Changes In Plasma Cortisol Concentrations Research Articles

Salivary Cortisol: A Nontraumatic Sampling Technique for Assaying Cortisol Dynamics

Changes in cortisol dynamics are important correlates of various psychophysiological states in children. The two most important measures of the cortisol dynamics are changes in plasma cortisol concentrations at predetermined times and the dexamethasone suppression test (DST). Unfortunately, much restandardization of adult norms is required before these tests can be applied to infants. Measurements of salivary cortisol appear to be a reliable, accurate and nontraumatic sampling technique for assaying cortisol dynamics. Salivary cortisol values should provide a noninvasive method in the application of the DST to the investigation of psychophysiological states in infants and children.

Reduced cortisol latency in depressive illness.

Depressed patients commonly have disturbances in their sleep and cortisol secretory patterns. When the sleep-related changes in plasma cortisol concentration were measured in 14 patients with a primary major depressive illness, they differed significantly from the changes measured in 14 age- and sex-matched healthy control subjects. The nadir of the nocturnal plasma cortisol concentration was significantly greater in the group of depressed patients, and the nocturnal increase in the plasma cortisol concentration occurred significantly closer to sleep onset in these patients. The circadian activity within the hypothalamic-pituitary-adrenal axis of these depressed patients showed a subtle but significantly disturbed temporal relationship to sleep onset. This reduced time between sleep onset and the nocturnal increase in cortisol secretion suggests a possible biologic correlate of a depressive illness that might be useful as an illness marker in depressed patients.

Hormonal responses to acute volume changes in anephric subjects

The response of plasma aldosterone and cortisol concentrations to acute volume depletion was studied in 18 chronically anephric subjects and four recently nephrectomized subjects. Volume-depleting hemodialysis and hemodialysis without volume depletion produced insignificant changes in plasma aldosterone concentrations in chronically anephric subjects. Failure of volume depletion to increase plasma aldosterone concentrations in these subjects could not be attributed to reductions in plasma potassium concentrations and was in marked contrast to the effect on plasma cortisol concentrations, which increased significantly during volume depletion. Changes in plasma cortisol concentrations exhibited a negative correlation with changes in diastolic blood pressure (r = -0.712, P less than 0.001) and were shown to correspond to similar changes in plasma ACTH concentrations. Comparable increases in plasma cortisol and ACTH concentrations were also demonstrated in the studies on recently nephrectomized subjects, who, in contrast to chronically anephric subjects, exhibited increases in plasma aldosterone concentrations which were concordant with the changes in plasma cortisol and ACTH concentrations. These findings suggest that plasma aldosterone concentrations are regulated by a volume-sensitive mechanism in recently nephrectomized subjects but not in chronically anephric subjects. We interpret these data as evidence of aldosterone responsiveness to ACTH that persists for a limited time only after removal of the stimulus provided by the renin-angiotensin system. Volume-related changes in plasma cortisol and ACTH concentrations occur in the absence of stimulation by a functioning renin-angiotensin system.

The cortisol fluctuations in plasma in relation to human regulatory nonshivering thermogenesis.

It is known that many stressful situations are accompanied by an increase in plasma cortisol concentration. This study was undertaken to see if a standardized and moderate exposure to cold under simultaneous peripheral vasodilation, which is known to result in increased oxygen consumption and plasma concentration of noradrenaline, can be considered a stress, based on changes in plasma cortisol concentration. Since the nonshivering thermogenesis induced is dependent on normal thyroid function, nine of the 19 adult humans exposed to cold were normo-, four hyper-, and six hypothyroid. The cold exposure was carried out in every case between 9 a.m. and 11 a.m. Since the cortisol secretion reflects the circadian cycle, a further six normothyroid persons were exposure to cold between 5 a.m. and 7 a.m. The exposure in this study does not reflect any stress condition, as the plasma cortisol concentration during the investigations between 9 a.m. and 11 a.m. decreased significantly by mean values of 0.1 mmol/l (29%) (range: -0.07--0.2 mmol/l) in the normothyroid group, by 0.23 mmol/l (68%) (range: 0.09--0.44 mmol/l) in the hyperthyroid group, and by 0.16 mmol/l (29%) (range: 0.03--0.38 mmol/l) in the hypothyroid group. The normothyroid persons investigated between 5 a.m. and 7 a.m. showed a significant fall similar to that mentioned above. The differences in the results obtained between the normo- and dysthyroid groups, before and during the exposure, merely reflected variations known from non-stressful conditions.

ADRENOCORTICAL FUNCTION TESTS IN DOGS WITH HYPERFUNCTIONING ADRENOCORTICAL TUMOURS

The response has been studied in nine dogs with hyperadrenocorticism due to adrenocortical tumours to the administration of dexamethasone, insulin, lysine-vasopressin and tetracosactide by measuring the changes in plasma cortisol concentration. Administration of dexamethasone did not produce a decrease in the plasma concentration of cortisol in any of these dogs. Administration of insulin caused slight increases in the plasma concentration of cortisol in four out of eight dogs. Lysine-vasopressin increased the plasma concentration of cortisol in eight out of nine dogs, three responded supranomally. Eight out of the nine dogs responded to tetracosactide administration, three responded supranormally, It is concluded that in the dog, in contrast to man, the lysine-vasopressin test cannot be used to differentiate between pituitary-dependent hyperadrenocorticism and hyperadrenocorticism due to an adenocortical tumour. Apparently pituitary ACTH is not completely depleted in dogs with hyperfunctioning adrenocortical tumours.

Adrenal status assessed by direct radioimmunoassay of cortisol in whole saliva or parotid saliva.

We describe a direct radioimmunoassay for cortisol in 10-microliter volumes of parotid saliva or whole saliva. Binding proteins are absent from these fluids, as demonstrated by the excellent correlation between results for samples assayed directly and by a comparison procedure involving extraction with 1,2-dichloroethane. The direct assay is specific, precise, and had a lower limit of sensitivity of 4 pg per assay tube. Comparison of cortisol concentrations in plasma, parotid saliva, and whole saliva in persons undergoing investigations for assessing adrenal function, including stimulation with cosyntropin (Synacthen) and suppression with dexamethasone, indicated that changes in plasma cortisol concentration were accurately and immediately reflected in saliva from either the parotidgland or whole saliva. A marked circadian rhythm has also been demonstrated for cortisol in parotid-gland saliva and whole saliva. We had to modify the 1,2-dichloroethane extraction procedure for accurate determination of cortisol in parotid saliva and whole saliva of patients undergoing treatment with metyrapone.

Treatment of asthma in children with triamcinolone acetonide aerosol

Triamcinolone acetonide aerosol, 100 μg qid, was administered for 8 wk to 5 steroid-dependent asthmatic children and 10 who had not previously required continual corticosteroid treatment. Symptomatic control and pulmonary function improved in all 15 children despite discontinuation of oral corticosteroids in 3 of the steroid-dependent children. Determination of morning plasma cortisol concentrations disclosed no evidence of substantial adrenal suppression. Satisfactory symptomatic control has subsequently been maintained for 6 to 32 mo with doses of 100 μg bid to 300 μg qid without more extreme changes in plasma cortisol concentrations than were observed during the first 8 wk.

Anesthetic and Handling Stress on Survival and Cortisol Concentration in Yearling Chinook Salmon (Oncorhynchus tshawytscha)

Brief anesthetization with 50 mg/L buffered MS-222® (ethyl m-aminobenzoate methanesulfonate) of yearling chinook salmon (Oncorhynchus tshawytscha) during mild handling caused no change in plasma cortisol concentrations compared with levels in non-anesthetized fish. Prolonged exposure (180 min) to a depressing dose of buffered MS-222® (25 mg/L) elevated cortisol more than an immobilizing dose (50 mg/L), while 100 mg/L was lethal within 30 min. Fish anesthetized (50 mg/L MS-222®) during a severe 30-min handling stress had significantly lower mortality than controls to a second handling stress applied when the fish were no longer anesthetized. Anesthetization during the first stressor also prevented the cortisol stress response evident in the control fish. Anesthetic (with or without buffer) administered before initial capture was most effective at increasing survival during a second stressor, while anesthetic supplied after initial capture may have been slightly less effective. A 0.5% NaCl solution supplied after capture was less effective than any anesthetic treatment in increasing future survival, but was better than no treatment. Saline treatment did not attenuate the cortisol stress response. A rapid method of plasma sample preparation for competitive protein binding assay of cortisol was developed. Key words: chinook salmon, cortisol, stress, anesthetic, cortisol assay, survival

The reproductive cycle of Coregonus lavaretus (L) in Loch Lomond, Scotland, inrelation to seasonal changes in plasma cortisol concentration

The reproductive cycle of Coregonus lavaretus (L.) in Loch Lomond, Scotland, was investigated by monthly sampling. Spawing takes place during the first 3 weeks of January, on offshore gravel banks. Males congregate on the spawning‐grounds throughout the spawning period, while ripe females cruise in unisexual shoals in deeper water. Individual females migrate to the spawning‐grounds as ovulation takes place, spawn, and return to deep water. After spawning, the gonadosomatic ratio and somatic condition factor of both sexes decrease until June or July. Gonad recrudescence occurs in males between July and October, and in females between July and December. The somatic condition factor of both sexes rises from its minimum in June or July to its maximum in September. A competitive protein binding assay was used to determine cortisol levels in 0–1 ml plasma samples of individual fish. The lowest cortisol levels occurred in fish caught by seine‐netting and killed immediately by anaesthesia in MS 222 (Sandoz). Seine‐netting and killing by concussion induced higher cortisol levels, in the range of 3–5 ng/100 ml. Cortisol levels in fish caught by gill‐netting for 18 h were 3–6 times higher than in seine‐netted fish, and the method of killing was immaterial in this case. The length of time spent in the gill‐net had no significant effect on cortisol level, but maintenance of the fish in aquaria for 24–80 h elicited high cortisol levels of over 50 μg/100 ml. Post‐mortem delay before blood‐sampling resulted in lowered cortisol levels. Seasonal variations in cortisol level were determined in gill‐netted fish throughout the year, and in seine‐netted fish when available. Cortisol levels were high in both sexes in September; and very high in ovulating females caught on the spawning‐grounds, though not in ovulating females caught off the spawning‐grounds.

Studies on the production and metabolic clearance rates of cortisol in the European eel. Anguilla anguilla (L.)

Aspects of cortisol metabolism have been studied in the eel, Anguilla anguilla L., adapted to fresh water and sea water environments. The effects of hypophysectomy and removal of the corpuscles of Stannius on cortisol dynamics were assessed. High specific activity tritiated cortisol reached a steady state in plasma 7 h after beginning a constant intravenous infusion. Plasma cortisol concentrations were determined in hourly blood specimens during the steady state situation. Plasma cortisol concentration, its metabolic clearance and production rates were obtained for the various experimental groups. Plasma electrolytes were also determined. Similar cortisol concentrations occur in fresh water and sea water eels. Sea water adapted eels had higher metabolic clearance and production rates than fresh water animals. After hypophysectomy both fresh water and sea water adapted eels had reduced plasma cortisol concentrations and cortisol production rates, although the metabolic clearance rates were significantly elevated. These alterations in cortisol dynamics following hypophysectomy were returned to normal by infusion of mammalian ACTH in a group of sea water adapted eels. In fresh water eels removal of the corpuscles of Stannius produced almost twofold increases in the metabolic clearance and production rates of cortisol without there being any change in plasma cortisol concentration. Removal of the corpuscles of Stannius from sea water adapted eels induced a slight decrement in plasma cortisol concentration.

Plasma cortisol concentration and the rate of intestinal water absorption in the eel, Anguilla japonica.

Changes in plasma cortisol concentration and the rate of intestinal water absorption in vitro were examined at intervals after transferring the eel from fresh water to sea water and after treating the freshwater eel with ACTH or cortisol. When eels were transferred from fresh water to sea water, plasma cortisol level increased temporarily after 2 to 4 hr. The highest concentration observed 2 hr after transfer was 9.6±1.6μg/100ml; after 24hr, the concentration returned to the initial freshwater level (3.8±0.9μg/100ml). On the other hand, the increase in the rate of water absorption in the gut was observed 12hr after transfer, and maximum increase was attained after 48 hr. Thereafter the intestine maintained a higher rate than that of the freshwater eel. Essentially similar changes in plasma cortisol and intestinal water flux were observed in the freshwater eel injected with ACTH or cortisol; maximum cortisol level was observed 1-2hr after injection, and intestinal water flux increased maximally after 24 hr, although the highest concentration of cortisol was about 20, μg/100ml, and intestinal water flux returned to the initial level 7 days after the injection. These results indicate that the increased rate of water absorption in the seawater eel is induced by the short-term increase in circulating cortisol. Furthermore, the delayed and prolonged response of the gut to circulating cortisol suggests involvement of some metabolic process for induction and maintenance of increased rate of water absorption in the eel gut in sea water.

The significance of changes in plasma cortisol concentration and renal excretion of corticosteroids after a water load.

SUMMARY 1. Plasma cortisol concentrations, and the urinary output of free and conjugated Porter-Silber reacting steroids, 17-ketosteroids (17-KS), 'total 17-OH CS', urinary cortisone and cortisol, free and conjugated tetrahydrocortisone and cortisol were measured before and after a 1 l. water load. 2. The plasma cortisol concentration fell within 30 min of water ingestion, and tended to increase as diuresis declined. 3. There was a simultaneous increase in the urinary output of 17-KS, total 17-OH CS, and free Porter-Silber reacting steroids. In contrast, urinary excretion of glucuronide-conjugated corticosteroids did not increase during diuresis. 4. The implications of these findings are discussed and it is concluded that (a) the enhanced corticosteroid output during water diuresis is renal in origin, suggesting that tubular factors play a part in the excretion of these hormones; and (b) the role of the adrenal in the excretion of a water load is permissive.