Cortisol Activity Research Articles

Therapeutic Effect of Corticosteroids for Critical COVID-19 Patients

The rapid spread of severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection has resulted in an unprecedented public health, economic, and social crisis worldwide. As therapeutics that can effectively clear the virus and terminate transmission are not available, supportive therapeutics are the main clinical methods for Corona Virus Disease (COVID-19) including corticosteroids, respiratory support, and extracorporeal membrane oxygenation for salvage therapy, while subsequent agents and vaccine candidates are still under investigation. COVID-19 is a two-phase disease: in the early phase, the pathology of the virus dominates; in the later phase, Immunopathology drives the disease. Low-dose dexamethasone treatment suppresses COVID-19-related Immunopathology by complementing endogenous cortisol activity, while avoiding the adverse effects of high-dose glucocorticoids therapy. Corticosteroids, as one of the main means of anti-inflammatory adjuvant, are controversial about its role in the treatment of COVID-19. Here, we retrospectively evaluate the therapeutic effect of corticosteroids by comparing the clinical data of patients with or without corticosteroids therapy at different severity level.

Cortisol Receptor Sensitivity as a Risk Factor for Depression

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic‐Anterior‐Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).Our research has examined mutations known as single‐nucleotide‐polymorphisms (SNPs) relating to cortisol‐receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and depression. The relationship between SNPs relating to receptor sensitivity and depression in patients will be established by analysis of SNPs in coordination with data from psychological inventory assessments collected for each patient. Patient samples and clinical information was collected from adult patients diagnosed with depression by collaborating physicians. Quantitative polymerase chain reaction (qPCR) was used for genotyping. Analysis of the data yielded no significant correlation between SNPs relating to GR or MR and depression as scored by the Beck Depression Inventory (BDI). However one SNP in GR (rs33389) and one SNP on the 11β‐hydroxysteroid dehydrogenase type 1 gene (rs12086634) correlated with scores on the Mindful Attention Awareness Scale and State Trait Anxiety scale, respectively.Current studies focus on SNPs involved in the regulation of GR and MR activity that are not directly found in those receptors such as the FKBP5 GR co‐regulator protein. Investigating other non‐GR and MR SNPs could provide alternate explanations for cortisol sensitivity beyond the receptors themselves. In analyzing genetic differences relating to cortisol sensitivity in patients clinically diagnosed with depression, we aim to determine if an imbalance in an individual’s response to cortisol is linked to depression. If such a relationship can be established, this can provide physicians with a screening tool to better inform them of a patient’s risk factors for depression.

Using complexity science to understand the role of co-sleeping (bedsharing) in mother-infant co-regulatory processes

Human infants spend most of their time sleeping, but over the first few years of life their sleep becomes regulated to coincide more closely with adult sleep (Galland et al., 2012; Paavonen et al., 2020). Evidence shows that co-sleeping played a role in the evolution of infant sleep regulation, as it is part of an ancient behavioral complex representing the biopsychosocial microenvironment in which human infants co-evolved with their mothers through millions of years of human history (Ball, 2003; McKenna 1986, 1990). This paper is a conceptual, interdisciplinary, integration of the literature on mother-infant co-sleeping and other mother-infant co-regulatory processes from an evolutionary (biological) perspective, using complexity science. Viewing the mother-infant dyad as a “complex adaptive system” (CAS) shows how the CAS fits assumptions of regulatory processes and reveals the role of the CAS in the ontogeny of mother-infant co-regulation of physiological (thermoregulation, breathing, circadian rhythm coordination, nighttime synchrony, and heart rate variability) and socioemotional (attachment and cortisol activity) development.

Syndromes of Pseudo-Hyperaldosteronism.

Syndromes of Pseudo-Hyperaldosteronism.

THE STATE OF GLUCOCORTICOSTEROID BACKGROUND IN PATIENTS WITH VIRAL HEPATITIS DEPENDING ON THE ETIOLOGICAL FACTOR

Adrenal insufficiency in patients with a severe course of viral hepatitis is common and leads to unstable hemodynamics, liver failure and a high mortality rate. In many cases of severe course of viral hepatitis there is an increase in cortisol in the blood. Our studies assessed the level of cortisol and transcortin in patients with viral hepatitis. It was revealed that lack of functional activity of endogenous cortisol depends on decrease of transcortin level in blood. Free fraction of cortisol was more elevated in patients with HDV and HBV infection in comparison with patients with HCV infection and this increase was accompanied by lowering of transcortin in the blood.

Physical Fitness and Inflammatory Response to the Training Load of Wheelchair Rugby Players.

The aim of the study was the evaluation of the hormonal response of wheelchair rugby participants under the half-year training cycle. The study sample included 11 members of the Polish national wheelchair rugby team with spinal cord injury at the cervical level, ranging in age from 21 to 41 years, body weight (72.2 ± 11.53 kg), and body height (182.3 ± 6.11 cm). The disabled individuals with spinal cord injury subjected to the study constitute a homogeneous group in terms of age, body height, weight, and injury level. The study was carried out at the beginning and at the end of a 6-month training period. In the first and second examination, measurements of the peak oxygen uptake (peakVO2) and blood biochemical analysis were performed (Lactate dehydrogenase (LDH) activity and concentration of creatinine (Cr), total testosterone (TT), free testosterone (FT), and cortisol (C)). A significant change was observed in the concentration of C in the Wheelchair Rugby players’ blood between two research periods (p < 0.05 (ES:0.76)) and a correlation between the post-training change in FT/C concentration and the change in Cr concentration (r = −0.6014, p < 0.05). The 6-month training period did not result in overloads within the group of players. However, due to the significant loss of the capacity of the spinal cord injury (SCI) and the possibility of a life-threatening trend, the anabolic/catabolic status of the players should be monitored using blood biochemical indices.

Dietary glycine supplementation modulates antioxidant and immune responses of beluga, Huso huso, juveniles

Glycine is a non-essential amino acid used in fish nutrition, and possess several important roles in physiological process. Despite such functions, little is known about the glycine roles in fish, particularly in sturgeons. Therefore, the present study aimed at assessing the effects of dietary glycine supplementation on growth performance, antioxidant, and immunological parameters in beluga, Huso huso. Four hundred eighty fish (~ 48 g) were randomly distributed in 12 fiberglass tanks (1200 L) at a stocking density of 40 fish per tank. Four diets supplemented with 0% (control), 0.25% (Gly0.25), 0.5% (Gly0.5), and 1% (Gly1) glycine were offered to the fish (each diet to a batch of three tanks) for eight weeks at water temperature of 23.2 ± 0.70 °C. At the end of the feeding trial, the fish were blood-sampled for blood leukocyte count, plasma cortisol, glucose, triglyceride, cholesterol, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA), lysozyme, and alternative complement activity (ACH50) analysis. The results indicated there were no significant differences in the fish final weight (197–213 g; P = 0.511), weight gain (299–311%; P = 0.956) specific growth rate (2.46–2.52%/d; P = 0.944), feed conversion ratio (0.97–1.03; P = 0.863), protein efficiency ratio (2.29–2.45; P = 0.775), and survival (91.7–100%; P = 0.306) among the treatments. Plasma cortisol level significantly decreased in Gly0.25 treatment, compared to the control (24.7 vs. 28.8 ng/mL; P = 0.035). Plasma glucose levels exhibited significant (P < 0.001) elevation in Gly0.5 (51.0 mg/dL) and Gly1 (53.0 mg/dL) treatments, compared to the control (42.0 mg/dL). The treatment Gly0.5 showed significant elevations in blood leukocyte count (11.4 vs. 8.23 ×1000cell/µL; P = 0.032), plasma triglyceride (581 vs. 410 mg/dL; P = 0.017), cholesterol (71.3 vs. 59.8 mg/dL; P = 0.011), GSH (2.67 vs. 2.21 mM/mL; P = 0.003), GPx (243 vs. 217 U/mL; P < 0.001), and MDA (123 vs. 99 mM/L; P < 0.001), compared to the control treatment. Plasma GR (P < 0.001) showed significant decrease in Gly0.5 (1154 vs. 1784 U/mL) and Gly1 (1171 vs. 1784 U/mL) treatments. Besides, Gly0.25 and Gly0.5 treatments showed significantly higher plasma lysozyme (45.8–45.9 vs. 36.5 U/mL; P = 0.001) and ACH50 (138–139 vs. 130 U/mL; P < 0.001), compared to the control. Based on the results, dietary glycine supplementation at 0.25–0.5% could suppress plasma cortisol levels and improve antioxidant and immunological parameters on beluga, although has no beneficial effects on the fish growth performance.

Assessment of salivary alpha-amylase and cortisol as a pain related stress biomarker in dogs pre-and post-operation

BackgroundThe use of salivary biomarkers has garnered attention because the composition of saliva reflects the body’s physiological state. Saliva contains a wide range of components, including peptides, nucleic acids, electrolytes, enzymes, and hormones. It has been reported that salivary alpha-amylase and cortisol are biomarkers of stress related biomarker in diseased dogs; however, evaluation of salivary alpha-amylase and cortisol pre- and post- operation has not been studied yet. The aim of this study was to evaluate salivary alpha-amylase and cortisol levels in dogs before and after they underwent surgery and investigate the association between the salivary alpha-amylase and cortisol activity and pain intensity. For this purpose, a total of 35 dogs with disease-related pain undergoing orthopedic and soft tissue surgeries were recruited. Alpha-amylase and cortisol levels in the dogs’ saliva and serum were measured for each using a commercially available canine-specific enzyme-linked immunosorbent assay kit, and physical examinations (measurement of heart rate and blood pressure) were performed. In addition, the dogs’ pre- and post-operative pain scores determined using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF) were evaluated.ResultsAfter surgery, there was a significant decrease in the dogs’ pain scores (0.4-fold for the CMPS-SF, p < 0.001) and serum cortisol levels (0.73-fold, p < 0.01). Based on their pre-operative CMPS-SF scores, the dogs were included in either a high-pain-score group or a low-pain-score group. After the dogs in the high-pain-score group underwent surgical intervention, there was a significant decrease in their CMPS-SF scores and levels of salivary alpha-amylase, serum alpha-amylase, and serum cortisol. Additionally, there was a positive correlation between salivary alpha-amylase levels and CMPS-SF scores in both the high- and low-pain-score groups.ConclusionsThe measurement of salivary alpha amylase can be considered an important non-invasive tool for the evaluation of pain-related stress in dogs.

Change in toddlers’ cortisol activity during a year in childcare. Associations with childcare quality, child temperament, well-being and maternal education

Elevated levels of the stress hormone cortisol have been found in toddlers in childcare. Measuring cortisol may provide an indication of children’s experiences in childcare and help to adjust practices better to their needs. To the best of our knowledge, toddlers’ cortisol levels in childcare have not yet been investigated longitudinally. Furthermore, it is unclear which child and childcare factors contribute to cortisol elevation in toddlers. Using linear mixed model analyses, we investigated the full-day cortisol activity (10.00 h, 15.00 h, 18.00 h) of 156 toddlers (81 female, 56 male) during a year in childcare (September, January, June). We also investigated child cortisol levels at home in January. In addition, we tested the relation between cortisol activity and changes in cortisol activity across the year and childcare quality, temperament, well-being in childcare, and maternal education. We found increasing evening cortisol levels through the year while controlling for age. Afternoon cortisol levels were stable, but above morning cortisol levels in September and January and only slightly below morning cortisol levels in June. At home in January, afternoon levels were significantly below morning levels. Higher well-being in childcare was associated with lower overall cortisol levels and less increase in evening cortisol levels through the year in childcare. Further, less active toddlers seemed to accumulate some stress during the childcare day, indicated by higher evening cortisol levels. Rising evening cortisol levels may indicate accumulating stress across the year. Results point toward childcare being demanding for toddlers and their need for consideration from caregivers and parents, also after a longer period of childcare attendance. The findings underline the importance of observing, promoting, and further researching children’s well-being in childcare.

Cortisol changes in healthy children and adolescents during the COVID-19 pandemic

The Coronavirus Disease 2019 (COVID-19) pandemic has caused massive disruptions to daily life in the United States, closing schools and businesses and increasing physical and social isolation, leading to deteriorations in mental health and well-being in people of all ages. Many studies have linked chronic stress with long-term changes in cortisol secretion, which has been implicated in many stress-related physical and mental health problems that commonly emerge in adolescence. However, the physiological consequences of the pandemic in youth remain understudied. Using hair cortisol concentrations (HCC), we quantified average longitudinal changes in cortisol secretion across a four-month period capturing before, during, and after the transition to pandemic-lockdown conditions in a sample of healthy youth (n = 49). Longitudinal changes in HCC were analyzed using linear mixed-effects models. Perceived levels of pandemic-related stress were measured and compared to the physiological changes in HCC. In children and adolescents, cortisol levels significantly increased across the course of the pandemic. These youth reported a multitude of stressors during this time, although changes in HCC were not associated with self-reported levels of COVID-19-related distress. We provide evidence that youth are experiencing significant physiological changes in cortisol activity across the COVID-19 pandemic, yet these biological responses are not associated with perceived stress levels. Youth may be especially vulnerable to the deleterious impacts of chronic cortisol exposure due to their current status in the sensitive periods for development, and the incongruency between biological and psychological stress responses may further complicate these developmental problems.

Sarcopenia in the setting of nonalcoholic fatty liver

Nonalcoholic fatty liver is a worldwide common problem with more prevalence in non-Asian populations that is closely correlated with the muscle-related disorder sarcopenia. The incidence of both health issues has been observed to be strongly interlinked where presence of one exacerbates the other. Nonalcoholic fatty liver disease (NAFLD) pathophysiology increases the muscle loss, while the onset of NAFLD in sarcopenic patients aggravates the liver problems as compared to non-sarcopenic patients. Scarcity of research on the subject provides very little evidence about the cause and effect of disorders. No FDA approved drugs are available to date for NAFLD and sarcopenia. Research is underway to understand the complex biochemical pathways involved in the development of both disorders. This review is a small contribution toward understanding sarcopenia in the setting of NAFLD that provides insight on the common pathophysiological profile of sarcopenia and NAFLD and portrays a novel way of delving into the subject by introducing the concept of cortisol crosstalk with the muscle-liver axis. Sarcopenia and NAFLD are considered metabolism-related problems, and cortisol, being a glucocorticoid, plays an important role in metabolism of fats, carbohydrates, and proteins. Cushing’s syndrome, characterized by abnormally elevated concentrations of blood cortisol/enhanced intracellular activity, shares many pathologic conditions (such as insulin resistance, metabolic syndrome, abnormal levels of specific cytokines, and obesity) with NAFLD and sarcopenia. Hence, cortisol can be a potential biomarker in sarcopenia and NAFLD. As cortisol activity at cellular level is controlled by 11β-hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/2) enzymes that convert inactive steroid precursor into active cortisol, these enzymes can be targeted for the study of sarcopenia and NAFLD. Combined studies on NAFLD and sarcopenia with respect to cortisol open a new avenue of research in the understanding of both disorders.

Mooseer (Allium hirtifolium) boosts growth, general health status, and resistance of rainbow trout (Oncorhynchus mykiss) against Streptococcus iniae infection

In large-scale aquaculture, the fast growth rate of fish is positively influenced by feed additives such as medicinal plants. This is however; infectious disease may reduce fish growth and cause devastating economic loss. The present study investigated in vitro antibacterial efficacy of Mooseer (Allium hirtifolium) extract against Streptococcus iniae and its in vivo effects on growth, biochemical parameters, innate immunity of rainbow trout (Oncorhynchus mykiss). Therefore, six experimental diets were designed to include different levels of Mooseer from zero (as control), 5, 10, 15, 20, and 25 g per kg diet respectively referred to as M1 to M5. Results from the antibacterial evaluation showed that Mooseer extract inhibits S. iniae growth with MIC and MBC values of 128 and 256 μg ml−1. Appreciable results were obtained in the groups supplemented with Mooseer. Mooseer enhanced growth performance, and modulated serum biochemical and immunological parameters (total protein, albumin, triglyceride, glucose, cortisol, cholesterol, lysozyme, Ig, ACH50, ALP, and protease activity), and liver enzymes (ALT, AST and ALP). The greatest effects were found for higher doses of Mooseer supplementation (M4 and M5). Meanwhile, results from the survival rate of fish challenged with S. iniae showed higher survival in M2 and M4 treatments. The present findings suggest the beneficial use of Mooseer in rainbow trout diet, with 20 g kg−1 inclusion as the recommended dose.

Contribution of the human cytochrome P450 2C subfamily to the metabolism of and the interactions with endogenous compounds including steroid hormones.

The objectives of this study were as follows: 1) to compare the metabolic activities of endogenous compounds and their effects on dopamine formation and hydroxylation of steroid hormones, mediated by human cytochrome P450 (CYP), including CYP2C9.1 and CYP2C19, as well as the variants CYP2C9.2 (Arg144Cys) and CYP2C9.3 (Ile359Leu); and 2) to assess the effects of steroid hormones on the activities of CYP2C9.1, CYP2C9.2, and CYP2C19 to estimate the contribution of the CYP2C subfamily to metabolism and drug-drug interactions of endogenous compounds. Dopamine formation from p -tyramine and 6β- and 21- (for progesterone) hydroxylation of testosterone, cortisol, and progesterone by CYP2C9 variants, CYP2C19, CYP2D6, and CYP3A4 were determined using HPLC. The effects of steroid hormones such as testosterone, cortisol, and progesterone on tolbutamide methyl hydroxylation mediated by CYP2C subfamily members were investigated. Only CYP2D6 catalyzed dopamine formation. The 6β-hydroxylation activities of testosterone, cortisol, and progesterone catalyzed by CYP2C9 variants and CYP2D6 were less than 5% of those by CYP3A4. Although cortisol did not inhibit tolbutamide methyl hydroxylation catalyzed by CYP2C9.1, CYP2C9.2, or CYP2C19 and testosterone did not inhibit CYP2C19 activity, the reactions catalyzed by CY2C9.1 and CYP2C9.2 were inhibited by testosterone. The inhibition of progesterone by CYP2C19 was stronger than that by CYP2C9.1 and CYP2C9.2. CYP2C9.1 and CYP2C19 noncompetitively and competitively inhibited tolbutamide methyl hydroxylation with inhibition constants of 43.2 μM and 1.03 μM, respectively. Clinical interactions among endogenous compounds would vary within the CYP2C subfamily, although the contribution of the CYP2C subfamily may be of minor importance for dopamine formation and the detoxification (6β-hydroxylation) of endogenous steroid hormones.

Altered relationship between cortisol response to social stress and mediotemporal function during fear processing in people at clinical high risk for psychosis: a preliminary report

Evidence suggests that people at Clinical High Risk for Psychosis (CHR) have a blunted cortisol response to stress and altered mediotemporal activation during fear processing, which may be neuroendocrine–neuronal signatures of maladaptive threat responses. However, whether these facets are associated with each other and how this relationship is affected by cannabidiol treatment is unknown. We examined the relationship between cortisol response to social stress and mediotemporal function during fear processing in healthy people and in CHR patients. In exploratory analyses, we investigated whether treatment with cannabidiol in CHR individuals could normalise any putative alterations in cortisol-mediotemporal coupling. 33 CHR patients were randomised to 600 mg cannabidiol or placebo treatment. Healthy controls (n = 19) did not receive any drug. Mediotemporal function was assessed using a fearful face-processing functional magnetic resonance imaging paradigm. Serum cortisol and anxiety were measured immediately following the Trier Social Stress Test. The relationship between cortisol and mediotemporal blood-oxygen-level-dependent haemodynamic response was investigated using linear regression. In healthy controls, there was a significant negative relationship between cortisol and parahippocampal activation (p = 0.023), such that the higher the cortisol levels induced by social stress, the lower the parahippocampal activation (greater deactivation) during fear processing. This relationship differed significantly between the control and placebo groups (p = 0.033), but not between the placebo and cannabidiol groups (p = 0.67). Our preliminary findings suggest that the parahippocampal response to fear processing may be associated with the neuroendocrine (cortisol) response to experimentally induced social stress, and that this relationship may be altered in patients at clinical high risk for psychosis.

Light colour affect the survival rate, growth performance, cortisol level, body composition, and digestive enzymes activities of different Snubnose pompano (Trachinotus blochii (Lacépède, 1801) larval stages

Snubnose pompano (Trachinotus blochii) are widely cultured in the world. Light colours are among factors affecting fish performance in captivity. Snubnose pompano larvae often reared under white light. However, no study supports its choice or informs the extent of its effect or its constituent colour. The study investigated the influence of green, blue, yellow, purple, and white lights on growth, survival, cortisol, body composition, and digestive enzymes activities of one-day post-hatch Snubnose pompano larvae reared in light magenta tanks under a photoperiod of 24 Light:0 Dark hours for 25 days. Overall, the best growth performance of snubnose pompano larvae was in purple and white, and green lights during early and late larval stages, respectively. White light promoted survival rate while that of green light reduced. Larvae were less stressed and had enhanced body contents under white and purple light environments. Purple and yellow lights influenced low trypsin and pepsin activities. The study reports for the first time the effect of the light colour environment on the digestive enzyme activities and body composition of the finfish larvae. Generally, the study provides novel insights on optimal light colour in the larval rearing protocol of this species. Through this study, the use of white light during the first feeding (zero to four days post-hatch) and purple light in later stages (five days post-hatch until metamorphosis) is encouraged while discourages green and yellow lights in the larval rearing of Snubnose pompano.

Changes in salivary proteome before and after cigarette smoking in smokers compared to sham smoking in nonsmokers: A pilot study.

INTRODUCTIONSmoking is the leading cause of preventable disease. Although smoking results in an acute effect of relaxation and positive mood through dopamine release, smoking is thought to increase stress symptoms such as heart rate and blood pressure from nicotine-induced effects on the HPA axis and increased cortisol. Despite the importance in understanding the mechanisms in smoking maintenance, little is known about the overall protein and physiological response to smoking. There may be multiple functions involved that if identified might help in improving methods for behavioral and pharmacological interventions. Therefore, our goal for this pilot study was to identify proteins in the saliva that change in response to an acute smoking event versus acute sham smoking event in smokers and non-smokers, respectively.METHODSWe employed the iTRAQ technique followed by Mass Spectrometry to identify differentially expressed proteins in saliva of smokers and non-smokers after smoking cigarettes and sham smoking, respectively. We also validated some of the salivary proteins by ELISA or western blotting. In addition, salivary cortisol and salivary amylase (sAA) activity were measured.RESULTSIn all, 484 salivary proteins were identified. Several proteins were elevated as well as decreased in smokers compared to non-smokers. Among these were proteins associated with stress response including fibrinogen alpha, cystatin A and sAA. Our investigation also highlights methodological considerations in study design, sampling and iTRAQ analysis.CONCLUSIONSWe suggest further investigation of other differentially expressed proteins in this study including ACBP, A2ML1, APOA4, BPIB1, BPIA2, CAH1, CAH6, CYTA, DSG1, EST1, GRP78, GSTO1, sAA, SAP, STAT, TCO1, and TGM3 that might assist in improving methods for behavioral and pharmacological interventions for smokers.

Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells.

Background: Resistance to antiproliferative chemotherapies remains a significant challenge in the care of patients with solid tumors. Glucocorticoids, including endogenous cortisol, have been shown to induce pro-survival pathways in epithelial tumor cells. While pro-apoptotic effects of glucocorticoid receptor (GR) antagonism have been demonstrated under select conditions, the breadth and nature of these effects have not been fully established.Materials and Methods: To guide studies in cancer patients, relacorilant, an investigational selective GR modulator (SGRM) that antagonizes cortisol activity, was assessed in various tumor types, with multiple cytotoxic combination partners, and in the presence of physiological cortisol concentrations.Results: In the MIA PaCa-2 cell line, paclitaxel-driven apoptosis was blunted by cortisol and restored by relacorilant. In the OVCAR5 cell line, relacorilant improved the efficacy of paclitaxel and the potency of platinum agents. A screen to identify optimal combination partners for relacorilant showed that microtubule-targeted agents consistently benefited from combination with relacorilant. These findings were confirmed in xenograft models, including MIA PaCa-2, HeLa, and a cholangiocarcinoma patient-derived xenograft. In vivo, tumor-cell apoptosis was increased when relacorilant was added to paclitaxel in multiple models.Conclusions: These observations support recently reported findings of clinical benefit when relacorilant is added to paclitaxel-containing therapy in patients with ovarian and pancreatic cancers and provide a new rationale for combining relacorilant with additional cytotoxic agents.

Prognostic Value of Cortisol Index of Endobiogeny in Acute Myocardial Infarction Patients.

Background and Objectives: Serum cortisol has been extensively studied for its role during acute myocardial infarction (AMI). Reports have been inconsistent, with high and low serum cortisol associated with various clinical outcomes. Several publications claim to have developed methods to evaluate cortisol activity by using elements of complete blood count with its differential. This study aims to compare the prognostic value of the cortisol index of Endobiogeny with serum cortisol in AMI patients, and to identify if the risk of mortality in AMI patients can be more precisely assessed by using both troponin I and cortisol index than troponin I alone. Materials and methods: This prospective study included 123 consecutive patients diagnosed with AMI. Diagnostic coronary angiography and revascularization was performed for all patients. Cortisol index was measured on admission, on discharge, and after 6 months. Two year follow-up for all patients was obtained. Results: Our study shows cortisol index peaks at 7–12 h after the onset of AMI, while serum cortisol peaked within 3 h from the onset of AMI. The cortisol index is elevated at admission, then significantly decreases at discharge; furthermore, the decline to its bottom most at 6 months is observed with mean values being constantly elevated. The cortisol index on admission correlated with 24-month mortality. We established combined cut-off values of cortisol index on admission > 100 and troponin I > 1.56 μg/las a prognosticator of poor outcomes for the 24-month period. Conclusions: The cortisol index derived from the global living systems theory of Endobiogeny is more predictive of mortality than serum cortisol. Moreover, a combined assessment of cortisol index and Troponin I during AMI offers more accurate risk stratification of mortality risk than troponin alone.

Cortisol activity partially accounts for a relationship between community socioeconomic position and atherosclerosis

Compared to others, individuals living in communities of socioeconomic disadvantage experience more atherosclerotic cardiovascular disease (CVD) and a greater extent of preclinical atherosclerosis. Although the mechanisms underlying these associations remain unclear, it is widely hypothesized that alterations in normative cortisol release from the Hypothalamic Pituitary Adrenal (HPA) axis may play a role in linking lower community socioeconomic position (C-SEP) to CVD risk. The current study examined this hypothesis in relation to a marker of preclinical atherosclerosis among 488 healthy midlife adults (30–54 years, Mean age= 43, 52% Female, 81% White). All participants were employed and without clinical CVD. C-SEP was estimated from census tract data, and atherosclerosis was measured as intima-medial thickness of the carotid arteries (cIMT) by duplex ultrasonography. Four indicators of HPA activity [cortisol at awakening and the cortisol awakening response (CAR), rate of diurnal decline in cortisol (diurnal slope), and total output expressed as area under the curve (AUC)] were derived from salivary cortisol measurements obtained from 5 samples on each of 3 working days. Path analyses were used to examine associations of C-SEP with cIMT and HPA activity and to test whether individual differences in HPA activity could account for any association of C-SEP with cIMT using bootstrapping (5000 iterations). All models were adjusted for age, sex, race, and composite measures of both individual-level socioeconomic position (income, education, occupation), and cardiometabolic risk (systolic and diastolic blood pressure, waist circumference, fasting lipids and glucose). Lower C-SEP was related to both greater cIMT (b = −0.004, p = .021) and a flatter diurnal slope of cortisol (b = −0.001, p = .039). An indirect effect showed attenuated diurnal slope to partially mediate the relationship between C-SEP and cIMT (95% CI = −0.0018 to −0.0001), and a residual direct effect of C-SEP on cIMT remained significant (95% CI = −0.0097 to −0.004). These results suggest that low C-SEP associations with preclinical atherosclerosis may be due in part to correlated variation in adrenocortical activity.

Interpreting Normetanephrines-the Significance of Clinical Context

Introduction: Pheochromocytoma ranges in presentation, but the diagnostic hallmarks are increased catecholamine secretion in patients with an adrenal mass. However, interpretation requires consideration of the clinical state. Case: A 60-year-old man presented with 6 months of episodic flushing, night sweats, fatigue, back pain, and 20-pound weight loss. Vitals were notable for hypotension and mild tachycardia. He was thin with evidence of hyperpigmentation. Contrasted CT showed 15 cm heterogeneous masses of both adrenals and a rib lesion. Plasma normetanephrines were elevated on two separate measures (526 and 1,398 pg/mL, nl <=148). Plasma metanephrines were normal. Urine normetanephrines were increased 4-fold (2,165mcg/g Cr, n 108–524). Labs noted low DHEA-S (2 mcg/dL, n 38–313), high ACTH (204 pg/mL, n 6–50), random cortisol (5.2 mcg/dL, n 3.5–18.3), undetectable aldosterone, and high plasma renin activity (83 ng/mL/h, n 2.9–10.8). Cortisol peaked at 6.7 mcg/dL 1 hour after 250mcg of cosyntropin. MRI revealed over 15cm infiltrating masses arising from adrenals with modest flare on T2 imaging. Dotatate PET/CT showed mild uptake of bilateral adrenals and metastases to liver and bone. He was started on steroid replacement and doxazosin for presumed pheochromocytoma.He was transferred to our facility where he remained hypotensive despite adequate glucocorticoid and mineralocorticoid replacement. Once stabilized, repeat plasma normetanephrines were insignificant (218 pg/mL, n 0–145) and chromogranin was normal (68 ng/mL, n<93). Biopsy of the rib lesion confirmed diffuse large B-cell lymphoma. Discussion: Pheochromocytoma classically presents in the outpatient setting with palpitations, diaphoresis, pallor, and paroxysmal hypertension. Rarely, it results in hypertensive emergencies requiring hospitalization. In patients with catecholamine excess and an adrenal mass, pheochromocytoma is usually suspected. 3-fold or more increases of normetanephrines or metanephrines above upper cutoffs are rarely false-positives. However, this assumes clinical stability. Sympathoadrenal activation is a physiologic response to acute illness. Metanephrines in critically ill patients without pheochromocytoma approached those of pheochromocytoma in one study. Levels normalized upon recovery from illness, highlighting the importance of verifying biochemistries once the patient is stable. The degree of elevation in normetanephrines seen in this patient was a physiologic response to adrenal insufficiency and clinical instability. Pathology confirmed lymphoma rather than pheochromocytoma for which he was started on chemotherapy. Conclusion: Elevated normetanephrines is an appropriate physiological response in the acutely ill. Careful consideration of the clinical picture in conjunction with biochemical data is critical.