Diurnal Variation Of Plasma Cortisol Research Articles

Cortisol dynamics following acute severe brain injury.

To study the diurnal rhythm of plasma cortisol and corticosteroid binding-globulin (CBG) in brain-injured patients managed in an intensive care unit (ICU). Observational clinical study. Twelve-bed medical/surgical critical care facility. Fifteen acute brain-injured (coma-inducing) patients: nine following trauma and six with subarachnoid haemorrhage (SAH). One morning and one evening blood sample were obtained from each patient via an existing arterial line at times which coincided with clinically indicated blood tests. The total cortisol measurements in this sample of brain-injured patients is similar to the normal reference range. Only two patients had morning total cortisol measurements greater than the reference range, 140-690 nmol/l, and five patients had evening measurements greater than the 80-330 nmol/l reference range. Eight patients demonstrated diurnal variation of plasma cortisol. Plasma CBG was significantly decreased in all 15 brain-injured patients. All patients had a free cortisol percentage greater than the quoted reference of 5% and five patients had measurements between 12-23%. No diurnal variation in CBG was detected. There was no association between age or mode of injury and cortisol secretion. Following acute severe brain injury, total serum cortisol is not elevated. This may indicate 'relative' hypocortisolaemia in relation to the clinically assessed stress. However, because of the decline in plasma CBG, plasma free cortisol is increased after acute severe brain injury.

Incidentally discovered adrenocortical adenomas are not fully nonfunctioning: immunohistochemical and dispersed adrenocortical cell study.

To clarify the precise function of incidentally discovered adrenocortical adenoma, immunohistochemical and dispersed adrenal cell studies were performed. We have recently seen five patients with so-called nonfunctioning adrenocortical adenoma. Diurnal variation in plasma cortisol and suppression of plasma cortisol and urine 17-hydroxycorticosteroids in response to dexamethasone administration revealed adrenocortical function within normal limits in all cases, and no signs or symptoms of adrenal steroid hormone excess were evident. Since a high uptake of iodomethylnorcholesterol was recognized in each adrenal mass, it was supposed that these adrenal tumors produced steroid hormone to a certain extent, and each patient received unilateral adrenalectomy. P450c17, a key enzyme involved in cortisol production, was expressed in the tumor region in all cases in an immunohistochemical study. Upon in vitro steroidogenesis with dispersed adrenal cells in two cases, all steroid hormones measured except for aldosterone (progesterone, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolone, 11-deoxycortisol, cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, dehydroepiandrosterone and androstenedione) were produced in a culture medium. The results indicated that these tumors possessed the capacity for cortisol production, which was in agreement with the results of an iodomethyl-norcholesterol scintigraphy. All patients with mild hypertension or diabetes mellitus had no signs or symptoms of steroid hormone excess, but they could potentially develop a steroid excess syndrome such as Cushing's syndrome in the future.

Diurnal variation of plasma cortisol and homovanillic acid in healthy subjects.

We investigated the relationship between plasma levels of cortisol, the dopamine metabolite homovanillic acid (HVA) and norepinephrine in healthy human subjects. Plasma cortisol and HVA levels were measured at 0800h, and in an integrated sampling procedure involving samples every 15 min between 1300 and 1600h. Plasma norepinephrine was measured at 0800 and 1300h. Cortisol, HVA and norepinephrine indices did not show significant correlations with each other. Both cortisol and HVA showed significant decreases over time. Longitudinal Random Effects (LRE) models were used to test whether individual cortisol and HVA curves over time were correlated; significant correlations were not found with this procedure. While significant correlations between cortisol and catecholamine indices have been reported in depressed patients, our results do not suggest such correlations in healthy subjects.

Renal Failure Obfuscates the Diagnosis of Cushing’s Disease

THE DIAGNOSIS of Cushing's syndrome can be challenging in the patient with chronic renal failure (RF). Spurious overestimation of plasma cortisol, 1 abnormal cortisol binding, 2,3 poor gastrointestinal tract absorption of dexamethasone, 4 and abnormal response to dexamethasone 5 have all been reported to occur in this setting. The hypophyseal-pituitary-adrenal axis appears to be altered in RF, even in patients who lack overt features of Cushing's syndrome, although diurnal variation of plasma cortisol is usually preserved. 5 While much attention has been focused on the laboratory abnormalities in RF patients, little has been published about the occasional RF patient with clinical manifestations of hypercortisolism. The usual diagnostic criteria, standardized for patients with normal renal function, may not be adequate to make the diagnosis. Report of a Case A 43-year-old man had a history of type II diabetes mellitus of eight years' duration, hypertension, congestive heart failure, hypertriglyceridemia, and chronic RF

Renal Failure Obfuscates the Diagnosis of Cushing's Disease

THE DIAGNOSIS of Cushing's syndrome can be challenging in the patient with chronic renal failure (RF). Spurious overestimation of plasma cortisol, 1 abnormal cortisol binding, 2,3 poor gastrointestinal tract absorption of dexamethasone, 4 and abnormal response to dexamethasone 5 have all been reported to occur in this setting. The hypophyseal-pituitary-adrenal axis appears to be altered in RF, even in patients who lack overt features of Cushing's syndrome, although diurnal variation of plasma cortisol is usually preserved. 5 While much attention has been focused on the laboratory abnormalities in RF patients, little has been published about the occasional RF patient with clinical manifestations of hypercortisolism. The usual diagnostic criteria, standardized for patients with normal renal function, may not be adequate to make the diagnosis. Report of a Case A 43-year-old man had a history of type II diabetes mellitus of eight years' duration, hypertension, congestive heart failure, hypertriglyceridemia, and chronic RF

Abnormal circadian rhythm of melatonin in diabetic autonomic neuropathy.

The circadian rhythm of melatonin secretion from the pineal body is entrained to the light-dark cycle and is controlled via sympathetic fibres originating from the superior cervical ganglia. We have therefore examined plasma melatonin profiles in diabetics with and without evidence of autonomic neuropathy and in normal matched controls. The physiological increase in nocturnal plasma melatonin concentration was not observed in diabetics neuropaths. There was no consistent pattern in the diabetics without neuropathy; only three out of the eight subjects in this group had a sustained nocturnal increase in melatonin. Normal diurnal variation of plasma cortisol was present in all groups of subjects. The present study shows that diabetic patients with evidence of autonomic neuropathy lack the normal circadian changes of plasma melatonin concentration. This provides confirmation for the control of pineal function via the sympathetic nervous system in man. The impaired melatonin profiles observed in diabetic patients without apparent autonomic neuropathy suggest that a subclinical state of sympathetic denervation may exist in this group of diabetics.

Diurnal variation of plasma cortisol and corticosterone in dogs.

雄3頭と雌5頭についてイヌの血中FKとBKの日内変動の有無を調べる実験を行なった。すなわち,2時間の間隔で採血を行ない,24時間内の血中FKおよびBKの測定を行なった。その結果,血中FKの平均値は14.4±1.0ng/ml,BKは4.7±0.3ng/mlを示し,測定検体の95%はFK:36ng/ml以下,BK:10ng/ml以下の値を示した。さらに,イヌの血中FKとBK値は,ヒトやウシ等で認められているepisodicな変動パターンを一応示し,血中FK値は深夜から早朝では低く,8~9時に大きなピークを示し,それ以後,午後にかけて中等度の値を示す,いわゆる日内変動が認められた。以上の成績と文献によって示された諸報告より,イヌにおいては血中FK値に日内変動を示す個体が多いこと,および午前8時前後にFK値のピークを示すものが多いらしいことがわかったので,副腎皮質機能を調べる臨床検査において,このことについて注意を払う必要があると考える。

Frequency of Abnormalities of Cortisol Secretion and Water Metabolism in Patients With Small Cell Carcinoma of the Lung and Other Malignancies

Previous studies have suggested that ectopic production of adrenocorticotropic hormone (ACTH) or antidiuretic hormone (ADH) may occur commonly in patients with small cell carcinoma of the lung (SCCL) and that evidence of such production may be elicited only by provocative tests of water excretion and adrenal function. We studied 28 patients with SCCL and 29 patients with other cancers. Adrenal function, assessed by measuring the 8 am plasma cortisol, the 8 am to 4 pm diurnal variation in plasma cortisol, and the suppressibility of the 8 am plasma cortisol following administration of 1 mg of dexamethasone, was found to be abnormal in 28.5, 71, and 25 percent, respectively, of the patients with SCCL, compared with 18, 65, and 29.5 percent in patients with other types of cancer (P greater than 0.3). The possibility of ectopic ADH secretion was assessed by a standard water loading test, which showed excretion impairment in 60 percent of patients with SCCL and 68 percent of patients with other cancers (P greater than 0.9). Neither the stage of neoplastic disease, sites of metastatic deposits, nor performance status of the patients correlated with abnormalities of water and cortisol metabolism, indicating that such abnormalities are common in patients with all types of cancer. These data do not suggest that subclinical disturbances of adrenal function or water excretion are characteristic of any histologic type of cancer. The precise mechanism(s) underlying these abnormalities are unknown.

Licorice Raises Urinary Cortisol in Man*

The finding that urine cortisol excretion was increased in patients with hypokalaemic hypertension induced by licorice addiction led to this study on the effect of licorice in normal subjects. Thirteen normal volunteers ate either 100 or 200 g licorice for 1-4 weeks and assessment of pituitary-adrenal function was made before, during, and 1 week after cessation of licorice ingestion. Urine cortisol excretion more than doubled in 10 of 13 subjects (mean, 33.8 +/- 15.6 SD before and 83.3 +/- 56 SD micrograms/24 h at 1 week after commencing licorice) and excretion rates similar to those observed in Cushing's syndrome were seen in 7 subjects (range, 91-226, compared to normal range of 11-82 micrograms/24 h). Urine cortisol excretion remained significantly elevated (P less than 0.01) above control levels for at least 1 week after licorice was withdrawn. Despite these increases, urinary steroid metabolite (tetrahydrocortisol, tetrahydrocortisone, tetrahydro-11-deoxycortisol, 17-ketogenicsteroids, and 17-ketosteroids) excretion was not affected, plasma cortisol and ACTH values were unchanged, and normal 0800-1600-h diurnal variation of plasma cortisol was maintained. The direct intraadrenal infusion of the active mineralocorticoid component of licorice, glycyrrhetinic acid, in two sheep with autotransplanted adrenal glands failed to stimulate cortisol secretion acutely. It is concluded from these studies that the licorice-induced changes in cortisol excretion are not a result of adrenocoritcal stimulation but more likely represent a change in the renal handling of cortisol.

PITUITARY FUNCTION IN PATIENTS RECEIVING INTERMITTENT CYTOTOXIC AND CORTICOSTEROID THERAPY FOR MALIGNANT LYMPHOMA

Diurnal variation in plasma-cortisol was studied immediately before and after intermittent steroid therapy in seven patients receiving monthly courses of quadruple chemotherapy for Hodgkin's or non-Hodgkin's lymphoma over a period of 6 months. The serum-thyroid-stimulating-hormone (T.S.H.) response to intravenous T.S.H.-releasing factor was also measured before and during the first course and before the second and fourth courses. The morning plasma-cortisol concentration fell significantly over 6 months when measured immediately before the start of each course. The mean evening cortisol concentration also fell over this period. In most patients the T.S.H. response showed a downward trend during treatment, although in two patients the response returned to normal whilst they were still undergoing therapy.

Adrenal function in normal infants and in marasmus and kwashiorkor: Cortisol secretion, diurnal variation of plasma cortisol, and urinary excretion of 17-hydroxycorticoids, free corticoids, and cortisol

Normal infants exhibited circadian rhythmicity of plasma F concentration. Infants from 2.1 to 3.2 months of age had CSR significantly higher than those of older infants. THF/THE urinary excretion ratios increased with age. The 17OHCS excretion was higher in the younger infants. Urinary excretions of free corticoids and cortisol were similar in all age groups. In marasmus, plasma F concentrations in the morning and evening were significantly elevated. Normal diurnal variation returned following therapy. CSR and 17OHCS excretions were not different from age controls, but were significantly lower than size controls, THF/THE ratios, urinary excretion of free corticoids and cortisol were normal. In marasmic kwashiorkor, plasma F concentrations were significantly elevated in the morning and evening. There was a suggestive decrease with therapy. CSR was low before and after treatment. THF/THE ratios, urinary 17OHCS excretion, and urinary free corticoids and cortisol were not significantly different from infants matched for size or patients with marasmus.

CUSHING'S SYNDROME IN CHILDHOOD

A patient with Cushing's syndrome whose clinical manifestations began at approximately 9 years of age was followed for a period of four years. Initial laboratory studies revealed urinary 170HCS and 17 KS levels which were elevated for her age, with a normal diurnal variation of plasma cortisol and normal suppression of urinary 170HCS by 1.5 mg. of dexamethasone daily. It was not until four years after the onset of the disease that laboratory studies unequivocally supported the diagnosis of Cushing's syndrome resulting in definitive therapy. Clinical features consisted primarily of cessation of growth, obesity, and hirsutism, with no evidence of protein depletion. It is suggested that the clinical and laboratory features of Cushing's syndrome in childhood may present differences from those found in the adult. Failure to recognize these differences may result in delay in therapy with subsequent persisting stigmata of the disorder.

Steroid hormone concentrations in blood plasma from residents of Zambia, belonging to different ethnical groups.

ABSTRACT Using competitive protein binding assays, the concentrations of progesterone, oestradiol, testosterone and cortisol have been measured in blood plasma from groups of men and women living in Zambia, but having European, African or Asian origins. All subjects were in apparent good health. For the women, blood was taken in both follicular and luteal phases of the menstrual cycles. In a separate study, the diurnal variation in cortisol was examined. Oestradiol concentration was higher in blood from African men than from men of the other two groups. Asian women showed the lowest luteal phase plasma oestrogen level. African men had lower mean testosterone in plasma than the other groups, while African women had higher results. There were no ethnic differences in progesterone concentrations. Plasma cortisol was significantly higher in African subjects of both sexes than for the other groups, while the diurnal variation in plasma cortisol was much reduced in the Africans.

EFFECTS OF SURGERY ON PLASMA LEVELS OF CORTISOL, CORTICOSTERONE AND NON-PROTEIN-BOUND-CORTISOL

ABSTRACT The diurnal variation in plasma cortisol, corticosterone and non-protein-bound cortisol was investigated using altogether 991 plasma samples obtained from preoperative chronically ill (control) subjects and patients during and following major surgery. A fluorimetric method using an elution chromatography on Amberlite IRC-50 and the equilibrium dialysis method were used for the determinations. The diurnal variation in plasma cortisol of the preoperative control subjects reached a peak (17.3 μg/100 ml) at 6 a.m. and declined to the lowest level (2.3 μg/100 ml) between 10 p.m. and midnight. The maximum value in the levels of corticosterone (0.6 μg/100 ml) was observed at 6 a.m. Surgery caused a steep rise in plasma cortisol showing a maximum value (30.0 μg/100 ml) 2 to 4 hours after the end of the operation. Although the average of the morning levels of plasma cortisol returned to the control levels within 4 to 5 days, the evening levels returned on the 6th day after the operation. The response of plasma corticosterone in the surgery group was found to parallel the change in plasma cortisol. However, the increase in the corticosterone concentration was significantly higher than that of cortisol. The percentage of non-protein-bound cortisol in the plasma of the preoperative control subjects was found to be 2.5 to 3.3 per cent at 6 and 8 a.m. and 1.5 per cent at midnight, while the percentage remained almost unchanged (about 2%) at 10 a.m., 12 a.m. and 6 p.m. The percentage increased significantly during and for 4 days following the operation, concomitant with the increase in the levels of plasma cortisol. It is suggested that stressful situations are associated with markedly increased plasma levels of biologically active cortisol.

Abnormal diurnal variation of plasma cortisol in patients with renovascular hypertension.

ABSTRACT Variation of diurnal plasma cortisol concentration has been studied in a group of patients with hypertension resulting from renal artery obstruction, a process known to cause release of increased amounts of renin. Twelve of 16 patients had grossly abnormal diurnal variation of plasma cortisol concentration with high late evening concentration and low-normal to normal morning concentration. Excretion of 17-hydroxycorticoids was elevated in only 3 of 12 patients, while aldosterone excretion was normal in all of 13 patients studied. The data suggest that angiotensin at low concentrations affects smooth muscle in peripheral arterioles and has no effect on the adrenal cortex. The effect on the adrenal in man, as in experimental animals, is apparently diffuse rather than specific.