Cortisol Area Under The Curve Research Articles

Adrenal Glucocorticoid and Androgen Precursor Dissociation in Anorexia Nervosa

Anorexia nervosa is characterized by hypogonadism and relative hypercortisolemia. We have demonstrated that free testosterone levels are low in women with anorexia nervosa, with the lowest levels in those receiving oral contraceptives (OCPs), and that dehydroepiandrosterone (DHEA) sulfate is reduced only in those receiving OCPs. The aim of the study was to determine whether adrenal steroidogenesis dysregulation contributes to decreased androgen levels in anorexia nervosa. We conducted a cross-sectional study in a General Clinical Research Center. We studied 20 women with anorexia nervosa [10 women with anorexia nervosa receiving OCPs (AN+E) and 10 not receiving OCPs (AN-E)] and 20 healthy controls [10 healthy controls receiving OCPs (HC+E) and 10 not receiving OCPs (HC-E)]. We measured DHEA and cortisol levels in response to 250-microg cosyntropin stimulation after 1-mg overnight dexamethasone suppression. Mean basal and stimulated, peak stimulated, and area under the curve (AUC) cortisol levels were higher in AN-E than HC-E, but mean basal and stimulated, peak and AUC DHEA were comparable. Mean AUC and peak cortisol were higher and DHEA AUC was lower in AN+E than AN-E. However, after controlling for cortisol binding globulin levels, peak and AUC cortisol were comparable between AN+E and AN-E. After controlling for albumin levels, AUC DHEA was comparable between AN+E and AN-E. Adrenal glucocorticoid and androgen precursor secretion are dissociated in anorexia nervosa, with relative hypercortisolemia and a preservation of DHEA secretion. Reduced DHEA response to cosyntropin in women receiving OCPs is attributable to decreased albumin levels. In the setting of relative hypercortisolemia, reduced adrenal androgen precursor secretion is not a mechanism underlying low testosterone levels in anorexia nervosa.

Interleukin-6, Cortisol, and Depressive Symptoms in Ovarian Cancer Patients

Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients. Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP). Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005). These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.

Effects Of A Dual Challenge On Stress Hormones, Th1/th2 Cytokines, And Lymphocyte Responses In Firefighters

Absent from the literature is an examination of the effects of a dual mental and physical challenge on stress hormones cortisol (CORT), epinephrine (EPI), norepinephrine (NE), Th1 and Th2 cytokines (IL-2, IL-6), and lymphocytes (CD8, CD56) in firefighters. PURPOSE: The purpose of this study was to examine the changes in CORT, EPI, NE, IL-2, IL-6, CD8, and CD56 in firefighters exposed to a decision-making challenge (firefighting strategies and tactics drill) while participating in moderate intensity exercise. Furthermore, relationships among these variables were examined. METHODS: Nine professional firefighters (VO2max = 36.94 ± 5.60 ml/kg/min) were asked to participate in two exercise conditions on a cycle ergometer: 1) 37 min at 60% VO2max along with 20 min of mental stress (firefighting strategies and tactics decision-making challenge (FSC)), and 2) 37 min at 60% VO2max without FSC. Stress hormones and cytokines were obtained at 0 min (baseline), after 37 minutes of exercise, and at 30 and 60 min post-exercise. Lymphocytes were analyzed at 30 min and 37 min during exercise and at 60 min post-exercise. RESULTS: A significant condition by time interaction was revealed in EPI, NE, and IL-2 In addition, significant main effects for time were observed in CORT and CD56, whereas IL-6 and CD8 demonstrated no significant changes. EPI area under the curve (AUC) was correlated with NE AUC, CORT AUC, and peak CD56 (r = 0.72, r = 0.74, and r = 0.66, respectively). NE AUC was correlated with CORT AUC and peak IL-2 (r = 0.64 and r = 0.51, respectively). CORT AUC was correlated with peak CD56 (r = 0.65). IL-6 and CD8 were not related to any of the variables assessed. CONCLUSION: Firefighters participating in a firefighting simulation task (dual challenge) responded with elevations in stress hormones that are related to elevations in IL-2 (Th1) and not related to IL-6 (Th2). These results suggest that firefighting can activate the immune system in support of a response to a possible antigen invasion. However, it is likely that if these stress hormones remained elevated or increased further, a shift from Th1 to Th2 could occur, which may suppress immune function.

Stress responses in lambs castrated with three different methods

The present work was conducted to evaluate the animal response to stress in lambs caused by three different castration techniques. Forty-six male lambs aged 4-5 months were randomly allocated to one of four groups including Burdizzo (B), scrotal ablation (SA), orchiectomy (OR) and control handling (H). Local anaesthesia (lidocaine 2%) was administered in both spermatic cords and the scrotal neck of lambs before each treatment. Blood samples were collected at -30, -10, +1, +20, +40, +60, +120, and +180 minutes. Serum cortisol concentrations were determined using a competitive immunoassay and the area under the curve (AUC) was calculated for each lamb. The following biochemical parameters were assayed for each animal at each time point: alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and glucose (GLU). The time needed for total lesion resolution and weight gain of each animal was recorded. Orchiectomy elicits the greatest cortisol response, significantly greater than that seen in similarly handled controls (P≤0.01), Burdizzo and scrotal ablation groups (P≤0.05). The serum cortisol AUC was higher in the scrotal ablation group (P≤0.05) than controls, but lower than in the orchiectomy group (P≤0.05). The Burdizzo group didn’t differ from controls. Serum glucose levels of the castrated lambs differed significantly from the control group, following a trend similar to cortisol. No change was seen in ALT, AST, LDH or CK. No difference in weight gain was seen among the groups. Our results suggest that use of the Burdizzo is the preferable castration technique for adult lambs, while scrotal ablation is a valid surgical alternative to orchiectomy and permits more rapid wound healing that is ideal for extensive management where flocks are not under close observation.

Plasma profiles of adrenocorticotropic hormone, cortisol, α-melanocyte-stimulating hormone, and growth hormone in dogs with pituitary-dependent hyperadrenocorticism before and after hypophysectomy

The 6-h plasma profiles of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte-stimulating hormone (alpha-MSH), and GH were studied in 17 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and after hypophysectomy. The aim of the study was to investigate the relation between the hormone profile characteristics and recurrence of PDH after surgery. The hormones were secreted in a pulsatile fashion. The basal plasma cortisol concentration and area under the curve (AUC) for cortisol were significantly higher in the PDH cases than in eight controls. The characteristics of the plasma profiles of ACTH and alpha-MSH were not significantly different between the PDH cases and the controls. In the PDH cases, less GH was secreted in pulses than in the controls, but the difference was not significant. The basal plasma cortisol concentration, the AUC for ACTH and cortisol, and the pulse frequency of ACTH and cortisol decreased significantly after hypophysectomy for the group of PDH cases. The basal plasma concentrations of ACTH and alpha-MSH, the AUC for alpha-MSH, and the characteristics of the plasma GH profiles of the PDH cases remained unchanged after hypophysectomy. No pulses of alpha-MSH were observed after hypophysectomy. The co-occurrence between the ACTH and cortisol pulses decreased significantly with hypophysectomy. The postoperative pulse frequency of ACTH was the only characteristic with predictive value for the recurrence of PDH after hypophysectomy. The results of this study demonstrate that ACTH, cortisol, alpha-MSH, and GH are secreted in a pulsatile fashion in dogs with PDH. Hypophysectomy effectively reduces the secretion of ACTH and cortisol. The presence of ACTH pulses after hypophysectomy is a risk factor for the recurrence of hyperadrenocorticism.

61: Adolescent girls with conduct disorder: HPA axis reactivity in response to psychological stress

Previous work demonstrated HPA axis hypoactivity in the morning in girls with Conduct Disorder (CD) compared to girls with no psychiatric disorder. The purpose of this study was to further characterize HPA axis function in girls with CD, comparing them to girls who had no psychiatric illness (NC) and girls who had depression or anxiety (DEP). This report describes preliminary analyses on the first two sets of assays completed. Girls, ages 15-16 years old and in Tanner Stage V, were recruited from the community. The participants and a parent received a structured psychiatric diagnostic interview and girls were categorized into three groups: CD, n=22; DEP, n=7; NC, n=8. We used the Trier Social Stress Test (TSST) as the psychological stressor. Serum cortisol and plasma adrenocorticotropin hormone (ACTH) levels were assessed at the following times: −90, −60, 0, +15, +30, +60, and +90 minutes (0 was the beginning of the TSST). Response to the stressor was measured with area under the curve (AUC) analysis, and mean AUC was examined for a group effect. All the groups exhibited some activation of the HPA axis in response to the psychological stressor; ANOVA demonstrated a significant difference between the groups in both the ACTH and cortisol response (FACTH= 3.42; p = .05; FCortisol= 4.98; p = .01). Post-hoc analyses indicated that the girls with CD had mean AUC responses for both hormones that were significantly lower than those in the DEP group, but were not different from the NC group. The DEP group mean AUC for ACTH and cortisol were also significantly higher than those in the NC group. These preliminary findings suggest that girls with CD may have HPA axis responses to a psychological stressor that are similar to those found in girls without any psychiatric disorder. The high responsivity of the girls in the DEP group is somewhat surprising since previous studies have reported that adolescent depression is not associated with HPA axis abnormalities. All of our findings need to be further tested in a larger sample to insure generalizability. However, if we continue to find the same associations, this could have important implications in understanding the mechanisms underlying adolescent depression and anxiety in girls.

The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density

This study was designed to test the hypothesis that cortisol mediates the relationship between bone density and depression in postmenopausal women. Nineteen women aged 52-79 who had been assessed for bone mineral density by dual-energy x-ray absorptiometer (DEXA) were evaluated for depression and anxiety. Diurnal and stress-induced measures of salivary cortisol were obtained during the following week and at a laboratory session involving a speech task. Nine volunteers reported depression while 10 were never depressed. Ever depressed women had significantly lower total lumbar and right femur DEXA Z scores than never depressed (t(17) = 2.5, p = .019 and t(17) = 2.06, p = .05, respectively). Ever depressed women demonstrated a significant increase in salivary cortisol (area under the curve (AUC) = 27.83, SD = 37.64) compared to never depressed women (AUC = -13.34, SD = 19.55) (t(17) = -3.041, p = .007) during a psychological challenge. There were significant inverse relationships between salivary cortisol AUC values and bone density Z scores at every measured bone site. Mediation analyses suggest that 51 - 67% of the association between depression and bone density could be attributed to stress-induced changes in cortisol. Cortisol hypersecretion in response to stress may, in part, explain the impact of depression on bone density in post-menopausal women.

Cortisol Levels During an Oral Glucose Tolerance Test in Lean and Obese Women

Because of the similarities between Cushing’s syndrome and insulin resistance syndrome, cortisol metabolism in obesity has been investigated in numerous studies. Our study investigates serum glucose, insulin, and cortisol response to oral glucose stimulation in a group of obese and lean normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese [body mass index (BMI) 37.7 ± 6.3 kg/m2) and 14 lean (BMI: 21.5 ± 1.0 kg/m2) age-matched healthy premenopausal women were included in the study. Serum glucose, insulin, and cortisol levels were measured at 30-minute intervals during 120 minutes of oral glucose tolerance testing (OGTT). Mean serum glucose and insulin levels were significantly higher in the obese group compared with lean subjects, and cortisol levels were similar during OGTT. There was not a significant difference for cortisol area under the curve (AUC) during OGTT between the two groups. No correlation between cortisol AUC, insulin AUC, and glucose AUC was noted for both groups. During OGTT, a decrease in cortisol levels was observed in both groups. The decrement occurred at 30 minutes of the OGTT in the obese group and at 60 minutes of the OGTT in the lean group. At 90 and 120 minutes of the OGTT, serum cortisol levels were similar to basal levels in both the obese group and the lean group. Previous studies reported altered hypotalamic-pituitary-adrenal axis activity, altered levels of urinary cortisol excretion, and increased metabolic clearance of cortisol in obesity. In our study in obese women, the only detected difference from lean subjects was a quicker suppression and recovery in serum cortisol levels after glucose administration.

Disturbed Adrenal Function in Adolescents with Chronic Fatigue Syndrome

To investigate adrenal function in children and adolescents with chronic fatigue syndrome (CFS) compared with age-matched controls. Case-control study of low dose (500 ng/m2) synacthen tests (LDST) in 23 adolescents with CFS and 17 age-matched controls. Serum cortisol concentrations were measured at 5-min intervals from 10 to 45 minutes. Peak serum cortisol concentration, time to peak, rise in cortisol and area under the curve (AUC) were derived. Patients with CFS had significantly lower mean cortisol levels during the LDST (p <0.001), lower peak cortisol (p <0.025), reduced cortisol AUC (p <0.005) and longer time to peak cortisol (p <0.05). Abnormalities were seen in both sexes but were more pronounced in females. Unstimulated adrenal androgen and 17-hydroxyprogesterone concentrations were normal. Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands. The more pronounced effects in females may reflect differential central effects of stress on hypothalamic-pituitary-adrenal axis regulation between the sexes.

Adrenocortical responses to submaximal exercise in postmenopausal black and white women

The purpose of this study was to determine whether racial differences exist in the dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and cortisol concentrations of black and white postmenopausal women at rest and in response to submaximal exercise. Twenty-three postmenopausal women (13 white and 10 black) were studied on 2 occasions. On one occasion subjects rested quietly for 4 hours (control day), whereas on the other occasion after 50 minutes of rest, subjects exercised at 70% of V o 2 peak for 30 minutes on a cycle ergometer (exercise day). Blood was sampled at rest, during exercise, and during recovery and assayed for DHEA, DHEAS, and cortisol concentrations. Resting DHEA and cortisol concentrations and integrated area under the curve (AUC) were similar between the black and white women; however, the black women had lower resting DHEAS concentrations compared with the white women (DHEAS, black: 1.32 ± 0.29 v white: 2.18 ± 0.25 μmol · L −1, P < .05). Regardless of race, DHEA and cortisol AUC increased significantly above resting values ( P < .01), but the exercise AUC for DHEA and cortisol were not different between the black and white women (DHEA: 607 ± 133 and 824 ± 108 min × nmol · L −1; cortisol: 9,604 ± 1,247 and 8,076 ± 1,093 min × nmol · L −1, respectively). No exercise-induced change in integrated DHEAS AUC was found in either group. In conclusion, racial differences exist in the resting DHEAS levels of postmenopausal women, but with no racial differences in resting DHEA and cortisol concentrations. Race had no impact on these adrenal hormone responses to submaximal exercise.

Neuroendocrine Response to the Serotonin Agonist M-Chlorophenylpiperazine in Women with Menstrual Status migrainosus

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and luteal phases (LP: –4, –6) of the same menstrual cycle. Ten women with MSM (migraine attacks occurring within 2 days of the onset of menstrual bleeding but lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of the onset of menstrual bleeding with a typical duration of attacks) were studied. Six healthy women served as controls. Blood samples were taken at times –30, 0 and every 30 min over 4 h. Statistical analysis was performed using MANOVA followed by Duncan’s post hoc comparisons. We found that the PRL response to the m-CPP test was significantly blunted in MSM compared with MM and controls in both phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM (F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the other hand, the pattern of the plasma cortisol response to m-CPP was similar in MM and controls throughout the menstrual cycle. In addition, the basal plasma cortisol levels were significantly higher in MSM compared with controls (p < 0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased over time. Thus, no significant effect of the menstrual cycle phase and diagnosis on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p < 0.001) on %Δ_max plasma cortisol levels was evident and consistent with the lack of cortisol response to m-CPP in MSM during the FP and LP compared with MM and controls. A derangement in central 5-HT control of pituitary PRL, and even more so in cortisol release, is present in women with MSM, but not with MM, regardless of the phase of the menstrual cycle, suggesting the involvement of some 5-HT₁ and 5-HT₂ receptor subtypes in the occurrence of extremely severe migraine attacks triggered by menstruation.

Predicting cardiovascular risk factors from plasma cortisol measured during oral glucose tolerance tests

Increasing evidence suggests that activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to the pathogenesis of the metabolic syndrome and obesity. The mechanisms are unknown but may involve alterations in the metabolic responses to feeding that interact with the HPA axis. As it is known that plasma cortisol falls during an oral glucose tolerance test (OGTT), changes in cortisol measured during an OGTT may be altered in the metabolic syndrome. We measured changes in plasma cortisol during OGTTs in a large study of 593 men and women to determine correlates of changes in cortisol with features of the metabolic syndrome and the extent to which these relationships are confounded by obesity. In men and women, higher cortisol area under the curve (AUC) during the OGTT was associated with higher glucose AUC and higher systolic blood pressure. Higher cortisol AUC was associated with reduced insulin increment in men, but higher 2-hour insulin and insulin AUC in women. However, the decline in plasma cortisol after glucose administration was poorly predictive of features of the metabolic syndrome. Obesity was associated with lower cortisol AUC but not with percentage decline in cortisol. Plasma cortisol and obesity had independent effects on plasma glucose and were the strongest predictors of plasma glucose in multiple regression analysis. Measurements of plasma cortisol during the OGTT reinforce the previously observed relationships of activation of the HPA axis in the metabolic syndrome. However, the altered HPA response to feeding does not appear to be primarily responsible for HPA activation in subjects with the metabolic syndrome. © 2003 Elsevier Inc. All rights reserved.

Hormonal response of pregnant gilts fed a high fiber or a concentrate diet once or twice daily

The effects of fiber intake and feeding frequency on endocrine status were studied. Gilts were fed 2.2 kg d-1 of a concentrate diet (n = 6; 5.3% crude fiber) or 3.1 kg d-1 of a high-fiber diet (n = 7; 18.2% crude fiber) as of day 23 of gestation. For a 1-mo period, starting on day 60 of gestation, three or four animals within each dietary treatment received one daily ration at 0800 h while the others received two meals at 0800 and 1430 h. Feeding frequency was then reversed for the following 1-mo period. Jugular catheters were inserted on day 23 of each 1-mo period and serial blood samples were obtained from 0730 to 1630 h on day 25, to measure cortisol, insulin, glucose and free fatty acids (FFA). The mean of three samples obtained before the morning or afternoon mealtime was used to establish a preprandial baseline and samples thereafter were used to measure area under the curve (AUC) and maximal values. Fiber intake had no effect on any baseline values (P &gt; 0.1), but decreased overall insulin AUC (P &lt; 0.05) and glucose maximal values (P &lt; 0.05) and increased morning FFA AUC (P &lt; 0.05). Compared to one daily meal, twice daily feeding increased afternoon baseline cortisol (P &lt; 0.05) and decreased morning cortisol AUC and baseline FFA (P &lt; 0.001). It also increased afternoon insulin maximal values and AUC (P &lt; 0.05) as well as morning and afternoon maximal glucose (P &lt; 0.05) and decreased morning maximal FFA (P &lt; 0.05). Insulin was the only variable affected by the fiber intake × number of meals interaction with twice daily feeding lowering morning maximal (P &lt; 0.05) and AUC (P &lt; 0.001) values in concentrate-fed gilts while not altering those values in gilts fed a high-fiber diet. Addition of fiber to the diet of pregnant gilts altered their hormonal response to meals, while once daily feeding created a post-absorptive state in the morning and increased cortisol concentrations postprandially. Key words: Gestation, pigs, fiber intake, feeding frequency, insulin, glucose

Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination

There are many reports of psychological morbidity in spousal carers of patients with dementia. The consequences of this increased stress on the immune system are unclear. We investigated whether antibody responses to influenza vaccination differed between carers and a control group, and the relation of the antibody response to the hypothalamic-pituitary-adrenal (HPA) axis. 50 spousal carers of dementia patients, median age 73 years (IQR 66-77), and 67 controls (68 years [66-71]) of similar socioeconomic status were enrolled. Anxiety and depression were measured by the Savage Aged Personality Screening Scale and stress by the Global Measure of Perceived Stress scale. Principal-component analysis was used to yield a summary score of emotional distress from these two scales. Salivary cortisol concentrations were measured over a single day at three times (0800-1000, 1100-1300, and 2000-2200). Participants received a trivalent influenza vaccine and IgG antibody titres to each strain were measured on days 0, 7, 14, and 28. Mean scores of emotional distress were significantly higher in carers at each time point than in controls (all p<0.0003). Mean (SD) salivary cortisol concentrations, calculated as area under the curve (AUC), were higher in carers than controls at all three assessments (6 months 16.0 [8.0] vs 11.2 [4.4], p=0.0001; respectively). Eight (16%) of 50 carers and 26 (39%) of 67 controls had a four-fold increase in at least one of the IgG titres (p=0.007). There was an inverse relation between AUC cortisol and IgG antibody titre to the Nanchang strain that was significant on day 14 (r=-0.216, p=0.039). Elderly carers of spouses with dementia have increased activation of the hypothalamic-pituitary-adrenal axis and a poor antibody response to influenza vaccine. Carers may be more vulnerable to infectious disease than the population of a similar age.

The combined dexamethasone/corticotropin-releasing hormone stimulation test is more closely associated with features of diurnal activity of the hypothalamo—pituitary—adrenocortical system than the dexamethasone suppression test

The dexamethasone suppression test (DST) is a widely used endocrine test in psychiatry, but was reported to not allow reliable inferences with regard to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system. We compared the association of the standard DST and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters of diurnal cortisol profiles. We performed a DEX/CRH challenge and 24-hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years) and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). A path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH status) to be dependent upon minimal 24-hour cortisol and evening frequency of pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST status) was related to 24-hour mean cortisol. Simple linear regressions supported an association of cortisol AUC with several parameters of the diurnal cortisol profiles, which was not true for the standard DST. We conclude that the combined DEX/CRH challenge test is more closely associated with the activity of the HPA system than the standard DST in healthy and depressed subjects.