Association Of Cortisol Levels Research Articles

Upregulation of Cortisol in Sepsis and Its Association with Markers of Hemostatic Dysregulation

Introduction:Sepsis is a life-threatening condition in which the host's response to a systemic infection contributes significantly to mortality. Patients with sepsis are at risk of developing a coagulation disorder leading to disseminated intravascular coagulation (DIC). In DIC, widespread activation of the coagulation cascade leads to microvascular thrombosis and organ failure. This consumes platelets and coagulation factors, putting the patient at risk for bleeding. Cortisol is a steroid hormone released in response to stress. Cortisol levels have been found to be increased in sepsis patients, and high cortisol levels have been correlated with increased mortality. However, the association of cortisol levels with the severity of coagulopathy in patients with DIC remains unclear. Cortisol levels may also be relevant to disease progression as a link between the stress response and the immune system. The purpose of this project is to assess the association of plasma cortisol levels with severity of coagulopathy in a population of patients with sepsis and clinically confirmed DIC. Furthermore, the association of cortisol with markers of hemostatic status, inflammation, and platelet function were also assessed.Materials and Methods:Citrated, de-identified plasma samples were collected from 52 adults with sepsis and suspected DIC at the time of ICU admission. Samples were collected at the University of Utah and transferred to LoyolaUniversity Chicago under an IRB approved protocol. Plasma samples from healthy individuals were acquired from a commercial source (George King Biomedical, Overland, KS). Samples were stored at -80˚C prior to analysis. Platelet count was determined as part of standard clinical practice. PT/INR and fibrinogen were measured using standard techniques on the ACL-ELITE coagulation analyzer. Cortisol, D-dimer, PAI-1, CD40L, inflammasomes (NLRP3), and microparticles were measured using commercially available ELISA kits and were performed according to the manufacturer's instructions. DIC score was calculated using the ISTH scoring algorithm. A score of 0-2 was classified as no DIC, 3-4 was classified as non-overt DIC, and 5 or greater was classified as overt DIC. Results were analyzed using GraphPad Prism.Results:Cortisol showed significant variation based on DIC status (Kruskal-Wallis ANOVA, p < 0.0001) . Patients with non-overt DIC and overt DIC exhibited significantly elevated cortisol levels compared to healthy controls (p < 0.0001 for both groups). Furthermore, cortisol levels showed significant variation amongst sepsis patients based on DIC score. Patients with sepsis and overt DIC had elevated cortisol compared to patients with sepsis and no DIC (p = 0.0069). Data is shown in Figure 1.Correlations were evaluated between cortisol and the hemostatic markers platelets, fibrinogen, INR, D-Dimer, and PAI-1 as well as with the inflammatory marker, inflammasomes (NLRP3) and the platelet markers CD40L and microparticles. Cortisol showed significant correlations with D-Dimer, PAI-1, and INR. (D-Dimer Spearman r = 0.480, p = 0.001; PAI-1 Spearman r = 0.415, p = 0.002; INR Spearman r = 0.305, p = 0.037). No significant correlations were observed between cortisol and the markers of inflammation or platelet activation.Conclusions:Cortisol showed a significant association with hemostatic status in a population of patients with sepsis and well-defined coagulopathy. Cortisol levels were significantly elevated in patients with overt or non-overt DIC compared to healthy individuals and in patients with overt DIC compared to those with sepsis without DIC. Cortisol also showed significant correlations with markers of hemostatic activation but not with markers of inflammation and platelet activation. This suggests that elevated levels of cortisol may play a specific role in the progression of hemostatic dysregulation observed in sepsis and DIC. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The association of cortisol levels with leukocyte distribution is disrupted in the metabolic syndrome

Leukocyte glucocorticoid sensitivity (GCS) pertains to the responsivity of leukocytes to the regulating actions of glucocorticoids, such as cortisol. Impaired endocrine regulation may link the metabolic syndrome (MetS) to the development of cardiovascular disease. We tested if the physiological association between endogenous cortisol levels and peripheral leukocyte composition becomes disrupted in individuals with MetS. MetS was assessed among 689 German industrial employees. The covariance between cortisol levels and hematologic parameters (i.e., proportions of neutrophils and lymphocytes) and their ratio was explored, which has been proposed as a proxy for GCS in vivo. Cortisol level before blood collection was assessed by repeated saliva collection, and the area under the curve was calculated. Linear regression models were adjusted for potential confounders including age, gender, BMI, income, and lifestyle factors. Cortisol levels did not differ between subgroups. Participants without MetS (n = 552) showed the expected association of cortisol with hematologic parameters (β = 0.207 to 0.216; p values < 0.001). No association (β = 0.078 to 0.083; p values > 0.10) was found among those with MetS (n = 137), consistent with a reduced GCS. Analyses of separate MetS components showed that reduced GCS was associated specifically with decreased high-density lipoprotein and elevated fasting plasma glucose. Utilizing a novel statistical approach to infer GCS, this study provided first epidemiological evidence of aberrant physiological regulation of leukocyte distribution by endogenous cortisol levels among individuals with MetS. These findings underline the idea that MetS may involve disruption of endocrine-immune regulation.

Cortisol levels among older people with and without depression and dementia.

Cortisol dysregulation has been reported in dementia and depression. Cortisol levels and its associates were investigated among older people living at home and in nursing homes, in a cross-sectional study. A sample of 650 older people, from the community (home and nursing homes) and specialized care (memory clinics and old age psychiatry wards), mean age 76.8 (SD = 10.3) (dementia n = 319, depression, n = 154, dementia plus depression n = 53, and reference group n = 124), was included. Assessment included the Mini Mental State Examination (MMSE), Cornell scale for depression in dementia, activities of daily living scales, and salivary cortisol. Number of drugs was registered. The results showed that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. Characteristics significantly associated with cortisol levels were higher MMSE score (in patients with dementia and co-morbid depression), male gender (in people with dementia), and number of medications (in the reference group). We conclude that the cortisol ratio was highest among patients with dementia and co-morbid depression in comparison to those with either depression or dementia and the reference group. The association of cortisol level with MMSE score among patients with dementia and depression could further indicate that increased stress is related to cognitive function.

Biologic effects of stress and bonding in mother-infant pairs.

Maternal stress in humans influences behavior of children and can be assessed using biological markers. Mothers and their one-month-old infants were recruited from an existing study to examine baseline maternal serum oxytocin and hypothalamic-pituitary-adrenal axis response to infant blood heel stick stress as measured by salivary cortisol in the dyads. Objectives were to explore (1) relationships between mother and infant cortisol levels, (2) gender differences in infant biologic cortisol response, and (3) the association of cortisol levels in the dyads and maternal oxytocin levels Forty-two mother-infant dyads provided biologic samples and self-report data. Maternal oxytocin samples were obtained. Initial salivary cortisol was assessed in both the mother and infant, followed by a heel stick blood draw. Twenty minutes later, salivary cortisol was collected again from dyads. Self-report measures were negative for depression and risk for childhood neglect. Although oxytocin and baseline cortisol in the infants was higher in mothers that did some breast-feeding, there was no statistically significant difference (p = 0.2 and p = 0.1, respectively). Analyses showed (a) higher baseline cortisol in mothers was related to higher baseline cortisol in infants (p ≤ 0.0001), (b) following the stressor, female infants had a larger positive change in cortisol, after adjusting for baseline cortisol (p = 0.045), and (c) there was no relationship between dyad cortisol levels and maternal oxytocin. Maternal and infant biologic stress measures are related. Female infants have a larger hypothalamic-pituitary-adrenal response to a blood draw stressor as measured by salivary cortisol than male infants.

Cortisol levels and metabolic parameters in middle- and advanced- age subjects: associations with age.

It has been reported that morning cortisol levels increase with age, although there is some controversy in the literature. The aim of this study was to examine associations of cortisol levels with advancing age in an elderly population and investigate possible interactions with metabolic and hormonal parameters. From 372 subjects initially evaluated, we studied 251 ambulatory subjects aged 51-90 yr, median 71 yr (169 women), all permanent residents of a small town in southern Greece. Anthropometric parameters, glucose, insulin, cortisol, and biochemical parameters were recorded. Fasting cortisol levels (08:00-09:00 h) varied between 150.9- 854 nmol/l (mean 362.4 nmol/l). A significant association was found between age and cortisol levels (Spearman's rho =0.170, p=0.01). There was a positive correlation between cortisol levels and creatinine (Spearman's rho =0.144, p=0.023), homocysteine (Spearman's rho =0.283, p<0.001) and a negative correlation with body mass index (Spearman's rho =-0.128, p=0.047). Multivariate analysis showed that when creatinine was taken into account, the association of cortisol with age and with homocysteine was no longer significant. When, however, diabetic subjects were included in the analysis, the adjusted for creatinine association of cortisol with age was significant (β=0.168, p<0.05). It is concluded that, in elderly ambulatory subjects, the reported associations between cortisol levels, age, and homocysteine may be affected by coexisting co-morbidities or possibly by a decline in renal function. In subsequent studies it is important that fasting glycemia is taken into account.