Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension

The effect of potassium loading on plasma adrenocortical hormones concentrations in 9 patients with essential hypertension (EH) was investigated. The plasma renin activity (PRA), plasma concentrations of growth hormone (GH), ACTH, cortisol, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC) and aldosterone, and serum electrolytes were measured before and after potassium chloride (KC1) infusion (0.33 mEq/kg/h, for one hour). The KC1 infusion caused significant increases in serum potassium levels and plasma levels of GH, ACTH, cortisol, DOC, 18-OH-DOC and aldosterone, while PRA remained unchanged. Regression analysis at 30 min revealed significant positive correlations between delta ACTH and delta cortisol, between delta ACTH and delta DOC, between delta ACTH and delta 18-OH-DOC. However, the relationship between delta ACTH and delta aldosterone was not statistically significant. These results suggest that (1) acute potassium loading causes a significant increase in the plasma ACTH level and increased levels of adrenocortical hormones may be produced by increased ACTH secretion, and (2) it may be considered that a part of the increased level of plasma aldosterone following acute potassium loading may arise from increased ACTH secretion in EH.     

Urinary free 18-hydroxy-11-desoxycorticosterone excretion in normal and hypertensive patients.

One hundred fourteen hypertensives and 20 normal controls were examined using a new clinical technique of measuring 24-h urinary free 18-hydroxy-11-desoxycorticosterone (18-OH-DOC) excretion in response to dietary salt manipulations and ACTH injections. The object was to avoid potential errors of random plasma sampling. Mean urinary free 18-OH-DOC in normals on 110 milliequivalent sodium diet was 1.84 +/- 0.69 microgram (mean +/- SD) and represented about 2% of the daily secretion rate of this steroid. Both in normals and hypertensives, urinary free 18-OH-DOC approximately doubled on low salt (P less than 0.01 for each) and rose about 10 times in response to ACTH injection (P less than 0.05 and P less than 0.01, respectively). Plasma and urinary free 18-OH-DOC showed good correlation in patients with essential hypertension on a low salt diet (r = 0.45, P less than 0.01). Suppressed renin patients showed no propensity toward excess 18-OH-DOC excretion and hypertensives with elevated 18-OH-DOC could not be distinguished by their aldosterone levels, cortisol levels, nor their responses to various stimuli. These data suggest 18-OH-DOC is predominantly secreted under ACTH control and, to a smaller extent, in response to salt changes. Hypertension characterized by chronic overproduction of 18-OH-DOC forms only a small percentage of the hypertensive population. It is proposed that measuring 24-h urinary free 18-OH-DOC excretion may be the best method of assessing its rate of secretion without resorting to injection of radiolabeled material.     

Diurnal 18-hydroxy-11-deoxycorticosterone pattern in human stable hypertension.

Diurnal 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) pattern was studied with RIA technique in 33 hypertensive patients in supine position and on normal sodium diet. The compound was evaluated every 2 h from 0800-2000 h. Simultaneously, plasma aldosterone and cortisol were measured. Abnormal 18-OH-DOC behavior was observed in only 2 out of 4 patients with Cushing's disease, while sporadic and slight elevations, synchronous with F, were seen in 5 out of 24 stable essential hypertensive patients [1 with normal plasma renin activity (PRA), 1 with low PRA, and 3 with high PRA]. 18-OH-DOC was normal in 2 cases of hypertension due to renal artery stenosis, in 1 patient with nephrosclerosis, and in 1 patient with horseshoe kidney. From these results, 18-OH-DOC does not seem to play an important pathogenetic role in stable essential hypertension, considering also the low mineralocorticoid activity of the compound.     

Mineralocorticoid response to low dose adrenocorticotropin infusion

The adrenocorticoid responses to low dose ACTH of plasma aldosterone (aldo), corticosterone (B), 11-deoxycorticosterone (DOC), 18-hydroxycorticosterone (18-OHB), 18-hydroxycorticosterone (18-OH-DOC), and cortisol (F) were compared. Alpha ACTH-)1-24) was infused beginning at 0800 h at increasing rates from 12.5-200 mIU/30 min in supine normal subjects under the following conditions: 1) regular Na (120 meq) diet, 2) low Na (10 meq) diet, 3) dexamethasone preadministration (0.5 mg every 6 h for 48 h), and 4) night study (2000 h; 120 meq Na intake). Plasma 18-OH-DOC and B demonstrated quantitatively the greatest responses to ACTH, while DOC and 18-OHB responses were intermediate. Increments in aldo and F were least after ACTH and were maximum at 50 mIU/30 min ACTH, whereas other corticosteroids demonstrated linear responses up to infusion rates of 200 mIU/30 min. All corticosteroids, however, were similar in their threshold responses to ACTH which were at infusion rates of approximately 7-9 mIU/30 min. Na restriction enhanced aldo and 18-OHB responses to ACTH 2- to 3-fold but did not alter the other corticosteroid responses. Dexamethasone pretreatment augmented aldo, 18-OHB, and F responses but did not change the responsitivity of the other corticosteroids to ACTH. Adrenal corticosteroid responses to ACTH were not significantly different between 0800 and 2000 h in subjects on 120-meq Na intake. Thus, corticosteroids show markedly different responses to physiological doses of ACTH, which may have more importance in their regulation than heretofore proposed. Dexamethasone pretreatment enhances aldo, 18-OHB, and F responses to ACTH but does not affect the responses of other corticosteroids. Contrary to reports in experimental animals, corticosteroid responses to ACTH in man do not differ from day to night.     

Selective hypoaldosteronism despite prolonged pre- and postoperative hyperreninemia in primary aldosteronism.

In a prospective study of 7 patients with aldosterone-producing adenoma (APA), long-term (6-72 months) preoperative stimulation of plasma renin activity (PRA) by diuretic therapy (spironolactone plus hydrochlorothiazide) did not prevent selective aldosterone deficiency postoperatively. In all patients aldosterone excretion rate (AER) fell to subnormal values (from a mean of 97 to 2.6 mug/24 h) following removal of APA, although PRA remained elevated. Generalized adrenocortical insufficiency was excluded by the demonstration of normal baseline plasma cortisol and urinary 17-OHCS and the appropriate response to ACTH stimulation. In 6 of 7 patients studied 1-3 months postoperatively, short-term (4 days) sodium deprivation evoked normal increases in PRA, but AER response was blunted (except in 1). Restudy of 3 of 6 patients after 6-12 months revealed that aldosterone production had returned to normal. These results indicate that renin deficiency is not the principal cause of postoperative selective hypoaldosteronism in these patients. On the other hand, they appear to substantiate the possibility raised by in vitro and in vivo studies that spironolactone can directly inhibit aldosterone biosynthesis.     

Plasma corticosteroid concentrations during spironolactone administration: evidence for adrenal biosynthetic blockade in man

Spironolactone, a mineralocorticoid antagonist, may also inhibit aldosterone biosynthesis. In vitro studies suggest that spironolactone and its major metabolites inhibit adrenal 18- and 11 beta-hydroxylase activity. We examined various adrenal corticosteroids and their precursors, plasma renin activity, aldosterone excretion rate, and serum and urine electrolytes in normal subjects before and on days 5 and 10 of spironolactone administration (400 mg/day). Plasma corticosteroids were also examined 60 min after ACTH (Cortrosyn) 0.25-mg iv bolus. RIAs were performed after extensive chromatography; there was no interference of spironolactone and its metabolites in the assays. All studies were performed in supine subjects in metabolic balance on a constant 120-meq sodium intake. Plasma renin activity was increased (P less than 0.001) on both days 5 and 10 of spironolactone. Plasma aldosterone (PA) and the aldosterone excretion rate increased (P less than 0.01) on day 5 of spironolactone but decreased (P less than 0.01) from day 5 to 10. Both 11-deoxycorticosterone and 18-hydroxycorticosterone were increased from day 5 to 10. Corticosterone, progesterone, and dehydroepiandrosterone did not increase significantly during spironolactone administration. Incremental PA response to ACTH was less than control on day 10 of spironolactone, but other corticosteroid responses to ACTH were not different during control and days 5 or 10 of treatment. Reduction in PA and further elevation in its precursors during the second 5-day period of spironolactone therapy suggests inhibition of aldosterone biosynthesis during this phase of treatment in normal man. The disproportionate increments in 18-hydroxycorticosterone and 11-deoxycorticosterone suggest biosynthetic inhibition at the 18-dehydrogenase and 11 beta-hydroxylase sites.     

Low dose adrenocorticotropin infusion in continuous ambulatory peritoneal dialysis patients

The adrenocorticoid responses to low doses of ACTH (0.03-10 ng/min) in sodium-deplete normal subjects and end-stage renal disease patients maintained on continuous ambulator peritoneal dialysis (CAPD) were compared. All subjects were pretreated with dexamethasone. ACTH was administered by graded iv infusions in doses of 0.03, 0.3, 1.0, 3.0, and 10 ng ACTH/min. Each rate of infusion was maintained for 30 min. Plasma aldosterone, 18-hydroxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, and cortisol were measured in plasma sampled at the end of each rate of infusion in both groups. Plasma 11-deoxycorticosterone was measured in CAPD patients. The plasma steroid levels in the CAPD patients after each infusion rate were equal to or greater than the levels in normal subjects. The slopes of the cumulative increases above baseline in plasma steroid levels in the CAPD patients were equal to or greater than those in the normal subjects. In both groups, plasma corticosterone increased the most and aldosterone the least. Kinetic analyses indicated that the adrenal responses to low dose ACTH were not linear. A distinct threshold for ACTH-stimulated increase in plasma adrenocorticoid levels, if present, is very low. The responses of plasma adrenocorticoids to low dose ACTH are normal in CAPD patients.     

Increased Excretion of 18-Hydroxycorticosterone in Patients with Adrenal Adenomas and Hypertension

Two female patients, 54 and 34 years old, each presented with an adrenal adenoma and hypertension. Blood pressure fell after removal of the tumors. The first patient had high urinary 18-hydroxycorticosterone and periodically elevated 18-hydroxy-deoxycorticosterone excretions. The second patient had elevated 18-hydroxycorticosterone and free cortisol excretions. Urinary aldosterone, aldosterone metabolites and plasma aldosterone were not increased. Plasma renin activity was suppressed and serum potassium levels were normal. After surgery, no elevated steroid values were found. Elevated 18-hydroxycorticosterone excretion may be an indicator of yet unknown hypertensinogenic mechanisms. The role of 18-hydroxycorticosterone in the etiology of hypertension is still unknown.     

The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration.

The plasma cortisol response to hypoglycemia is widely used as a test of hypothalamic-pituitary-adrenal function. It was the aim of this study to determine whether this test gives a reliable indication of pituitary corticotropin (ACTH) release in patients recovering from adrenocortical suppression due to corticosteroid or ACTH therapy. The 16 patients who were studied (6 on more than one occasion) had received in excess of 5 mg predinisone or equivalent daily for over 12 months. The insulin tolerance tests were carried out 18 h after stopping steroid therapy. The tests were then repeated three to four days after adrenal function had been restored (as indicated by urinary oxogenic steroid excretion of greater than 35 mg/24 h) by zinc tetracosactrin administration. The ACTH response to hypoglycemia was significantly impaired in the steroid-treated group. However with the exception of one patient who had persistently elevated resting ACTH levels there was a significant correlation (P less than 0.01) between the maximum increments in plasma cortisol and ACTH during hypoglycemia. No significant difference in sensitivity to endogenous ACTH could be demonstrated between the steroid-treated group and 12 normal control subjects. Following ACTH administration the plasma ACTH and growth hormone responses to hypoglycemia were significantly reduced, but the response in plasma cortisol was not significantly affected. It is concluded that the plasma cortisol response to hypoglycemia gives a useful indication of ACTH release in steroid-treated patients provided that they have not recently received exogenous ACTH.     

Response of several adrenal steroids to ACTH stimulation in essential hypertension.

Plasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F), and aldosterone were measured in 8 control subjects and in 10 patients with low and normal renin essential hypertension (EH) before and 4 and 8 h after an iv infusion of 25 units of ACTH. Secretion rates of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured for the 24 h prior to and the day of the ACTH infusions. The hypertensive patients had significantly higher plasma levels of aldosterone, DOC and S after ACTH than the controls, whereas plasma B levels were significantly lower. The low renin subgroup considered separately had significantly higher plasma levels of aldosterone and DOC than controls, and higher levels of B and lower levels of F than the normal renin subgroup in response to ACTH. Although not significantly different, the plasma levels of P and the secretion rate of 18-OH DOC tended to be higher, and plasma 17-OH P and F levels lower after ACTH in patients with EH than in controls. The low renin subgroup tended to have the highest plasma S levels and 18-OH DOC secretory rates and lowest F levels. Estimations of adrenal 11beta-hydroxylating efficiency in response to ACTH in patients and controls by plasma steroid ratios revealed significantly lower B/DOC ratios in both low and normal renin patients compared to controls, supported by somewhat lower F/S ratios in these patients, especially those in the low renin subgroup. Altered 17-hydroxylating efficiency seen by significantly lower 17-OH P/P ratios were also found in those with EH, supported by somewhat lower F/B and S/DOC ratios in these patients, agian especially in the low renin subgroup. These data are compatible with a pattern of altered adrenocortical steroid biosynthesis in essential hypertension bearing features similar to adrenal 11beta and 17alpha-hydroxylation deficiencies.     

Confirmatory testing in normokalaemic primary aldosteronism: the value of the saline infusion test and urinary aldosterone metabolites

OBJECTIVE: Primary aldosteronism has recently been recognized as the most frequent cause of secondary hypertension. Since most patients are normokalaemic, differentiation to essential hypertension is challenging. As differentiation by baseline aldosterone/renin ratio may be insufficient, diagnosis should be confirmed by additional tests. However, as most confirmatory tests have been evaluated in hypokalaemic primary aldosteronism only, we reassessed the value of the saline infusion test and 24 h urinary aldosterone metabolites as confirmatory tests for both normo- and hypokalaemic primary aldosteronism under current antihypertensive medication. PATIENTS AND METHODS: 25 patients with primary aldosteronism (11 hypokalaemic, 14 normokalaemic), 29 patients with essential hypertension and 47 normotensive subjects were studied. The hypertensives received their usual medication with the exception of spironolactone. All subjects underwent a standard saline infusion test (determination of plasma aldosterone before and after 2.0 liters of isotonic saline for 4 hours i.v.) and collected a 24 h urine sample for examination of urinary tetrahydroaldosterone and aldosterone-18-glucuronide. RESULTS: In hypokalaemic primary aldosteronism the saline infusion test showed a reasonable sensitivity (91%) and specificity (90%). However, the test failed to differentiate sufficiently between essential hypertension and normokalaemic primary aldosteronism (sensitivity 57%, specificity 90%). Similarly, urinary tetrahydroaldosterone had higher sensitivity in hypokalaemic than in normokalaemic primary aldosteronism (sensitivity 64% vs 36%, specificity 100%), whereas for aldosterone-18-glucuronide, no differences in hypo- and normokalaemic primary aldosteronism were found (sensitivity 45% and 43%, specificity 100%). CONCLUSIONS: These data show that the saline infusion test as an established test in classical hypokalaemic primary aldosteronism is not a reliable test in the normokalaemic variant of the disease. Due to its low accuracy, determination of urinary aldosterone metabolites did not prove useful in confirming either normo- or hypokalaemic patients. We conclude from our data that these tests should not be used as confirmatory testing in the normokalaemic variant of primary aldosteronism.     

原发性醛固酮增多症功能诊断试验可靠性分析

原发性醛固酮增多症是最常见的导致继发性高血压的病因之一，在高血压人群中发病率高达10％-18％。在原发性醛固酮增多症的诊断中，功能诊断非常重要。目前临床常用的功能试验有血醛固酮／肾素比值的测定、静脉盐水滴注抑制试验、24h尿醛固酮及其代谢物的测定以及开博通试验等。本文将对此类功能试验的诊断可靠性作一综述。     

HORMONAL RESPONSES DURING TREATMENT OF ACUTE DIABETIC KETOACIDOSIS WITH CONSTANT INSULIN INFUSIONS

Changes in glucagon, growth hormone (GH), cortisol, renin and aldosterone accompanying the metabolic disturbances and dehydration of severe diabetic ketoacidosis were studied over a 24 h period in eight patients treated with a constant intravenous insulin infusion. Mean steady state plasma-free insulin levels achieved were 28.6--49 mu/1 in patients receiving 2 u/h but a satisfactory rate of fall of glucose was not always obtained until the infusion dose was increased to 4 u/h or more. The total insulin dose administered was positively correlated with the level of plasma glucagon and cortisol on admission. During insulin infusion, both glucagon and cortisol fell but the rate of fall was not related to dose or plasma level of free insulin achieved. In six of eight patients studied increments in plasma GH above admission levels were observed during insulin treatment. Admission values of both plasma renin activity and plasma aldosterone were raised. The renin levels were highest in newly diagnosed diabetics, and two patients with long-established diabetes showed only small increments despite profound dehydration. Plasma renin activity, but not plasma aldosterone correlated with the fluid and sodium retention over the initial 24 h treatment period, but not with potassium requirements. The urinary excretion rates of the small molecular weight proteins GH and insulin, were considerably elevated over the treatment and convalescent periods.     

24 HOUR PROFILE OF 18-HYDROXY-11-DEOXYCORTICOSTERONE IN NORMAL SUPINE MAN: RELATIONSHIP WITH CORTISOL AND ALDOSTERONE

Daily profiles of plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) were studied in four normal supine men on a normal sodium intake. Blood was taken every hour from 01.00 to 24.00 hours. Plasma cortisol (F) and aldosterone (A) were determined hourly for comparative studies. 18-OH-DOC fluctuated considerably during the 24 h period of investigation, the highest values being found during the early morning hours in synchrony with F. The episodic secretions of 18-OH-DOC were also significantly correlated with those of A, which in turn paralleled those of F. We conclude that ACTH, plays a definite role in the regulation of 18-OH-DOC in normal supine men on a normal sodium diet.     

Pathophysiology of deoxycorticosterone-secreting adrenal tumors

Two patients with hypermineralocorticoidism due to deoxycorticosterone (DOC) excess are described. The plasma 17-deoxysteroids of the zona fasciculata (ZF), namely DOC, corticosterone, 18-hydroxydeoxycorticosterone, and 18-hydroxycorticosterone, were elevated. Plasma androgen concentrations were normal, and plasma aldosterone and renin levels were low. One patient, who had benign adrenocortical adenoma, had normal plasma cortisol levels. The other patient, who had metastatic adrenocortical carcinoma, had low plasma cortisol, presumably due to elevated plasma corticosterone levels. While tumors producing only 17-deoxysteroids are rare, they have provided new insights into the regulation of 17-deoxysteroid secretion by the ZF. Presumptive suppression of a non-ACTH factor by adenoma-produced DOC transiently impaired the early postoperative responses to ACTH of the ZF 17-deoxysteroids of the contralateral adrenal. The dissociation of 17-deoxysteroids from cortisol in normal subjects given either dexamethasone or DOC acetate provides additional evidence for such a factor.     

Relationship of 19-nor-deoxycorticosterone to other mineralocorticoids in low-renin hypertension

A number of mineralocorticoids have been proposed as etiologic factors in low-renin hypertension. In this study, urinary free 19-nor-deoxycorticosterone (UF 19-nor-DOC) was compared to other mineralocorticoids--aldosterone, deoxycorticosterone (DOC), and 18-OH-DOC, in 11 low-renin hypertensive patients on a controlled diet in a metabolic unit. Results demonstrated that both UF 19-nor-DOC and tetrahydro-DOC (TH-DOC) excretion were elevated (2086 +/- 926, nl = 339-579 ng/day, and 18 +/- 7, nl = 5-15 mcg/day, respectively), and positively correlated (r = 0.95). Neither 18-OH-DOC nor aldosterone secretion rates were elevated, and neither of these hormones correlated with UF 19-nor-DOC, with exception of the supine plasma aldosterone (SPA) (r = 0.86). In conclusion, both UF 19-nor-DOC and TH-DOC were increased and positively correlated in the present series of hypertensives. This association is possibly indicative of a precursor-product relationship between DOC and 19-nor-DOC. 19-Nor-DOC, furthermore, correlated with supine plasma aldosterone (SPA), which could, in part, reflect their shared adrenocorticotropic hormone (ACTH) dependence.     

Plasma 18-oxocortisol levels in the patients with adrenocortical disorders

OBJECTIVES 18-Oxocortisol (18oxoF) shares structural characteristics with cortisol and aldosterone and is secreted from the adrenal cortex. It has been reported that 18oxoF has weak gluco and mineralo-corticoid activities and increases blood pressure when administered to animals. We tried to clarify the characteristics of the production of 18oxoF in patients with adrenocortical disorders compared with the control subjects.
DESIGN AND PATIENTS In patients with primary aldosteronism due to aldosterone producing adenoma (APA) ( n = 21) and Cushing's disease or syndrome (Cushing's disease n = 13; adrenocortical adenoma n = 10), plasma 18oxoF level early in the morning following an overnight fast was evaluated as well as plasma cortisol and aldosterone levels.
RESULTS The plasma 18oxoF levels were significantly higher in the patients with adrenocortical disorders than in control subjects. The ratios of 18oxoF/cortisol and 18oxoF/ aldosterone were high in APA and in Cushing's disease and syndrome patients, respectively. In the control subjects and combined group of patients with Cushing's disease and syndrome, plasma 18oxoF level significantly correlated with plasma cortisol level but not with aldosterone level. However, in APA patients plasma 18oxoF level correlated significantly with both cortisol and aldosterone levels.
CONCLUSION The production of 18oxoF was elevated as a result of the hyperactivity of 18-hydroxylase and excess cortisol production in APA patients and in patients with Cushing's disease and syndrome, respectively. An excess 18oxoF production could be playing a role in the pathogenesis of hypertension in these patients. The correlation of plasma 18oxoF levels with plasma cortisol and aldosterone levels suggests that the production of 18oxoF is more dependent on the supply of cortisol than on 18-hydroxylase activity in normal subjects and patients with Cushing's disease and syndrome.     

Increased urinary cortisol and androgen metabolites in a young female with hypertension: partial glucocorticoid resistance syndrome

A 21-year-old woman with hypertension confirmed on ambulatory blood pressure monitoring and unresponsive to beta-blockers, diltiazem and amiloride was found to have serum potassium, renin and aldosterone levels at or just below the lower end of normal. Urinary glucocorticoid metabolite analysis revealed high excretion of cortisol and androgen metabolites, with normal serum cortisol levels. This pattern suggests a partial glucocorticoid resistance syndrome; such patients are more responsive to ACE inhibitors and spironolactone.     

Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism

Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.     

Aldosterone metabolic clearance is normal in low-renin essential hypertension.

The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritium-labeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 +/- 69 (mean +/- SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 +/- 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 +/- 66 liters/24 hours. These values were not significantly different from those of normal subjects. Although aldosterone secretion rates in both groups of hypertensive patients were within the normal range, patients with low-renin essential hypertension, under the conditions of this study, had significantly higher secretion rates than patients with normal-renin essential hypertension. We have concluded that the maintenance of plasma aldosterone in low-renin essential hypertension reflects sustained aldosterone secretion despite suppression of plasma renin activity, rather than reduced aldosterone metabolism. The maintenance of normal aldosterone secretion in low-renin essential hypertension appears to be inappropriate and is not explained by alterations of known regulatory mechanisms.