atrial-natriuretic-factor and Adenoma

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists in a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with primary aldosteronism are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51% and 44% respectively. They had similar BP levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma had also higher values of the aldosterone precursor 18-OH-B, and of atrial natriuretic peptide (ANP), probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radio-cholesterol scintiscan provided similar results (85% accuracy): adrenal vein catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dex-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldo, 18-OH-B, 18-OH-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Atrial Natriuretic Factor; Captopril; Carcinoma; Cytochrome P-450 CYP11B2; Cytochrome P-450 Enzyme System; Dexamethasone; Diagnostic Imaging; Humans; Hyperaldosteronism; Hyperplasia; Posture; Renin; Retrospective Studies; Steroid 11-beta-Hydroxylase

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones with natriuretic and vasodilator actions. The present study was carried out to determine the natriuretic peptide that is closely related to cardiac load and volume retention in patients with primary aldosteronism (PA).. We examined 11 patients with PA due to aldosterone-producing adrenal adenoma before and after surgical resection. Plasma levels of ANP and BNP were measured by specific immunoradiometric assays, and total blood volume was determined by a plasma tracer method with (131)I-human albumin.. Plasma levels of ANP and BNP were elevated in the PA patients compared with normotensive control subjects (P < .01), and the elevated ANP and BNP levels were reduced (P < .01) after adenoma resection. When analyzed with the pre- and postoperative data, a significant relationship was observed between mean blood pressure and plasma levels of ANP (r = 0.64, P < .01) and BNP (r = 0.58, P < .01). The BNP was significantly correlated with the SV1 + RV5 voltage (r = 0.65, P < .01) and with total blood volume (r = 0.57, P < .01), but this was not the case for ANP.. The present results suggest that the plasma level of BNP is more closely related to cardiac load or volume status than ANP is, in patients with PA due to adrenal adenoma.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Atrial Natriuretic Factor; Biomarkers; Blood Volume; Cardiac Volume; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuretic Peptide, Brain

Normotensive primary hyperaldosteronism is exceedingly rare. We report two new cases of this syndrome in two middle-aged women, one of Asian origin. The presenting signs were tetany in one case and an adrenal mass in the other. Neither patient had hypertension, despite repeated measurements with a manual armlet. A typical biological profile of primary hyperaldosteronism was demonstrated in both patients, including hypokalemia with inappropriate kaliuresis, elevated resting plasma aldosterone, and undetectable plasma renin activity. The circadian rhythm of blood pressure was studied by ambulatory monitoring pre- and post-operatively. It confirmed the lack of hypertension, but the circadian rhythm of blood pressure was lost before surgery in one patient. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia. The main finding in these two patients was spontaneously low blood pressure in the post-operative period. This suggests that excess aldosterone induced relative hypertension in these patients whose blood pressure was spontaneously very low. Genetic screening for dexamethasone-sensitive hyperaldosteronism was negative in both patients.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Blotting, Southern; Chromatography, High Pressure Liquid; Dexamethasone; Female; Gas Chromatography-Mass Spectrometry; Humans; Hyperaldosteronism; Hypertension; Potassium; Radioimmunoassay; Renin; Tetany; Tomography, X-Ray Computed

Atrial natriuretic factor (ANF) was suggested to be involved as neurohormone in the modulation of hypothalamus-pituitary-adrenal axis in humans. However, this role is still controversial and widely discussed. In order to evaluate whether ANF is secreted in the hypothalamus-pituitary system in humans, plasma ANF concentrations were assayed in samples collected in the inferior petrosal sinus (IPS) blood of patients subjected to IPS sampling for diagnostic purposes or neurosurgical indications. In this retrospective study were included 22 patients: 10 with Cushing's disease (CD) and 12 patients with GH or PRL-secreting pituitary adenoma, used as control group. In the patients with CD, plasma ANF concentration was also assayed after CRH test (hCRH 100 micrograms as i.v. bolus with blood samples after 5, 10 and 15 min). Both in patients with CD and in patients with GH- or PRL-secreting pituitary adenoma, no significant difference was found in plasma ANF levels between IPS ipsilateral (13.0 +/- 1.5 and 12.2 +/- 1.2 pmol/l) or controlateral (13.0 +/- 1.6 and 12.2 +/- 1.4 pmol/l) to the adenoma and peripheral blood (14.2 +/- 2.0 and 13.7 +/- 1.5 pmol/l, respectively). Similarly, no difference was found between the IPS ipsilateral and controlateral to the adenoma in both groups of patients. In patients with CD, CRH administration induced a significant increase of ACTH levels (periphery: 34.9 +/- 6.2 vs 11.5 +/- 2.3 pmol/l, p < 0.05) but it did not induce any significant change of plasma ANF levels (14.0 +/- 2.0 vs 13.4 +/- 1.4 pmol/l in the ipsilateral IPS and 13.4 +/- 1.6 vs 13.4 +/- 1.5 pmol/l in the ipsilateral IPS and 13.4 +/- 1.6 vs 13.4 +/- 1.5 pmol/l in the contralateral IPS). In conclusion, the lack of ANF concentration gradient between IPS and peripheral blood, the lack of any difference in ANF concentrations between patients with CD and acromegalics or hyperprolactinemics and the absence of ANF response to CRH administration do not support the hypothesis of a role for ANF as neurohormone involved in the hypothalamus-pituitary control and particularly in the hypothalamus-pituitary-adrenal axis modulation in humans.

Topics: Adenoma; Adolescent; Adrenocorticotropic Hormone; Adult; Atrial Natriuretic Factor; Corticotropin-Releasing Hormone; Cushing Syndrome; Female; Human Growth Hormone; Humans; Male; Middle Aged; Petrosal Sinus Sampling; Pituitary Neoplasms; Prolactin; Retrospective Studies

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Blood; Drinking; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuresis; Osmolar Concentration; Postoperative Period; Potassium; Time Factors; Urine; Vasopressins

Previous studies have shown a significant association between allelic frequencies at the ANP gene locus and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma (APA). We searched for any gross insertions or deletions in the ANP gene in APA and any associations between allelic frequencies at the Hpa II and Sca I RFLP sites within the ANP gene and angiotensin-responsive and unresponsive APA and normal subjects. We also searched for possible point mutations in the promoter region of the ANP gene (-595 to transcription start site) in peripheral blood and tumor DNA from 59 patients with APA and in peripheral blood DNA from 39 normal subjects by polymerase chain reaction and single strand conformation polymorphism (PCR-SSCP) analysis. No large alterations in the ANP gene were observed, and no difference in allelic frequencies at the RFLP sites were seen between the two tumor subtypes, angiotensin-responsive and angiotensin-unresponsive APA, or between the APA group and normal subjects. SSCP analysis, however, did reveal mutations in the promoter region of the ANP gene (-375 to -595) in both peripheral blood and tumor DNA from 8 of 59 (14%) patients with APA, compared with only one of 39 normal controls (2.6%). This study suggests that alterations in the proximal promoter region of the ANP gene in APA may be important in the regulation of ANP transcription and may be involved in the underlying pathophysiology of aldosterone-producing adenoma in at least some patients.

Topics: Adenoma; Adrenal Cortex Neoplasms; Aldosterone; Atrial Natriuretic Factor; Base Sequence; Deoxyribonucleases, Type II Site-Specific; DNA; Humans; Molecular Sequence Data; Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; Promoter Regions, Genetic

Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II-responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA.

Topics: Adenoma; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Deoxyribonucleases, Type II Site-Specific; Genotype; Humans; Hyperaldosteronism; Polymorphism, Restriction Fragment Length

C-type natriuretic peptide (CNP) in human adrenal glands and adrenal tumors was measured with a specific radioimmunoassay for CNP. Tissue immunoreactive (IR-) CNP concentrations were 0.54 +/- 0.40 pmol/g wet tissue (gwt) (mean +/- SD) in 14 pheochromocytomas, 0.69 +/- 0.19 pmol/gwt in six adrenocortical tumors, and 0.49 +/- 0.22 pmol/gwt in seven normal adrenal glands (cortex and medulla mixed). These concentrations were comparable to those found in tissues from human brains. Sephadex G-50 superfine column chromatography and reverse-phase high performance liquid chromatography revealed that IR-CNP in normal adrenal glands and pheochromocytoma consisted of at least two components: a component in low molecular weight form chromatographically identical to CNP-22 and the other, a high molecular weight form very similar to human CNP-53. This study has shown that IR-CNP is present in human adrenal glands and adrenal tumors with similar molecular forms and comparable concentrations to those in the human brain.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Aged; Atrial Natriuretic Factor; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Pheochromocytoma; Radioimmunoassay

To investigate the possible role of dopamine, a catecholamine with natriuretic properties, in modulating the escape from the sodium-retaining effects of mineralocorticoids, we submitted six aldosterone-producing adenoma (APA) patients and six low-renin essential hypertensive patients to acute volume expansion by head-out water immersion with or without dopaminergic blockade by metoclopramide. Water immersion alone induced a marked, comparable natriuresis (P < 0.001) in both hypertensive groups where a slight reduction of already suppressed renin-angiotensin system and a marked stimulation of atrial natriuretic peptide was also observed (P < 0.03 and P < 0.002, respectively). Water immersion plus dopaminergic blockade by metoclopramide did not significantly affect the natriuresis observed during water immersion alone in APA patients; conversely, there was a blunted natriuretic response in low-renin hypertensives during water immersion plus metoclopramide, in comparison with that obtained during water immersion alone (P < 0.006). Furthermore, metoclopramide did prevent the suppression of plasma aldosterone levels produced by central volume expansion alone in low-renin hypertensives, although it did not affect plasma aldosterone levels during water immersion in APA patients. Our data suggest that dopaminergic blockade does not counteract the natriuretic ability of the other hemodynamic and humoral mechanisms involved in the escape phenomenon of APA patients, thus casting serious doubt on the possible role of dopamine in mediating the escape from the sodium-retaining effects of mineralocorticoids.

Topics: Adenoma; Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Creatinine; Dopamine; Female; Hemodynamics; Humans; Hyperaldosteronism; Hypertension; Immersion; Isotonic Solutions; Kidney; Male; Metoclopramide; Middle Aged; Mineralocorticoids; Potassium; Renin; Renin-Angiotensin System; Sodium; Sodium Chloride; Urination

Atrial natriuretic peptide (ANP) can be elevated in conditions which are characterized by increased atrial pressure and or expanded plasma volume. We and others have previously shown a significant increase of ANP plasma levels in a small number of patients with primary aldosteronism. In this study we have extended the assay of plasma ANP to a larger number of patients. We studied ANP plasma levels before and after upright posture and acute sodium load in 16 patients with aldosteronoma (APA) and 13 with idiopathic aldosteronism (IHA). The study was repeated also after the removal of aldosteronoma. In patients with primary aldosteronism, the mean supine ANP plasma level was significantly higher than in the age matched normal subject group; supine ANP was significantly higher in the APA than in the IHA group. The decrease of ANP levels after upright posture was significant in both groups. The ANP increase after acute saline load was similar in APA and in IHA. After the removal of aldosteronoma ANP values returned to normal. In conclusion, it is confirmed that plasma ANP levels are elevated in primary aldosteronism and could reflect a greater volume expansion in patients with APA. Despite this difference, ANP still responds to physiological stimuli in both groups. Finally, ANP measurement can provide an additional tool in the differential diagnosis between APA and IHA.

Topics: Adenoma; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Diagnosis, Differential; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Osmolar Concentration; Posture; Renin-Angiotensin System; Sodium Chloride

The previous study demonstrated that the aldosterone secretion of aldosterone-producing adrenocortical adenoma failed to be suppressed by human atrial natriuretic peptide, based on the data in synthetic alpha-human atrial natriuretic peptide infusion in vivo and the effect on in vitro secretion from cultured adenoma cells. Using the membrane fractions prepared from human adrenal tissues and an aldosterone-producing adenoma tissues, we characterized the binding sites for [125I] alpha-human atrial natriuretic peptide by the binding study and affinity-labeling of [125I] alpha-human atrial natriuretic peptide. Both normal adrenal and adenoma tissue membrane fractions possessed specific binding sites, however the relative binding capacity for [125I] alpha-human atrial natriuretic peptide in the adenoma preparations was markedly lower than that in the normal adrenal tissue preparation. The specific binding sites for [125I] alpha-human atrial natriuretic peptide were detected at the region of 140 KD and 67-70 KD only in the normal adrenal membrane fractions. Our data suggest that the refractoriness to the effect of atrial peptide may be due to the reduced receptor sites in aldosterone-producing adenoma cells.

Topics: Adenoma; Adrenal Cortex Neoplasms; Aldosterone; Atrial Natriuretic Factor; Binding Sites; Humans; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Tumor Cells, Cultured

Human adrenal gland and aldosterone-producing adenoma (APA) obtained from adrenalectomy could be maintained in vitro for one to two months. The explants continued to secrete aldosterone for the duration of culture. This method was superior to monolayer cell culture. The influence of alpha-human atrial natriuretic factor (alpha-hANF) was investigated by treating cultures of normal adrenal cortex and APA with alpha-hANF (10(-8) mol/L and 3 x 10(-8) mol/L respectively). We measured aldosterone in culture media collected at 2h before alpha-hANF treatment and 0.5, 2, 4 and 24h after. It was found that alpha-hANF stimulated aldosterone secretion of normal adrenal tissue but slightly inhibited that of APA.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Culture Techniques; Female; Humans; Hyperaldosteronism; Male; Middle Aged

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aged; Atrial Natriuretic Factor; Female; Humans; Hyperaldosteronism; Male; Middle Aged

The effects of the alpha-human ANF and angiotension II on aldosterone secretion in vitro from cultured human adrenal tissues and the aldosterone-producing adenoma (APA) tissues were studied. The fresh human normal adrenal and APA tissues were obtained surgically from five patients. The tissues were mined 1.0 mm3 with scissors, put in DMEM containing 0.25% trypsin, and digested at 37 degrees C for 10 min. Then the tissues were washed with DMEM. The tissues were incubated in 4 ml DMEM containing 10% fetal calf serum at 37 degrees C under 5% CO2 in air for seven days and the aldosterone levels of the culture medium were determined by radioimmunoassay (RIA). The experiments were started on the tenth to fiftieth day of culture. The results show that the effect of alpha-human ANF (10(-8) mol/L final concentration) on aldosterone secretion from normal adrenal tissues was increased at 30 min following a decrement, but do not inhibit the aldosterone secretion in APA tissues. The aldosterone of short duration was inhibit by alpha-human ANF (3 x 10(-8) mol/L or 5 x 10(-8) mol/L) and the aldosterone secretion in a dose-dependent manner in the adenoma tissues. The aldosterone responses were not stimulated by angiotensin II (10(-9) mol/L) in normal adrenal and adenoma tissues, but angiotensin II (5 x 10(-9) mol/L) can stimulate APA tissues. Our results indicate the lack of effect of alpha-human ANF and angiotensin II on APA tissues could be due to the absence of receptors or a variance of the receptors, and/or the enzymes of steroidogenesis were abnormal. These tissues had a marked aldosterone response to ANF and angiotensin II during culturing in one month.

Topics: Adenoma; Adrenal Gland Neoplasms; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Culture Techniques; Humans; Hyperaldosteronism

In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.

Topics: ACTH Syndrome, Ectopic; Adenoma; Adrenal Cortex Diseases; Adrenal Cortex Neoplasms; Adrenocortical Hyperfunction; Adult; Angiotensin II; Atrial Natriuretic Factor; Cushing Syndrome; Desoxycorticosterone; Humans

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Diseases; Adrenal Glands; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Dexamethasone; Diagnosis, Differential; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoids; Potassium; Sodium

In order to evaluate the role of calcium metabolism in blood pressure regulation, 15 patients with primary hyperparathyroidism and 9 healthy control subjects were studied before and during angiotensin II infusion. The patients were re-investigated 2-5 months after removal of the parathyroid adenoma. Blood pressure, plasma levels of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide, and creatinine clearance were determined. Blood pressure and the blood pressure response to angiotensin II infusion were both the same before and after the operation. Angiotensin II and arginine vasopressin during basal conditions were significantly higher before than after the operation (angiotensin II: 17 (median) to 10 pmol/l, P less than 0.02; arginine vasopressin: 2.9 to 1.9 pmol/l, P less than 0.01), whereas aldosterone, atrial natriuretic peptide, and creatinine clearance were unchanged. During angiotensin II infusion, aldosterone, arginine vasopressin, and atrial natriuretic peptide increased to approximately the same levels before and after the operation. Blood pressure was not correlated to any of the hormones measured. Thus, patients with primary hyperparathyroidism have elevated plasma levels of angiotensin II and arginine vasopressin which may be compensatory phenomena counteracting volume depletion owing to a decreased renal concentrating ability induced by hypercalcemia, and owing to PTH-induced inhibition of renal sodium reabsorption.

Topics: Adenoma; Adult; Aged; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Osmolar Concentration; Parathyroid Neoplasms; Potassium

Plasma concentrations of atrial natriuretic factor and some vasoactive substances were determined in 8 patients with aldosterone-producing adenoma, 10 with idiopathic adrenal hyperplasia, 10 normotensive subjects and 12 patients with essential hypertension. Plasma atrial natriuretic factor concentration in patients with aldosterone-producing adenoma was the highest among the examined groups. Adrenal surgery reduced plasma concentrations of atrial natriuretic factor and aldosterone concomitant with the elevation in urinary sodium excretion, plasma renin activity and urinary sodium-to-potassium ratio. Withdrawal of trilostane (3 beta-hydroxysteroid dehydrogenase inhibitor) in patients with idiopathic adrenal hyperplasia increased plasma concentrations of atrial natriuretic factor and aldosterone, and decreased the urinary sodium-to-potassium ratio, plasma renin activity and urinary sodium excretion. However, reduced urinary sodium excretion following trilostane treatment returned to the control level successively despite the high levels of plasma atrial natriuretic factor and aldosterone. Acute infusion of saline remarkably increased plasma atrial natriuretic factor concentration in patients with idiopathic adrenal hyperplasia and aldosterone-producing adenoma. These results suggest that a high level of atrial natriuretic factor is a characteristic feature in patients with aldosterone-producing adenoma caused chiefly by the expansion of extracellular fluid volume, and circulating atrial natriuretic factor may contribute to regulation of the sodium escape phenomenon in patients with aldosterone-producing adenoma or idiopathic adrenal hyperplasia.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; Female; Humans; Hyperaldosteronism; Hyperplasia; Male; Middle Aged; Natriuresis; Potassium; Renin

1. In Bartter's syndrome, atrial pressures were low, consistent with volume contraction, while atrial natriuretic peptide (ANP) levels were unexpectedly elevated. Infusion of normal saline increased both right atrial pressure (RAP) and ANP levels, while administration of prostaglandin inhibitors raised RAP, probably due to volume expansion, but ANP levels fell paradoxically. 2. In Gordon's syndrome, atrial pressures were unexpectedly low or normal despite volume expansion, while ANP levels were normal. Pressor infusions of angiotensin II either raised right and left atrial pressures (LAP) without increasing ANP, or increased ANP without increasing atrial pressures. 3. In these two syndromes, atrial pressures and ANP levels were poorly correlated, leading to the proposal that other regulators of ANP may be important.

Topics: Adenoma; Adolescent; Adrenal Gland Neoplasms; Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Blood Pressure; Child; Child, Preschool; Cyclooxygenase Inhibitors; Female; Humans; Hyperaldosteronism; Infant; Infusions, Intravenous; Male; Middle Aged; Radioimmunoassay; Renin

Several studies demonstrated that aldosterone secretion, by bovine, rat and human glomerulosa cells, is inhibited in vitro by atrial natriuretic factor (ANF). This effect has also been investigated with conflicting results in cells taken from aldosterone-producing tumors. In the present study, atrial natriuretic factor has been tested on aldosteronoma cells obtained from 4 patients with primary aldosteronism. The cells were studied both with perfusion and incubation systems. Aldosterone secretion was stimulated by ACTH, angiotensin II and potassium with or without ANF 10 microM. In this study ANF lacked to inhibit either basal and stimulated aldosterone secretion, indicating some alterations of ANF-adrenal interaction in this syndrome.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Humans; Hyperaldosteronism; Perfusion; Potassium; Tumor Cells, Cultured

The effect of synthetic alpha-human atrial natriuretic peptide (ANP) on aldosterone secretion was studied in human aldosterone producing adrenocortical adenoma obtained surgically from a patient with primary aldosteronism and in human apparently normal adjacent adrenal cortical tissues obtained from a patient with pheochromocytoma, in vitro. Apparently normal adrenal cortical tissue responded to ANP with the known inhibition of aldosterone secretion. In contrast, the aldosterone producing adenoma did not respond to ANP. When stimulated by either ACTH or angiotensin II, there is no inhibition by ANP in the adenoma tissue, whereas normal tissue was inhibited. Immunohistochemical examination utilizing an ANP-receptor antiserum demonstrated that there was no evidence of binding site in the cortical adenoma, in contrast, zona glomerulosa cells in the cortical tissues adjacent to either aldosterone producing adenoma or pheochromocytoma were densely stained. This apparent lack of ANP-receptors is an associated finding with the hypersecretion of aldosterone in the aldosterone producing adenoma.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Aldosterone; Atrial Natriuretic Factor; Humans; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Recombinant Proteins

The effects of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) on cortisol secretion by adrenocortical adenoma cells from patients with Cushing's syndrome (CS cells) in primary monolayer cultures, compared to cultured normal adrenal cells, were studied. alpha-hANP significantly inhibited cortisol secretion by human normal adrenal cells in culture, but had no direct effect on cortisol secretion from CS cells, in the presence or absence of 10(-8) M ACTH. alpha-hANP enhanced the accumulation of intracellular cyclic GMP in normal adrenal cells in culture, but not in CS cells. Visualization of [125I] iodo-alpha-hANP-specific binding sites by an in vitro receptor autoradiographic technique showed that these sites were lacking in adrenocortical adenoma tissues. These results suggest that the loss of alpha-hANP inhibitory effect on cortisol secretion in CS cells may be due to the absence of alpha-hANP receptor sites.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Glands; Adult; Aldosterone; Atrial Natriuretic Factor; Cells, Cultured; Cushing Syndrome; Cyclic GMP; Female; Humans; Hydrocortisone; Middle Aged; Peptide Fragments; Tumor Cells, Cultured

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Aldosterone; Atrial Natriuretic Factor; Female; Furosemide; Humans; Hyperaldosteronism; Hyperplasia; Isotonic Solutions; Male; Middle Aged; Radioimmunoassay; Sodium Chloride; Spironolactone

The effect of human atrial natriuretic peptide (hANP) on aldosterone, 18-OH-cortisterone, corticosterone, deoxycorticosterone, and cortisol secretion was examined in isolated human aldosteronoma cells from five patients with primary aldosteronism. hANP exerted a nearly identical inhibitory action on basal secretion of each of these steroids and antagonized also the stimulating effects of ACTH, serotonin, metoclopramide and vasoactive intestinal polypeptide. The results suggest that in human aldosteronoma cells hANP may be a non-selective inhibitor of corticosteroid biosynthesis and that the site of inhibition of steroidogenesis may be localized to the early pathway of steroid biosynthesis.

Topics: Adenoma; Adrenal Cortex Hormones; Adrenal Gland Neoplasms; Aldosterone; Atrial Natriuretic Factor; Cosyntropin; Humans; In Vitro Techniques; Kinetics; Metoclopramide; Vasoactive Intestinal Peptide

1. Saline infusion was performed in normal subjects, in essential hypertensives and in patients with aldosterone-producing adenoma (APA), with serial measurements of plasma aldosterone, cortisol and atrial natriuretic peptide (ANP). The effect of recumbency alone was also observed in the normal subjects. 2. Plasma aldosterone after saline infusion was less than 7 ng per 100 ml in the essential hypertensives and normal subjects, but greater than 9 ng per 100 ml in the patients with APA. 3. The aldosterone/cortisol ratio in normal subjects and in essential hypertensives was unchanged or fell during saline infusion, but rose in five of eight patients with APA. 4. Thus, an increase in aldosterone/cortisol ratio after saline infusion appears to be diagnostic of APA, but its absence does not exclude it.

Topics: Adenoma; Aldosterone; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Humans; Hydrocortisone; Hypertension; Infusions, Intravenous; Radioimmunoassay; Sodium Chloride

Low-dose angiotensin II (ANG II) infusion raised plasma atrial natriuretic peptide (ANP) levels only when endogenous renin-angiotensin levels were low, as in aldosterone-producing adenoma. When plasma renin activity (PRA) levels rose tenfold following removal of the tumour, low-dose ANG II infusion no longer stimulated ANP, but fivefold higher doses did. Indomethacin lowered both PRA and ANP in Bartter's syndrome and in normal subjects. The effect of indomethacin on ANP is probably not direct, since it did not lower ANP in aldosterone-producing adenoma. Neither did it lower PRA in aldosterone-producing adenoma, and in most studies ANP and PRA moved in parallel, consistent with positive regulation of ANP by ANG II. When ANG II infusion stimulated ANP, it also raised blood pressure, which could therefore be mediating the effects of ANG II on ANP. However, both PRA and ANP are high in Bartter's syndrome, while blood pressure is normal or low, and indomethacin lowers PRA and ANP in Bartter's syndrome and in normal subjects without lowering the blood pressure. The relative importance of regulatory factors such as central blood volume/atrial pressure and ANG II level probably varies in different situations. In aldosterone-producing adenoma, a high central blood volume appears to over-ride the effect of a low ANG II level. In Bartter's syndrome a high ANG II level appears to over-ride the effect of low central blood volume.

Topics: Adenoma; Adolescent; Adrenal Cortex Neoplasms; Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Bartter Syndrome; Blood Pressure; Child; Child, Preschool; Humans; Hyperaldosteronism; Indomethacin; Middle Aged; Renin

Topics: Adenoma; Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Cushing Syndrome; Humans; Hyperaldosteronism; Pheochromocytoma; Pituitary Neoplasms

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Diuresis; Female; Hemodynamics; Humans; Male; Middle Aged

The effect of alpha-human atrial natriuretic polypeptide (ANP) on adrenal steroidogenesis was studied in human adrenal tissues obtained surgically from four patients with Cushing's syndrome due to an adrenal adenoma and five patients with an aldosterone-producing adenoma (APA). ANP significantly inhibited basal and ACTH (3.4 X 10(-8) M)-stimulated cortisol and aldosterone secretion in both the adenomas and adjacent adrenocortical tissues from patients with Cushing's syndrome. ANP inhibited ACTH-stimulated, but not basal, secretion of cortisol and aldosterone in the adjacent tissues from patients with APA. In addition, ANP significantly inhibited both basal and ACTH-, angiotensin II (10(-6) M)-, and potassium chloride (10 mM)-stimulated secretion of aldosterone from the adenomas of patients with APA. ANP-induced changes in cortisol and aldosterone secretion were accompanied by a decrease in cAMP and an increase in cGMP secretion. These results suggest that ANP may be a possible regulator of cortisol as well as aldosterone secretion in humans, and these effects might be due to concomitant alteration in cyclic nucleotide metabolism.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Aldosterone; Atrial Natriuretic Factor; Cushing Syndrome; Cyclic AMP; Cyclic GMP; Female; Humans; Hydrocortisone; In Vitro Techniques; Male; Middle Aged

Topics: Adenoma; Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Plasma Volume; Radioimmunoassay; Syndrome

To examine whether human atrial natriuretic peptide (hANP) has an agonistic effect on dopaminergic pathways, we studied the natriuretic action and the suppressive effect of hANP on aldosterone secretion before and during treatment with haloperidol or pergolide in nude mice harbouring heterotransplanted human CONN's adenoma tissue. Nude mice with heterotransplanted tumour material without hormonal activity served as controls. The natriuretic efficacy of hANP remained unchanged by haloperidol or pergolide both in controls and in nude mice with heterotransplanted CONN's adenoma tissue. On the other hand, hANP had no effect upon the haloperidol-induced increase in aldosterone excretion in the control animals. Thus, preliminary evidence emerges that hANP has no effect on dopaminergic pathways and that the aldosterone inhibiting action of hANP is only of minor physiological significance.

Topics: Adenoma; Aldosterone; Animals; Atrial Natriuretic Factor; Haloperidol; Humans; Mice; Mice, Nude; Natriuresis; Neoplasm Transplantation; Pergolide; Receptors, Dopamine

The effects of synthetic alpha-human atrial natriuretic polypeptide (alpha hANP) on aldosteronogenesis in normal and aldosterone-producing adenoma cells (APA cells) in primary monolayer cultures were studied. alpha hANP significantly inhibited aldosterone secretion from normal adrenal cells in culture, but had no inhibitory effect on aldosterone secretion from APA cells in the presence or absence of 10(-8) M ACTH. alpha hANP enhanced the accumulation of intracellular cGMP in normal adrenal cells in culture, but not in APA cells. Visualization of [125I]iodo-alpha hANP-specific binding sites in APA and adjacent normal adrenal tissues by an in vitro receptor autoradiographic technique showed that these sites were localized only in normal adrenal tissue, but not in APA tissue. These results suggest that the lack of an inhibitory effect of alpha hANP on aldosteronogenesis in APA cells may be due to the absence of alpha hANP-specific receptor sites in APA cells.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adult; Aldosterone; Atrial Natriuretic Factor; Autoradiography; Cells, Cultured; Cyclic GMP; Female; Humans; Middle Aged; Radioligand Assay; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

The effect of synthetic alpha-human atrial natriuretic peptide (alpha hANP), a potent natriuretic and vasorelaxant polypeptide recently isolated from human atria, on aldosterone secretion was studied in vitro in collagenase-dispersed adrenal adenoma cells from a patient with primary aldosteronism. alpha hANP (3.2 X 10(-7) M) significantly inhibited both basal and potassium (16 mM)-stimulated aldosterone secretion, whereas it had little or no effect on aldosterone secretion submaximally or maximally stimulated by ACTH (3.4 X 10(-10)-3.4 X 10(-9) M) or angiotensin II (10(-8)-10(-9) M). The less potent effect of alpha hANP on aldosterone secretion by dispersed human adrenal tumor cells compared to that in in vitro animal studies may reflect decreased affinity and/or number of specific receptors for ANP on the tumor cells. Whether ANP plays a physiological role in regulation of aldosterone secretion in humans in vivo remains to be determined.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenocorticotropic Hormone; Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Female; Humans; In Vitro Techniques; Muscle Proteins; Potassium