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Biomedical subjects

M Schambelan

Publications and source records attributed to M Schambelan.

15 recordsLinked to original sources
PubMed1979

Adrenocorticotropin inhibition of mineralocorticoid hormone production.

1. Adrenocorticotropin (ACTH)-induced steroidogenesis, obtained by continuous administration of ACTH for 3 days, produces in man (a) sustained elevations of plasma deoxycorticosterone and cortisol concentrations, (b) transient elevations of plasma aldosterone and 18-hydroxycorticosterone concentrations that return to near-control values, and (c) brisk initial increases in plasma 18-hydroxydeoxycorticosterone and corticosterone concentrations that fall to 20-68% of peak values 30 h thereafter. 2. Dexamethasone (8 mg/day, orally) treatment for 2 days in man permits a greater postural increase in plasma aldosterone and 18-hydroxycortisone concentrations. A dampening effect of ACTH is suggested. 3. An ACTH-initiated inhibition of 11 beta- and 18-hydroxylation is proposed to be operative in regulation of mineralocorticoid hormones.

18-Hydroxycorticosterone↗
PubMed1979

The significance of elevated levels of plasma 18-hydroxycorticosterone in patients with primary aldosteronism.

Plasma 18-hydroxycorticosterone (180HB) concentration was measured in 23 patients with primary aldosteronism. After overnight recumbency, the levels were markedly elevated and were 6 times higher in patients with aldosterone-producing adenomas than in patients with hyperplasia. A value of 100 ng/dl or greater at 0800 h after overnight recumbency distinguished an adenoma from hyperplasia. There was no overlap of values, as was observed with plasma aldosterone concentration (PAC) at 0800 h and after 4 h of upright posture at 1200 h. There was a significant negative correlation between the ratio of 180HB to PAC and the potassium concentration in patients with primary aldosteronism due to hyperplasia. Potassium repletion with potassium chloride and/or spironolactone in patients with aldosterone-producing adenomas decreased the 180HB:PAC ratio by decreasing 180HB and increasing PAC. 180HB is an effective discriminator of an adenoma and may be a useful marker of the events in late aldosterone synthesis.

18-Hydroxycorticosterone↗
PubMed1977

Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism.

In four patients with renal hyperchloremic acidosis and hyperkalemia, hyporeninemic hypoaldosteronism and chronic renal insufficiency (glomerular filtration rates of 13, 31, 35 and 44 ml per minute per 1.73 m2), prolonged administration of fludrocortisone increased urinary potassium and net acid excretion, corrected hyperkalemia and substantially ameliorated acidosis. Except in the patient with the lowest glomerular filtration rate, the increased net acid excretion was due mostly to increased ammonium excretion. Urine pH decreased initially in each patient, but in the three patients with the highest filtration rates, it increased subsequently as ammonium excretion increased, indicating that renal ammonia production increased. Urinary ammonium excretion correlated inversely with serum potassium concentration and did not decrease on discontinuation of therapy if hyperkalemia was prevented from recurring. In patients with renal acidosis and hyporeninemic hypoaldosteronism, administration of mineralocorticoid hormone can augment both renal hydrogen-ion secretion and, by correction of hyperkalemia, renal ammonia production, and thereby ameliorate metabolic acidosis.

Acidosis, Renal Tubular↗
PubMed1977

Concurrent hypercortisolism and hypermineralocorticoidism.

Hypertension and hypokalemia occur in patients with Cushing's syndrome whereas aldosterone production is normal and plasma renin activity is usually normal or increased. A normal aldosterone level in the face of suppressed plasma renin activity is unusual and suggests excess mineralocorticoid hormone activity. Our patient, who had Cushing's syndrome due to adrenocortical adenoma, can be classified as having low renin hypertension (suppressed renin and normal aldosterone levels). The mineralocorticoid hormone in excess was deoxycorticosterone which suppressed renin. The aldosterone production was normal and was produced solely by the adenoma. Contralateral adrenal gland suppression of both the zona glomerulosa by deoxycorticosterone via renin, and of the fasciculata by cortisol via ACTH was demonstrated after removal of the adenoma. Normal adrenal function was gradually restored.

Adenoma↗
PubMed1977

Treatment of high-renin hypertension with propranolol in children after renal transplantation.

Ten children with hypertension poorly controlled with other drugs and high peripheral plasma renin activity after renal transplantation were treated with propranolol. The mean systolic pressure decreased from 139 to 127 mm Hg (p less than 0.05) and the mean diastolic pressure from 98 to 83 mm Hg (p less than 0.01). Eight children had an antihypertensive response; two did not respond. The maximum dose of propranolol in responders varied from 1.0 to 6.2 mg/kg/day and duration of treatment until response varied from four to 49 days. PRA, repeated in seven responders, decreased in all (p less than 0.01). There was no correlation between changes in PRA and blood pressure. Propranolol was well tolerated and was a valuable antihypertensive drug in these children.

Adolescent↗
PubMed1976

Location of aldosterone-producing adenomas with 131I-19-iodocholesterol.

We used 131I-19-iodocholesterol as an adrenal-imaging agent in 27 hypertensive patients who had biochemical evidence of abnormalities in the renin-angiotensin-aldosterone system. In 10 of 12 patients in whom the biochemical findings suggested the presence of an aldosterone-producing adenoma the adrenal uptake was asymmetric. The adenoma was subsequently confirmed in all eight patients in this group who underwent operation. In contrast, the adrenal uptake was asymmetric in only one of 13 patients with biochemical evidence of iodopathic hyperaldosteronism or low-renin essential hypertension. Two patients with adrenal carcinoma causing primary aldosteronism did not concentrate the isotope in their tumors. When metabolic studies suggest an aldosterone-producing adenoma, adrenal imaging with 131I-19-iodocholesterol may locate the tumor before operation.

Adenoma↗
PubMed1976

Studies in a phenotypic female with 17-alpha-hydroxylase deficiency.

In a 19-year-old phenotypic female (46, XY) with hypertension and hypokalemia, studies confirmed 17-alpha-hydroxylase deficiency. Prior to diagnosis she had been considered to have testicular feminization. Increased plasma progesterone and urinary pregnanediol levels were present before treatment. Increased secretion rates of deoxycorticosterone and corticosterone and abnormally low production of cortisol and aldosterone were present. Following treatment with hydrocortisone, plasma progesterone, serum potassium, and urinary pregnanediol levels and DOC and B secretions were normal. Aldosterone secretion six months after treatment remained low. Normal blood pressure measurements were achieved during treatment with hydrocortisone and oral estrogen with the patient at rest; however, mild elevations in blood pressure (130/90 mm Hg) have been noted despite continued hydrocortisone therapy.

Adult↗
PubMed1976

Role of steroids in hypertension: evaluation of plasma mineralocorticoid activity with aldosterone receptors.

1. A competitive "mineralocorticoid" receptor-binding technique has been used to study plasma "mineralocoroticoid" activity in normal and hypertensive states. The binding reaction mixture contains the competitor steroids in undiluted plasma, [3H]aldosterone and rat kidney slices. Thus plasma binding and receptor occupancy can be simultaneously considered. 2. Competitor activities relative to that of aldosterone (100%) were: deoxycorticosterone (DOC), 16%, cortisol, 0-4%; 18-hydroxydeoxycorticosterone (18-OH-DOC), 0-1%; 16beta-OH-dehydroepiandrosterone and 16-oxo-androstenediol, inactive. (Binding characteristics for aldosterone and the other steroids tested with the rat receptor were found to be similar to those with receptors in slices from human kidney, obtained at operation.) These steroids and the spironolactone SC14266 were less active in plasma than in buffer, suggesting that they bind significantly to plasma and that reduces their capacity to occupy the receptors. 3. These competition data also suggest that at normal and even mildly elevated concentrations, cortisol does, but DOC and 18-OH-DOC do not, contribute significantly to the plasma mineralocorticoid activity. Competitor activity in plasma samples taken at 12.00 hours from normal subjects (upright) was greater than that in those taken at 08.00 hours (supine). This physiological change, corresponding to an increase in aldosterone, was detected even though there was an associated decrease in plasma cortisol. Competitor activity in plasma from patients with primary aldosteronism was markedly elevated as compared with that of normal subjects. However, an increase in plasma steroids which bind to the mineralocorticoid receptor was not detected in plasma from patients with "low-renin essential hypertension".

Aldosterone↗
PubMed1976

Segmental renal vein sampling for renin.

Segmental renal vein sampling was performed in 25 hypertensive patients. In those with no arteriographic abnormalities or stenosis of only the main renal artery, renin levels from segmental veins were the same as those from the ipsilateral main renal vein. In patients with an infarction of a renal segment or stenosis of a segmental renal artery, the renin level from the corresponding segmental vein was often much higher than that from the main renal vein. Segmental vein sampling may reveal a significant source of renin production not apparent in samples from the main renal vein.

Catheterization↗
PubMed1976

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxy-corticosterone and d18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 8-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16beta-hydroxy-dehydro-epiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity. Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samples had higher aldosterone and lower cortisol levels than the 8 a.m. samples, the competitor activity under these physiological circumstances reflects aldosterone more than cortisol. The competitor activities of plasmas from patients relative to normal subjects (100+/-12.1%; mean+/-SEM) were: normal renin "essential" hypertension, 117+/-14%; low-renin essential hypertension, 101+/-6.6%; and primary aldosteronism, 176+/-14.3%. Thus a significant increase in activity of steroids that interact with mineralocorticoid receptors was detected in primary aldosteronism (P LESS THAN 0.01) BUT WAS NOT DETECTED IN LOW-RENIN OR NORMAL-RENIN ESSENTIAL HYPERTENSION.

Aldosterone↗
PubMed1976

Circadian rhythm and effect of posture on plasma aldosterone concentration in primary aldosteronism.

The effect of circadian rhythm and alterations in posture on plasma aldosterone concentration was studied in 13 patients with primary aldosteronism (six adenoma, five idiopathic hyperplasia, two carcinoma) to define the regulatory mechanism in each of these pathologic subtypes. Blood samples for aldosterone, cortisol, renin, and potassium concentrations were obtained every 4 h during prolonged recumbency (32 h) and upright posture (16 h). During recumbency, aldosterone and cortisol followed a normal circadian pattern in patients with adenoma and hyperplasia, with peak values at 0400-0800 h and the nadir at 1600-2400 h. Normalized aldosterone and cortisol values correlated significantly in both groups (adenoma r=+0.66, P less than 0.001; hyperplasia r=+0.42, P less than 0.01). With upright posture, aldosterone levels declined parallel to the normal circadian fall in cortisol in patients with adenoma (r=+0.68, P less than 0.001); whereas aldosterone levels increased in patients with hyperplasia parallel to small increments in renin (r=+0.65, P less than 0.001) and potassium (r=+0.64, P less than 0.001). During the administration of dexamethasone, aldosterone no longer correlated with cortisol in patients with adenoma but continued to correlate with renin during upright studies in patients with hyperplasia (r=+0.77, P less than 0.01). Aldosterone circadian rhythm was abnormal in patients with carcinoma and no effect of posture was noted. Unilateral adrenalectomy restored the normal postural relationship in four patients with adenoma. These studies suggest that aldosterone secretion is under continuous ACTH control regardless of posture in patients with adenoma, whereas persistent adrenal responsiveness to small increments in renin and/or potassium mediate the postural increase in plasma aldosterone in patients with hyperplasia. True adrenal autonomy occurs only in patients with adrenal carcinoma and when ACTH is suppressed in those with adenoma.

Adult↗
PubMed1976

Mineralocorticoid receptors in human kidney.

Cytosol binding of [3H]aldosterone was measured after incubation of the hormone at 37 C with slices of human kidney obtained after surgical removal. High affinity [3H]aldosterone binding with an apparent equilibrium dissociation constant (Kd) of approximately 0.5 nM was observed to probably "mineralo-corticoid receptors." [3H]aldosterone binding of lower affinity and higher capacity (probably to "glucocorticoid receptors") was also observed. Binding of other steroids by the mineralocorticoid receptors was determined by competitive analysis using a low concentration of [3H]aldosterone (so that [3H] binding is predominantly by the mineralocorticoid receptors). The binding activities relative to aldosterone (100%) were: deoxycorticosterone, 48%; cortisol, 1.5%; 18-hydroxy-deoxycorticosterone, 1.2%; and 18-hydroxy-corticosterone, 0.2%. The relative sodium-retaining potencies of these steroids in vivo correlate well with their binding activities. These data provide further support to the view that the major high affinity [3H]aldosterone binding is by mineralocorticoid receptors. Two steroids, 16beta-hydroxy-dehydroepiandrosterone and 16-oxo-androstenediol, recently shown to have sodium-retaining activity in the rat, and also implicated in low-renin "essential" hypertension in man, showed no competitive binding activity. The affinity of [3H]aldosterone for binding to these mineralocorticoid receptors and the relative steroid binding activities are similar to the values previously reported in the rat. Thus, human and rat mineralocorticoid receptors appear to be similar in their affinity for aldosterone and their specificity for binding a number of other steroids.

Aldosterone↗
PubMed1975

Selection of patients and operative approach in primary aldosteronism.

A system for discriminating between adrenal adenoma and hyperplasia based on the levels of aldosterone production, plasma renin concentration, severity of electrolyte disturbances, plasma aldosterone patterns during recumbency and after assuming erect posture, and 131I-19-iodocholesterol scan has been developed. Indicated for operation are patients with adenomas whose elevated blood pressure cannot be continuously controlled with usual doses of medication and patients with documented deterioration of target organ function. Adrenalectomy has been performed 83 times in 81 patients with a diagnosis of primary hyperaldosteronism. Results of excision of adrenal adenomas have been excellent with significant lowering of blood pressure in all cases and cure of hypertension in over 60%. Results of total or subtotal adrenalectomy for hyperplasia have been poor with almost all patients still requiring medication for hypertension. Adenomas have always been unilateral, and usually can be localized so that unilateral exploration is curative. Therefore, we have tried to distinguish preoperatively between adenoma and hyperplasia. Anterior transperitoneal adrenalectomy has been effective with few complications, and no postoperative hypercortisolism after unilateral adrenalectomy for adenoma. The unilateral extraperitoneal approach gives shorter morbidity and potentially fewer serious complications.

Adenoma↗