Effects of naloxone on adrenal cortex regulation in patients with primary aldosteronism

Excess production of proopiomelanocortin (POMC)-derived peptides with aldosterone-stimulating activity has been suggested to play a pathogenetic role in idiopathic hyperaldosteronism (IHA). To further investigate this issue, the opiate receptor antagonist naloxone was administered to 14 patients with primary aldosteronism, 6 with an aldosterone-producing adenoma (APA) and 8 with IHA. Clinical and hormonal effects of iv administration of naloxone (10 mg as a bolus) were compared with those obtained in 8 normal subjects. In normals as well as in APA and IHA patients, naloxone caused a significant increase in plasma cortisol, and no change in ACTH, plasma renin activity (PRA) and aldosterone levels. All subjects were retested after 2 mg dexamethasone. ACTH and cortisol were reduced and PRA was unchanged in all groups, without modifications after naloxone. Baseline aldosterone showed no significant changes in all groups. While normal subjects and APA failed to show any aldosterone response to naloxone after dexamethasone, IHA patients demonstrated a significant decrease. beta-endorphin concentrations were in the normal range before and after dexamethasone. In conclusion, naloxone may have a direct action upon adrenal zona fasciculata increasing the cortisol responsiveness to physiological levels of ACTH in either normals or APA and IHA patients. The decrease of aldosterone induced by naloxone in IHA may be due to an intraadrenal opioid control of zona glomerulosa in this disorder.     

Adrenal steroid responses to ACTH in glucocorticoid-suppressible aldosteronism

To investigate adrenal responses to adrenocorticotrophin (ACTH), we infused graded doses of ACTH (1.25 to 20.0 mIU/30 minutes) in normal subjects, patients with low-renin essential hypertension (LREH), primary aldosteronism (PA), and glucocorticoid-suppressible hyperaldosteronism (GSH). Plasma aldosterone, cortisol, corticosterone, and 18-hydroxycorticosterone were measured. The results revealed a greater increase in the plasma aldosterone and 18-hydroxycorticosterone levels evoked by ACTH in the GSH group than in any other group, which suggested enhanced responsiveness of the aldosterone-producing cells to ACTH and a probable adrenal abnormality.     

Beta-endorphin attenuates the serum cortisol response to exogenous adrenocorticotropin

Controversy surrounds the issue of whether beta-endorphin affects adrenal steroidogenesis. Recent work has both supported and refuted the claim that beta-endorphin stimulates a rise in serum aldosterone. We investigated the role of beta-endorphin in adrenal steroidogenesis by examining its potential modulation of the response of serum cortisol to exogenous ACTH (Cosyntropin). Four of five normal men received: 1) synthetic beta-endorphin (1 microgram/kg X min) for 30 min, followed by a bolus dose of 0.2 micrograms ACTH; 2) beta-endorphin (100 micrograms, iv), followed by 0.2 micrograms ACTH iv; 3) 0.2 micrograms ACTH iv; and 4) beta-endorphin (100 micrograms iv) alone. The integrated cortisol response to exogenous ACTH, calculated as the area under the cortisol response curve, was significantly less when the ACTH infusion was preceded by the 30-min beta-endorphin infusion than when administered alone [163 +/- 50 (SE) microgram/dl X min vs. 282 +/- 51 micrograms/dl X min, respectively; P less than 0.01]. By contrast, there was no difference between the integrated cortisol response to exogenous ACTH alone and exogenous ACTH after the bolus dose of beta-endorphin (282 +/- 51 vs. 293 +/- 39 micrograms/dl X min, respectively). Beta-Endorphin (30-min infusion or 100-micrograms bolus dose alone) caused no change in serum aldosterone, dehydroepiandrosterone, or PRA. Serum PRL levels, however, were raised significantly (P less than 0.05) by the 30-min infusion of beta-endorphin. The infusion and bolus doses of beta-endorphin raised plasma beta-endorphin levels to over 100,000 pg/ml and 5,000 pg/ml, respectively. We conclude that very high plasma levels of beta-endorphin may influence the response of cortisol to ACTH through a direct effect on the adrenal cortex. However, even in disease states such as Addison's and Nelson's diseases, such levels of plasma beta-endorphin are not known to be achieved.     

Impaired beta-endorphin response to human corticotropin-releasing hormone in obese children

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.     

Effects of proopiomelanocortin peptides and angiotensin II on steroidogenesis in isolated aldosteronoma cells

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A II), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, gamma 3MSH and the C-terminal fragment beta-lipotropin (beta LPH) and its derivative beta-endorphin. At concentrations similar to those of ACTH and A II (10(-12)-10(-10) M), 16K, gamma 3MSH, and beta LPH selectively stimulated aldosterone production, which reached levels close to those obtained with A II. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, gamma 3MSH, and beta LPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. beta-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10(-10) M). The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 +/- 0.013 (+/- SEM)] was significantly larger than that induced by A II (0.127 +/- 0.007; P less than 0.001). By contrast, the A/B ratio in response to ACTH (0.061 +/- 0.003) was significantly smaller than that in response to A II (0.159 +/- 0.010; P less than 0.001). The values obtained with 16K (B/F, 0.106 +/- 0.010; A/B, 0.192 +/- 0.028) and gamma 3MSH (B/F, 0.122 +/- 0.012; A/B, 0.178 +/- 0.020) were close to those obtained with A II. 16K and gamma 3MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 +/- 0.003 for ACTH alone to 0.100 +/- 0.008 for 16K plus ACTH (P less than 0.005) and to 0.092 +/- 0.005 for gamma 3MSH plus ACTH (P less than 0.001). The findings suggest that the stimulation of aldosterone production by 16K and gamma 3MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.     

Plasma immunoreactive proopiolipomelanocortin-derived peptides in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.     

Adrenocorticotropic hormone is produced in the ventricle of patients with essential hypertension

OBJECTIVE: Aldosterone is produced in the ventricle of patients with hypertension. The present study was designed to examine whether adrenocorticotropic hormone (ACTH) and cortisol are also produced from the heart in patients with essential hypertension. METHODS: The study population consisted of 57 patients with essential hypertension and 28 control subjects. Plasma levels of ACTH, aldosterone, and cortisol were measured in the aortic root, the anterior interventricular vein and the coronary sinus during cardiac catheterization. RESULTS: The plasma levels of ACTH were significantly higher at the anterior interventricular vein and coronary sinus than at the aortic root (12.7 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001; and 12.3 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. The plasma levels of aldosterone were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root (261.7 +/- 16.4 versus 239.1 +/- 15.1 pmol/l, P < 0.001; and 258.8 +/- 17.0 versus 239.1 +/- 15.1 pmol/l, P < 0.01, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. CONCLUSIONS: ACTH as well as aldosterone is produced, but cortisol is not produced, from the ventricle of patients with essential hypertension.     

Hormones Other Than Aldosterone May Contribute to Hypertension in 3 Different Subtypes of Primary Aldosteronism

Blood pressure (BP) level is similar in patients with 3 subtypes of primary aldosteronism (PA), even though aldosterone levels may vary. Glucocorticoids and adrenomedullary hormones may be influenced and may contribute to hypertension in PA. The authors' objective was to investigate the influence of PA on adrenal gland secretion and the roles of these hormones in hypertension. Patients diagnosed with PA (229 cases) were enrolled and classified into 3 subgroups: aldosterone‐producing adenoma (APA), unilateral nodular adrenal hyperplasia (UNAH), and idiopathic hyperaldosteronism (IHA). Patients with essential hypertension served as the control group (100 cases). Concentration of the above hormones was measured and compared between groups. Level of plasma adrenocorticotrophic hormone (ACTH) in patients with APA was significantly lower than that in patients with IHA (P<.001) and UNAH (P<0.5). The 24‐hour urinary free cortisol and adrenomedullary hormone levels were highest in patients with IHA, lower in patients with APA, and lowest in patients with UNAH. Systolic BP level was positively correlated with 8 am plasma cortisol level (r=0.142, P=.039) and plasma ACTH level (r=0.383, P=.016). Cortisol and adrenomedullary hormones were different between PA subtypes and they might involve regulation of BP in those patients.     

The effect of ACTH and cortisol on aldosterone and cortisol clearance and distribution in plasma and whole blood.

The mechanisms of increased aldosterone and cortisol metabolic clearance rates (MCR) following ACTH or cortisol administration were studied in 13 subjects undergoing cardiac catheterization and in 9 healthy controls. In control subjects, the MCR (plasma) of both steroids increased by 29% (aldosterone: from 936 +/- 57 to 1204 +/- 55 l/day/m2, cortisol: from 205 +/- 12 to 264 +/- 17 l/day/m2 +/- SE) after ACTH (12 units/h) for 1 to 4 h, and by 20 and 32%, respectively, after cortisol (12 mg/h) for 1 to 2 h. In contrast, aldosterone MCR (whole blood) did not change with ACTH or cortisol administration (from 1276 +/- 57 to 1330 +/- 59 l/day/m2), indicating that the plasma MCR increase results from a redistribution of aldosterone from plasma to red cells. Aldosterone splanchnic extraction was 92 +/- 1% (n = 12) with normal morning cortisol levels, and extraction was unchanged after ACTH administration. For cortisol, however, the splanchnic extraction increased from 8 +/- 0.8% to 17.8 +/- 5.0%, and the MCR (whole blood) likewise increased by 15 to 31% (from 295 +/- 23 to 357 +/- 30 l/day/m2), after ACTH or cortisol administration. In vivo and in vitro measurements (at 37 C) of tracer aldosterone concentration in plasma and in red cells showed an increase in distribution to red cells with increasing cortisol concentrations. The results suggest that a fraction of aldosterone is bound in plasma and displaced by cortisol into red cells. There is an increased aldosterone plasma MCR, but unaltered whole blood MCR, since the liver extracts aldosterone almost completely from both plasma and red cells. The increase in cortisol MCR (plasma) results from both an increased splanchnic extraction as plasma binding sites approach saturation and a redistribution into red cells.     

Plasma adrenocorticotrophin, cortisol and aldosterone responses to ovine corticotrophin-releasing factor and vasopressin in sheep

Ovine corticotrophin-releasing factor (oCRF) (1 microgram/kg) and arginine vasopressin (AVP) (1 microgram/kg) were injected iv in sheep, both separately and in combination. Plasma levels of immunoreactive ACTH (IR-ACTH), cortisol, and aldosterone were measured for 3 h after the injections. Mean levels before injections were 8 +/- 4 pmol/l for ACTH, 7 +/- 3 nmol/l for cortisol, and 28 +/- 9 pmol/l for aldosterone. CRF caused a rapid rise in IR-ACTH and a peak level of 125 +/- 52 pmol/l was obtained 15 min after injection. Highest values for cortisol and aldosterone levels were 40 +/- 9 nmol/l and 64 +/- 13 pmol/l, respectively, 30 min after injection. AVP also increased IR-ACTH (maximum level: 202 +/- 77 pmol/l at 5 min) and aldosterone (128 +/- 36 pmol/l at 15 min), whereas the cortisol increase was lower than after CRF. Simultaneous injection of CRF and AVP produced an addition of the IR-ACTH response (295 +/- 82 pmol/l at 15 min), but the changes in cortisol levels were similar to those obtained after CRF alone and those in aldosterone levels resembled those induced by AVP alone. Plasma Na and K, osmolality, and plasma renin activity (PRA) were not modified by either CRF or AVP. It is suggested that the increase in aldosterone levels after CRF could be mediated by ACTH and that after AVP by an IR-ACTH peptide with less effect on cortisol secretion.     

The constant plasma 18-hydroxycorticosterone to aldosterone ratio: an expression of the efficacy of corticosterone methyloxidase type II activity in disorders with variable aldosterone production

Aldosterone and 18-hydroxycorticosterone (18-OHB) are produced by the adrenocortical zona glomerulosa. Under normal conditions, plasma 18-OHB levels parallel and are influenced by the same trophic factors that regulate aldosterone production. To evaluate corticosterone-methyl-oxidase II activity, the final step of aldosterone biosynthesis, in conditions associated with chronic derangements of the pituitary-adrenal and/or renal-adrenal axis, we measured the plasma 18-OHB to aldosterone ratio, cortisol, PRA or plasma renin concentration, and potassium (K) in 104 such patients and 15 normal subjects. The 18-OHB to aldosterone ratios in the pituitary-adrenal group were not significantly different from normal regardless of elevated or reduced ACTH and/or cortisol levels [patients with Cushing's syndrome, 3.55 +/- 0.68 (+/-SE); ACTH deficiency, 2.03 +/- 0.34; 21-hydroxylase deficiency, 3.09 +/- 0.23; normal subjects, 2.50 +/- 0.15]. The renal-adrenal group also had normal ratios regardless of plasma renin concentration and K levels [patients with aldosterone-producing adenomas, 2.85 +/- 0.15; idiopathic hyperaldosteronism, 2.14 +/- 0.19; salt-losing nephropathy, 3.06 +/- 0.54; Bartter's syndrome, 2.89 +/- 0.20; isolated (hyporeninemic) hypoaldosteronism, 3.20 +/- 0.39]. Only in patients with 17 alpha-hydroxylase deficiency (230.1 +/- 118.6) was the ratio abnormally high. Chronic perturbations of aldosterone production by ACTH, the renin-angiotensin system, and/or K did not alter this last step of aldosterone biosynthesis (corticosterone-methyloxidase II), as defined by their plasma concentrations. Any influence of these trophic factors must be proximal to the site of 18-OHB production.     

Determination of urinary 18-hydroxycortisol in the diagnosis of primary aldosteronism.

Urinary excretion of 18-hydroxycortisol (18-OHF), 18-hydroxycorticosterone (18-OHB) and aldosterone 18-glucuronide (Aldo-18-glu) was measured in 10 patients with primary aldosteronism; 5 with aldosterone-producing adenoma (APA) and 5 with idiopathic hyperaldosteronism (IHA), 10 patients with essential hypertension (EHT) and 11 normotensive subjects. In EHT patients, urinary 18-OHF (172 +/- 15 micrograms/24h) and 18-OHB (3.1 +/- 0.6 micrograms/24h) values were not significantly different from 18-OHF (142 +/- 35 micrograms/24h) and 18-OHB (3.6 +/- 0.5 micrograms/24h) in the controls. Urinary 18-OHF values were significantly higher in APA (640 +/- 213 micrograms/24h) when compared with controls and EHT, whereas 18-OHB (11.3 +/- 1.5 micrograms/24h) values were only slightly elevated. Both 18-OHF and 18-OHB were significantly increased in APA compared with 18-OHF (232 +/- 56 micrograms/24h) and 18-OHB (4.6 +/- 0.3 micrograms/24h) in IHA. The two urinary steroids, especially 18-OHF proved to be a useful marker for the diagnosis of APA, confirming the previous findings. Aldo-18-glu was not significantly different between APA and IHA. In normal subjects when sodium intake was restricted to 48meq/day for four days the urinary 18-OHF was increased two fold to 383 +/- 59 micrograms/24h (p less than 0.01 vs control period) associated with comparable rise in plasma renin activity. This suggests that the biosynthesis of 18-OHF is partly under control of renin-angiotensin axis in normal subjects.     

Treatment of familial hyperaldosteronism type I: only partial suppression of adrenocorticotropin required to correct hypertension

In familial hyperaldosteronism type I, inheritance of a hybrid 11beta-hydroxylase/aldosterone synthase gene leads to ACTH-regulated overproduction of aldosterone (causing hypertension) and of "hybrid" steroids, 18-hydroxy- and 18-oxo-cortisol. To determine whether complete suppression of the hybrid gene is necessary to normalize blood pressure, we sought evidence of persisting expression in eight patients who were rendered normotensive for 1.3-4.5 yr by glucocorticoid treatment. At the time of the study, six patients were receiving dexamethasone (0.125-0.25 mg/day) and two patients were taking prednisolone (2.5 or 5 mg/day). Urinary 18-oxo-cortisol levels during treatment demonstrated close correlation with mean "day curve" (blood collected every 2 h for 24 h) cortisol (r = 0.74), consistent with regulation by ACTH. Although urinary 18-oxo-cortisol levels were lower during than before treatment (mean 12.6 +/- 2.4 SEM vs. 35.0 +/- 5.6 nmol/mmol creatinine; P < 0.01), they remained above normal (0.8-5.2 nmol/mmol creatinine) in all eight patients. Although mean upright plasma potassium levels during treatment were higher, aldosterone levels lower, PRA levels higher, and aldosterone to PRA ratios lower than before treatment, PRA levels were uncorrected (< 13 pmol/L x min) and aldosterone to PRA ratios were uncorrected (>65) during treatment in four patients. For each of the eight patients, day curve aldosterone levels during treatment correlated more tightly with cortisol (mean r for the eight patients, 0.87 +/- 0.05 SEM) than with PRA (mean r = 0.36 +/- 0.10 SEM). Hence, control of hypertension by glucocorticoid treatment was associated, in all patients, with only partial suppression of ACTH-regulated hybrid steroid and aldosterone production. Normalization of urinary hybrid steroid levels and abolition of ACTH-regulated aldosterone production is not a requisite for hypertension control and, if used as a treatment goal, may unnecessarily increase the risk of Cushingoid side effects.     

Dissociation of Plasma Atrial Natriuretic Peptide Responses to Upright Posture and Furosemide Administration in Patients with Normal-, Low Renin Essential Hypertension and Primary Aldosteronism

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6± 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8± 6 pg/ml), IHA (54.1± 6.3 pg/ml) and APA before (62.4± 4.9 pg/ml) but not after adrenal surgery (22± 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p < 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.     

Adrenal function in HIV infected patients

Since anatomopathological lesions of the adrenal gland have been frequently observed at autopsy in AIDS, we investigated the glucocorticoid function in 63 patients (51 men, 12 women) infected by the human immunodeficiency virus (HIV) in order to determine the incidence and the nature of any adrenocortical abnormalities at various stages of HIV infection. The patients were classified according to the Centers for Disease Control (CDC) recommendations into group II (asymptomatic; N = 13), group III (lymphadenopathy; N = 27) and group IV (clinical manifestations; N = 23). Plasma ACTH and cortisol before and after an exogenous ACTH stimulation test were measured in patients as in 30 age-matched controls. Plasma renin activity and plasma aldosterone before and after ACTH stimulation were also measured in 31 patients (group II: 12; group III: 10; group IV: 9). Compared with controls patients from group II-III had higher levels of ACTH (39.11 +/- 17.01 vs 29.73 +/- 8.53 ng/l; p = 0.003) and basal cortisol (232 +/- 91.2 vs 184.3 +/- 30.9 micrograms/l; p = 0.03). No significant differences were noted between group IV patients and controls as to ACTH and basal and stimulated cortisol levels. Among the 63 patients, only one from group IV had a blunted cortisol response after ACTH stimulation test. Plasma renin activity, and basal and stimulated aldosterone levels in the 3 groups of patients were not different from control values. In conclusion: 1. Adrenal insufficiency does not seem very frequent in group IV patients and is likely to be a late complication in AIDS. 2. The increased ACTH and basal cortisol levels found in group II and group III patients argue for an early dysregulation of the adrenocortical axis in HIV infection. The exact physiopathological mechanism is not yet known, but an enhanced CRH production by interleukin 1 and/or a direct role of the HIV envelope glycoprotein (gp 120) may explain the high ACTH level in HIV patients.     

The effects of glucose ingestion and fasting on plasma immunoreactive beta-endorphin, adrenocorticotropic hormone and cortisol in obese subjects.

It has been demonstrated that opioid peptides are involved in the stimulation of food intake in rats and that the circulating beta-endorphin levels are increased in genetically obese rodents. Therefore, to assess whether the changes in food intake may influence circulating beta-endorphin levels in obese subjects, plasma beta-endorphin, ACTH and cortisol concentrations were determined in obese patients after an oral glucose load and during a 7-day total starvation. Baseline plasma beta-endorphin concentrations were significantly higher in obese patients than in control normal-weight subjects, while ACTH and cortisol levels were similar in both groups. Plasma beta-endorphin, ACTH and cortisol concentrations were not affected by the ingestion of 75 g glucose, neither were plasma beta-endorphin concentrations modified during prolonged starvation. Moreover, the lack of nycthemeral variations in beta-endorphin levels, documented before and during starvation while plasma ACTH and cortisol were significantly reduced in the evening, suggests that some extra anterior pituitary sources or some obesity-related changes in beta-endorphin metabolism may contribute to the pool of circulating beta-endorphin in obese subjects. On the other hand, even the extreme changes in nutritional conditions, such as total food deprivation or glucose ingestion, are devoid of any detectable influence on circulating beta-endorphin levels.     

Propranolol enhances the effect of ACTH on plasma cortisol, but not on aldosterone in man

An accidental observation led to the suspicion that propranolol (P) enhances the effect of exogenous ACTH on plasma cortisol. To examine this matter further, large-dose ACTH tests (25 IU im) were performed in 10 normal young males: i) without treatment (n =10); ii) after 11/2 days of P treatment (n = 10); iii) after 11/2 days of metoprolol treatment (n = 6). Six other subjects received infusions of 0.2 IU of ACTH/hour for 12 h: i) without pretreatment; ii) after 11/2 days of P treatment. P pretreatment (80 mg t.i.d.) led to a small but significant decrease in plasma cortisol (9.4 +/- 0.8 micrograms/100 mg; mean +/- SE, vs. 11.3 +/- 0.7 micrograms/100 ml in controls). The maximum percentage increase of plasma cortisol after ACTH injection was 383% +/- 35% (mean +/- SE) after P and 253% +/- 22% in controls (p less than 0.05). The enhancement of the absolute and relative increase of plasma cortisol after ACTH injection seems to be mainly due to lowering of basal cortisol levels, since the effect of ACTH on plasma cortisol in normal subjects in inversely related to basal cortisol. The effect of metoprolol on basal cortisol and the cortisol response to ACTH was less pronounced than that of P. In the long-term-infusion study the effect of P was less apparent than in the acute study. P had no significant effect on basal plasma aldosterone or on the aldosterone response to ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)     

β-Endorphin and adrenocortical function in obesity

OBJECTIVE: To test the hypothesis that the hyperendorphinaemia in obesity originates from outside the pituitary. DESIGN: Intravenous administration of corticotrophin-releasing hormone (CRH) after overnight suppression with 2 mg of dexamethasone in normal-weight controls and in obese subjects before and after weight reduction. PATIENTS: Eleven obese females, age (mean +/- SEM) 30 +/- 2.1 years, body mass index (BMI) 41.2 +/- 1.9 kg/m2. Eight normal-weight females served as controls, age 26 +/- 2.1 years, BMI 21.4 +/- 0.5 kg/m2. Five obese subjects were also studied after weight loss of 18.4 +/- 1.0% of original weight. MEASUREMENTS: Plasma beta-endorphin, ACTH and cortisol. Cortisol production rate in 24-hour urine. Basal (without dexamethasone suppression) plasma beta-endorphin levels. RESULTS: Basal (without dexamethasone suppression) beta-endorphin levels were 7.7 +/- 0.8 pmol/l in the obese and 3.8 +/- 0.5 pmol/l in the control subjects (P less than 0.005). The degree of suppression of beta-endorphin after dexamethasone was similar in the obese (23.2 +/- 3.7%) and in the control subjects (28.2 +/- 0.12%). Administration of CRH following dexamethasone suppression resulted in a small but significant increase of plasma beta-endorphin in both obese (from 1.55 +/- 0.12 to 2.32 +/- 0.28 pmol/l) and control subjects (from 0.98 +/- 0.24 to 1.69 +/- 0.33 pmol/l). The groups did not differ regarding this response, nor regarding the release of ACTH and cortisol after CRH. Cortisol production rate was higher (P less than 0.001) in the obese (68.7 +/- 3.3 mumol/24 h) than in the controls (40.0 +/- 3.0 mumol/24 h). No correlation between cortisol production rate and basal beta-endorphin levels was found. Weight loss appeared to have no influence on cortisol production rate, basal beta-endorphin levels, or on the responses to dexamethasone or CRH. CONCLUSIONS: Plasma beta-endorphin in obese subjects can be affected by manipulations of the hypothalamic-pituitary-adrenocortical axis; the hypothesis that the hyperendorphinaemia of obesity originates from outside the pituitary cannot be confirmed.     

Levels of mineralocorticoids in whites and blacks.

Blacks appear, on average, to retain more Na than whites. A higher production rate of mineralocorticoids could explain the greater Na retention in blacks. Although production of aldosterone has been shown to be lower in blacks, the level of another mineralocorticoid may be increased. Plasma levels of deoxycorticosterone and cortisol were measured in young whites (n=23; age=16.4+/-3.1[SD] years) and young blacks (n=25; age=13.8+/-1.3 years). Blacks had lower plasma levels of renin activity and aldosterone and lower urinary aldosterone excretion rates; thus, they appeared to be representative of blacks that retain additional Na. Plasma deoxycorticosterone levels were lower in blacks than in whites both at baseline (247+/-161 versus 381+/-270 pmol/L, P=0.048) and after stimulation with adrenocorticotropic hormone (822+/-294 versus 1127+/-628 pmol/L at 30 minutes, P=0.047; 925+/-366 versus 1440+/-834 pmol/L at 60 minutes, P=0.013). Cortisol levels were also lower in blacks at baseline (P=0.014) but were not significantly different from levels in whites after stimulation with adrenocorticotropic hormone. In a larger cohort of 407 whites (age=12.0+/-2.9 years) and 247 blacks (age=12.9+/-3.1 years), 18-hydroxycortisol excretion rates were also lower in blacks (P=0. 021). In conclusion, increased Na retention in blacks does not appear to be secondary to increased production of either aldosterone, deoxycorticosterone, cortisol, or 18-hydroxycortisol. A primary renal mechanism may mediate the increase in Na reabsorption in blacks.     

肾上腺静脉采血在原发性醛固酮增多症分型诊断中的应用

目的探讨肾上腺静脉采血（AVS）检查在原发性醛固酮增多症（原醛症）分型诊断中的应用价值。方法收集瑞金医院近4年来39例临床确诊的原醛症患者[23例特发性醛固酮增多症（特醛症），16例醛固酮瘤]，经肾上腺静脉插管检查，取双侧肾上腺静脉以及肾静脉水平下的下腔静脉血液，测各点醛固酮和皮质醇水平，并将结果与影像学检查、体位激发试验（PST）及术后病理结果进行比较。结果（1）23例特醛症患者体位激发后血醛固酮较基础值均升高；16例醛固酮瘤患者血醛固酮升高者占56．3％（9／16）；（2）特醛症患者肾上腺B超检查符合率为69．6％（16／23），醛固酮瘤患者为56．3％（9／16）；肾上腺CT检查特醛症患者符合率为73．9％（17／23），醛固酮瘤患者为81．3％（13／16）；（3）AVS检查以两侧醛固酮之比作为判定标准时符合率为71．8％，以醛固酮与皮质醇之比为判定标准则达到100％。醛固酮瘤患者生化异常程度较特醛症患者明显。PST在特醛症及醛固酮瘤中有部分重叠；体位激发后血醛固酮升高者不能排除醛固酮瘤，而血醛固酮下降者可诊断为醛固酮瘤。结论单纯依赖影像学检查对于原醛症患者进行分型诊断易发生误诊。AVS检查的准确性高，对于影像学检查未能发现明显占位性病变者须进行该检查以明确诊断；对于AVS结果，用两侧醛固酮与皮质醇的比值之比分析较单纯比较两侧醛固酮之比更为可靠。