Renin-angiotensin system and plasma aldosterone in Cushing's syndrome

The renin-angiotensin system was studied in eight patients with Cushing's syndrome (four with adrenal adenoma and four with adrenal hyperplasia) and in five normal controls. Basal plasma renin activity (PRA) and aldosterone concentration (PAC) were similar in supine position among Cushing's syndrome due to adrenal adenoma (PRA; 1.0 +/- 0.3 ng/ml/h, PAC; 7.4 +/- 1.0 ng/dl, mean +/- SE), those due to adrenal hyperplasia (1.0 +/- 0.2, 6.9 +/- 0.8) and the controls (0.8 +/- 0.1, 6.4 +/- 0.4). The PRA after furosemide (1 mg/kg i.v.) and 120 min. upright posture stimulation was similar among Cushing's syndrome due to adrenal adenoma (2.2 +/- 0.7 ng/ml/h), those due to adrenal hyperplasia (2.6 +/- 1.7) and the controls (2.5 +/- 1.2). However, the PAC response after the stimulation in Cushing's syndrome due to adrenal hyperplasia (7.1 +/- 1.2 ng/dl) was significantly lower than that in the controls (17.5 +/- 2.1) (p less than 0.01), although there was no significant difference between the PAC response in Cushing's syndrome due to adrenal adenoma (12.6 +/- 1.0) and the controls. These results indicate that PAC response to furosemide and upright pasture stimulation might be suppressed in Cushing's syndrome due to adrenal hyperplasia.     

Neutrophil function in Bartter's syndrome

Bartter's syndrome is a state associated with hyperprostaglandinemia and high urinary excretion of prostaglandin derivatives. Because of numerous reports on prostaglandins acting as local modulators of the immune system, we have studied parameters of phagocytic function and of cellular and humural immunity in four patients with this disease.An augmentation in chemotaxis was identified in Bartter's syndrome neutrophils. Despite some minor deviations in other parameters measured, no other gross derangement in immune function could be identified.     

Plasma aldosterone level in a female case of pseudohyperaldosteronism (Liddle's syndrome)

A 22-yr-old female suffering from hypertension, hypokalemic alkalosis and suppressed plasma renin activity was studied. The plasma aldosterone concentration (PAC) ranged between subnormal and normal levels while the other adrenal mineralocorticoids were normal. Examinations through computed tomography and ultrasonography showed no abnormal findings. For differential diagnosis, dexamethasone, spironolactone and triamterene were administered. Triamterene alone corrected the abnormalities in this case, and the therapeutic effect was further enhanced by sodium restriction. Therefore, the present case is strongly suggested to be one of Liddle's syndrome, which is characterized by a primary defect in renal tubular sodium handling and can be corrected with triamterene. However, the patient in our study is different from the first reported case in which aldosterone secretion was estimated to be low. Analysis of the changes in PAC has shown that PAC is parallel with the level of plasma progesterone in accordance with the rhythm of the menstrual cycle and, in the follicular phase, PAC is rather low. It is concluded that the patient was suffering from Liddle's syndrome, and it is assumed that PAC is not always subnormal and, as same as in normal females, PAC may change in accordance with the rhythm of the menstrual cycle in a female case of Liddle's syndrome.     

The effect of sodium balance on sweat sodium secretion and plasma aldosterone concentration

The effect of manipulating sodium intake upon sweat sodium secretion was investigated during heat acclimation. Twenty-five male subjects were confined to an environmental chamber at a temperature of 25°C for 3 days, and then acclimated to heat by a further 5 days at 40°C. The subjects' daily sodium intake was controlled throughout as follows: high (HNa), 348.4 (0.8) mmol · day⁻¹, n = 7; moderate (MNa), 174.1 (0.6) mmol · day⁻¹, n = 9; or low (LNa), 66.3 mmol · day⁻¹, n = 9. Sodium losses were estimated from urinary, faecal and sweat collections using a whole-body washdown method. Plasma aldosterone concentration was also measured from venous blood sampled each morning. Measurements of body temperature and heart rate during the heat exposure phase indicated a degree of heat acclimation. During this heat phase there was a reduction (P < 0.01) in sweat sodium secretion for all three conditions which was greatest for the LNa condition, although this finding was not significant (P < 0.1). In the LNa condition, plasma aldosterone concentration increased (P < 0.05) prior to heat exposure, and the secretion of aldosterone was potentiated (P < 0.01) during the heat exposure in comparison with the MNa condition. In contrast, the HNa diet produced a fall (P < 0.05) in plasma aldosterone concentration prior to heat exposure and an attenuation of aldosterone secretion thereafter. These findings are inconsistent with the hypothesis that retention of sweat sodium is dependent upon a net body sodium deficit, but demonstrate that aldosterone secretion is potentiated under such conditions. Accepted: 22 May 1988     

Diurnal fluctuation in saliva aldosterone concentration

We have measured saliva aldosterone concentration (SA) at frequent intervals in subjects going about their normal daytime activities. Four hourly sampling sufficed to give a reasonable estimate of mean diurnal SA but hourly sampling is necessary if it is desired to study the temporal pattern of SA. In subjects with normal or elevated mean levels, SA fluctuated considerably suggestive of several distinct episodes of aldosterone secretion. Such fluctuations show little correlation with the concentrations in saliva of glucocorticoids (cortisol + cortisone) nor are they consistent with a circadian rhythm of aldosterone secretion. We suggest that they may represent responses to such stimuli as eating, drinking or physical activity, and possibly to other as yet unidentified factors. These observations show the importance of comprehensive diurnal assessment of aldosterone level in physiological and pathological investigations. Because of its non-invasive nature and the high productivity of the assay, measurement of SA is ideally suited for this purpose.     

Extra- and intracellular potassium concentration and prostaglandin production of skin fibroblasts grown from patients with Bartter's syndrome

In studies on human skin fibroblasts originating from three patients with Bartter's syndrome and in corresponding age and sex matched controls, the bradykinin stimulated release of PGE2, PGI2, PGF2a and of arachidonic acid was examined. The studies were aimed at demonstrating the possible changes of prostaglandin production under the influence of changing extracellular potassium concentrations (0–12 mmol K/l) in the two study groups. Earlier studies were confirmed and extended by one more pair of fibroblast cultures, showing a decreased bradykinin stimulated PGE2 production in fibroblasts from patients with Bartter's syndrome as compared to control. The difference in bradykinin stimulated PGE2 production was significant, irrespective of the extracellular potassium concentrations, to which the cultures were exposed. The bradykinin stimulated PGE2 and PGF2a-production by control fibroblasts was directly proportional to extracellular potassium concentrations, whereas the PG-production of Bartter's syndrome fibroblasts remained uninfluenced by extracellular potassium. Extra- and intracellular potassium concentrations were directly proportional and there was no difference in this relationship between controls and Bartter's syndrome.The direct proportionality between bradykinin stimulated PGE2 production and potassium concentrations in control fibroblasts is, despite the apparent contradiction, in accordance with findings in the literature. The lack of a comparable proportionality in fibroblasts from patients with Bartter's syndrome is interpreted to correspond to an insensitivity to changes of potassium concentrations and thus to an insensitivity to one of the modulators of AA metabolism.     

Bartter's syndrome associated with indirect hyperbilirubinemia: a possible clinical variety

This report deals with three cases of Bartter's syndrome whose symptomatology was associated with indirect hyperbilirubinemia. The bilirubin disorder was suggestive of Gilbert's syndrome, with no pathological findings being detected as far as the liver function was concerned. Furthermore, the unconjugated fraction of bilirubin increased after fasting. The therapy with indomethacin exerted beneficial effects on both electrolytes and bilirubin disorders, and the patients recovered a good healthy state. These findings suggest the possibility that Bartter's syndrome may coexist in a variety associated with indirect hyperbilirubinemia.     

Effects of two different experimental situations of hypothyroidism on serum aldosterone concentration and plasma renin in rats

When hypothyroidism is induced surgically in early steps of development in the rat, an increase in serum aldosterone concentration (AC), in absence of changes in plasma renin activity (PRA), is observed. In contrast, in propylthiouracil (PTU) induced hypothyroidism, in adult animals, both AC and PRA decrease. Potassium iodide (KI) or triiodo-L-thyronine (T3) administration to thyroidectomized rats restores AC to normal levels, increasing PRA during the latter treatment. A close relationship between AC and plasma renin concentration (PRC) is observed in these experimental situations. The decrease in urinary aldosterone concentration (ACu), and the relation found between AC/ACu ratio and T3 concentration, suggest that metabolic clearance of aldosterone might be related to peripheric T3 levels in thyroidectomized animals, treated with KI or T3. These observations support the hypothesis, previously reported, which suggests different mechanisms involved in the control of aldosterone and renin release during the two different types of hypothyroidism.     

Solid phase radioimmunoassay of plasma aldosterone

A solid phase radioimmunoassay for the measurement of aldosterone in plasma is described. The antiserum was produced by immunizing rabbits with 3-carboxymethyloxime of aldosterone-18–21-diacetate coupled to bovine serum albumin. This antiserum was covalently linked to an iminocellulose according to the procedure of Wide and used in the assay at a $\text{1}\text{1050}$ final dilution. It contained antibodies with association-constant of 1.1 × 10¹⁰ M^?1 and was fairly specific since with the exception of aldosterone acetates, none of the tested steroids cross-reacted more than 0.05 per cent.Aldosterone was extracted with dichloromethane, purified by paper chromatography, then submitted to the assay. The intra-assay reproducibility varied between 4 and 13 % and the inter-assay reproducibility between 13 and 21 %. The least detectable amount was 5 pg per tube. This method is very simple and, with the exception of the chromatographic step, can be completed in half a working day.     

Solid phase radioimmunoassay of plasma aldosterone

A solid phase radioimmunpassay for the measurement of aldosterone in plasma is described. The antiserum was produced by immunizing rabbits with 3-carboxymethyloxime of aldosterone-18-21-diacetate coupled to bovine serum albumin, This antiserum was covalently linked to an iminocellulose according to the procedure of Wide and used in the assay at a $\text{1}\text{1050}$ final dilution. It contained antibodies with association-constant of 1.1 × 10¹⁰M^?1 and was fairly specific since with the exception of aldosterone acetates, none of the tested steroids cross-reacted more than 0.05 per cent.Aldosterone was extracted with dichloromethane, purified by paper chromatography, then submitted to the assay. The intra-assay reproducibility varied between 4 and 13 % and the inter-assay reproducibility between 13 and 21 %. The least detectable amount was 5 pg per tube. This method is very simple and, with the exception of the Chromatographie step, can be completed in half a working day.     

Results of adrenal surgery in patients with hypertension,aldosterone excess,and low plasma renin concentration.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.     

Effect of heat stress and drinking water salt supplements on plasma electrolytes and aldosterone concentration in broiler chickens

An experiment was conducted to evaluate the effects of supplementing drinking water with isomolar (0.067 mol/l) KCl or NaCl on mass gain, food and water consumption, rectal temperature, and plasma concentrations of aldosterone, Na⁺, and K⁺ in broiler chickens reared in thermoneutral and cycling heat stressing environments. Heat stress decreased (P0.05) mass gain, food consumption, and plasma concentrations of Na⁺ and K⁺, while increases (P0.05) in plasma concentrations of aldosterone, rectal temperature, and water consumption were observed. Drinking water supplemented with either KCl or NaCl increased (P0.05) broiler mass gain and water consumption, but had no effect (P>0.1) on the other variables evaluated. The results of this study indicate that broiler chickens in a heat stress environment are under osmotic stress and supplementing drinking water with 0.067 mol/1 KCl or NaCl does not lessen this stress.     

Somatostatin 1-28 circulates in human plasma

The gel filtration profile of immunoreactive somatostatin in human plasma in the fasting state is not well established as a consequence of insufficient sensitivity of the combined chromatography and radioimmunoassay procedures usually employed. We here report the gel filtration profiles of plasma samples after somatostatin concentration by batchwise immunoaffinity chromatography. The results clearly and reliably document the presence of a circulating peptide in human plasma with a gel permeation chromatography profile identical to the one of synthetic somatostatin 1-28. Approximately 46% of the total somatostatin-like immunoreactivity in plasma is due to this component.