Short-term fluctuations in plasma cortisol in Cushing's syndrome.

Short-term fluctuations in plasma cortisol were determined overnight in twelve patients with Cushing's syndrome: eight patients with bilateral adrenal hyperplasia of hypothalamic-pituitary orgin, three patients with a cortisol producing adenoma and one patient with a carcinoma of the adrenal cortex. While either secretory episodes in plasma cortisol or a fixed pattern of cortisol secretion were observed both in patients with pituitary dependent and in those with pituitary independent hypercorticism, a typical night-day variation in plasma cortisol was only found in one of the eight patients with Cushing's syndrome of hypothalamic-pituitary origin. The patient with a cortisol producing carcinoma showed only minor fluctuations in plasma cortisol throughout the test period. The results indicate that no discrimination can be made between patients with pituitary dependent or independent Cushing's syndrome by demonstrating an episodic or a fixed secretion of cortisol. It seems, however, that the finding of a typical night-day variation in hormone secretion points to hypercorticism of hypothalamic-pituitary orgin.

Control of plasma aldosterone during hemodialysis in patients with terminal renal failure.

The control of plasma aldosterone during hemodialysis was investigated in 31 patients with terminal renal failure. While before hemodialysis renin predominantly influenced aldosterone, this effect dissipated during hemodialysis. In addition, no relationship was observed between changes in aldosterone and those in sodium, potassium and plasma cortisol. In a group of 10 patients isokalemic and isonatremic hemodialysis failed to document an effect sodium or potassium on hemodialysis induced changes in aldosterone. Our data suggest that none of the four factors - renin, ACTH, sodium and potassium - had constantly caused the observed changes in aldosterone during hemodialysis.

Control of plasma aldosterone in terminal renal failure before and after nephrectomy and after renal transplantation.

In two patients with terminal renal failure the night-day rhythm of plasma aldosterone (PA) renin activity (PRA) and plasma cortisol (PC) were examined before and after bilateral nephrectomy and after renal transplantation. Before nephrectomy changes in abnormally high PA coincided with PC whereas no significant correlation was observed between PA and PRA. In the anephric state secretory episodes of PA occurred independent from those of PC while PRA was undetectable. After renal transplantation a lack of night-day variation in renin secretion was observed in both patients; only one of the two patients showed episodic secretion of PA while PC was suppressed in both patients probably due to the chronic administration of prednisone. Our results indicate, that before nephrectomy under the conditions described in this study plasma aldosterone was predominantly controlled by ACTH. In the anephric state and after renal transplantation other (yet unidentified) factors might have caused episodic secretion of aldosterone. Finally, the lack of night-day variation and secretory episodes in renin secretion after transplantation points to an important role of the sympathetic nervous system in the control of circadian and episodic renal renin release.

Plasma renin activity (PRA) and aldosterone (PA) in patients with chronic glomerulonephritis (GN) and hypertension.

Patients with chronic glomerulonephritis and mild hypertension show a consistent behaviour in their renin-aldosterone-system. There is a close correlation between the elevation of mean blood pressure and destruction of glomeruli. No correlation has been found between renin values and the degree of hypertension. Thus the cuase of mild hypertension occurring in the early stages of chronic GN remains to be elucidated. Normal PRA values in spite of hypertension and expansion of ECFV accompaning progression of chronic glomerulonephritis could be a sign of "relative hyperreninemia". Apparently various mechanisms are involved in the pathogenesis of renal hypertension. These include sodium retention, increased cardiac output. anemia, renin, aldosterone, prostaglandins, expanded plasma volume and peripheral vasoconstriction. These factors are more or less active in the different stages of hypertension and renal failure.

Control of plasma aldosterone in normal man during upright posture.

Plasma aldosterone, plasma renin activity (PRA), plasma cortisol as parameter of ACTH activity and the serum concentrations of sodium and potassium were determined at short time intervals in 10 healthy students after an overnight bedrest and during three hours of ambulation. While PRA rose significantly within 15 minutes of orthostasis in all students, plasma aldosterone showed a similar rapid increase in some of the subjects only. These persons demonstrated also a simultaneous increase of serum potassium or of plasma cortisol. Plasma aldosterone rose not before 30 to 60 minutes after change to the upright position in subjects who showed neigher plasma cortisol nor serum potassium increases. It is concluded that the immediate rise of plasma aldosterone during orthostasis seems to depend on a stimulation by ACTH of by potassium. The main stimulus of plasma aldosterone during orthostasis appears to be the renin angiotensin system. If the aldosterone response to posture is mediated only through this system a delay of 30 to 60 minutes is observed.

Diurnal variations of plasma aldosterone in supine man: relationship to plasma renin activity and plasma cortisol.

In order to investigate the role of renin secretion and of ACTH on the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), plasma cortisol (PC) and PA were determined at short-time intervals in 10 normal supine men. Six subjects were studied under a normal sodium intake and 4 under sodium restriction. In 4 subjects the secretion of ACTH was suppressed by dexamethasone. Under normal sodium intake changes in PA seemed to be more in parallel with changes in PC than by those in PRA as indicated by a higher significant correlation between PA and PC than between PA and PRA in 3 of the 4 subjects. In 1 subject no correlation was observed between PA and PC despite visual synchronism between the plasma concentrations of both hormones. Under dexamethasone medication fluctuations in PA were followed by those in PRA while PC was less than 2 mug/100 ml. In the sodium restricted state, changes in PA were closely paralleled and significantly correlated to PRA while no correlation was seen between PA and PC. Under dexamethasone medication the significant correlation between PA and PRA persisted. Our results indicate that in normal supine man the influence of ACTH and renin on PA may vary with different sodium intakes. Under normal sodium intake ACTH seems to be the dominant factor controlling PA, whereas under sodium restriction changes in PA are mediated through the renin angiotensin system. When the secretion of ACTH is suppressed by dexamethasone, renin controls PA both under normal and low sodium intake.

Effect of propranolol and prindolol on renin secretion in normal supine man.

To investigate the effect of propranolol and prindolol on renin secretion plasma renin activity (PRA) was determined overnight at short-time intervals in 10 sodium-restricted normal supine subjects. 4 of them were on a 4-days medication with propranolol, 3 were rreated with prindolol and 3 were used as control group. In normal controls renin was secreted episodically and showed characteristic night-day variations. Both in propranolol and in prindolol-treated subjects secretory episodes in renin secretion either did not occur or were less frequent than in normal controls. With one exception night-day variations in renin secretion were not observed. Mean PRA values were significantly lower than in the control group (p less than 0.001). Our results show that both propranolol and prindolol lower PRA and eliminate or reduce the frequency of secretory episodes. It is concluded that the sympathetic nervous system plays an important role in regulating night-day variations and short-time fluctuations of renin secretion in normal supine man.

Severe arterial hypertension caused by chronical abuse of a topical mineralocorticoid.

A 24-year-old woman was referred to our clinic because of severe hypocalemic hypertension and latent myocardial insufficiency. Plasma renin activity and plasma aldosterone concentration were lowered. Plasma cortisol concentrations and the urinary excretion of vanillin mandelic acid were found within normal range. Some efforts to identify a specific adrenal enzymatic defect were unsuccessful. By combined therapy with spironolactone, methyldopa and clonidine, the blood pressure was significantly lowered, but not normalized. Triamterene had also an expressed hypotensive effect and induced orthostatic phenomena. After six months of hypotensive drug therapy, the patient's mother reported that her daughter consumed for more than seven years high doses of special nasal drops containing, beside ephedrine and naphazoline, the potent mineralocorticoid 9-alpha-fluoroprednisolone. A strong drug-dependence to the naphazoline component could be evaluated. The application of the mineralocorticoid was stopped, and only a slight low-sodium diet had to be added to restore the long-standing elevated blood pressure to normal

Effect of angiotensin II and of an angiotensin II analogue (Sar1-Ile8-angiotensin II) on blood pressure, plasma aldosterone and plasma renin activity in the dog.

1. The effect of infusions of equimolar doses of angiotensin II (AII) and of the angiotensin analogue Sar1-Ile8-angiotensin II on arterial blood pressure, plasma aldosterone and plasma renin activity were compared in normal anaesthetized dexamethasone suppressed dogs. 2. Angiotensin II induced a significant increase of blood pressure and of plasma aldosterone whereas plasma renin activity decreased. The blood pressure was only slightly affected by large doses of the analogue. Plasma aldosterone, however, increased and plasma renin activity decreased. These changes were significant but less pronounced than after the infusions of angiotensin II. Plasma aldosterone remained high and renin activity low for 40 min after the infusions of the analogue. 3. The results suggest a strong agonistic potency of Sar1-Ile8-angiotensin II at the adrenal and renal angiotensin receptors, and that it is almost ineffective at the vascular receptors. The inhibition of renin secretion by angiotensin seems not be related to its vasoconstrictive activity.

Effect of immunization against angiotensin II on blood pressure and on plasma aldosterone in the rabbit.

1. Rabbits were actively immunized aganist angiotensin II (AII). 2. Basal plasma aldosterone concentration was 0-058 plus or minus 0-027 pmol/ml (20-7 plus or minus 9-6 pg/ml) (mean plus or minus SD) in immunized and 0-056 plus or minus 0-021 pmol/ml (20-2 plus or minus 7-5 pe. When the endogenous formation of AII was stimulated by frusemide, by haemorrhage or by feeding with low sodium diet, a significant increase of plasma aldosterone was observed with no difference between immunized and non-immunized animals. 3. In non-immune rabbits, the average mean arterial blood pressure rose 13 mmgHg during the infusion of AII (5 pmol min--1 kg-1) and 27 mmHg during the infusion of 50 pmol min-1 kg-1. In contrast, there was no clear increase in blood pressure in the immunized animals. The blood pressure rose in immune animals (15 mmHg) and in non-immune animals (36 mmHg) during the infusion of 200 pmol min-1 kg-1 ALL. Plasma aldosterone rose in all animals in response to each of the three infusions with no significant difference between the two groups. 4. It is concluded that the immunization against ALL blocked only the pressor effect of the peptide but had no clear influence on the response of plasma aldosterone to increased ALL. Differences between the affinities of the adrenal and vascular AII receptors may explain these findings.

Circadian rhythm of plasma renin activity and plasma aldosterone in normal man and in renal allograft recipients.

In normal supine man, a marked circadian rhythm was found in plasma renin activity (PRA) and in plasma aldosterone concentration, with highest levels in the morning and lowest in the evening. Short-term suppression of ACTH by dexamethasone did not eliminate the circadian variation of plasma aldosterone. In patients with a transplanted and thus denervated kidney, no such rhythm of PRA could be observed. From our data it is suggested that the normal circadian rhythm of PRA depends on intact renal innervation and is controlled by the central nervous system.

[Effect of hemodialysis on plasma aldosterone in anephric patients (author's transl)]. / Einfluss der Hämodialyse auf die Plasmaaldosteronkonzentration bei nierenlosen Patienten

Plasma aldosterone, plasma cortisol and the serum concentrations of sodium and potassium were determined in 5 anephric patients before and at short time intervals up to 180 minutes after hemodialysis. Plasma aldosterone increased in 4 of 5 patients during hemodialysis while in all patients plasma cortisol, sodium and potassium decreased. Only one patient showed a fall in aldosterone during hemodialysis. After hemodialysis plasma aldosterone gradually decreased over a period of 3 hours in 3 of 5 patients, whereas the remaining two patients showed typical secretory episodes of aldosterone. In each patient serum potassium rapidly increased while serum sodium showed only minor variations. Plasma cortisol followed the normal circadian rhythm. We suggest that a still unkown factor had caused the observed increases in plasma aldosterone during hemodialysis. There are reasons to believe that over the period observed after hemodialysis the intracellular potassium concentration and not serum potassium levels has influenced adrenal aldosterone release. This would explain the paradoxical decrease in plasma aldosterone in 3 of the 5 patients while serum potassium increased.