Urinary Cortisol Excretion Rate Research Articles

The overnight dexamethasone test is the procedure of choice in screening for Cushing's syndrome

This study was undertaken to examine the performance of the overnight dexamethasone test, i.e., plasma cortisol level at 8–9 AM following dexamethasone 1 mg by mouth at midnight, in screening for Cushing's syndrome. The participants included 19 patients with Cushing's syndrome (17 with Cushing's disease, 1 with adrenal carcinoma, and 1 with ectopic ACTH syndrome) and 96 patients in whom the possibility of Cushing's syndrome was raised but who did not have the disorder. Utilizing our original very conservative cutoff point of plasma 100 nmol/L (3.62 μg/dL) above which Cushing's syndrome was suspected, the sensitivity of the test was 100% but the false positive rate was an unsatisfactory 12.5%. However, the lowest plasma cortisol level achieved following the overnight dexamethasone test in patients with Cushing's syndrome was 259 nmol/L (9.39 μg/dL). A plasma cortisol cutoff point of 250 nmol/L (9.06 μg/dL) yielded no false negatives and the false positive rate fell to 6.25%. Using a cutoff point of 200 nmol/L (7.24 μg/dL) the false positive rate was 7.3%. These performance characteristics of the overnight dexamethasone test compare very favorably with the reported experience of all other screening procedures for Cushing's syndrome including the urinary free cortisol excretion rate and the 48h dexamethasone test, while the overnight dexamethasone procedure is the simplest for both patients and medical personnel. Since it is possible that some very unusual patients may suppress to plasma cortisol levels lower than that seen in the present study, we now recommend the overnight dexamethasone test using a plasma cortisol cutoff point of 200 nmol/L as the procedure of choice when screening for patients with Cushing's syndrome. (Steroids 59: 296–298, 1994)

Elevated plasma adrenocorticotropin concentration as evidence of limited adrenocortical reserve in patients with adrenomyeloneuropathy.

Adrenal insufficiency occurs in approximately two thirds of patients with adrenomyeloneuropathy. Its development may precede or follow the onset of neurological disease. To define the sensitivity of various tests of adrenal cortical function, we reviewed adrenocortical function tests in 28 patients with adrenomyeloneuropathy who had normal ACTH stimulation tests at the time of enrollment into an ongoing dietary study. Endocrine studies performed at 6-month intervals included a conventional ACTH stimulation test, plasma ACTH and cortisol concentrations, and 24-h urinary cortisol and aldosterone excretion rates. Eleven patients (39%) developed an elevated plasma ACTH concentration after a median follow-up of 3 yr. Their 24-h urinary cortisol and plasma basal and ACTH-stimulated cortisol concentrations were all normal. The mean basal cortisol level tended to be lower in patients who had increased plasma ACTH levels than in patients who maintained a normal plasma ACTH concentration during the study period (408 +/- 22 vs. 491 +/- 33 nmol/L; P = 0.05). Patients who had an increased plasma ACTH concentration and symptoms consistent with adrenal insufficiency had a lower mean 24-h urinary free cortisol level than those with normal plasma ACTH (196 +/- 22 vs. 281 +/- 30 nmol/day; P < 0.05). Plasma ACTH concentrations were persistently elevated in six patients in whom subsequent values were available. One individual later developed a subnormal ACTH-stimulated cortisol concentration consistent with overt adrenal insufficiency. Our results suggest that conventional provocative and integrative tests of adrenocortical function may not be sufficient to identify patients with adrenomyeloneuropathy who have compensated adrenal hypofunction. An elevated plasma ACTH concentration may represent an early marker for adrenocortical dysfunction and incipient adrenal insufficiency in AMN patients.

The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution.

To investigate whether obese subjects with abdominal obesity may be characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis, we examined two groups of obese women with a waist to hip ratio (WHR) lower than 0.80 (n = 13), therefore having peripheral body fat distribution (P-BFD), or a WHR higher than 0.85 (n = 12), thus having abdominal body fat distribution (A-BFD). A group of seven normal weight healthy women served as controls. All subjects underwent the following protocol study that included 1) measurement of daily urinary free cortisol excretion rate; 2) a CRF test (human CRF, 1 microgram/kg BW, as iv bolus), with blood samples taken at regular intervals for ACTH and cortisol determination; and 3) an ACTH test, performed by administering two boli of ACTH (Synacthen, 0.2 microgram/kg BW, iv), at 90-min intervals, with blood samples taken for cortisol determination. Each woman also had a control saline study. Basal levels of both ACTH and cortisol rose significantly after CRF administration in all groups, but this increase was significantly higher in A-BFD than in P-BFD and control women. A significant correlation was found between the incremental area of cortisol and that of ACTH during the CRF test (r = 0.502), but not between these parameters and WHR values. Although the cortisol increase after the ACTH test was higher in A-BFD than in the other groups, these differences were only significant at 60 min during the test and when the analysis for repeated measures was applied. On the contrary, the incremental cortisol area after the ACTH test was not significantly different in the three groups. Moreover, it was not significantly correlated with the incremental cortisol area after CRF test or WHR values. Daily urinary free cortisol excretion rates (per g creatinine), however, were significantly higher in A-BFD than in P-BFD and control women. These results, therefore, suggest that obese women with A-BFD may have hyperactivity of the hypothalamic-pituitary-adrenal axis. This abnormality could be central in origin, due to hypersecretion of CRF or ACTH; alternatively, it could represent an adaptive phenomenon secondary to a state of functional cortisol resistance.

Urinary free cortisol versus 17-hydroxycorticosteroids: a comparative study of their diagnostic value in Cushing's syndrome.

We evaluated the usefulness of the basal urinary 24-h excretion rates of free cortisol versus 17-hydroxycorticosteroids in the diagnosis of Cushing's syndrome. On an outpatient basis, both urinary free cortisol and 17-hydroxycorticosteroids levels were determined in 48 patients with Cushing's syndrome, as well as in 95 obese and 94 healthy control persons of normal weight. Determination of the urinary free cortisol content allowed a clear-cut distinction between the patients with hypercortisolism and the controls, resulting in a sensitivity of 100% and specificity of 98% for the diagnosis of Cushing's syndrome. The diagnostic accuracy of urinary free cortisol was distinctly superior to that of 17-hydroxycorticosteroids, which showed a wide overlap of values between the groups, with a sensitivity of 73% and a specificity of 94%. In conclusion, the measurement of basal urinary free cortisol provided an excellent diagnostic sensitivity and specificity in the assessment of adrenocortical function. This simple and accurate test thus seems to be particularly useful in the outpatient evaluation of patients with suspected Cushing's syndrome.

Metabolism of cortisol in anorexia nervosa

In patients with anorexia nervosa 24-h mean plasma concentration of cortisol were 0.44 +/- 0.09 mumol/l (normal less than 0.28 mumol/l). Following stimulation by ACTH (1-24) urinary excretion rates of cortisol were stimulated from 0.22 +/- 0.08 to 4.85 +/- 2.78 mumol/24 h. Similarly, plasma concentrations of the glucocorticoid metabolite, tetrahydrocortisone, increased from 23.3 +/- 9.0 to 47.3 +/- 30.2 nmol/l; urinary excretion rates of tetrahydrocortisone increased from 3.61 +/- 0.90 to 8.40 +/- 1.72 mumol/24 h. The relative share of the sulphate, glucuronide and free fractions of tetrahydrocortisone in the patients' urine did not indicate any defect in metabolization of this steroid metabolite. Excretion rates of the four glucocorticoid tetrahydro-metabolites, tetrahydrocortisone, allotetrahydrocortisone, tetrahydrocortisol, and allo-tetrahydrocortisol, expressed as percent of total steroid excretion, were similar in patients with anorexia and in healthy women under basal conditions (24 +/- 6 vs 23 +/- 6%) and during stimulation by ACTH (1-24) (36 +/- 10 vs 45 +/- 6%). The share of the two androgen metabolites, androsterone and etiocholanolone, was 24 +/- 5% of total steroid excretion (basal; healthy women: 27 +/- 8%) and 13 +/- 2% (ACTH stimulation; healthy women: 12 +/- 4%) in patients with anorexia nervosa. Thus, analysis of urinary steroid excretion rates did not indicate a shift in adrenocortical function. The results confirmed enhanced secretion of cortisol in patients with anorexia nervosa under basal conditions and during/following stimulation by ACTH. The ACTH-induced increase in the concentrations of the tetrahydro-glucocorticoid metabolites in urine was less pronounced than that of cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

The physiological measurement of acute stress (public speaking) in bank employees

An evaluation of a number of non-invasive physiological measures of stress was conducted, using bank employees attending a two-weak residential course. The stressor involved was the preparation and delivery of a 15-min public lecture. The physiological parameters measured were urinary excretion rates of noradrenaline (NA), adrenaline (A), dopamine and cortisol, the ratio of NA/A, salivary cortisol levels, heart rate and blood pressure. Measurements were taken at 08.30, 10.30, 12.30, 15.30 and 17.30 h on the day of the public lecture and on the following (control) day. The public lectures were given between 10.30 and 12.30 h. The urinary excretion rates of adrenaline and cortisol were significantly elevated immediately following, but not before, the public lectures. The ratio NA/A was significantly decreased and the salivary cortisol levels were significantly increased both immediately before and after the public lecture. Urinary excretion rates of noradrenaline and dopamine, blood pressure and heart rate were unchanged by the stressor. Measurement of salivary cortisol levels, as well as providing a simple, stress free, non-invasive collection procedure, more closely reflects in time the changes in plasma levels of the hormone, not suffering from the large lag-time involved with urinary hormone measurements. Salivary cortisol measurement would appear to be the measurement of choice in human stress studies where individual stress factors are to be identified and studied. The significance of the stress-induced elevation in cortisol and catecholamine levels in the link between illness and occupational stress is discussed.

Urinary cortisol excretion and mood ratings in aircraft cabin crew during a tour of duty involving a disruption in circadian rhythm

A psychophysiological study was carried out on 28 cabin crew, comprising two teams, who were to travel from Sydney to Los Angeles and return, with stopovers in Los Angeles of 58 and 82 hr respectively. Every urine sample for a period of nine days, commencing 2 days before the flight, was collected. The volume and time the sample was passed were recorded so that urinary cortisol secretion rates could be calculated. Mood was also rated on a scale scored 0–9 at the same time the urine sample was collected. A control group matched for age, sex ratio, and degree of manual labour involved in their occupation, but not involved with the flights, was included in the study for comparison. On the basis of urinary cortisol excretion rates, the crews in Sydney before the flight and in Los Angeles were more highly stressed than the control group. The urinary cortisol excretion rates were significantly greater than those of the control group in Sydney before the flight, in Los Angeles, and during the return flight, but not on the flight on. The high excretion rates before the flight were attributed to an apprehension factor, whereas the elevated values in Los Angeles and during the flight back were attributed to a disruption in circadian rhythm. A factor analysis of mood ratings showed three major factors assessing vitality, distress, and relaxation. Analysis of variance of the mood ratings showed significant changes over the tour of duty for 13 of the 14 moods.

20-Dihydroisomers of Cortisol and Cortisone in Human Urine: Excretion Rates under Different Physiological Conditions

The urinary excretion rates of free cortisol and cortisone as well as of their 20-dihydroisomers have been studied in normal subjects under different physiological or pharmacological conditions. For the estimation of steroid excretion rates, a fully automated, liquid-chromatographic method was used. In normal subjects, the median steroid excretion rates of free cortisol, cortisone, 20-alpha-dihydrocortisol, 20-beta-dihydrocortisol, 20-alpha-dihydrocortisone and 20-beta-dihydrocortisone were 6.7, 8.0, 9.8, 5.2, 5.7 and 1.3 mumol/mol creatinine. The excretion rates measured at three different intervals of the day followed a circadian rhythm similar to that known for the cortisol secreting activity of the adrenal gland. After adrenal stimulation by i.v. application of 250 micrograms of tetracosactide hexaacetate, (Synacthen, corticotropin beta 1-24) excretion of urinary cortisol was significantly higher than those of the other steroids. During a 24 h infusion of corticotropin beta 1-24, the excretion rates of cortisol and its C-20 reduced isomers increased to a significantly greater extent than those of cortisone and its C-20 reduced isomers. During a four-hour infusion of hydrocortisone, the relative increase of cortisol excretion was greater than that of the other steroids. During a five-hour infusion of metyrapone at different dosages, the excretion of all steroids decreased in a dose-dependent manner. The present data indicate that the 20-dihydroisomers of cortisol and cortisone in human urine primarily originate from the peripheral metabolism of cortisol rather than from adrenal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Occlusal dysfunction and stress. An experimental study in macaque monkeys.

A dysfunctional occlusal relationship was produced in six macaca irus monkeys by insertion of occlusal splints which raised the vertical dimension of occlusion by 3--4 mm and incorporated interferences into the occlusion. Cortisol levels of plasma and 24 h urine samples were measured by competitive protein-binding analysis. After insertion of the splints there was an immediate, approximately two-fold rise of the mean 24 h urinary cortisol excretion rate and a significant decrease of urinary volume and body weight. The plasma cortisol level did not rise significantly. During the 3 weeks experimental period the teeth showed increasing mobility and occlusal wear facets developed on the splints. Urinary cortisol excretion rates were significantly elevated throughout the experimental period. Urinary cortisol levels declined to basal values when the splints were removed. This animal model produces experimental evidence in support of the hypothesis that a dysfunctional occlusal relationship may result in bruxism associated with emotional stress.

Diurnal Patterns and Regulation of Cortisol Secretion in Pregnancy*

Plasma concentrations of cortisol and corticosteroid-binding globulin are elevated substantially in pregnancy; only the free cortisol fraction is biologically active. Previous suggestions that plasma free cortisol increased above nongravid levels in pregnancy were difficult to reconcile with the absence of manifestations of hypercortisolism. Furthermore, any such elevation should be associated with some alteration in the regulation of cortisol secretion. Therefore, the physiology of cortisol secretion was studied by measuring plasma cortisol at 20-min intervals for 24 h. Free cortisol levels were evaluated by determining the plasma free cortisol index and the rate of urinary cortisol excretion. Circadian cortisol patterns in pregnant and nonpregnant subjects were virtually identical, but total plasma cortisol was significantly higher in pregnancy. Calculated plasma biological half-lives and production rates of cortisol were increased significantly in gravidas (t½: pregnant, 104.6 min; nonpregnant, 69.5 min; daily production rate: pregnant, 28.0 mg; nonpregnant, 11.2 mg). Such increases should produce rises in plasma free cortisol, an assumption supported by finding elevations of the free cortisol index in gravidas at 0800 and 2400 h (pregnant, 14.9 ± 1.9 and 3.3 ± 0.2; nonpregnant, 4.0 ± 0.6 and 1.2 ± 0.3) and elevations of the 24-h urinary cortisol excretion rate. Normal circadian rhythmicity despite elevated free cortisol suggests that maternal hypothalamic-pituitary regulation is altered. Resetting of feedback and lack of manifestations of hypercortisolism could be explained by tissue refractoriness to the effects of cortisol in pregnancy.

A 3-month study in monkeys of occlusal dysfunction and stress.

A dysfunctional occlusal relationship was produced in six Macaca irus monkeys by insertion of occlusal splints in the maxilla which raised the vertical dimension of occlusion by 3-4 mm and incorporated interferences into the occlusion (test side). Cortisol levels of plasma and urine were measured by competitive protein binding analysis. At week 1 and week 3 after insertion of the splints there was a significant increase of 24 h urinary cortisol excretion rate and plasma cortisol concentration, indicating emotional stress. Furthermore, there was evidence of acute trauma from occlusion of the mandibular teeth of the test side, including a significant increase of tooth mobility and GI; radiographically there were signs of breakdown of margial and interradicular alveolar bone. One animal developed periodontal pockets of 4-5 mm adjacent to the teeth of the test side. At week 6 and week 12 urinary and plasma cortisol levels had declined to basal values whereas tooth mobility, GI and PI remained elevated. There was no clinical or radiographic evidence of further loss of bone or increase of pocket depth adjacent to the teeth of the test side during the latter part of the experimental period. The results suggest that emotional stress may be involved in periodontal reactions associated with acute trauma from occlusion.

Urinary cortisol excretion rates and anxiety in normal 1-year-old infants.

Urinary cortisol excretion rates were determined for each voiding during 8 hours on 3 days for 20 infants. The first day served as the control. On the second day stress was imposed by having the mother leave the infant for an hour. On a third day the child was stimulated by novel toys and socialization for an hour in the mother's presence. There was no significant difference between mean cortisol excretion rates on control and stress days. Variability in cortisol levels was significantly greater on the day of stress than on the other 2 days. Ratings of separation anxiety and levels of cortisol excreted 40 to 160 min after the imposed stress were positively correlated (r = 0.46, P less than 0.01). Cortisol levels also differentiated between anxious infants who were agitated from those who were withdrawn. No altered levels of cortisol were associated with excitement.

Differences in perception between hypertensive and normotensive populations.

A group of hypertensive patients (N = 19) and a control group of normotensive patients (N = 15) were shown two movies depicting two types of doctor-patient interaction. In the first movie, the doctor was rude and disinterested in the patient (the bad doctor). In the second movie, the doctor was relaxed and warm (the good doctor). After viewing the two movies, all patients were interviewed as to their impressions of the two scenes. During the viewing, blood pressure and pulse rate responses in the hypertensive group were small but significantly greater than those in the normotensive group; during the interview, the significantly greater response in the hypertensives was physiologically meaningful. The urinary catecholamine and cortisol excretion rates were no different between the 2 groups. Most striking was the finding that the hypertensive group tended to deny seeing any differences between the doctors depicted in the two movies, while the normotensive group could clearly identify differences in the behavior of the good doctor versus that of the bad doctor. In a second experiment, the same movies were shown to a hypertensive group and to 3 normotensive groups. The patients were asked to fill out a questionnaire derived from auditing the tape recordings in the first experiment. This questionnaire made it possible to differentiate significantly between the hypertensive and normotensive groups. These data are compatible with the hypothesis that the hypertensive patient may perceptually screen out potentially noxious stimuli as a behavioral response to his hyperteactive pressor system.

GENETIC ASPECTS OF CORTISOL HYDROXYLATION IN GUINEA PIGS: URINARY EXCRETION AND PRODUCTION RATES OF CORTISOL AND 2-ALPHA-HYDROXYCORTISOL.

The mode of inheritance of the ability to form hydroxylated derivatives of cortisol (polar corticosteroids) in the guinea pig, with special emphasis given to 2α-hydroxycortisol, was studied. Two homozygous strains of short-haired English type guinea pigs differing greatly in this trait were crossed. The F1 generation exhibited polar corticosteroid excretion intermediate between that found in the parents but no significant difference in the excretion of cortisol. The F2 generation could be categorized (bringing the distribution of the F1 progeny into account) into 3 classes: low, medium and high hydroxycortisol excretors having a frequency consistent with the 1:2:1 genotypic ratio. Mating of a high excretor from the F2 generation with homozygous low excretors resulted in progeny of medium excretors. The fact that the ability to form hydroxycortisol derivatives is genetically determined suggests that the determination of urinary levels (or production rates) of these compounds may be useful in assessing the ...

Urinary cortisol excretion as a test of adrenal cortical function

Urinary Cortisol excretion rates have been measured before and during ACTH administration in normal subjects and in patients having or suspected of having adrenal cortical abnormalities. Patients with the following disorders were included in the study; Cushing's syndrome, idiopathic hirsutism, Stein-Leventhal syndrome, exogenous obesity, hypopituitarism, and Addison's disease. Patients with Cushing's syndrome had baseline Cortisol excretion rates 10 to 800 times the normal baseline values. This was true in some cases even though the baseline 17-ketogenic steroid excretion rates were normal or only slightly elevated. Those patients studied had a noticeably greater response than normal to ACTH, and in 2 patients the excessive excretion rate of Cortisol above their high baseline values continued for 1 or more days after intravenous ACTH was discontinued. The patients with adrenal-cortical adenomas had brisk increases in urinary Cortisol excretion rates during ACTH. Patients with “idiopathic” hirsutism had a greater than normal response to ACTH as measured by urinary Cortisol excretion rate. Two of 4 patients with Stein-Leventhal syndrome showed relatively little increase in urinary Cortisol excretion in response to ACTH. Ovarian resection in 1 patient had no influence on the responsiveness to ACTH; however, administration of estinyl estradiol for 2 weeks resulted in a normal increase in urinary Cortisol excretion in response to ACTH. Patients with exogenous obesity had normal baseline excretion rates of urinary Cortisol and the response to ACTH was normal.