Excessive Aldosterone Production Research Articles

Effect of dibutyryl cyclic AMP on plasma renin activity in normal men and patients with primary aldosteronism

Dibutyryl cyclic AMP (DBcAMP) directly stimulates the release of renin from the juxtaglomerular (JG) cells in vitro. We investigated the effect of DBcAMP on plasma renin activity (PRA) in 6 normal men and in 8 patients with primary aldosteronism (PA). A 20-min infusion of 0.33 mg/kg/min of DBcAMP significantly increased PRA in normal men, but had little effect on PRA in patients with PA. Infusion of DBcAMP significantly reduced the blood pressure and the levels of serum sodium and potassium in normal men and the patients with PA. Infusion of DBcAMP significantly increased urine volume in normal men, but not in patients with PA. Urinary excretion of sodium increased in both groups after the infusion of DBcAMP. Thus, DBcAMP did not stimulate renin release in patients with PA, suggesting that the chronic excess production of aldosterone suppresses the release of renin from JG cells.

Evaluation of Diagnostic Tests in the Differential Diagnosis of Primary Aldosteronism: Unilateral Adenoma Versus Bilateral Micronodular Hyperplasia

Effective management of primary aldosteronism is dependent upon correct localization of excessive aldosterone production. We report our results of localization studies in patients with biochemically and pathologically confirmed primary aldosteronism. Retrospective chart review identified 69 patients with unilateral adrenal adenoma and 11 with adrenal hyperplasia. Correct unilateral versus bilateral localization of excessive aldosterone production was predicted in 70% versus 71%, respectively, by adrenal venography, 100% versus 63% by adrenal vein hormone sampling, 46% versus 56% by adrenal nuclear scanning and 69% versus 13% by anomalous postural decline of aldosterone. Adrenal computerized tomography appeared to localize correctly 86% versus 80% of the lesions. Unilateral adrenalectomy normalized blood pressure in 79% of the patients with unilateral adenomas versus only 18% of those with adrenal hyperplasia. Once primary aldosteronism is confirmed, localization by adrenal vein sampling, adrenal venography and adrenal computerized tomography is most effective in directing antihypertensive therapy.

Human NCI-H295 adrenocortical carcinoma cells: a model for angiotensin- II-responsive aldosterone secretion

Excessive secretion of aldosterone from the adrenal results in the most common form of endocrine hypertension. An understanding of the regulatory processes involved in aldosterone synthesis and release is needed to define the biomolecular mechanisms controlling excessive production of aldosterone. However, in vitro studies regarding the regulatory mechanisms of human aldosterone production have been limited because of difficulties in obtaining tissue and the subsequent isolation of aldosterone-secreting glomerulosa cells. Herein we describe an adrenocortical carcinoma cell line, NCI-H295, which provides a suitable angiotensin-II (AII)-responsive model system to investigate the acute and chronic regulation of aldosterone synthesis. The cells were characterized with regard to the effects of AII on second messenger systems, aldosterone release, and levels of aldosterone synthase (P450c18) mRNA. In the presence of lithium, AII caused a rapid, but transient, increase in the production of inositol tris- and bisphosphates, whereas a prolonged gradual accumulation of inositol monophosphate occurred. Treatment with AII resulted in a 4.5-fold increase in total inositol phosphates in a concentration-dependent manner and an increase in intracellular cytoplasmic free Ca2+. Significant increases in aldosterone (3.5-fold) were detected within 1 h of AII addition. Aldosterone release occurred in a concentration-and time-dependent manner. The type 1 AII (AT1) receptor was shown to be responsible for activation of phosphoinositidase-C, increased intracellular free Ca2+, and aldosterone production, as determined by use of the AT1 receptor antagonist DuP753. In addition, AII treatment resulted in a time-dependent increase in levels of P450c18 mRNA, as detected by RNAse protection assay. In summary, NCI-H295 cells provide a valuable model system to define mechanisms regulating human aldosterone production.

Human NCI-H295 adrenocortical carcinoma cells: a model for angiotensin-II-responsive aldosterone secretion.

Excessive secretion of aldosterone from the adrenal results in the most common form of endocrine hypertension. An understanding of the regulatory processes involved in aldosterone synthesis and release is needed to define the biomolecular mechanisms controlling excessive production of aldosterone. However, in vitro studies regarding the regulatory mechanisms of human aldosterone production have been limited because of difficulties in obtaining tissue and the subsequent isolation of aldosterone-secreting glomerulosa cells. Herein we describe an adrenocortical carcinoma cell line, NCI-H295, which provides a suitable angiotensin-II (AII)-responsive model system to investigate the acute and chronic regulation of aldosterone synthesis. The cells were characterized with regard to the effects of AII on second messenger systems, aldosterone release, and levels of aldosterone synthase (P450c18) mRNA. In the presence of lithium, AII caused a rapid, but transient, increase in the production of inositol tris- and bisphosphates, whereas a prolonged gradual accumulation of inositol monophosphate occurred. Treatment with AII resulted in a 4.5-fold increase in total inositol phosphates in a concentration-dependent manner and an increase in intracellular cytoplasmic free Ca2+. Significant increases in aldosterone (3.5-fold) were detected within 1 h of AII addition. Aldosterone release occurred in a concentration-and time-dependent manner. The type 1 AII (AT1) receptor was shown to be responsible for activation of phosphoinositidase-C, increased intracellular free Ca2+, and aldosterone production, as determined by use of the AT1 receptor antagonist DuP753. In addition, AII treatment resulted in a time-dependent increase in levels of P450c18 mRNA, as detected by RNAse protection assay. In summary, NCI-H295 cells provide a valuable model system to define mechanisms regulating human aldosterone production.

Genitoplasty for intersex anomalies.

The child born with ambiguous genitalia requires prompt diagnosis, sex assignment and treatment. The incidence of intersex is approximately 1 in 30,000 newborns [7]. These patients are categorized based on the their gonadal presentation into female pseudo-hermaphrodites, male pseudohermaphrodites, true hermaphrodites and mixed gonadal dysgenesis [2, 6] (Table 1). The majority of these cases (60-70%) will be female pseudohermaphrodites secondary to the adrenogenital syndrome (types I-IV) (Table 2). Simply put, these patients suffer from a block in the normal production of cortisone which by negative feedback from the pituitary results in the continued stimulation and overproduction of the by products of steroid metabolism in the adrenal gland. High levels of androgenic steroids leads to various degrees of masculinization in the XX fetus with exclusively ovarian tissue for gonads. Variable degrees of phallic enlargement, fusion of the urethral folds to form a phallic urethra and proximal entry of the vagina into the urogenital sinus are the resulting effects. These babies may look like males with bilateral cryptorchidism and hypospadias. Secondary to an increase in ACTH production, these patients may also have hyperpigmentation of their skin over the external genitalia and nipples. Rarely, abnormal androgen stimulation in the fetus may come from the mother either from exogenous ingestion of androgen hormones or from maternal androgen secreting tumors [2, 6]. Excessive aldosterone production leads to salt wasting which is life threatening if not recognized and treated. Male pseudohermaphrodites encompass a wide group of patients with varying etiologies that may present as intersex patients in the newborn period or during hormonal changes associated with puberty. Together these patients all have exclusively testicular tissue with a 46,XY karyotype. The pathology in this group results from the inability of the testis to synthesis testosterone or the failure of target tissues to respond to circulating testosterone (androgen insensitivity). The decision to raise the child as a male centers around the potential for the phallus to function adequately in later sexual relations. Presently, attempts at phallic reconstruction have been disappointing [34, 35]. Because of this, in questionable cases, the tendency has been to choose a female sexual identity.

1 Case of Primary Aldosteronism Caused by Adrenal Hyperplasia

Primary aldosteronism is a disease that the stimulus for the excessive aldosterone production resides within the adrenal gland. It was first described by conn in 1955. And many cases were reported by physicians at present in the world. But it is relatively rare in Korea, probably due to lack of attension and medical facilities. Only about 13 cases have been reported at present. The clinical, biochemical features in 1 case of primary aldosteranism caused by adrenal hyperplasia that was diagnosed at Yeungnam University Hospital was observed and the following result were obtained. 1. Clinical feature: The present case was 27-year-old woman who was admitted due to general weakness and easy fatigability. The above mensioned chief complaints occurred 8 months prior to admission when she delivered of second baby by cesarian section. Symptoms such as above chief complaints, intermittent muscle paralysis and cramping were noticed. Trousseau's sign was also present. The average blood pressure ranged from 170/90 to 200/120. 2. Biochemical abnormalities: Severe hypokalemia lower than 2.5 mEq/L was presented and 24 hours urine potassium showed markedly increased urinary loss.(228 mEq/day). Plasma renin activity was decreased under normal range with furosemide administration.(Basal renin; 0.01ng/ml/hr, stimulated renin 0.12ng/ml/hr). Saline suppression test revealed markedly elevated levels of aldosterone higher than normal range. (Basal aldosterone; 320.68pg/ml stimulated aldosterone; 451.86pg/ml). And posture test showed decreased plasma renin activity and increased plasma aldosterone level. - PRA(ng/ml/hr)=Bsal: 0.05(0.15~2.33), Stimulated: 0.22(1.31~3.95) - Aldosterone(pg/ml)=Bsal: 242.77(10~160), Stimulated: 432.09(40~310) 3. Adrenal CT scan revealed no abnormal findings. 4. Treatment and course: Spironolactone was given at OPD with regular follow-up. Her blood pressure ranged from 150/90 to 160/100 and symptoms were improved. The effect of treatment was satisfactory and further follow up would be performed.

Primary aldosteronism: diagnosis and differentiation of subtypes.

Editorials1 February 1984Primary Aldosteronism: Diagnosis and Differentiation of SubtypesMYRON H. WEINBERGER, M.D.MYRON H. WEINBERGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-2-300 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptNearly 30 Years have passed since the initial description of primary aldosteronism, a syndrome caused by the excessive production of mineralocorticoid hormones from an adrenal tumor (1, 2). Hypertension, hypokalemic alkalosis, normal glucocorticoid function, and excessive production of aldosterone were the original features of the syndrome. Elucidation of the marked suppression of renin activity, resulting from the mineralocorticoid-induced increase in extracellular fluid, provided a useful marker for detecting this potentially curable form of hypertension (3). However, subsequent studies of plasma renin activity in hypertension have found that a large population of patients have renin suppression, most of whom do not...

The changing clinical spectrum of primary aldosteronism

In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), “refractory” hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.

Primary hyperaldosteronism

Primary aldosteronism is a rare hypertensive disorder characterized by excessive aldosterone production. Hypokalemia and a suppressed and poorly responsive reninangiotensin system usually accompany the high aldosterone secretion. The differential diagnosis of the Syndrome from other hypertensive and hypokalemic diseases can be made by evaluation of the renin-angiotensin—aldosterone system. Separation of patients with non-adenomatous disease (15–20 per cent) who will show a poor response to surgery, can be achieved by measurement of the plasma aldosterone response to posture or by evaluation of a combination of metabolic and biochemical data. This latter procedure is based on the finding that non-adenomatous disease is generally of less severity than that observed with an adenoma. Techniques to lateralize the tumor prior to surgery are now widely used. Those involving adrenal vein cannulation and steroid measurement produce results with a satisfactory precision. Treatment is by surgery for patients with an adenoma. In patients with non-adenomatous disease or others in which surgery is not advised a satisfactory response can usually be achieved with spironolactone or amiloride. These drugs which primarily inhibit the aldosterone induced sodium retention are also potassium sparing and result in normalization of the hypokalemia and alkalosis together with a fall in blood pressure.

Primary aldosteronism with unusual secretory pattern.

ABSTRACT An adrenocortical tumor that secreted normal amounts of aldosterone was successfully removed and the classic findings of hypokalemic alkalosis and hypertension in primary aldosteronism were corrected. The tumor failed to alter aldosterone excretion during potassium repletion, desoxycorticosterone administration, sodium restriction and pituitary suppression. Normal aldosterone secretion probably resulted from the degree of potassium depletion but was sufficient under this condition to produce the manifestations of excessive aldosterone production. Failure to reduce aldosterone secretion during administration of desoxycorticosterone acetate in the presence of strong clinical evidence for primary aldosteronism should warrant surgical exploration for a tumor.

Whole Body Hematocrit in Women with Idiopathic Edema: Evidence of an Abnormal Plasma Distribution.

s1 November 1965Whole Body Hematocrit in Women with Idiopathic Edema: Evidence of an Abnormal Plasma Distribution.George D. Webster Jr., M.D., F.A.C.P., William Siegel, M.D., Emanuel G. Tulsky, M.D.George D. Webster Jr., M.D., F.A.C.P.Search for more papers by this author, William Siegel, M.D.Search for more papers by this author, Emanuel G. Tulsky, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-921_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIdiopathic edema is a syndrome of obscure and perhaps diverse etiologies. It is characterized by edema formation, frequently cyclic in nature, occurring almost exclusively in women and not related to detectable parenchymal disease of the cardiovascular, renal, or endocrine systems. Its milder forms merge with the fluid retention associated with the menstrual cycle. Physiologic studies in these patients are relatively few; excessive aldosterone production and an inability to excrete a standard water load have been described, and posture, environmental temperature, and psychic stress have been found to play a role.The present studies were undertaken to assess the role of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 921-921KeywordsBlood plasmaEdemaEndocrine systemEtiologyHematocritMenstrual cyclePostural controlRenal diseasesRenal systemTemperature Issue Published: 1 November 1965 PDF downloadLoading ...

INFLUENCE OF THE PITUITARY AND THE RENIN-ANGIOTENSIN SYSTEM ON THE SECRETION OF ALDOSTERONE, CORTISOL, AND CORTICOSTERONE.

There is evidence suggesting that the control of aldosterone secretion is relatively independent of the pituitary gland. This is based on morphological studies in the rat (1), on indirect assessments of adrenal secretion during metabolic studies in man (2), and on direct estimations of adrenal hormone secretion in the rat (3, 4) and dog (5-7). The morphological studies of Deane and Masson (8), which indicate that renin may stimulate the adrenal cortex in the rat, the results of Genest and his colleagues (9), which suggest that arterial hypertension may be associated with an increased excretion of aldosterone in man, and the demonstration by Genest ( 10, 11 ) and Laragh (12) and their colleagues that angiotensin II stimulates excretion (10, 11) and secretion (12, 13) of aldosterone suggest that the kidney may have some influence on the rate of secretion of adrenal hormones. Recently, Pronove, MacCardle, and Bartter (14) described a dwarfed, normotensive child who was suffering from the effects of excessive production of aldosterone. This was associated with a remarkable hypertrophy and hyperplasia of the juxtaglomerular apparatus in the kidney. The syndrome has been found subsequently in two other patients with hyperaldosteronism (15, 16). The observations suggested that the kidney itself was in some way responsible for the overproduction of aldosterone. The present experiments, performed in the dog, were designed to test the hypothesis that the normal kidney contains material capable of stimulating the adrenal cortex. This was found to be so (17, 18), in agreement with results simultaneously obtained by Mulrow, Ganong, Cera, and Kuljian (19) and by Davis and associates (20, 21). Accordingly, further studies were designed to see whether the pattern of response of the three important adrenocortical steroid hormones (aldosterone, cortisol, and corticosterone) was such as to suggest that this renal stimulus is involved in the mediation of aldosterone secretion physiologically.

Conn's syndrome, caused by adrenocortical hyperplasia; pathogenesis of the signs and symptoms.

In 1955 Conn described a syndrome caused by excessive production of aldosterone, the main manifestations being polyuria, polydipsia, hypertension, intermittent paralyses and tetany. The renal concentration power was severely disturbed, but the other renal functions were not affected to any significant degree. The serum potassium was markedly lowered, the sodium level increased, and there was a metabolic alkalosis. The latter proved not to be always present in cases observed later on (Chalmers et al., 1956). As far as we know, only adenomas or carcinomas of the adrenal cortex have so far been found in these cases.