Significant Increase In Plasma Cortisol Research Articles

Responsiveness to corticotropin-releasing hormone and vasopressin in canine Cushing's syndrome.

Corticotropin-releasing hormone (CRH) and vasopressin are the most important hypothalamic factors regulating adrenocorticotropic hormone (ACTH) secretion. In this study we have investigated the responsiveness of the pituitary-adrenocortical axis to intravenous administration of CRH or lysine vasopressin (LVP) in 16 control dogs, 22 dogs with pituitary-dependent hyperadrenocorticism and five dogs with hyperadrenocorticism due to an adrenocortical tumor, using doses of CRH and LVP that caused equivalent ACTH responses in the control dogs. After CRH administration, the increment in plasma ACTH was significantly (p < 0.05) lower in dogs with pituitary-dependent hyperadrenocorticism (221 +/- 53 ng/l) than that in control dogs (279 +/- 41 ng/l). In the dogs with pituitary-dependent hyperadrenocorticism, the relative increases in ACTH after CRH were significantly (p < 0.05) lower than those after LVP. Despite the absence of an increase in ACTH following LVP administration in dogs with hyperadrenocorticism due to an adrenocortical tumor, there was a significant increase in plasma cortisol, the increment (790 +/- 238 nmol/l) being not statistically different from that in the control dogs (412 +/- 37 nmol/l). We conclude that in spite of the changes inherent to pituitary-dependent hyperadrenocorticism, i.e. neoplastic transformation of corticotropic cells and hypercortisolism, there is persistence of responsiveness to hypophysiotropic hormones. The ACTH secretion by corticotropic cells in pituitary-dependent hyperadrenocorticism was relatively less sensitive to stimulation with CRH than with LVP. Adrenocortical tumors develop an aberrant sensitivity to LVP.

Plasma cortisol response in dairy cows to vaginoscopy, genital palpation per rectum and artificial insemination.

Response of plasma cortisol concentrations after vaginoscopic examination, palpation of the genital organs per rectum and artificial insemination were investigated in six Holstein-Friesian cows weighing between 510 to 620 kg. Blood samples were collected by indwelling jugular catheter. The experiment was begun at 09:00 hours on the day when cows came into estrus. Blood samples were collected from 30 minutes before to 60 minutes after each treatment at intervals of 5 to 10 minutes. Cows were initially blood-sampled for 90 minutes at the same intervals without giving any treatment and then were subjected to vaginoscopy for 1.5 minutes, palpation of the uterus and ovaries per rectum for 4 minutes and artificial insemination by the recto-vaginal method for 5 minutes. No significant increase in plasma cortisol was shown in cows in estrus following vaginoscopy. Palpation per rectum as well as artificial insemination caused a significant increase in plasma cortisol (P < 0.01) 5 to 10 minutes after the initiation of treatments in cows in estrus. There was a tendency for cows in the luteal phase to show higher plasma cortisol levels after the vaginoscopy than cows in estrus. Adrenal response to palpation per rectum in cows in the luteal phase was similar to that in cows in estrus. Thus, in cows in estrus, palpation per rectum as well as artificial insemination may be potential stressors for cows, causing an increase in plasma cortisol levels. However, the pathophysiological importance of the rise in plasma cortisol levels is not known.

Effects of Hypophysectomy on Coho Salmon Interrenal: Maintenance of Steroidogenic Pathway and Restoration of in Vitro Responsiveness to Adrenocorticotropin after Handling

The role of the pituitary in regulating interrenal activity in coho salmon ( Oncorhynchus kisutch) was examined using short- (1 week) or long- (10 week) term hypophysectomized (Hx) animals. In experiments in which Hx animals were injected with ovine growth hormone (oGH), triiodothyronine, or vehicle, plasma cortisol was significantly lower (close to nondetectable, 1 ng/ml) in vehicle-injected or hormone-treated short- and long-term Hx animals compared to vehicle-treated sham-operated (SO animals). Treatment of long-term Hx animals with oGH led to a significant increase in plasma cortisol, in comparison to other Hx groups. Interrenal responsiveness to ACTH or cAMP was not consistently affected by hypophysectomy or hormone treatment. Pregnenolone-supported cortisol production by tissue from Hx groups was at least as great as that by tissue from SO animals: production by tissue from GH-treated, long-term Hx animals was significantly greater than that by tissue from Hx or SO animals. Similar experiments utilizing handling stress (handling and anesthesia) instead of hormone injection as a variable revealed that the response of tissue from Hx animals to ACTH or cAMP was significantly reduced in the absence of handling in comparison with SO animals. However, utilization of pregnenolone as a substrate by tissue from Hx animals was no different from that by tissue from SO animals and was independent of handling. These results indicate that the maintenance of the steroid-biosynthetic pathway is pituitary independent. The decrease in tissue responsiveness to ACTH or cAMP in undisturbed Hx animals may be partially attributable to: (1) the absence of nonpituitary/ nonpituitary-mediated factors that are stimulated by handling and which probably upregulate ACTH receptors and mediating systems; and/or (2) to the presence of inhibitory factors which are decreased after handling.

Lack of Enhanced Responsiveness of Plasma 18-Hydroxycorticosterone and Aldosterone to Adrenocorticotropin as well as to Angiotensin-II during Moderate Sodium Depletion in Type II Diabetic Subjects with Normoreninemia

Responses of plasma aldosterone (PA) and its precursor steroids to alpha ACTH-(1-24) (85.2 nmol, iv) injection and graded angiotensin-II (AII) infusions (3.90 and 7.80 pmol/kg.min for 30 min at each dose) on both 170 and 100 mmol sodium intakes were assessed in 25 type II diabetic subjects with normoreninemia and 11 age-matched normal subjects. The diabetic subjects and the normal subjects did not differ in mean blood pressure, serum electrolytes, and creatinine clearance, except for an increase in fasting plasma glucose (P less than 0.001) in the diabetic subjects. A 100-mmol sodium intake for 4 days produced an increase in basal plasma renin activity (P less than 0.01), plasma 18-hydroxycorticosterone (18-OHB; P less than 0.05), and PA (P less than 0.05), and a decrease in urinary sodium excretion (P less than 0.001) in the two groups. These parameters were similar in the two groups. ACTH injection produced significant increases in plasma cortisol, plasma corticosterone, plasma 18-OHB, and PA (P less than 0.005 or P less than 0.001), and graded AII infusions produced significant increases in plasma 18-OHB and PA (P less than 0.05 or P less than 0.01) during both 170- and 100-mmol sodium intakes in the two groups. In the diabetic subjects, however, the responses of plasma 18-OHB and PA to both ACTH injection and graded AII infusions on a 100-mmol, but not on a 170-mmol, sodium intake were subnormal (P less than 0.05 or P less than 0.01) and were similar to those on a 170-mmol sodium intake. These results indicate a lack of enhanced responsiveness of plasma 18-OHB and PA to both ACTH and AII during moderate sodium restriction in nonazotemic type II diabetic subjects with normoreninemia. It appears that these subjects have selective unresponsiveness of adrenal zona glomerulosa to sodium depletion per se, but not to ACTH or AII.

A Simple Stress Test For The Evaluation of Hypothalamic-Pituitary-Adrenal Axis during the First 6 Months of Life

In 33 normal infants, divided into 3 age groups (less than 1 month, 1-3 months, and 3-6 months) plasma cortisol was measured at 2230, 2300, and 2330 h. Baseline plasma cortisol at 2230 h. was, as expected, low in all infants, with mean +/- SEM values of 41 +/- 5, 72 +/- 14, and 97 +/- 17 nmol/L in each group, respectively. Thirty and 60 min after the painful stimulus of the venipuncture, plasma cortisol increased significantly (P less than 0.0005), reaching a maximum increase up to 458 +/- 50, 392 +/- 66, and 455 +/- 97 nmol/L in each age group, respectively. We conclude that in these infants the hypothalamic-pituitary-adrenal axis was functionally intact and responded to the painful stimulus of the venipuncture by a significant increase in plasma cortisol. This test may be used as a simple procedure for the evaluation of the integrity of the hypothalamic-pituitary-adrenal axis without the administration of pharmacological agents. Its usefulness, however, should be validated with patients having a disorder of the system.

Effects of a Long-Acting Somatostatin Analogue on Pituitary-Adrenocortical Secretion in Normal Human Subjects.

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma profiles of the N-terminal peptide of proopiomelanocortin in the rainbow trout with reference to stress

Plasma levels of the N-terminal peptide of proopiomelanocortin (NPP) were measured in rainbow trout, Salmo gairdneri, following treatment of handling stress with or without administration of dexamethasone, adaptation to white and black background, and maintenance on a constant light/dark cycle. Effects of exogenously administered NPP on plasma constituents were also examined to provide insight into the biological significance of NPP. Thirty minutes of handling stress in shallow water had no effect on plasma levels of NPP during and after the stress period, whereas significant increases in plasma cortisol and glucose were observed. Intraperitoneal administration of dexamethasone blocked the stress-induced elevation of plasma levels of cortisol and caused a depression of plasma NPP. No difference was observed in plasma levels of NPP between trout adapted to a white background and those adapted to a black background. No diurnal changes in NPP were observed under an artificial light/dark cycle (14L/10D light cycle, 0500–1900 hr light) in May and September. Thus, plasma levels of NPP were considerably constant under various physiological conditions, and no synchronism was observed between plasma NPP and cortisol, although NPP modifies the corticotropin-induced release of cortisol from the interrenal. Plasma constituents such as cortisol, total protein, albumin, plasma amino nitrogen, glucose, free fatty acid, ketone body, sodium, potassium, calcium, and magnesium were not altered by intraperitoneal injections of NPP (1 or 10 μg) once daily for 6 days (total of six injections) or once every other day for 28 days (14 injections). High concentrations of NPP were found in the plasma 24 hr after cessation of the serial injections of NPP (10 μg), suggesting slow metabolic clearance of the peptide.

A preliminary study of the effects of intravenous [formula omitted], a serotonin agonist, in elderly subjects

m- Chlorophenylpiperazine (m- CPP), a serotonin receptor agonist, is currently being investigated as a probe of serotonergic responsivity in various neuropsychiatrie disorders. The safety of m- CPP in elderly populations and its potential usefulness in exploring possible serotonergic dysfunction in Alzheimer's disease and normal aging were assessed by examining the behavioral, neuroendocrine, and physiological effects of this agent in 15 elderly subjects (mean age 69 ± 2 years): 9 Alzheimer patients and 6 healthy normal volunteers. Intravenous m- CPP (0.08 mg/kg) was well tolerated in all subjects and produced no serious adverse effects. The behavioral effects were modest; in particular, minimal anxiety was observed, a finding that contrasted to results from an earlier study reporting that intravenous m- CPP at a slightly higher dose induced marked anxiety and panic attacks in younger subjects. m- CPP produced significant increases in plasma cortisol and prolactin, and significant changes in blood pressure and temperature in these elderly subjects. The results of this preliminary study suggest that intravenous m- CPP is safe and well-tolerated in elderly subjects. Future studies at higher doses can now proceed to study more definitively the question of possible age- and disorder-related reductions in central nervous system (CNS) serotonergic responsivity.

Tumor necrosis factor and the acute metabolic response to tissue injury in man.

Tumor necrosis factor (cachectin), a protein produced by monocytes and macrophages, has been implicated as an important mediator of the lethal effects of endotoxic shock and the cachexia of chronic infection. Recombinant human tumor necrosis factor alpha (rTNF) was given intravenously to patients as part of an antineoplastic trial. Fever, tachycardia, and at higher doses, hypotension occurred after a single injection of rTNF. Metabolic effects after rTNF administration were dose related and included enhanced energy expenditure with elevated CO2 production, increased whole body protein metabolism and peripheral amino acid efflux from the forearm, and decreased total arterial amino acid levels associated with a significant increase in plasma cortisol. Elevated serum triglycerides, as well as increased glycerol and free fatty acid turnover were seen, suggesting increased whole body lipolysis and fat utilization after rTNF. These findings indicate that administration of TNF in man reproduces many of the acute physiologic and metabolic responses to tissue injury, including energy substrate mobilization.

Hormone and hemodynamic responses to atrial natriuretic peptide in conscious sheep and effect of hemorrhage.

The effect of rat atrial natriuretic peptide (ANP) on basal hemodynamic and hormonal function and on the response to acute hemorrhage was studied in eight conscious sheep. ANP infusions (3 micrograms/kg BW bolus, followed by 50 ng/kg.min for 70 min) increased plasma immunoreactive ANP levels from less than 12 pmol/liter to steady state levels of 523 +/- 20 pmol/liter, reduced arterial pressure by 14% (P less than 0.002), increased heart rate by 26% (P less than 0.06), and increased plasma norepinephrine levels (P less than 0.015) compared to control values. These changes were associated with a significant increase in plasma cortisol (P less than 0.05) and smaller increases in plasma ACTH and arginine vasopressin (AVP), but plasma angiotensin II (AII) and aldosterone were unaffected. When hemorrhage (15 ml/kg BW over 10 min) was performed during ANP or control infusions, hypotension was greater (P less than 0.0004) during ANP treatment and the responses of plasma ACTH, AVP, catecholamines, and AII were enhanced compared with those to control hemorrhage. Plasma immunoreactive ANP during ANP infusions was significantly higher after hemorrhage (mean, 833 +/- 46; P less than 0.003), but the disappearance rate after the termination of ANP infusion was the same (3.1 min) with or without hemorrhage. These studies show that ANP infusions, achieving plasma levels observed in pathological states such as congestive heart failure, inhibit the expected responses of plasma AII and aldosterone to mild acute hypotension, but do not inhibit the responses of plasma AVP, ACTH, AII, and aldosterone associated with acute moderate hemorrhage in conscious sheep.

The effect of stocking density during 4 hour transport to slaughter on behaviour, blood constituents and carcass bruising in Friesian steers

The aim of this work was to assess the response of Friesian steers to road transportation at low, medium and high ( ca 200, 300 and 600 kg/m 2) stocking densities in terms of physiology, behaviour and carcass bruising. Stocking density was determined by adjusting the number of animals per pen (3 runs) or by adjusting pen size (3 runs). Plasma cortisol and glucose increased ( P < 0·001) with stocking density, as did plasma CK activity ( P < 0·001) and carcass bruising ( P < 0·01) both of which indicate muscle damage. At constant stocking density stress increased with pen location towards the tail of the truck, as reflected by a significant increase in plasma cortisol. Stocking density influenced standing orientation within the truck. At low stocking density animal movement was unrestricted and the preferred orientation was standing parallel to the direction of travel; there was a strong bias against diagonal orientations. Losses of balance were associated with specific driving events, notably braking and cornering. Minor losses of balance were observed at all stocking densities, but major losses of balance including animals going down underfoot were associated with high density. When an animal went down at high stocking density it did so involuntarily and was sometimes trapped down, destabilizing other members of the group in a domino effect. Exploratory, sexual and aggressive behaviours were inhibited at high stocking density, with the exception of mounting and pushing, which increased in frequency with stocking density. It was concluded that the high stocking density adversely affected animal welfare and lowered carcass quality when compared with the medium and low stocking densities.

Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 μg hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.

The influence of the muscarinic agonist RS 86 on the cortisol system

To test the assumption that activation of the hypothalamic-pituitary-adrenocortical (HPA) axis is mediated by cholinergic neurons, the cortisol response to the administration of the muscarinic agonist RS 86 was investigated in 12 healthy volunteers. In addition, prolactin and growth hormone secretion patterns were assessed. No significant increase in plasma cortisol or growth hormone was observed after the administration of 1.5 and 3.0 mg RS 86, respectively. However, there was a slight increase in prolactin serum concentration after 3.0 mg RS 86. As RS 86, when used in the same dose range, causes a shortening of rapid eye movement (REM) latency and displays antimanic properties, it is unlikely that a reduced dosage of RS 86 in itself accounts for the lack of stimulation of the HPA axis. If one assumes that in humans the stimulation of the HPA axis is under cholinergic control, then the failure of RS 86 to increase cortisol might be attributable to the fact that different subtypes of muscarinic neurons, for which RS 86 is not a full agonist, are involved, or else nicotinic neurons are implicated in the activation of the HPA axis.

Plasma adrenocorticotropin and cortisol responses to brief high-intensity exercise in humans.

The purpose of this study is to examine plasma cortisol and adrenocorticotropin (ACTH) levels following a brief high-intensity bout of exercise. Each subject (n = 6) performed a 1-min bout of exercise on a cycle ergometer at 120% of his maximum O2 uptake. Blood samples were collected at rest, immediately following the exercise bout, and at 5, 15, and 30 min postexercise. Mean (+/- SE) plasma ACTH levels increased significantly (P less than 0.05) from 2.2 +/- 0.4 pmol/l at rest to 6.2 +/- 1.7 pmol/l immediately following exercise. Mean (+/- SE) plasma cortisol levels increased significantly from 0.40 +/- 0.04 mumol/l at rest to 0.52 +/- 0.04 mumol/l at 15 min postexercise. These data show that brief high-intensity exercise results in significant increases in plasma cortisol and ACTH levels. Furthermore, the temporal sequence between the two hormones suggests that the increase in plasma cortisol levels following brief high-intensity exercise is the result of ACTH-induced steroidogenesis in the adrenal cortex.

Multiple, single-dose naltrexone administrations fail to effect overall cognitive functioning and plasma cortisol in individuals with probable Alzheimer's disease

A double-blind placebo-controlled study was conducted in 10 individuals with probable Alzheimer's disease to assess the effects of varying doses of Naltrexone (0, 25, 50 and 100 mg) on cognitive functioning and on plasma cortisol. Each individual participated in four separate sessions at least three days apart. Naltrexone was found to improve performance in only one of the six psychometric tasks employed (Token Test). However, enhancement of Token Test performance was limited to the 25 mg Naltrexone dose and was mainly the result of an improvement on the part of the two most severely impaired patients. In contrast to the previous reports of elevations of plasma cortisol following administration of opiate antagonists to younger, non-demented subjects, Naltrexone administration failed to produce any significant increase in plasma cortisol in Alzheimer's patients.

The effects of ACTH on the renin-aldosterone system in normotensive man.

The present study examined the effects of low dose ACTH administration (0.1 mg/day for 2 days) on plasma renin concentration, (PRC), activity (PRA) and substrate (PRS), cortisol and aldosterone in man. Six healthy male volunteers on a diet calculated to contain 150 mmol Na/day received an infusion of 5% dextrose (6 ml/h) for 24 hours, then ACTH (Synacthen, Ciba-Geigy) was added to the infusion at the rate of 100 micrograms per day, for 48 h. Blood samples were taken four hourly for determination of plasma cortisol, aldosterone, PRC, PRA and PRS. There was a highly significant increase in plasma cortisol and aldosterone concentrations during ACTH infusion compared with dextrose infusion, but no significant increase in active or inactive PRC, PRA or PRS. In a separate study of 15 healthy male volunteers, dexamethasone (1 mg at 2300 h) suppressed plasma cortisol but had no effect on PRC. These results do not support the view that stimulation of aldosterone by ACTH is mediated through the renin angiotensin system.

Temperature and endocrine activity during sleep in man. Activation of cortisol and thyroid-stimulating hormone, inhibition of human growth hormone secretion by raised or decreased ambient and body temperatures.

1. Polygraphic night sleep recordings in eight healthy male volunteers with simultaneous measurement of rectal temperature, plasma growth hormone (HGH), cortisol, and TSH concentrations were performed during normal, raised, and lowered ambient and body temperature. 2. There was a statistically significant increase in plasma cortisol and TSH levels during cold nights with a smaller rise during high temperatures. 3. Growth hormone levels, measured as the mean highest plasma concentration in the first two NREM-REM sleep cycles, were slightly lower during hot and cold nights than corresponding baseline values. It is suggested that there may be an inverse relation between ACTH and HGH secretion by the anterior pituitary gland. 4. During the nights of high ambient temperature, decreased total duration of sleep and particularly low values of paradoxical sleep were observed. Night sleep in low ambient temperature with a significant decrease of body temperature is not different from baseline conditions. 5. The results suggest that a pronounced increase in stress hormone secretion may occur without changes in polygraphic EEG criteria.