High Cortisol Excretion Research Articles

The Association of Cortisol Excretion with Weight and Metabolic Parameters in Nondiabetic Patients with Morbid Obesity

Introduction: Cortisol is involved in the regulation of gluconeogenesis and glucose utilization. In morbid obesity (MO), the association of cortisol excretion with metabolic parameters is not well-characterized. In our study, we evaluated cortisol excretion in nondiabetic subjects with MO and its effect on glucose metabolism. Methods: We included 1,249 nondiabetic patients with MO (79.8% females, mean BMI 44.9 ± 6.5 kg/m², mean age 38 ± 11 years). Anthropometric data and cardiovascular risk factors were assessed, and an oral glucose tolerance test for calculation of insulin resistance was performed. Cortisol excretion was assessed on 2 consecutive days (24 h urine specimens). Results: Regarding cortisol excretion, patients were divided into 3 tertiles (urinary cortisol ≤51.6, >51.6 and <117.6, and ≥117.6 μg/24 h, respectively). Patients in the highest tertile were younger (p = 0.003), more obese (BMI: p = 0.040), had lower diastolic blood pressure ([DBP]; p = 0.012), lower total (p = 0.032) and LDL cholesterol (p = 0.021), fasting (p = 0.049) and 2-h glycemia (p = 0.028), 2-h insulinemia (p = 0.020), and HbA1c (p < 0.001), and a higher estimated glomerular filtration rate (eGFR) (p < 0.001). The glucose (p < 0.001) and insulin (p = 0.011) area under the curve (AUC) were also lower. Urinary cortisol excretion adjusted for age, sex, and eGFR was positively correlated with body weight (BW, beta = 0.076, p = 0.004) and overall glucose tolerance (oral disposition index, beta = 0.090, p = 0.011), and negatively with HbA1c (beta = −0.179, p < 0.001), 2-h glycemia (beta = −0.075, p = 0.032), AUC glucose (beta = −0.103, p = 0.002), and DBP (beta = −0.139, p < 0.001). HbA1c, BW, and DBP remained significant after multivariable analysis. Discussion/Conclusion: Despite being more obese, patients with higher cortisol excretion have a more favorable metabolic profile. These results deserve further attention regarding the respective mechanisms.

278-OR: Increased Cortisol Excretion in Morbid Obesity Is Associated with Higher Body Weight but More Favorable Glucose Metabolism Parameters

Cortisol levels might be increased in obesity leading to enhanced gluconeogenesis and inhibited glucose utilization. Subsequent release of catecholamines might additionally promote obesity. In morbid obesity, the association of cortisol excretion to metabolic parameters is not well characterized. We included 1249 patients with MO (76.8% females, mean BMI 45.6± 6.2 kg/m², mean age 40±12 years). Anthropometric data and cardiovascular risk factors were assessed and a glucose tolerance test (oGTT) for calculation of Insulin Resistance and Sensitivity indices was performed. All patients collected 24h hour urine specimens to assess cortisol excretion on two consecutive days. Regarding cortisol excretion, patients were divided into three tertiles (fist&amp;lt; 39.1 µg/24h, second between 39.1and 139.9 µg/24h and third &amp;gt;139.9 µg/24h. Patients in the highest tertile had a higher BMI (p= 0.015) and waist circumference (p= 0.029), however, exhibited a lower diastolic blood pressure (p=0.001), 1-hour (p=0.001) and 2-hour glucose (p= 0.003) as well as HbA1c (p=0.047) values. Area under curve (AUC) for glucose (p&amp;lt;0.001) as well as insulin (p= 0.018) were lower, and HOMA-beta was increased (p=0.006). We did not find any differences regarding OGIS or QUICKI. In a correlation analysis, cortisol levels were inversely associated with glucose-AUC (r=-0.206; p&amp;lt;0.001), HOMA beta (r= 0.084; p= 0.005), BMI r= 0.099; p=0.002), glucose 1-hour (r=-0.107; p&amp;lt;0.001) and glucose 2-hour levels (r=-0.107; p&amp;lt;0.001). Despite being more obese, patients with higher cortisol excretion present with a more favorable metabolic profile compared to those with lower cortisol excretion. These results deserve further attention regarding the respective potential mechanisms. Disclosure J. Brix: None. E. Krzizek: None. A. Tura: None. G. Pacini: None. B. Ludvik: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Sanofi, Takeda Development Centre Europe Ltd. Research Support; Self; Akebia Therapeutics, Eli Lilly and Company, Novartis AG, Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp &amp; Dohme Corp.

Urinary free cortisol and androgens in the population—Hormone interactions and the relationship with body composition and bone status

ObjectiveAbnormal secretion of thyroid hormones, growth hormone, cortisol and androgens influences body composition. We hypothesised that higher cortisol excretion, in combination with higher androgen and IGF-I concentrations, had a synergistic, favourable effect on body mass and bone. Design, patients and methodsThis was a cross-sectional study on a population sample of 290 women and 93men. The mean age was 65.4±7.2yearsinwomen and 59.7±10.0yearsinmen. Body composition was assessed with bioimpedance, and skeletal health with calcaneal quantitative ultrasound and fracture rate. The influence of urinary free cortisol (UFC), serum DHEAs (women), testosterone (men), free T4andIGF-I on the outcome was studied with regression analyses adjusted for age and body mass index. ResultsIn women, higher concentrations of UFC, DHEAs, IGF-I and lower free T4, were associated with higher fat-free mass. Only a higher UFC concentration was associated with favourable calcaneal measurements. In men, higher testosterone was associated with higher fat-free mass and lower fat mass. Higher IGF-I concentration, but not UFC, was independently associated with higher fat-free mass in men. Interaction analyses did not reveal any additive effects of hormones on body composition or bone in either sex. In both men and women, only age was associated with osteoporotic fractures. ConclusionSerum concentrations of androgens together with IGF-I were positively associated with body composition in both sexes. Urinary cortisol was positively associated with fat-free mass and bone status in women only. Increasing age, but not hormones, was the major determinant of osteoporotic fractures in this population sample.

The association between urinary cortisol excretion and cardiovascular risk factors, bone status and quality of life in the population

ObjectivePatients with glucocorticoid excess have increased cardiovascular risk, decreased bone mineral density and impaired quality of life (QoL). The aim of this study was to evaluate the association between urinary cortisol excretion and cardiovascular risk factors, bone status and QoL in the population. We hypothesized that higher cortisol excretion was associated with adverse cardiovascular risk profile, worse skeletal health and QoL. Design, patients and methodsThis was a cross-sectional study including a population sample (n=348), aged 38–77years. The mean age in women was 64.0±8.5years (n=276) and 60.3±10.2years in men (n=72). The metabolic syndrome, body composition measured with bioimpedance, calcaneal quantitative ultrasound, fractures and QoL evaluated with the Nottingham Health Profile, Psychological General Well-Being (PGWB) and the Short Form 36 (SF-36) were studied. Urinary free cortisol (UFC) was measured using radioimmunoassay. ResultsUFC was higher in men (230±120nmol/L) compared to women (153±71; P<0.001) and decreased with increasing age (P<0.001). In a regression analysis, after adjustment for gender, age and body mass index, higher UFC was associated with higher fat-free mass (P<0.01), favourable calcaneal bone measurements (P<0.05), better general health measured with PGWB (P<0.01) and SF-36 (P=0.001) and tended to be negatively associated with the metabolic syndrome (P=0.07). ConclusionIn contrast to our hypothesis, UFC in the upper physiological range was associated with a favourable cardiovascular risk profile, bone measures and QoL.

The rate of urinary cortisol excretion at work is persistently elevated in women at familial risk for breast cancer

We recently reported that healthy women at familial risk for breast cancer (FH+) have higher urinary cortisol levels at work than women without familial risk (FH-). The purpose of this study was to evaluate whether this group difference persisted over a 1-month period. Subjects were healthy women (FH+, N = 42, age = 37.6 +/- 9.3, FH-, N = 93, age 38.4 +/- 9.0) employed primarily in clerical or technical positions at three medical centers in New York City who collected timed urine samples in three contrasting daily environments, at work ( approximately 11AM-3PM), home (approximately 6PM-10PM) and during sleep (approximately 10PM-6AM) on 2 mid-week workdays approximately 1 month apart. Two-way repeated measures ANOVA revealed that cortisol excretion differed across the environments (P < 0.001), and that there was also a significant interaction between daily environment and family history group (P < 0.049), such that FH+ women maintained higher cortisol excretion at work over the 2 days than FH- women. A Bland-Altman plot showed that both overall and by family history group, the rate of cortisol excretion at work was generally reproducible, although there was a heteroscadasticity in the relationship that likely reflected excessive stressfulness on one of the study days in a small minority of subjects. These results suggest that the presence of a potent background stressor (familial breast cancer risk) can influence more acute cortisol responses in daily life over time.

Low melatonin excretion during mechanical ventilation in the intensive care unit.

Biochemical markers for the circadian rhythm were studied in patients treated at the ICU (intensive care unit) of two regional hospitals. A normal rhythm is characterized by a relatively higher melatonin and a lower cortisol excretion at night. Disturbances affect sleep, mood and cognitive performance. All urine excreted between 07:00 and 22:00 hours (day) and between 22:00 and 07:00 hours (night) was collected and sampled throughout the entire ICU period (median, 10 days) in 16 patients for the excretion of 6-SMT (6-sulphatoxymelatonin), which is a metabolite of melatonin, and free cortisol. The overall excretion of 6-SMT was slightly lower and the cortisol excretion higher than reported for healthy reference populations. Mechanical ventilation was associated with a markedly lower 6-SMT excretion (median, 198 ng/h) compared with periods without such help (555 ng/h; P<0.0001), whereas infusion of adrenergic drugs increased the 6-SMT excretion (P<0.01). Five patients (31%) showed a virtually absent melatonin excretion for 24 h or more. The diurnal rhythms were consistently or periodically disturbed in 65% and 75% of the patients. These alterations cannot be explained by excessive exposure to light at night. In conclusion, there was hyposecretion of melatonin during mechanical ventilation, an overall high cortisol excretion and a disturbed diurnal rhythm of both of these hormones in most patients treated in two ICU departments.

Cognitive dietary restraint is associated with higher urinary cortisol excretion in healthy premenopausal women

Cognitive dietary restraint, assessed by the Three-Factor Eating Questionnaire restraint subscale, is associated with subclinical menstrual cycle disturbances. This association may be mediated by stress-activated cortisol release. We assessed whether 24-h urinary cortisol excretion differs between women with high and low restraint scores. Participants (aged 21.6+/-2.5 y; n = 62) with normal-length menstrual cycles and high (n = 33) or low (n = 29) restraint scores completed a questionnaire describing weight history, dietary practices, and exercise. Cortisol, calcium, and creatinine were measured in urine collected over 24 h on a day when all food and beverages were provided and measured. Previously, 3-d food records and anthropometric measurements were obtained. Age, height, weight, body mass index, and length of menstrual cycle were similar between groups. The reported amount of exercise was higher (3.4+/-1.7 compared with 2.2+/-1.8 h/wk; P<0.05) and energy intakes (assessed from 3-d and 24-h food records) were lower in the high- than in the low-restraint group. Ratios of urinary cortisol (nmol) to creatinine (mmol) were higher in the high-restraint than in the low-restraint group (42.9+/-12.9 compared with 36.3+/-8.9; P<0.05), whereas ratios of urinary calcium (mmol) to creatinine were lower (0.3+/-0.1 compared with 0.4+/-0.2; P<0.05) in the high-restraint group. Urinary cortisol was not associated with exercise, nutrient intakes, or anthropometric measurements. High dietary restraint scores are associated with urinary cortisol, a biological marker of stress, and high cortisol excretion may affect bone health. Our results suggest that further research is warranted to clarify these associations and to determine whether they persist over time.

Fecal corticoid metabolite measurement in the cheetah (Acinonyx jubatus)

This longitudinal study addresses the relationship of cortisol excretion to ovarian activity in captive female cheetahs. A radioimmunoassay was developed and validated to measure corticoid metabolite concentrations in feces. A restraint experiment was used to demonstrate that fecal cortisol is detectable following stressful episodes. In studies of 7 females, fecal cortisol output indicated that they could be placed into 3 different categories. Females of the high-in-cortisol category (∼200 ng/g feces, n = 2) were independently rated by caretakers as the most nervous individuals in the collection (n = 24). These females appeared to be compromised in their ovarian cycling, as indicated by fecal estrogen measurements. In contrast, reproducing females fell into the low and intermediate cortisol excretion categories. A non-cycling high-cortisol female had an episodic cycle following a period of relatively low (intermediate) cortisol levels, followed by resumption of acyclicity and high cortisol excretion. Stress and reproductive failure may, therefore, be associated in the female cheetah. The close proximity of conspecifics as a potential source of stress and, consequently, suppressed ovarian activity in some females is suggested by these results. Zoo Biol 16:133–147. 1997 © 1997 Wiley-Liss, Inc.

Patterns of cortisol and adrenaline variation in Australian aboriginal communities of the Kimberley region.

Urinary cortisol and adrenaline excretion rates were measured in three Australian Aboriginal communities in the Kimberley region in the north-west of the country. The three communities, Derby, Kalumburu and Kupungarri, differ in size and remoteness and some lifestyle parameters. Cortisol excretion rate is associated with age and urine flow rate, but there is no association with smoking or the consumption of alcohol. All three communities show very high cortisol excretion rates compared to a sample of UK (Oxford) residents and there are also differences between the three communities. Adrenaline excretion rate also shows associations with age and urine flow rate, but not with smoking. Aboriginal people in the Kimberley region excrete adrenaline at a slightly higher rate than that found in Oxford, which itself is high by world standards. There are no marked differences between communities in their adrenaline excretion rates. Alcohol drinkers in Derby, where alcohol is freely available, have higher adrenaline output than non-drinkers.

Increased neuroendocrine reactivity and decreased brain mineralocorticoid receptor-binding capacity in aged dogs.

The effects of aging on the regulation of the hypothalamus-pituitary-adrenocortical (HPA) system of the dog were investigated. For this purpose, we compared 11 healthy dogs, 11-14 yr old, with 14 young mature dogs, 18-24 months of age. Significantly higher basal HPA activity in the old dogs was indicated by their higher resting plasma concentrations of ACTH, alpha MSH, and cortisol over a 6-week period and higher cortisol excretion in 24-h urine. After stress by immobilization as well as by light electric foot shocks and after i.v. administration of 1 microgram/kg CRH, the old dogs had higher peak levels of ACTH and cortisol, but not of alpha MSH. The areas under the curve, corrected for the basal levels, for ACTH and cortisol after these challenges were also greater in the old dogs. The half-times to reach a 50% increment and a 50% decrement in the time-concentration curves of ACTH and cortisol were similar in old and young dogs. There were no differences between the old and young dogs in their response to i.v. administration of 0.01 mg/kg dexamethasone. The clearance of [14C]cortisol from plasma, as calculated in a two-compartment model, was significantly reduced in aged dogs. In the old dogs, the stress- and CRH-induced cortisol peaks were relatively higher than those of ACTH, and their adrenals weighed significantly more, suggesting chronic hyperadrenocorticotropism. Aging had a markedly different effect on the two types of corticosteroid receptors in brain and pituitary. The binding capacity of type II or glucocorticoid receptors (GRs) in the old dogs was unchanged compared with that in the young dogs in all investigated brain structures except the anterior pituitary, in which the number of GRs was increased up to 170%. Type I or mineralocorticoid receptor (MR)-binding capacity was largely decreased in the brain of old dogs. The MR levels in old dogs, expressed as a percentage of the corresponding levels in young dogs, were 34% in the dorsal hippocampus, 58% in the ventral hippocampus, 37% in the septum, and 54% in the hypothalamus. In the anterior pituitary, MR capacity was unchanged. There was no difference between Kd values of MR and GR binding in young and old dogs. We conclude that these aged dogs had elevated basal HPA activity, characterized by increased levels of basal ACTH and cortisol in plasma and of urinary cortisol excretion and by hyperreactivity of ACTH and cortisol secretion in response to challenge by stress or CRH.(ABSTRACT TRUNCATED AT 400 WORDS)

Urinary free Cortisol excretion shortly after ischaemic stroke

The cortisol axis and catecholamine excretion were studied in 20 patients within the first week after acute ischaemic stroke. Urine free cortisol and plasma cortisol levels after dexamethasone were significantly higher in stroke patients than in 80-year-old volunteers (n = 32; P = 0.03 and P = 0.003, respectively). Catecholamine excretion was found to be significantly correlated with urine cortisol concentration (r = 0.54, P less than 0.05) and limb paresis (r = 0.52, P less than 0.05). In a multiple regression analysis, urine cortisol values were shown to be positively associated with limb paresis (P = 0.003), disorientation (P = 0.03) and body temperature (P = 0.03). High cortisol excretion was associated with a poorer functional outcome in a discriminant analysis (P = 0.001). Thus acute ischaemic stroke is associated with an increased activity in the cortisol axis. This may have a number of negative effects on organ functioning, and is a predictor of a poorer functional outcome.

Effectiveness of defenses: A significant predictor of cortisol excretion under stress

Although stress theories assert that psychological characteristics influence illness through their effects on physiological reactions to psychosocial stimuli, it has been difficult to demonstrate substantial associations to support this contention. Effectiveness of defense (ED) is a clinical assessment based on emotional reaction to stress, disruption of physiological and social functioning, and the ability to mobilize additional defenses to deal with acute, superimposed stress. By convention, high scores on these assessments define ineffective defenses. In 6 of 7 samples studied to date, a significant ED-cortisol correlation was obtained (combined significance, p < 0.00006). The ED-cortisol correlation averaged r = 0.41 for the seven samples and evidence from two studies suggests that ED is particularly important during high stress. These findings indicate that ineffective defenses are associated with higher cortisol excretion and establish ED as a topic worthy of study in connection with psychosocial stress. Future research issues include determining the importance of individual components of the overall ED rating and ascertaining whether ED has other physiological correlates in addition to cortisol.