The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism.

The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus.     

Circadian rhythm of plasma aldosterone and plasma renin activity in steroid and non-steroid treated kidney transplanted patients.

The circadian rhythm of plasma aldosterone (PAC) and cortisol concentration (PCC), and renin activity (PRA) was measured in five steroid and five non-steroid treated kidney transplanted patients--all with denervated kidney grafts--and compared with four normal controls and two steroid-treated patients with non-renal disease and thus normal renal innervation. The non-steroid treated patients had a normal circadian thythm of PAC and PCC, but without variation of PRA, suggesting that denervation of the kidneys has no influence on the circadian rhythm of PAC. In both steroid treated groups the PAC showed an inverse diurnal variation--now correlating to the diurnal variation in PRA. The inverse circadian rhythm of PAC in patients with suppressed ACTH secretion remains unexplained, but is in accordance with the nocturnal peak of sodium and water excretion in steroid treated patients.     

Pre‐metrological variation of immunological quantities

The circadian rhythm of plasma aldosterone (PAC) and Cortisol concentration (PCC), and renin activity (PRA) was measured in five steroid and five nonsteroid treated kidney transplanted patients—all with denervated kidney grafts— and compared with four normal controls and two steroid-treated patients with non-renal disease and thus normal renal innervation. The non-steroid treated patients had a normal circadian thythm of PAC and PCC, but without variation of PRA, suggesting that denervation of the kidneys has no influence on the circadian rhythm of PAC. In both steroid treated groups the PAC showed an inverse diurnal variation—now correlating to the diurnal variation in PRA. The inverse circadian rhythm of PAC in patients with suppressed ACTH secretion remains unexplained, but is in accordance with the nocturnal peak of sodium and water excretion in steroid treated patients.     

The effect of dexamethasone on the control of plasma aldosterone concentration in normal recumbent man.

In order to evaluate the control of the circadian rhythm of plasma aldosterone concentration in man, plasma aldosterone, cortisol, sodium and potassium concentrations, and plasma renin activity (PRA) were measured in samples obtained at 20-minute intervals from 0200 to 0800 in sodium repleted (180 mEq. per day of diet) and sodium depleted (22 mEq. per day of diet) normal subjects. During sodium replete studies, plasma aldosterone and cortisol concentrations were significantly correlated (p greater than 0.01) in all 4 subjects. Plasma aldosterone also correlated with PRA (p greather than 0.01) in 2 subjects and with potassium (p greater than 0.01) in one. Episodic increases in plasma aldosterone concentration were observed despite suppression of ACTH by dexamethasone treatment. Plasma aldosterone concentrations were significantly correlated with PRA (p greater than 0.05 and p greater than 0.01) in only 2 of 4 subjects under these conditions. Following sodium restriction, plasma aldosterone concentrations were not significantly correlated with plasma cortisol and only infrequently with either PRA or potassium. When dexamethasone was administered during the low sodium diet, correlations with PRA (p greater than 0.001) were seen in 2 of 3 subjects and with potassium (p greater than 0.01) in 1 of 3 subjects. There was no significant correlation between plasma aldosterone and sodium concentration during any of the studies. These results are compatible with the concept that the relative importance of PRA, ACTH, and potassium in inducing changes in aldosterone production during the early morning hours is partially dependent upon dietary sodium, but also varies between individuals studied during similar sodium diets. The episodic alterations of plasma aldosterone concentration continued after ACTH was suppressed by dexamethasone pretreatment. These changes, in the absence of a consistent significant correlation with PRA and sodium and potassium concentrations, further suggest that another factor(s) may be important in controlling aldosterone production in recumbent normal subjects.     

Multiple plasma steroid responses to graded ACTH infusions in patients with primary aldosteronism

We measured the simultaneous responses of eight plasma steroids to the infusion of alpha 1-24 ACTH at incremental rates of 12.5 to 200 mlU/30 min in seven patients with primary aldosteronism (five with adenomas, two with adrenal hyperplasia) and in 10 normal controls studied on regular sodium intakes and while supine. Patients with primary aldosteronism from adenomas had relatively higher concentrations (p less than 0.05) of aldosterone, 18 OH-B, corticosterone, and DOC than the two with hyperplasia and, save corticosterone, above the range of the normal controls. We found inconsistent differences in plasma progesterone, 17-hydroxyprogesterone, deoxycortisol, and cortisol. These findings suggest that the intermediate steps in aldosterone biosynthesis are hypersensitive to physiologic amounts of ACTH in patients with aldosterone-producing adenomas. Plasma levels of steroids distal to progesterone, i.e., DOC, corticosterone, 18 OH-B, and aldosterone, are relatively higher after small amounts of ACTH in patients with adenomas than in normal subjects or those with adrenal hyperplasia.     

Primary aldosteronism in childhood due to primary adrenal hyperplasia

We present an unusual case of primary aldosteronism in childhood. A 9-year-old boy had hypertension, hypokalemia, hyporeninemia and hyperaldosteronism. Dexamethasone administration decreased plasma aldosterone transiently but failed to correct the hyperaldosteronism, excluding dexamethasone-suppressible hyperaldosteronism. Plasma aldosterone decreased with upright posture and showed a circadian rhythm. Spironolactone treatment normalized blood pressure and serum potassium and lowered aldosterone secretion. During the studies, plasma aldosterone correlated with serum cortisol but not with plasma renin. Preoperative results indicated that this patient presented the functional features of aldosteronoma. Adrenal computed tomography, scintigraphy and left venography were not diagnostic of adrenal lesions. The left adrenal venous sampling showed hypersecretion of aldosterone from the left adrenal gland. The left adrenalectomy revealed micronodular hyperplasia but resulted in a prompt and sustained reversal of hypertension and hyperaldosteronism. These findings suggest that primary aldosteronism in this patient resulted from primary adrenal hyperplasia. Thus, adrenal hyperplasia is a heterogenous group of disorders and carefully selected studies allow prospective selection of appropriate treatment.     

Effect of propranolol therapy on aldosterone responses to angiotensin II and adrenocorticotropic hormone in essential hypertension

1. The plasma aldosterone responses to exogenous angiotensin II and adrenocorticotropic hormone (ACTH) were studied before and after 1 month of propranolol therapy (120-240 mg/day) in eight patients with essential hypertension. 2. Basal supine plasma renin activity was decreased (P less than 0.001) after propranolol, whereas plasma aldosterone was unchanged. After 3 h of upright posture the increases in both plasma renin activity and aldosterone were decreased (P less than 0.05) after propranolol. 3. Plasma aldosterone responses to exogenous angiotensin II and ACTH were not significantly different after propranolol. Serum and urinary electrolytes and plasma cortisol were also unaffected by propranolol therapy. 4. It is concluded that changes in adrenal sensitivity are not responsible for maintaining unchanged supine plasma aldosterone concentrations after beta-adrenoceptor antagonism in essential hypertension.     

Acquired partial corticosterone methyl oxidase type II defect in diabetes mellitus. Case of hyperreninemic hypoaldosteronism

The aim of this study was to investigate the pathogenesis of hypoaldosteronism in diabetes. Endogenous elevation of plasma renin activity and exogenous corticotropin were used to study steroidogenesis. Observations were made over 12 yr on the evolution and treatment of hyperkalemia in a diabetic subject. In 1977, potassium, baseline cortisol, aldosterone, and renin activity were normal; renin activity increased normally with posture; and cortisol responded normally to ACTH infusion. Nine yr later, persistent hyperkalemia was documented. Upright renin activity was elevated to 5.26 ng.L-1.s-1, with concomitant elevation of 18-hydroxycorticosterone (18-OHB) and a low-normal aldosterone level. One hour after administration of 0.25 mg i.m. cosyntropin, cortisol increased normally, aldosterone increased from 220 to 360 pM, and 18-OHB increased from 3700 to 4800 pM. During treatment with fludrocortisone, fludrocortisone with furosemide, and furosemide alone, improvement of hyperkalemia was noted. Endogenous hyperreninemia and basal elevations of 18-OHB, accompanied by limited aldosterone responsiveness to renin and ACTH, suggest the presence of a partial corticosterone methyl oxidase type II defect. Evolution of hyperkalemia between 1977 and 1986 suggests this defect was acquired.     

Activation of aldosterone secretion in primary aldosteronism

Angiotensin infusion evokes marked increases in aldosterone secretion in primary aldosteronism and little change in secondary aldosteronism. The low plasma renin activity of primary aldosteronism and the elevated plasma renin activity of secondary aldosteronism are thought to account for this differential response. The effect of angiotensin on aldosterone and 18-hydroxycorticosterone secretion was studied during adrenal vein catheterization in seven patients with primary aldosteronism (whose plasma renin activity had been elevated following spironolactone therapy), one hypertensive patient with normal plasma renin activity and normal aldosterone secretion, two patients with secondary aldosteronism who had elevated plasma renin activity, and one anephric patient whose plasma renin activity was 0. Adrenal venous aldosterone and 18-hydroxycorticosterone were measured before and after a ten min sub-pressor angiotensin infusion.The cells of the aldosterone-producing adenoma (APA) respond to small increases in plasma angiotensin with large increases in secretion of aldosterone and 18-hydroxycorticosterone. The dose of angiotensin capable of evoking this response from the aldosterone-producing adenoma produces little or no change in the secretion of the steroids from nontumorous glands. The augmentation of aldosterone secretion, induced by angiotensin, in primary aldosteronism is due solely to increased secretion by the adenoma and not by the contralateral zona glomerulosa. The increased sensitivity of the aldosterone-producing adenoma is characteristic of the tumor. This response is independent of fluctuations in endogenous plasma renin activity. This sensitivity is not blunted by high plasma renin activity, nor is it a function of tumor mass for the effect is observed in aldosterone-producing adenomas regardless of size. ACTH injection after angiotensin infusion resulted in a marked increase in aldosterone concentration in the effluent from the nontumorous adrenal, but was not capable of producing further increases in aldosterone concentration in the effluent from the APA. In view of this exquisite sensitivity to infused angiotensin, it may be that the small variations in endogenous plasma renin activity that have been observed in primary aldosteronism may be capable of evoking large changes in aldosterone secretion in patients with aldosterone-producing adenomas.     

Effect on Plasma Aldosterone, Renin Activity and Cortisol of Acute Volume Depletion Induced by Ethacrynic Acid under Constant Infusion of Angiotensin II and Dexamethasone in Man

Abstract. The influence on plasma aldosterone of acute volume depletion induced by ethacrynic acid was studied in man. The experiments were performed during the morning in supine healthy males receiving a control infusion of 5 % glucose or an infusion of angiotensin II (All) to suppress endogenous renin production or an infusion of dexamethasone to suppress endogenous ACTH. Ethacrynic acid induced in all circumstances a similar diuresis and volume depletion. The rise of plasma renin activity (PRA) was effectively suppressed by All and the rise of plasma Cortisol by dexamethasone. Plasma aldosterone (PA) rose markedly even when the elevation of PRA or Cortisol were suppressed. Yet when both endogenous renin and ACTH secretion were blocked, PA rose much less after ethacrynic acid. This residual increase could be attributed mainly to a decrease of the metabolic clearance rate (MCR) of aldosterone which had been measured before and after ethacrynic acid administration. The data presented indicate that multiple factors influencing PA after acute volume depletion could be dissected out and that renin, ACTH and a decrease of the MCR each contribute to the elevation of PA.     

Continuous administration of synthetic ovine corticotropin-releasing factor in man. Physiological and pathophysiological implications.

The continuous 24-h infusion of a maximally stimulating dose (1 micrograms/kg per h) of ovine corticotropin-releasing factor (CRF) in man caused a modest elevation of plasma cortisol (17.2 +/- 1.4 micrograms/dl) and urinary-free cortisol (173 +/- 43 micrograms/24 h) concentrations, which was far less than that seen with a maximally stimulating dose of ACTH (50.4 +/- 2.2 micrograms/dl and 1,200 +/- 94 micrograms/24 h, respectively). The circadian rhythms of plasma ACTH and cortisol were preserved during CRF administration. An intravenous bolus injection of 1 microgram/kg of ovine CRF given to normal volunteers under basal conditions resulted in elevated plasma ACTH and cortisol peak levels (28 +/- 6 pg/ml and 15.0 +/- 1.0 micrograms/dl, respectively). However, no plasma ACTH and cortisol responses were observed when an identical CRF stimulation test was given at the end of the continuous infusion. These findings suggest that the stimulatory activity of exogenous CRF on the ACTH-secreting cells of the pituitary gland is restrained by the negative feedback of cortisol. The persistent circadian rhythm of ACTH, despite a constant level of plasma CRF during the infusion, suggests that the circadian variation in the activity of the hypothalamic-pituitary-adrenal axis cannot be explained solely by circadian periodicity of the endogenous CRF stimulus.     

Salivary cortisol for the evaluation of Cushing's syndrome

Cortisol concentrations were measured in matched plasma and salivary samples from 8 healthy controls, 8 patients with Cushing's syndrome and 4 patients suspected of having spontaneous hypercortisolism. In healthy subjects, the circadian rhythm in salivary cortisol paralleled that in plasma. Absence of the diurnal rhythm in Cushing's syndrome was seen in saliva as well as in plasma. After ACTH stimulation, mean peak cortisol in saliva showed a 3-fold increase while in plasma there was a 2.5-fold increment above baseline. Cushing's syndrome, due to pituitary or adrenal adenoma was diagnosed equally well by measuring the cortisol response to cosyntropin in either plasma or saliva. Finally, the low- and high-dose dexamethasone suppression test was reflected equally well in both plasma and saliva. In patients suspected of having Cushing's syndrome dynamic tests can be performed in both plasma and saliva. However, in some samples, the salivary cortisol measurement appears advantageous over plasma cortisol determination.     

Studies of the control of plasma aldosterone concentration in normal man: I. Response to posture, acute and chronic volume depletion, and sodium loading

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.     

The efficacy of calcium antagonists in circulatory failure in elderly patients with hypertension

As many as 52 patients with essential hypertension aggravated by circulatory failure were examined for the clinical, hemodynamic and neurohumoral parameters during furosemide stimulation. In elderly patients, the optimal vasodilatory dose of nifedipine amounted to 10 mg, that of verapamil to 40 mg per os or to 5 mg i.v. In patients with the stimulated activity of plasma renin, the concentration of plasma aldosterone remained unchanged. The plasma concentrations of ACTH and cortisol tended towards increase while vasopressin concentration dropped. Side effects could be frequently observed. Hemodynamic shifts appeared to be negative. During the first hour, forced diuresis was recorded. In patients with unstimulated plasma renin activity, plasma aldosterone concentration declined, whereas the concentrations of ACTH, cortisol and vasopressin rose. Side effects were less in number, the hemodynamic shifts were positive, and diuresis turned out 2-3 times less during the first hour than within the next 4 hours. It is suggested that the efficacy of the treatment with calcium antagonists can be predicted according to the magnitude of the hourly diuresis with regard to the type of hemodynamics.     

Aldosterone suppression with dopamine infusion in low-renin hypertension.

A dopaminergic mechanism has been proposed to suppress aldosterone secretion. To assess the possibility that a defect in the dopaminergic mechanism might enhance aldosterone secretion in hypertensive patients, we determined basal and adrenocorticotropic hormone (ACTH)-stimulated plasma aldosterone (PA), cortisol, renin activity, and potassium concentrations before and during dopamine receptor stimulation with dopamine infusion and bromocriptine administration and dopamine receptor blockade with metoclopramide. The patient study groups included: (a) seven patients with low-renin hypertension and abnormal aldosterone suppression with sodium loading and presumed bilateral zona glomerulosa hyperplasia (ZGHP); (b) two patients with aldosterone-producing adenoma; (c) five patients with low-renin hypertension but normal aldosterone suppression with sodium loading; and (d) six patients with normal-renin hypertension. Dopamine infusion in patients with ZGHP caused PA to fall (P less than 0.01) into the normal range, but did not block the enhanced (P less than 0.05) aldosterone response to ACTH that is characteristic of these patients. Dopamine infusion in patients with low-renin hypertension but normal aldosterone suppression also suppressed PA (P less than 0.01), whereas it had no effect upon PA in patients with normal-renin hypertension or aldosterone-producing adenoma and did not blunt the PA response to ACTH in either group. Bromocriptine administration had no effect upon basal or ACTH-stimulated PA. Dopamine infusion in patients with ZGHP also enhanced (P less than 0.05) diuresis and natriuresis in comparison with normal-renin patients. Metoclopramide administration increased (P less than 0.01) PA in all patients. Thus, a dopaminergic mechanism appears to be important in the regulation of aldosterone secretion in patients with ZGHP and in other low-renin hypertensives with normal aldosterone suppression with sodium loading. In contrast, this latter group does not exhibit an enhanced aldosterone response to ACTH. Both of these groups differ from normal-renin hypertensives, who have no PA suppression with dopamine infusion.     

Increased Adrenal Sensitivity to Angiotensin II in Low-Renin Essential Hypertension

Studies were undertaken to determine if the dissociation of aldosterone and plasma renin activity in low-renin essential hypertension is due to altered adrenal responsiveness to angiotensin II. The responsiveness of the adrenal glands to angiotensin II was determined by infusing graded doses of angiotensin II into normal subjects and into patients with essential hypertension and measuring changes in levels of plasma aldosterone in response to the infusion. To minimize the influence of endogenous angiotensin II and ACTH, supplemental sodium and dexamethasone were given before the infusions. Levels of plasma aldosterone and plasma renin activity were determined in normal subjects and in the same patients after the combined stimuli of furosemide and upright posture, a maneuver used to increase the level of endogenous angiotensin II. To determine if the changes in levels of plasma aldosterone during infusion of angiotensin II were due to alteration of the metabolic clearance of aldosterone, the metabolic clearance of aldosterone was measured before and during the infusion of angiotensin II.     

Studies of the control of plasma aldosterone concentration in normal man: II. Effect of dietary potassium and acute potassium infusion

The responses of plasma aldosterone, cortisol, and corticosterone to an infusion of 75 mEq of potassium chloride over 120 min were studied in 10 normal subjects. Five subjects were fed a 10 mEq and five a 200 mEq sodium diet, while all subjects ingested 40 mEq and 200 mEq potassium sequentially. Two potassium infusions were performed in each subject when in balance on a fixed sodium intake and low and then high potassium diets.Regardless of dietary intake, increases of serum potassium of 0.5-1.5 mEq/liter above preinfusion levels were usually associated with significant increments in plasma aldosterone concentration. Our data agree with previous evidence that the potassium ion stimulates the adrenal cortex directly to secrete aldosterone. Peripheral renin activity did not increase after the potassium infusion. Plasma cortisol and corticosterone levels generally followed the expected diurnal decline during the infusion, implying that ACTH secretion did not increase.The plasma aldosterone response to incremental changes in serum potassium was linear on each of the four diets. The slopes of these linear relationships increased significantly when the potassium intake was increased from 40 to 200 mEq. No increase in slope occurred on either potassium intake when dietary sodium was restricted from 200 to 10 mEq. Thus, identical increases in serum potassium were associated with greater increments in plasma aldosterone above preinfusion levels on either sodium intake when the 200 mEq potassium diet was compared with the 40 mEq potassium intake.     

多囊卵巢综合征伴或不伴高雄激素血症患者血浆促肾上腺皮质激素和皮质醇水平研究

目的 比较多囊卵巢综合征（PCOS）伴或不伴高雄激素血症患者血浆促肾上腺皮质激素（ACTH）、皮质醇水平有无差异.方法 选择PCOS患者109例和年龄匹配的健康对照36例.测量身高、体重、腰围、臀围,计算腰臀比、体质指数,进行多毛、痤疮评分;测定黄体生成素（LH）、卵泡刺激素（FSH）、总睾酮、雌二醇、泌乳素、性激素结合球蛋白（SHBG）、脱氢表雄酮硫酸酯（DHEAS）、8am及4pm血浆ACTH和皮质醇水平;计算LH/FSH比值、游离雄激素指数（FAI）、4pm/8am ACTH比值、4pm/8am皮质醇比值、ACTH昼夜节律消失率、皮质醇昼夜节律消失率.测定空腹血糖和胰岛素,采用稳态模型法评估胰岛素抵抗指数（HOMA-IR）和胰岛分泌功能（HOMA-β）;并行卵巢超声检查.比较PCOS患者和对照组临床生化特征和ACTH、皮质醇水平的差异;将所有的PCOS患者分为高雄组（FAI≥4.5）和非高雄组（FAI ＜4.5）,比较两组的临床生化特征和ACTH、皮质醇水平.为排除肥胖因素对ACTH、皮质醇结果的影响,又选取了体质指数正常（BMI在18.5～23.9 kg/m2）的PCOS患者与健康对照进行对比.结果 （1）PCOS组较对照组LH、LH/FSH、总睾酮、DHEAS、FAI水平显著升高（P＜0.01）,ACTH-8am、ACTH昼夜节律消失率显著升高（P＜0.05）,SHBG显著降低（P＜0.01）,余指标差异无统计学意义（P＞0.05）.（2）高雄组较非高雄组总睾酮、FAI水平显著升高（P＜0.01）,ACTH-8am、ACTH-4pm和ACTH昼夜节律消失率显著升高（P＜0.05）,余指标差异无统计学意义（P＞0.05）.（3）体质指数正常的PCOS患者ACTH-8am水平、ACTH昼夜节律消失率显著高于对照组,体质指数正常的高雄组PCOS患者较非高雄组PCOS患者ACTH-8am水平仍显著升高（P＜0.05）,余指标差异无统计学意义（P＞0.05）.结论 PCOS患者存在血浆ACTH水平异常,伴高雄激素血症患者异常更加显著.     

Studies of the Control of Plasma Aldosterone Concentration in Normal Man: III. RESPONSE TO SODIUM CHLORIDE INFUSION

The peripheral plasma levels of aldosterone, renin activity, potassium, sodium, corticosterone, and cortisol were measured in six normal subjects four times daily-10 a.m., 2 p.m., 5 p.m., 11 p.m.-on 3 consecutive days. A constant daytime activity program was maintained throughout the study. After 5 days on a 10 mEq sodium/100 mEq potassium isocaloric intake, the mean upright 10 a.m. plasma renin activity was 1773+/-186 ng/100 ml per 3 hr and the mean plasma aldosterone, 81+/-14 ng/100 ml. These two parameters fell continuously throughout the day parallel to the fall in plasma cortisol and corticosterone. In response to 2 liters of normal saline infused from 10 a.m. to 2 p.m. on 2 consecutive days, plasma aldosterone levels fell significantly to 13+/-5 ng/100 ml at 2 p.m. after the 1st day's infusion and to 6+/-1 ng/100 ml at 2 p.m. after the 2nd. Plasma renin activity demonstrated a parallel fall to 368+/-63 ng/100 ml per 3 hr and 189+/-27 ng/100 ml per 3 hr at 2 p.m. on the 1st and 2nd days, respectively. There was no significant alteration in plasma levels of cortisol, corticosterone, potassium, or sodium on the 2 days of sodium loading in comparison with the control day. In an additional study, five normal supine subjects received 500 ml saline/hr for 6 hr. As in the 2 day study, plasma aldosterone and renin activity had parallel decrements at 1, 2, 4, and 6 hr after the start of the saline infusion. From these studies, it is concluded that plasma renin activity is the dominant factor controlling plasma aldosterone when sodium-depleted normal subjects are acutely repleted.     

In vitro responses of aldosterone-producing adenomas to angiotensin II and ACTH after treatment with spironolactone before adrenalectomy

Aldosterone-producing adenomas in patients who have not been given spironolactone are more responsive to ACTH than to angiotensin II. In vitro, adenomas respond to ACTH, but their response to angiotensin II has not been clearly defined. Treatment with spironolactone has been given before the removal of some of the adenomas studied in vitro, and it can blunt increases in plasma aldosterone concentrations that occur in response to increases in renin activity. To assess the effect of preoperative spironolactone therapy on the responsiveness of aldosterone-producing adenomas in vitro, tissue from five patients with adenomas was incubated for 4 hours with and without angiotensin II and ACTH, 10(-7) to 10(-5) mol/L. The responsiveness of the adenomas was then related to the duration of preoperative spironolactone therapy. The serum potassium concentration was normal in the patients before the operations. Adenoma tissue from a patient given spironolactone for 4 days was responsive to angiotensin II and to ACTH. Treatment of longer duration with spironolactone appeared to be associated with a pattern of decreasing responsiveness to ACTH and an absence of response to angiotensin II in vitro. Aldosterone production by nonadenomatous adrenal tissue did not respond to angiotensin II or to ACTH. Our results suggest that preoperative spironolactone therapy might decrease the responsiveness of aldosterone-producing adenomas to angiotensin II and ACTH in vitro. Therefore, studies of aldosterone-producing adenomas in vitro should consider the possible effects of preoperative treatment with spironolactone on the responsiveness of the adenomas to angiotensin II and ACTH.