Carlo Sani

High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among italian hypertensives

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/R > or =35 were 95.4% and 28.3% at baseline, compared with 100% and 67.9% after captopril. Using postcaptopril A/R > or =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 potassium > or =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.

Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas

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.

Increased plasma levels of platelet-derived growth factor (PDGF-BB + PDGF-AB) in patients with never-treated mild essential 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.

−344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low renin hypertension

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 postcaptopril 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.

O-19: Primary aldosteronism in a referral hypertension center

1999. Screening of PA was performed with the captopril test. Final diagnosis was based on lack of suppression of aldosterone upon acute volume expansion. Aldosteronoma (A) was defined as a unilateral adrenal nodule on CT scan with enhanced uptake at I-cholesterol scintigraphy. The diagnosis of idiopathic hyperaldosteronism (IHA) was based on evidence of bilateral adrenal hyperplasia on CT scan and enhanced bilateral uptake at scintigraphy. Sixty-six (6.3%) pts were finally diagnosed as having PA. In 16 (24.2%) of these pts, A was demonstrated by adrenal CT and scintigraphy, and the diagnosis histologically confirmed in the 10 cases so far submitted to surgery. In the remaining 50 (75.8%) pts IHA was diagnosed. The pts with PA had slightly higher systolic blood pressure values than those with essential hypertension (EH)(171.8623.3 vs 166.9 614.1 mmHg, P,0.05 by t-test). Known duration of hypertension was greater in the pts with PA, although statistical significance was reached only in those with IHA (median (25°-75° percentile): EH 28 (6-60), IHA 60 (24-120), A 46 (5-87) mo; P50.004 by ANOVA). At the time of the first visit, 30/66 (45.4%) pts with PA were treated with 2 or more drugs, compared with 152/931 (16.3%) pts with EH ( x 33.117, P,0.0001); in the former group there were 23/50 (46%) cases of IHA and 9/16 (56.3%) cases of A ( x 0.182, P50.670). In the group of the untreated pts there were 536/931 (57.6%) cases of EH, 13/50 (26.0%) cases of IHA and 4/16 (25.0%) cases of A ( x 25.260, P,0.0001). In these untreated pts hypertension was classified as mild to moderate (i.e., 180/104 mmHg) in 318/536 (59.5%) cases of EH, 8/13 (61.5%) cases of IHA and 3/4 (75.0%) cases of A ( x 0.428, P50.807). Serum potassium values were significantly lower in the pts with either IHA or A compared with those with EH (EH 4.0 6 .3, IHA 3.660.3, A 3.360.5 mEq/l; P,0.0001 by ANOVA). However, 37/66 (56.1%) pts with PA had serum potassium values

Ifosfamide-induced renal Fanconi syndrome with associated nephrogenic diabetes insipidus in an adult patient

3.6 mEq/l; in this group there were 33/50 (66.1%) cases of IHA and 7/16 (43.7%) cases of A (x 1.668, P50.197). We conclude that: 1) PA is more frequent than traditionally thought; 2) it is not necessarily associated with severe and/or resistant hypertension; 3) IHA seems to be more prevalent than A; 4) hypokalemia is not a sensitive criterion for the screening of PA.