2+. The greater changes in the Ca2+/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.

In order to investigate the possible existence of abnormal calcium metabolism and parathyroid function in primary aldosteronism (PA), we have compared the calcium/parathyroid hormone (PTH) profile of patients with PA with the profile of healthy normotensive subjects and of patients with essential hypertension (EH). Furthermore, we have evaluated the effects of spironolactone and the surgical removal of aldosterone-producing adenomas on the calcium/PTH profile in the PA patients. Four groups of 10 subjects each participated in the study: 1) hypertensive patients with PA, 2) patients with low-renin EH (LREH), 3) patients with normal-renin EH (NREH), 4) normotensive healthy subjects (NS). The four groups were well-matched for age, sex, body mass index, and renal function. The three hypertensive groups were also matched closely for blood pressure values and for duration of hypertension. In all subjects, after 1 week of a controlled intake of Na and K, the following parameters were measured: urine excretion of Na, K, Ca, Mg, and P, plasma levels of K, Mg, inorganic P, total calcium and ionized calcium, and plasma renin activity, aldosterone concentration, and intact PTH. Blood pressure and laboratory parameters were determined again in all the PA patients after 1 month of 100 mg daily spironolactone administration, and in four out of the 10 PA patients 2 months after surgical removal of aldosterone-producing adenomas. All of these subjects had undergone the same controlled intake of Na and K indicated above. Serum intact PTH was higher in PA patients than in the other three groups (P < .01), and serum ionized calcium was significantly higher in normotensive subjects than in the three hypertensive groups (v PA P < .01, v LREH and v NREH P < .05). An increase in serum ionized calcium and a decrease in PTH level were associated with both spironolactone administration (P < .001) and surgical treatment (P < .05). These results suggest the presence of calcium metabolism alterations in both PA and EH patients, but that these alterations are more exaggerated in PA, so that higher PTH levels are needed for maintaining low-normal levels of serum ionized calcium.