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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.
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PMID:Effect of a single bolus of etomidate upon eight major corticosteroid hormones and plasma ACTH. 298 10

Long term use of ovine corticotropin-releasing hormone (oCRH) requires a convenient route of administration. The effects of 0.3, 3, and 30 micrograms/kg BW synthetic oCRH given as a sc injection and of 10 and 30 micrograms/kg given as an intranasal spray were studied in 10 normal men in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol levels were 14 +/- 1.9 pg/ml and 4.3 +/- 0.4 microgram/dl (mean +/- SEM). Peak IR-ACTH levels (mean +/- SEM) were 43 +/- 5.5, 53 +/- 8.1, and 64 +/- 8.9 pg/ml after the 0.3, 3, and 30 micrograms/kg doses of oCRH given sc, respectively, and 23 +/- 4.3 and 36 +/- 4.8 pg/ml after the 10 and 30 micrograms/kg doses of oCRH given intranasally, respectively. The lowest sc dose and both intranasal doses caused only single IR-ACTH peaks. After 3 and 30 micrograms/kg sc oCRH, IR-ACTH rose by 15 min, reached an initial peak at 45-60 min, fell rapidly until 90-120 min, and rose to a second peak at 3-5 h. This biphasic response is similar to that previously found after iv administration. IR-ACTH levels remained elevated for 4, 10, and at least 16 h after 0.3, 3, and 30 micrograms/kg sc oCRH, respectively, and for 1.5 and 3 h after 10 and 30 micrograms/kg intranasal oCRH respectively. The effect on IR-cortisol was similar, but more prolonged. Compared to the iv route, sc oCRH produced similar mean peak IR-ACTH and IR-cortisol levels and had a slightly longer duration of action. Intranasal oCRH was only about 1% as effective. Peak plasma IR-oCRH levels in 2 subjects receiving 3 micrograms/kg sc oCRH were 13 and 17 ng/ml at 90 min. These peaks were lower than those after iv administration of the same dose, but the levels remained elevated longer, probably accounting for the longer duration of action of sc oCRH. Peak plasma IR-oCRH levels in 4 subjects given 10 microgram/kg intranasal oCRH were only 64-122 pg/ml, presumably reflecting poor absorption through the nasal mucosa. These results demonstrate that sc injection of oCRH is at least as effective as the iv route with respect to plasma IR-ACTH and IR-cortisol responses. The convenience of this route of administration and the prolonged duration of action of oCRH suggest the feasibility of long term oCRH use.
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PMID:Effect of subcutaneous and intranasal administration of ovine corticotropin-releasing hormone in man: comparison with intravenous administration. 298 33

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.
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PMID:Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine. 298 91

The blood pressure and endocrine responses to cigarette smoking were studied in 19 hypertensive patients to determine whether smoking activates the renin-aldosterone axis. Blood pressure rose from 140 +/- 7/99 +/- 3 (mean +/- SEM) to 151 +/- 5/108 +/- 2 mm Hg (p less than 0.01) within 10 minutes after smoking, and pulse rate also increased significantly (69 +/- 2 to 96 +/- 4 beats per minute). Plasma renin activity did not change but rose 15 minutes after ambulation. In contrast, plasma aldosterone and plasma cortisol levels increased significantly after smoking and peaked at 20 minutes: 13.9 +/- 0.9 to 20.2 +/- 2.0 ng/dl (p less than 0.01) and 10.2 +/- 1.0 to 22.0 +/- 2.2 micrograms/dl (p less than 0.01), respectively. These responses were closely correlated (r = 0.6467, p less than 0.01), suggesting a pituitary-adrenal mechanism is activated during smoking. Plasma ACTH levels rose from 58 +/- 6 to 87 +/- 10 pg/ml in 10 minutes (p less than 0.001) and to 90 +/- 14 pg/ml at 20 minutes (p less than 0.01). Total plasma catecholamine levels also rose from 468 +/- 60 to 624 +/- 73 pg/ml 10 minutes after smoking (p less than 0.01) and to 724 +/- 69 pg/ml (p less than 0.01) 15 minutes after ambulation. In hypertensive smokers, cigarette smoking is associated with an increase in blood pressure, pulse rate, and plasma ACTH, cortisol, aldosterone, and plasma catecholamine levels. The long-term significance of these acute hormonal changes in regard to blood pressure homeostasis and vascular disease in cigarette smokers remains to be determined. Smoking should be avoided prior to blood pressure and endocrine determinations.
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PMID:Cigarette smoking in hypertensive patients. Blood pressure and endocrine responses. 298 31

Superphysiological doses of ACTH were administered for 3 consecutive days to nine patients with CAH, five with the classical simple virilizing (CSV) type and four with nonclassical simple virilizing type (NCSV; late onset), receiving a sodium-restricted diet. In the CSV patients, cortisol levels were lower [4.9 +/- 2.2 (+/- SEM) micrograms/dl] than in the NCSV patients (10.9 +/- 3.8; P less than 0.005) and normal subjects (10.7 +/- 4.0; P less than 0.05). ACTH produced a subnormal increase to only 14.5 micrograms/dl by day 3. In the NCSV patients, cortisol rose slowly during the first 24 h, but reached normal response levels by 48 h (42.5 +/- 11.5 micrograms/dl). In all patients, basal plasma corticosterone and 18-hydroxydeoxycorticosterone (18-OHDOC) levels were normal, but deoxycorticosterone (DOC) was elevated at 25.3 +/- 5.0 ng/dl (P less than 0.05). ACTH failed to increase plasma levels of DOC, corticosterone, and 18-OHDOC. Aldosterone and 18-hydroxycortisol were elevated in both groups [29.1 +/- 5.8 (P less than 0.02) and 83.8 +/- 15.3 (P less than 0.01) ng/dl, respectively] and increased briskly after the first 24 h of ACTH. However, neither steroid returned to normal levels in the CSV group, but both did in the NCSV group. Paired values of stimulated cortisol and aldosterone in normal subjects and CSV and NCSV patients (n = 76) were significantly negatively correlated (r = -0.63; P less than 0.001), suggesting that cortisol inhibits aldosterone biosynthesis. Prolonged ACTH administration after initial increases returned aldosterone and 18-hydroxycortisol levels from the zona glomerulosa to baseline values in the NCSV type, but not in the CSV type. The capacity to increase cortisol levels, which occurred only in NCSV patients, is linked to the reduction of aldosterone in the zona glomerulosa. In contrast, in both types of 21-hydroxylase deficiency, sustained impairment of both the 17-hydroxy pathway (cortisol) and the 17-deoxy pathway of the zona fasciculata (DOC, corticosterone, and 18-OHDOC) was demonstrated.
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PMID:Effects of continued adrenocorticotropin stimulation on the mineralocorticoid hormones in classical and nonclassical simple virilizing types of 21-hydroxylase deficiency. 298 85

To determine whether the plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol responses to ovine corticotropin-releasing hormone (oCRH) depend on the time of day, we administered 1 microgram/kg BW synthetic oCRH as an iv bolus dose to five normal men at their usual time of awakening between 0530-0740 h, at 1600 h, and at 2300 h. Mean basal plasma IR-ACTH and IR-cortisol levels were highest upon awakening, intermediate at 1600 h, and lowest at 2300 h, reflecting the diurnal rhythm of ACTH secretion. There was no significant difference in the plasma IR-ACTH response to oCRH at different times of the day. In contrast, the mean maximum plasma IR-cortisol increment and mean integrated response were 2- and 2.6-fold greater (P less than 0.05), respectively, at 2300 h than upon awakening. In another study, oCRH was given in the morning (0700-0900 h) to 22 normal men and in the late afternoon (1600-1800 h) to 24 normal men. Mean basal plasma IR-ACTH and IR-cortisol levels were significantly higher (P less than 0.001) in the morning [24 +/- 3 pg/ml (mean +/- SEM) and 10.6 +/- 0.8 micrograms/dl, respectively] than in the afternoon (13 +/- 2 pg/ml and 5.6 +/- 0.6 micrograms/dl, respectively). Mean peak plasma IR-ACTH was slightly greater in the morning (60 +/- 5.5 pg/ml) than in the afternoon (47 +/- 5.5 pg/ml), the mean maximum plasma IR-ACTH increments were the same (35 +/- 4 and 34 +/- 5 pg/ml, respectively), and the mean integrated IR-ACTH response was slightly less in the morning (2036 +/- 414 vs. 2365 +/- 358 pg . min/ml), but none of these differences was statistically significant. Mean peak plasma IR-cortisol concentrations in the morning and afternoon were similar (18.7 +/- 0.7 and 17.3 +/- 0.9 micrograms/dl, respectively), but the mean maximum plasma IR-cortisol increments (8.1 +/- 0.8 and 11.7 +/- 0.9 micrograms/dl, respectively; P less than 0.005), and the mean integrated IR-cortisol responses (588 +/- 115 and 976 +/- 95 micrograms . min/dl, respectively; P less than 0.01) were greater in the afternoon. There was an inverse correlation between basal plasma IR-cortisol concentration and the integrated IR-ACTH response (P less than 0.05), the maximum IR-cortisol increment (P less than 0.001), and the integrated IR-cortisol response (P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diurnal variation in the response of plasma adrenocorticotropin and cortisol to intravenous ovine corticotropin-releasing hormone. 298 16

The ACTH and cortisol responses to an intravenous bolus injection of 100 micrograms ovine CRF were studied in 19 patients with adrenal failure. In all eight patients with primary adrenal failure, plasma ACTH levels increased from a mean basal level of 1494 +/- 431 (SEM) pg/ml to peak value of 2601 +/- 1220 pg/ml at 10 min. In comparison with healthy subjects absolute ACTH increments after ovine CRF were significantly augmented in the patients with Addison's disease (P* less than 0.001), and the absolute ACTH responses after ovine CRF were positively correlated with the basal plasma ACTH levels. The 11 patients with secondary adrenal insufficiency could be subdivided into two groups: (A) those having little or no ACTH and cortisol response to ovine CRF (five patients) and (B) those having prolonged and pronounced ACTH responses with a biphasic pattern and a delayed second peak (six patients), followed in all patients by a marked cortisol increase. These data demonstrate that the CRF-test can discriminate between hypothalamic and pituitary causes of secondary adrenal failure.
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PMID:ACTH and cortisol responses to ovine corticotrophin-releasing factor in patients with primary and secondary adrenal failure. 299 Jul 63

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.
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PMID:Effects of proopiomelanocortin peptides and angiotensin II on steroidogenesis in isolated aldosteronoma cells. 299 20

Adrenal androgen secretion is decreased in patients with anorexia nervosa. To assess the reversibility of the decreased secretion with recovery of body weight, we measured ACTH-stimulated adrenal androgen levels at different stages of recovery. Basal plasma GH and somatomedin-C levels also were measured, because both have been proposed as potential stimuli for adrenal androgen secretion. When studied at low body weight [58 +/- 3% (+/- SEM) ideal BW], women with anorexia nervosa had decreased ACTH-stimulated levels of dehydroepiandrosterone (DHA), DHA sulfate (DHAS), and androstenedione and decreased DHA to cortisol, DHAS to cortisol, and androstenedione to cortisol ratios compared to normal women. Women who had recently completed a refeeding program (within 2-4 weeks, 81 +/- 2% ideal BW) had an increased somatomedin-C level compared to low weight patients, but similar ACTH-stimulated adrenal androgen levels. Long term weight-recovered women (86 +/- 4% ideal BW, recovery for more than 6 months, with resumption of menses), however, had significant increases in ACTH-stimulated DHA and DHAS levels and DHA to cortisol and DHAS to cortisol ratios, and their hormone levels and ratios were not different from those in normal women. GH levels fell during weight recovery, although the values in the three patient groups did not differ significantly. We conclude that the recovery of adrenal androgen secretion while GH levels were falling provides evidence against a direct effect of GH as a stimulus for adrenal androgen secretion. The recovery of somatomedin-C before the recovery of adrenal androgens, however, and the positive correlation between plasma somatomedin-C and the integrated level of plasma DHAS (r = 0.50; P less than 0.02) are consistent with the hypothesis that somatomedin-C is a stimulus for adrenal androgen secretion.
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PMID:Adrenocorticotropin-stimulated adrenal androgen secretion in anorexia nervosa: impaired secretion at low weight with normalization after long-term weight recovery. 299 44

We measured the cortisol and corticosterone responses to insulin-induced hypoglycemia in 13 growth hormone (GH)-deficient children and 30 short children without GH deficiency. Although there was no difference between the two groups in degree of hypoglycemia attained, baseline cortisol, baseline corticosterone, or cortisol 40 min after insulin injection, GH-deficient children had a significantly greater corticosterone response to this stress (3.6 +/- 0.4 versus 1.9 +/- 0.2 micrograms/dl). (All data are presented as mean +/- SEM.) In order to explore the effect of GH on corticosterone secretion, we measured cortisol and corticosterone responses to synthetic (1-24) ACTH before and after 3 days of exogenous GH (0.2 unit/kg/day). In 13 GH-deficient children, GH treatment caused a significant decrease in the corticosterone response to ACTH (2.2 +/- 0.2 micrograms/dl before GH to 1.6 +/- 0.2 micrograms/dl; t = 5.22, p less than 0.001; paired t test) despite the fact that there was no significant change in the cortisol response to ACTH (18 +/- 2 micrograms/dl before and 16 +/- 2 micrograms/dl after). When seven short children who were not GH deficient underwent a similar 3-day course of GH, the decrease in their corticosterone response was much less although still statistically significant (2.0 +/- 0.5 to 1.8 +/- 0.5 micrograms/dl; paired t test, p less than 0.05). Again, the stimulated levels of cortisol were not affected by GH treatment (19 +/- 4 versus 18 +/- 3 micrograms/dl) These results indicate that GH modulates the adrenal response to ACTH by suppressing corticosterone secretion without affecting cortisol secretion. In summary, this study presents two new findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of glucocorticoid secretion by growth hormone. 299 90


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