atrial-natriuretic-factor and Cushing-Syndrome

The second messenger, cAMP, is one of the most important regulatory signals for control of steroidogenesis. This review focuses on current knowledge about regulation of cyclic nucleotides by phosphodiesterases (PDEs) in steroidogenic tissues. The first PDE known to directly regulate steroidogenesis was PDE2, the cGMP-stimulated PDE. PDE2 mediates ANP/cGMP-induced decreases in aldosterone production. Recently, the PDE8 family has been shown to control steroidogenesis in two tissues. Specifically, PDE8A regulates testosterone production by itself and in concert with additional IBMX-sensitive PDEs. PDE8B modulates basal corticosterone synthesis via acute and chronic mechanisms. In addition to cAMP-dependent pathways, cGMP signaling also can promote steroidogenesis, and PDE5 modulates this process. Finally, PDE mutations may lead to several human diseases characterized by abnormal steroid levels.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 3',5'-Cyclic-GMP Phosphodiesterases; Adrenal Cortex; Adrenal Hyperplasia, Congenital; Aldosterone; Animals; Atrial Natriuretic Factor; Corticosterone; Cushing Syndrome; Cyclic AMP; Cyclic GMP; Female; Humans; Isoenzymes; Leydig Cells; Male; Mutation; Second Messenger Systems; Testosterone

To evaluate the effect of CRH administration on plasma AVP and ANF concentration in patients with Cushing's disease and healthy subjects.. Fifteen patients with Cushing's disease and 15 sex- and age-matched healthy subjects entered the study.. All subjects were randomly given i.v. 100 micrograms hCRH and placebo (NaCl 0.9%) on two non consecutive days. Blood samples for plasma AVP and ANF assay were taken before and every 15 min for 2 hr after CRH or placebo. Five out of the 15 patients with Cushing's disease underwent a repeat CRH test after surgical cure of the disease.. At baseline evaluation, plasma ANF concentrations were significantly higher in patients with Cushing's disease compared to healthy subjects (15.0 +/- 0.8 vs 10.8 +/- 0.6 pmol/l, P < 0.001) whereas plasma AVP concentrations were similar between the two groups of subjects (8.0 +/- 0.4 vs 6.8 +/- 0.6 pmol/l). CRH administration induced a significant increase in plasma ANF concentrations both in patients with Cushing's disease (24.0 +/- 1.6 pmol/l, P < 0.05) and healthy subjects (29.4 +/- 1.5 pmol/l, P < 0.05). Conversely, a significant increase in plasma AVP concentrations was found only in patients with Cushing's disease (14.7 +/- 1.4 vs 8.0 +/- 0.4 pmol/l, P < 0.05). In addition, patients with Cushing's disease had an increase in ANF levels after CRH significantly lower than that observed in healthy subjects (peak/basal ratio: 1.7 +/- 0.1 vs 3.1 +/- 0.4, P < 0.01). In 5 patients re-tested after disease cure, CRH administration significantly increased plasma ANF levels (26.8 +/- 1.1 vs 10.7 +/- 0.4 pmol/l, P < 0.05) but it did not modify plasma AVP levels (8.4 +/- 0.4 vs 7.3 +/- 0.5 pmol/l). ANF response to CRH in patients cured from Cushing's disease was similar to that recorded in healthy subjects (peak/basal ratio: 2.6 +/- 0.2 vs 3.1 +/- 0.4).. CRH stimulates ANF secretion both in patients with Cushing's disease and healthy subjects. Plasma ANF response to CRH is blunted in patients with Cushing's disease compared to patients cured from Cushing's disease and healthy subjects, probably because of hypercortisolism. By contrast, CRH stimulates AVP secretion only in patients with Cushing's disease, but not in patients cured from Cushing's disease and healthy subjects. This phenomenon could be related to the activity of the disease.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Arginine Vasopressin; Atrial Natriuretic Factor; Case-Control Studies; Corticotropin-Releasing Hormone; Cushing Syndrome; Female; Humans; Male; Middle Aged; Stimulation, Chemical

The role of atrial natriuretic peptide (ANP) in glucocorticoid hypertension is still controversial, as glucocorticoids enhance the secretion of ANP in vivo, but reduce its biological activity in vitro. In isolated cells, for example, the cGMP response to ANP is suppressed by dexamethasone. We tested the in vivo relevance of this observation by comparing the cGMP, endocrine, and renal responses to exogenous ANP in patients with Cushing's disease (CD; n = 10) and in a matched group of essential hypertensives (EH; n = 8) and normotensive controls (N; n = 4). alpha-human-ANP was infused at 0.01 microg/kg/min for 120 min with a 30-min recovery period; hormonal and arterial pressure measurements were performed at 30-min intervals, and renal parameters were measured at baseline and after infusion. There was a 4-fold increase in plasma ANP in all groups, but the increments in plasma cGMP were about 50% lower in CD than in N and EH; urinary cGMP was similarly lower in CD (247 +/- 61 vs. 529 +/- 146 and 384 +/- 54 nmol/150 min, respectively). This was associated with a reduced peak increase in hematocrit in CD (+2.6 +/- 0.9%) compared with N (+6.6 +/- 0.9%) and EH (+7.1 +/- 0.7%; P < 0.05 CD vs. both); the diuretic and natriuretic effects of ANP were also lower in CD than in EH with very similar systemic pressure levels (382 +/- 63 vs. 848 +/- 130 mL/150 min, and 61 +/- 14 vs. 113 +/- 14 mmol/150 min, respectively; P < 0.05 for both). The increments in plasma and urinary cGMP in response to physiological doses of ANP are thus blunted in CD patients compared with those in N and EH. This biochemical defect is associated with reduced capillary permeability and a lesser diuretic and natriuretic effect. These data are compatible with an impairment of the biological activity of ANP in glucocorticoid hypertension in humans.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Capillary Permeability; Cushing Syndrome; Cyclic GMP; Female; Humans; Kidney; Male; Middle Aged

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

While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH-stimulated ACTH secretion in vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic-pituitary-adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary-adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n = 4) and Addison's disease (n = 4).. On two different days all patients underwent the following procedures: (a) alpha-human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0.01 microgram/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 microgram/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+ were measured; heart rate and blood pressure were monitored.. In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 +/- 5 to 73 +/- 14 pmol/l; mean +/- SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 +/- 150 to 461 +/- 48 nmol/l; P < 0.05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 +/- 20 to 35 +/- 7 pmol/l P < 0.05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12 +/- 1 to 49 +/- 8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13.4 +/- 0.8 to 7.7 +/- 0.3 ng/ml/h). In all patients, heart rate, blood pressure and K+ were only slightly affected on both occasions.. (1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH-stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and is over-ridden by CRH stimulation.

Topics: Addison Disease; Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Adult; Aldosterone; Atrial Natriuretic Factor; Corticotropin-Releasing Hormone; Cushing Syndrome; Depression, Chemical; Female; Humans; Hydrocortisone; Male; Pituitary-Adrenal System

Topics: Aged; Atrial Natriuretic Factor; Carcinoid Tumor; Cushing Syndrome; Humans; Male; Thymus Neoplasms

Topics: Addison Disease; Adrenocorticotropic Hormone; Adult; Aldosterone; Atrial Natriuretic Factor; Cushing Syndrome; Female; Humans; Hydrocortisone; Infusions, Intravenous; Male; Middle Aged; Pituitary-Adrenal System

The pathogenesis of hypertension associated with Cushing's syndrome is incompletely understood. We have studied basal and saline-stimulated levels of plasma atrial natriuretic hormone in 10 subjects with active Cushing's syndrome (8 F: 2 M), aged 43 +/- 4 years (mean +/- SEM). Ten age- and sex-matched normal control subjects were also studied. Subjects fasted from 22.00 h, rose at 07.45 h, and remained ambulant until 09.45 h when blood was taken for plasma ANH, plasma renin activity and serum aldosterone. Subjects then rested supine until 10.00 h when blood was again taken, and blood pressure recorded. Then, while subjects remained supine, 21 of 0.9% NaCl were infused between 10.00 and 14.00 h. Blood was taken hourly. Basal plasma ANH was 8.0 +/- 0.9 pmol/l in Cushing's subjects and 6.9 +/- 2.5 pmol/l in controls. Levels increased in response to saline in both groups, and became significantly higher in the group of patients with Cushing's syndrome (14.00 h level 21.3 +/- 3.9 vs 10.4 +/- 1.9 pmol/l; p less than 0.05). Serum aldosterone and plasma renin activity were not different between groups. Mean blood pressure was higher in patients (114 +/- 4 vs 91 +/- 7 mmHg; p less than 0.05). Urinary sodium excretion was not different between groups before saline, but during the four hours of saline was higher in Cushing's subjects (133 +/- 12 vs 67 +/- 11 mmols; N = 6; p less than 0.05). Our results suggest that during salt loading the exaggerated natriuresis seen in the Cushing's group may have been caused by ANH.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Female; Humans; Male; Middle Aged; Renin; Sodium; Sodium Chloride

Atrial natriuretic peptide has been considered to be a major regulator in the body's water and salt homeostasis. Antagonizing those mechanisms leading to volume retention and overload (renin, angiotensin, aldosterone), ANP has been suggested to play a critical role in the pathology of certain diseases like renal failure, congestive heart failure or hypertension. In this regard, we measured ANP plasma concentration in normal healthy dogs and dogs with renal failure, congestive heart failure and Cushing syndrome. ANP levels were slightly decreased in dogs with Cushing disease (n = 9; 5.5 +/- 2 fmol/ml), increased in renal failure (n = 7; 16.2 +/- 5.8 fmol/ml, p less than 0.05) and markedly augmented in dogs with congestive heart failure (n = 14; 52.9 +/- 29.75 fmol/ml, p less than 0.01) as compared to healthy dogs (n = 6; 8.3 +/- 3.5 fmol/ml). Furthermore, characterization of the measured immunoreactivity (IR-ANP) revealed, that up to 50% of the IR-ANP in dogs with congestive heart failure corresponds to the ANP precursor molecule, not found in healthy subjects. This fact might present one possible explanation for the attenuated response to ANP in congestive heart failure. In addition, this finding may also serve a diagnostical purpose.

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Cushing Syndrome; Dog Diseases; Dogs; Female; Heart Failure; Kidney Failure, Chronic; Male

Atrial natriuretic peptide (ANP) is stored in atrial myocytes as a 126 amino acid precursor molecule (ANP 1-126) and is cleaved during its release into circulation into the biologically active C-terminal ANP (99-126) and the N-terminal counterpart, ANP (1-98). While interest has focused on ANP (99-126) under physiological and pathophysiological conditions, data for the cosecreted N-terminal sequence, ANP (1-98) are generally missing. Plasma levels of the N-terminal immunoreactive peptide (N-ANP [1-98]) were measured in normal dogs, and in dogs with impaired volume regulation (congestive heart failure; chronic renal failure or Cushing's syndrome and compared with those of C-ANP (99-126). The N-ANP (1-98) concentration was 593.1 +/- 81.1 fmol ml-1 in normal subjects, which is about 60-fold higher than the C-ANP (99-126) (10.8 +/- 2.6 fmol ml-1). In patients suffering from chronic renal failure ANP (1-98) was increased to 1582 +/- 196 fmol ml-1, and in dogs with congestive heart failure to 1612 +/- 244 fmol ml-1. In contrast, Cushing's syndrome dogs showed decreased N-ANP (1-98) concentrations (351 +/- 65.9 fmol ml-1). There was a positive correlation between plasma levels of N-ANP (1-98) and C-ANP (99-126) levels (correlation coefficients: normal: r = 0.78; congestive heart failure: r = 0.76; chronic renal failure: r = 0.86; Cushing's syndrome: r = 0.57). High pressure liquid chromatographic analysis of dog plasma showed one major peak of N-terminal immunoreactivity corresponding to ANP (1-98).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Cushing Syndrome; Diuretics; Dog Diseases; Dogs; Female; Heart Failure; Immune Sera; Kidney Failure, Chronic; Male; Peptide Fragments; Protein Precursors; Radioimmunoassay; Reference Values

Atrial Natriuretic Peptide (ANF), is secreted by atrial myocytes in response to atrial stretch. Its plasma levels have been found elevated in conditions leading to salt and fluid repletion and consequent atrial distention. Recently, it has been demonstrated that dexamethasone can enhance ANF secretion, by acting on ANF gene expression and mRNA synthesis. High plasma levels of ANF have been observed in normal man after administration of cortisol and ACTH. In the case of glucocorticoid excess, as in Cushing's disease, limited and conflicting data are available. Therefore, we measured ANF basal values and ANF response to postural changes and volume expansion in eight patients with Cushing's disease. In our patients ANF values were higher than normals. ANF responded to volume expansion, 47.8 +/- 5.1 pg/ml before sodium load and 69.9 +/- 7.0 pg/ml after sodium load, and changed minimally after postural manoeuvres, 47.3 +/- 3.2 pg/ml supine and 41.7 +/- 5.1 pg/ml upright. These data indicate that ANF secretion is enhanced in Cushing's disease, and its regulation is partially altered. Since in this condition hypervolemia has not been certainly demonstrated, a direct relationship between elevated ANF and glucocorticoid excess could be suggested.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Volume; Cushing Syndrome; Female; Humans; Male; Middle Aged; Posture; Renin; Sodium Chloride

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

The effects of synthetic human atrial natriuretic peptide (ANP) on the release of catecholamines, aldosterone, or cortisol were observed in human adrenal tumors obtained surgically from patients with pheochromocytoma, primary aldosteronism, or Cushing's syndrome, respectively. Each tumor tissue or adjacent normal cortical tissue was sectioned into slices, which were incubated in medium-199 in the presence or absence of adrenocorticotrophin (ACTH) and ANP. The amounts of epinephrine, norepinephrine, aldosterone, or cortisol released into the medium were measured. Existence of ANP receptors on the adrenal tissues was examined by binding assays, affinity labeling, and immunohistochemistry. Release of catecholamines from pheochromocytoma tissues was inhibited by ANP, and the presence of the ANP receptor on pheochromocytoma was further demonstrated by both binding assays and affinity labeling; Scatchard analysis revealed a single class of binding sites for ANP with a Kd of 1.0 nM and a Bmax of 0.4 pmol/mg of protein and the molecular size was estimated as 140 and a 70 kDa under nonreducing and reducing conditions, respectively. The presence of ANP receptors in pheochromocytoma was demonstrated by immunohistochemistry. ANP inhibited both basal and ACTH-stimulated aldosterone secretion in the slices of normal cortex, and localization of ANP receptors in zona glomerulosa cells was also demonstrated. However, ANP did not inhibit basal and ACTH-stimulated aldosterone and cortisol secretion in both tissue slices from aldosteronoma and Cushing's adenoma. Consistent with these observations, the absence of ANP receptors in adenoma tissues was determined by binding assays, affinity labeling, and immunohistochemistry.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenal Cortex; Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Cell Membrane; Cushing Syndrome; Humans; In Vitro Techniques; Iodine Radioisotopes; Pheochromocytoma; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface

A 62-year-old man arrived at our hospital with recurrence of Cushing's syndrome 14 years after successful surgery for adrenocortical carcinoma. Investigations demonstrated recurrence of a large tumor above the right adrenal area; it was found to be inoperable. The patient was treated initially with a new glucocorticoid antagonist, RU 486, and later with the adrenolytic agent mitotane (o,p'DDD). The latter achieved hypoadrenocorticism and a substantial reduction of tumor size. During the initial period, worsening hyperadrenocorticism resulted in a rise of atrial natriuretic factor and an inhibition of renin activity, consistent with an increase of cortisol and plasma volume. Changes in opposite direction were observed after treatment with mitotane.

Topics: Adrenal Gland Neoplasms; Atrial Natriuretic Factor; Carcinoma; Combined Modality Therapy; Cushing Syndrome; Humans; Male; Middle Aged; Mitotane; Neoplasm Recurrence, Local; Renin; Time Factors

The pharmacological effects of synthetic alpha-human atrial natriuretic peptide (alpha-hANP) in patients with Cushing's syndrome and primary aldosteronism were compared with those in normal volunteers. An infusion of synthetic alpha-hANP at 0.1 microgram/kg per min for 20 min produced a maximal plasma hANP level of 800-1200 pg/ml in patients with Cushing's syndrome and primary aldosteronism, and in normal subjects. There were significant decreases in the mean blood pressure (-10 to -15 mmHg) in patients with Cushing's syndrome and primary aldosteronism, similar to those in normal subjects. The plasma cyclic 3'5'-guanosine monophosphate (cGMP) concentrations of both groups of patients were increased fivefold over the baseline level following the infusion. Infusion of synthetic alpha-hANP caused a greater increase in the rate of sodium excretion in patients with Cushing's syndrome and primary aldosteronism compared with normal volunteers. The plasma cortisol and aldosterone concentrations did not, however, significantly change during alpha-hANP infusion in either the patients with Cushing's syndrome or those with primary aldosteronism. As synthetic alpha-hANP has a potent hypotensive effect in hypertensive patients with Cushing's syndrome and primary aldosteronism, a significant reduction in blood pressure and natriuresis seems to occur without affecting adrenocortical steroidogenesis.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Cyclic GMP; Female; Humans; Hyperaldosteronism; Male; Middle Aged; Natriuresis; Peptide Fragments; Renin

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

To examine a possible role for atrial natriuretic hormone (ANH) in the water and electrolyte disturbances associated with hypercortisolism, plasma ANH levels were measured in 18 patients with endogenous Cushing's syndrome. Nine patients had elevated plasma ANH levels compared to normal subjects. The mean plasma ANH concentration [72.5 +/- 13.0 (+/- SE) pg/mL (23.5 +/- 4.2 pmol/L)] in the Cushing's syndrome patients was significantly higher than that in 40 normal subjects [37.6 +/- 1.9 pg/mL (12.2 +/- 0.62 pmol/L)]. A significant positive correlation was found between plasma ANH and cortisol levels in individual patients. There were no significant correlations, on the other hand, between plasma ANH concentrations and PRA, plasma aldosterone levels, or mean blood pressure. After treatment, plasma ANH concentrations decreased in all 6 patients who had elevated plasma ANH levels preoperatively. In 1 patient with Cushing's disease, plasma ANH levels changed in parallel with plasma cortisol concentrations during o,p'DDD treatment. Fifteen patients who were receiving long term synthetic glucocorticoid therapy for the treatment of miscellaneous diseases had a significantly higher mean plasma ANH level [50.2 +/- 4.0 (+/- SE) pg/mL (16.3 +/- 1.3 pmol/L)] than that in normal subjects. These results suggest that plasma ANH levels are elevated in a substantial number of patients with Cushing's syndrome due to either a direct stimulatory effect of glucocorticoid on atrial ANH secretion or, alternatively, intravascular volume expansion resulting from excessive cortisol secretion.

Topics: Adolescent; Adrenalectomy; Adult; Aged; Atrial Natriuretic Factor; Cushing Syndrome; Female; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged

Using two radio-immunoassays for N-terminal and C-terminal fragments of human atrial natriuretic polypeptide (ANP) precursor, gamma-hANP [human atrial natriuretic factor-(1-126)], that is gamma-hANP(1-25) [human atrial natriuretic factor-(1-25)] and alpha-hANP [human atrial natriuretic factor-(99-126)], we studied the secretion of gamma-hANP-derived peptides into circulation from the heart in normal subjects and patients with essential hypertension and adrenal disorders. Volume expansion with 2 litres physiological saline increased plasma gamma-hANP(1-25)-like immunoreactivity concomitantly with plasma alpha-hANP-like immunoreactivity in normal subjects. Infusion of angiotensin II (20 ng/kg per min) or noradrenaline (200 ng/kg per min) also caused a parallel increase in plasma gamma-hANP(1-25)-like and alpha-hANP-like immunoreactivity. Plasma gamma-hANP(1-25)-like immunoreactivity levels were changed together with alpha-hANP-like immunoreactivity in patients with essential hypertension and adrenal disorders. These results indicate that gamma-hANP-derived peptides, alpha-hANP and the 10-k N-terminal fragment of gamma-hANP (N-peptide) are cosecreted from the heart and that the simultaneous measurement of N-peptide and alpha-hANP serves as an indicator of the cardiac endocrine function. The significance of N-peptide as a hormone must await further clarification.

Topics: Addison Disease; Adrenal Gland Diseases; Adrenal Gland Neoplasms; Angiotensin II; Atrial Natriuretic Factor; Blood Volume; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension; Immunoassay; Pheochromocytoma

Topics: Adrenal Insufficiency; Atrial Natriuretic Factor; Blood Pressure; Cushing Syndrome; Humans; Hyperaldosteronism; Hypertension, Malignant; Hyperthyroidism; Hypothyroidism; Inappropriate ADH Syndrome

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

Using the immunoperoxidase method with specific antibody, we examined the presence of atrial natriuretic peptide (ANP) in adrenal tissues of a patient with primary aldosteronism and those derived from a patient with Cushing's syndrome. We found cells immunopositive for ANP in primary aldosteronism but not in Cushing's syndrome. In primary aldosteronism, we noted positively stained cells mainly but not exclusively in the adenomatous tissue. These results demonstrate for the first time the presence of immunoreactive ANP in adrenal tissues of a patient with primary aldosteronism and suggest that adrenal ANP may have potentially important impacts on aldosterone secretion in this disorder.

Topics: Adrenal Glands; Adult; Atrial Natriuretic Factor; Cushing Syndrome; Humans; Hyperaldosteronism; Immunohistochemistry; Male

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