Diagnosis of primary hyperaldosteronism: importance of correlating CT findings with endocrinologic studies.

Twenty patients with primary hyperaldosteronism had endocrinologic and radiologic studies to distinguish aldosterone-producing adenoma from idiopathic hyperaldosteronism due to bilateral micro- or macronodular hyperplasia of the adrenal cortex. In addition to examination for changes in the plasma level of aldosterone associated with postural changes and measurement of the plasma level of 18-hydroxycorticosterone, all 20 patients had CT examination of the adrenal glands. In three patients with normal adrenal glands on CT and three patients with CT evidence of two solitary nodules, one in each adrenal gland, a diagnosis of idiopathic hyperaldosteronism was confirmed by endocrinologic findings (five patients) or 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy (one patient). In nine patients with a solitary adrenal nodule on CT, a diagnosis of aldosterone-producing adenoma was confirmed by surgery (seven patients) or hormone sampling via the adrenal veins (two patients). However, in three patients with a solitary adrenal nodule on CT, a diagnosis of idiopathic hyperaldosteronism was suggested by endocrinologic findings (three patients) and confirmed by the results of NP-59 scintigraphy (two patients) or adrenal venous sampling (one patient). In addition, in two patients with CT evidence of three adrenal nodules (two in one gland, one in contralateral gland), a diagnosis of aldosterone-producing adenoma was suggested by endocrinologic findings in both patients and confirmed by surgery in one. Although high-resolution CT is highly accurate for the detection of aldosterone-producing adenoma, significant diagnostic errors can occur in patients with primary hyperaldosteronism if CT findings are not correlated with results of endocrinologic studies.

Comparison of dopamine and fenoldopam effects on renal blood flow and prostacyclin excretion in normal and essential hypertensive subjects.

We recently reported that a low dose dopamine (DA) infusion in normal subjects increased renal blood flow (RBF) via prostacyclin (PGI2) formation without changes in PGE2 levels. The present study explores whether this mechanism is mediated by the DA1 receptor and evaluates the effect of DA on RBF and PGs in subjects with essential hypertension (EH). A low dose of DA (1 microgram/kg.min), which previously did not alter hemodynamics in normal subjects was infused into eight patient with EH to determine the role of DA stimulation in hypertensives. To assess the effect of DA1 stimulation, fenoldopam, a selective DA1 agonist, was infused (0.1 microgram/kg.min) into 10 normal and 10 hypertensive patients. Fenoldopam, unlike DA, significantly decreased diastolic blood pressure in hypertensives (96 +/- 3 to 85 +/- 2 mm Hg; P less than 0.01) along with a significant increase in pulse rate (68 +/- 2 vs. 73 +/- 2 beats/min; P less than 0.01). RBF measured by para-aminohippurate clearance increased only in normals during fenoldopam infusion from 1185 +/- 71 to 1533 +/- 84 L/min.m2 (PGI(2)01), and this was associated with an increase in PGI2 (6-keto-PGF1) excretion (149 +/- 19 vs. 214 +/- 32 ng/g creatinine; P less than 0.02). These effects of fenoldopam were similar to DA effects on RBF and PGI2 excretion in normals. In contrast, in hypertensive subjects, neither fenoldopam (867 +/- 113 vs. 1054 +/- 177 L/min.m2; P greater than 0.1) nor DA (1098 +/- 85 vs. 1061 +/- 101 L/min.m2; P greater than 0.1) increased RBF. Similarly, neither the DA nor the fenoldopam infusion stimulated PGI2 excretion in the hypertensives. The fenoldopam infusion in the hypertensives produced a significant natriuresis (22 +/- 3 to 49 +/- 9 mmol/3 h; P less than 0.05). Similar effects on Na+ excretion in this group were noted during DA infusion (17 +/- 3 to 36 +/- 3 mmol/3 h; P less than 0.05), suggesting that DA-induced natriuresis is not directly linked to DA-induced changes in RBF or PG excretion. The present study shows that in normal subjects, fenoldopam, a specific DA1 agonist, like DA, stimulates renal PGI2 release and RBF. In contrast, neither DA nor fenoldopam alters PGI2 or RBF in patients with EH, suggesting an alteration of dopaminergic tone in some hypertensives that is characterized by a defect in DA1 receptor sensitivity.

Mechanisms of blood pressure regulation by magnesium in man.

In order to determine the effect and mechanism of Mg on vascular tone, a 3-hour infusion of Mg (200 mg/h) was administered to normal subjects. The Mg infusion resulted in a drop in blood pressure (BP), a rise in renal blood flow, and an increase in urinary 6-keto-PGF1 alpha excretion. Cyclooxygenase inhibition with indomethacin and the calcium channel blocker, nifedipine, prevented these vascular effects of Mg. These data suggest that prostacyclin release via changes in Ca2+ flux may be the mechanism of Mg vasodilatory action. Since angiotensin II (AII) acts via the Ca2+ messenger system, we also studied the effects of Mg loading and dietary Mg depletion on AII responses. Mg loading blunted the rise in BP and the aldosterone-stimulating effect of AII, whereas Mg depletion significantly enhanced these AII effects. These results support the hypothesis that Mg may be an antagonist of the pressor and steroidogenic effects of AII.

Plasma atrial natriuretic hormone levels in patients with the syndrome of inappropriate antidiuretic hormone secretion.

This study explored whether atrial natriuretic hormone (ANH) might be involved in the escape from salt and water retention that occurs in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Sixteen patients with low serum Na+ concentrations [123 +/- 1 (+/- SE) mmol/L] were studied. Each patient excreted urine that was hyperosmolar (mean, 391 +/- 4 mosmol/kg) in relation to serum osmolality (mean, 258 +/- 4 mosmol/kg). Sodium excretion (81 +/- 20 mmol/L) also was inappropriate to the low serum Na+ level. The probable causes of SIADH were head trauma (4), pneumonia (5), lung cancer (3), and chlorpropamide therapy (4). In the nontumor patients, plasma and/or urinary vasopressin (AVP) concentrations were in the normal range, but inappropriate for serum osmolality. Urinary AVP values of 50 pg/mL or more (greater than 46 pmol/L) were found in the three tumor patients. The mean plasma ANH concentration was 6-fold higher than that in normal subjects [296 +/- 51 vs. 51 +/- 13 pg/mL (100 +/- 20 vs. 17 +/- 4 pmol/L); P less than 0.01]. Six SIADH patients were studied again after brief (1-3 days) water restriction. Although serum osmolality increased in each, their plasma AVP concentrations decreased very little, and urinary AVP excretion and plasma ANH did not change. These results indicate that plasma ANH levels are markedly increased in patients with SIADH. Their increased ANH secretion may antagonize water retention resulting from the inappropriate AVP secretion.

The renal vasodilating effect of dopamine is mediated by calcium flux and prostacyclin release in man.

A low dose of dopamine (DA; 1 microgram/kg.min for 3 h) was infused into 10 normal subjects to determine whether vasodilator prostaglandins might be involved in the vascular action of this vasoactive hormone. Although this DA dose did not alter blood pressure, pulse, or cardiac index, it significantly increased renal blood flow (RBF), as estimated by para-amino-hippurate clearance [1.40 +/- 0.10 (+/- SE) to 1.93 +/- 0.18 L/min.1.73 m2; P less than 0.02]. This increase was due to DA receptor action since it was blocked by metoclopramide, a DA antagonist, and was not altered by prazosin, an alpha-adrenergic antagonist. DA simultaneously increased the urinary excretion rate of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin [PGI2; 79 +/- 16 to 154 +/- 32 ng/g creatinine (2 +/- 0.40 to 3.88 +/- 0.78 pmol/mumol creatinine); P less than 0.02], but there was no change in PGE2 excretion. This dose of DA increased urinary Na+ and K+ excretion and slightly increased creatinine clearance from 0.12 +/- 0.01 to 0.16 +/- 0.02 L/min.1.73 m2 (P less than 0.05). Metoclopramide also blocked the increase in PGI2 excretion, indicating that this increase was due to DA. The relationship between RBF and PGI2 was supported by studies in which either indomethacin or ibuprofen, both cyclooxygenase inhibitors, blocked the increase in both RBF and PGI2 excretion rate. Since some DA actions may be mediated through calcium flux, we also administered nifedipine, a calcium channel-blocking drug, and found that the DA effect on RBF and PGI2 was significantly reduced. These studies suggest that the DA effect on RBF is mediated by calcium flux, which probably activates renal vascular phospholipase, leading to release of arachidonic acid and synthesis of PGI2, a potent vasodilator.