Frequency of clinical signs in patients with Cushing's syndrome and mild autonomous cortisol secretion (MACS): Overlap is common.

BACKGROUND: Cushing's syndrome (CS) can be difficult to diagnose. A timely diagnosis, however, is the cornerstone for targeted treatment, to reduce morbidity and mortality. One reason for the difficulties to identify early on patients with CS might be the presence of a mild phenotype. The aim of the study was to classify the phenotypic landscape of CS. We studied patients with overt CS and mild autonomous cortisol secretion (MACS). METHOD: The study was part of the German Cushing's registry. Patients were prospectively included at time of diagnosis and the number of comorbidities and clinical signs and symptoms were assessed in a standardized fashion. 129 patients with CS (Pituitary CS, n = 85, adrenal CS, n = 32, ectopic CS, n = 12, respectively) and 48 patients with MACS were included. Patients with clinical signs and/or comorbidities typical for CS and at least two pathological screening tests were classified as having CS. Patients with a 1mg-low-dose-dexamethasone-suppresion-test above 1.8µg/dl without being clinically overt CS were classified as having MACS. RESULTS: On average, patients with CS had two comorbidities (range 1-3) at time of diagnosis (pituitary CS: 2 (1-3), adrenal CS: 3 (2-4), ectopic CS: 3 (2-4)). Patients with MACS, however, had three comorbidities (range 2-3). Hypertension was the most common comorbidity in all subtypes of CS (78-92%) and in patients with MACS (87%).Of a total of 11 clinical signs, patients with CS had on average five with 28% of patients having between 0-3 clinical signs, 50% 4-7 signs and 22% more than 7 clinical signs. Patients with MACS had on average two clinical signs (range 1-3) at time of diagnosis. CONCLUSION: The phenotypic landscape of CS is quite variable. The frequency of comorbidities is similar between patients with CS and MACS. A relevant number of patients with overt CS has just a few clinical signs. There is also an overlap in frequency of symptoms and clinical signs between patients with CS and MACS. According to the current guidelines, 96% of our patients with MACS fall into the category ""consideration of adrenalectomy". This should be kept in mind when making treatment decisions in the latter group of patients.

Hatha yoga reduces momentary stress but does not impact diurnal profiles of salivary cortisol and alpha-amylase: A randomized controlled trial.

Does the practice of yoga impact stress? Various studies have suggested that yoga may reduce both self-reported stress and stress biomarkers, but the evidence for such claims remains inconclusive, especially for yoga styles with a focus on physical postures. In a randomized controlled trial with 98 participants, we therefore examined whether an eight-week Hatha yoga intervention (60 min, 3×/week or more) led to reduced levels of diurnal salivary cortisol (sCort), salivary alpha-amylase (sAA), and subjective momentary stress as compared to a waitlist control group. To ensure the concomitant assessment of self-report and biological measures in an ecologically valid setting, and to capture the diurnal profile of cortisol and alpha-amylase, we employed an ecological momentary assessment approach. Five times per day, participants reported their momentary stress levels on a visual analogue scale and collected saliva samples for the assessment of salivary biomarkers. The intervention led to a significant reduction of subjective momentary stress but there was no change in diurnal sCort or sAA levels. There are several potential explanations for these findings: The intervention may have helped participants to cope better with stress while leaving diurnal levels of stress biomarkers unaffected, or the change may at least not have been reflected in sCort and sAA. Alternatively, there may have been a self-report bias, insofar as a favorable disposition towards yoga may have led participants to report reductions in stress in order to indicate positive effects of the intervention. Our findings contribute to a better understanding of the effects of distinct yoga interventions, demonstrating their potential to serve as low-risk stress relief tools.

Hypothalamic-pituitary-adrenal axis function in the offspring of parents with bipolar disorder and the impact of the family environment: A pilot study of the Reducing Unwanted Stress in the Home (RUSH) prevention program.

BACKGROUND: The home environment of offspring of parents with bipolar disorder (OBD) has been characterized by high levels of stress and disorganization, which may impact development of the hypothalamic-pituitary-adrenal (HPA) axis and their subsequent risk for affective disorders. The present study examined the effects of a family-based preventative intervention on the OBD's HPA axis functioning and whether intervention-related changes in the home environment might have driven change in the HPA axis. METHODS: Fifty-five children (6-11 years) were recruited from families having a parent with bipolar disorder (n=26) or families having two parents with no current mental disorders (n=29). Only those families with a parent having bipolar disorder participated in the preventative intervention. Both groups completed assessments at baseline, post-prevention, 3-, and 6-months post-prevention. At each assessment, family organization, control, cohesion, conflict, and expressiveness, in addition to childhood internalizing problems, were measured, and offspring saliva samples were collected across two consecutive days. RESULTS: Hierarchical Linear Modelling found no significant differences in HPA axis functioning between groups at baseline or across time. Improvements in family organization, however, were associated with elevations in participants' cortisol awakening response (CAR; p =.004) and total daily output (p =.023), and a steepening of their diurnal slope (p =.003) across time. Similar findings were obtained for family cohesion with respect to CAR (p <.001) and, to a lesser degree, diurnal slope (p =.064). DISCUSSION: HPA axis functioning did not differ between the OBD and healthy controls at baseline or in response to the preventative intervention. However, intervention-related improvements in family organization and, to a lesser degree, cohesion, were associated with adaptive changes in HPA functioning over time.

CO2 challenge-evoked hormonal changes predicting TSST changes in cortisol and subjective distress.

The importance of stressor response in relation to the development of psychopathology has been recognized for decades, yet the relationship is not fully understood. The Trier Social Stress Test (TSST) is an established conditioned stressor and frequently used to assess cortisol response to acute stress in different psychopathologies. The 35 % CO2 Challenge is a biological stressor and has mostly been utilized to assess subjective responses in anxiety related disorders. In the current study (N=189), we assessed the hormonal effects (cortisol, testosterone) and subjective distress (stress, anxiety, and fear) of the 35 % CO2 Challenge, and several days later, assessed the hormonal and subjective distress effects of the TSST in a mixed-sex, college-aged sample, to test for predictive effects of the 35 % CO2 Challenge on TSST-evoked outcomes. No testosterone by cortisol interaction effects were found in females. In males, the 35 % CO2 Challenge-evoked interaction of testosterone and cortisol predicted TSST-evoked subjective stress, anxiety, and fear, with higher concentrations of testosterone predicting subjective distress, but only at (relatively) low concentrations of cortisol (one standard deviation below mean concentrations). This result - in line with the dual-hormone hypothesis - suggests the 35 % CO2 Challenge could be utilized in a wider array of laboratory stress response research.

Do stress hormones influence choice? A systematic review of pharmacological interventions on the HPA axis and/or SAM system.

The hypothalamus-pituitary-adrenal axis (HPA axis) and the sympathetic-adrenal-medullary system (SAM system), two neuroendocrine systems associated with the stress response, have often been implicated to modulate decision-making in various domains. This systematic review summarizes the scientific evidence on the effects of pharmacological HPA axis and SAM system modulation on decision-making. We found 6375 references, of which 17 studies fulfilled our inclusion criteria. We quantified the risk of bias in our results with respect to missing outcome data, measurements, and selection of the reported results. The included studies administered hydrocortisone, fludrocortisone (HPA axis stimulants), yohimbine, reboxetine (SAM system stimulants), and/or propranolol (SAM system inhibitor). Integrating the evidence, we found that SAM system stimulation had no impact on risk aversion, loss aversion or intertemporal choice, while SAM system inhibition showed a tentative reduction in sensitivity to losses. HPA axis stimulation had no effect on loss aversion or reward anticipation but likely a time-dependent effect on decision under risk. Lastly, combined stimulation of both systems exhibited inconsistent results that could be explained by dose differences (loss aversion) and sex differences (risk aversion). Future research should address time-, dose-, and sex-dependencies of pharmacological effects on decision-making.

Disruptions to protein kinase A localization in adrenal pathology.

Cell signaling fidelity requires specificity in protein-protein interactions and precise subcellular localization of signaling molecules. In the case of protein phosphorylation, many kinases and phosphatases exhibit promiscuous substrate pairing and therefore require targeting interactions to modify the appropriate substrates and avoid cross-talk among different pathways. In the past 10 years, researchers have discovered and investigated how loss of specific interactions and subcellular targeting for the protein kinase A catalytic subunit (PKAc) lead to cortisol-producing adenomas and the debilitating stress disorder adrenal Cushing's syndrome. This article reviews classical studies regarding PKA localization in glucocorticoid-producing adrenal cells and synthesizes recent evidence of disrupted PKA localization and selective regulatory interactions in adrenal pathology.

The molecular genetics of adrenal cushing.

Adrenal Cushing represents 20% of cases of endogenous hypercorticism. Unilateral cortisol-producing adenoma (CPA), a benign tumor, and adrenocortical carcinoma (ACC), a malignant tumor, are more frequent than bilateral adrenal nodular diseases (primary bilateral macronodular adrenal hyperplasia (PBMAH) and primary pigmented nodular adrenal disease (PPNAD)).In cortisol-producing adrenal tumors, the signaling pathways mainly altered are the protein kinase A and Wnt/ß-catenin pathways. Studying components of these pathways and exploring syndromic and familial cases of these tumors has historically enabled identification of many of the predisposing genes. More recently, pangenomic sequencing revealed alterations in sporadic tumors.In ACC, mainly due to TP53 alterations causing Li-Fraumeni syndrome, germline predisposition is frequent in children, while it is rare in adults. Pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, MSH6, and PMS2, which cause Lynch syndrome or alterations of IGF2 and CDKN1C (11p15 locus) in Beckwith-Wiedemann syndrome, can also cause ACC. Rarely, ACC is described in other hereditary tumor syndromes due to germline pathogenic variants in MEN1 or APC and, in very rare cases, NF1, SDH, PRKAR1A, or BRCA2. Concerning ACC somatic alterations, TP53 and genetic or epigenetic alterations at the 11p15 locus are also frequently described, as well as CTNNB1 and ZNRF3 pathogenic variants.CPAs mainly harbor somatic pathogenic variants in PRKACA and CTNNB1 and, less frequently, PRKAR1A, PRKACB, or GNAS1 pathogenic variants. Isolated PBMAH is due to ARMC5 inactivating pathogenic variants in 20 to 25% of cases and to KDM1A pathogenic variants in food-dependent Cushing. Syndromic PBMAH may be due to germline pathogenic variants in MEN1, APC, or FH, causing type 1 multiple endocrine neoplasia, familial adenomatous polyposis, or hereditary leiomyomatosis-kidney cancer syndrome, respectively. PRKAR1A germline pathogenic variants are the main alteration causing PPNAD (isolated or part of Carney complex).

Role of interdependent self-construal in predicting acute salivary cortisol response, hair cortisol concentrations, and their associations.

Numerous studies have associated interdependent self-construal (InterSC) with heightened acute salivary cortisol stress responses in collectivist cultures. Hair cortisol concentration (HCC) is an important biomarker of chronic stress and is associated with acute salivary cortisol stress response. However, few studies have explored the association between InterSC and HCC. This study aimed to investigate the role of InterSC in the acute salivary cortisol stress response, HCC, and their associations. Seventy-seven healthy Chinese participants underwent assessments of InterSC, social anxiety, and HCC. The ScanSTRESS paradigm was used to induce an acute stress response and saliva samples were collected. These results replicated earlier findings showing that InterSC was associated with rapid salivary cortisol reactivity and recovery during acute stress. Additionally, InterSC was positively correlated with HCC, and social anxiety mediated this association. Importantly, InterSC moderated the HCC-acute salivary cortisol stress response association. Specifically, high HCC predicted a blunted acute salivary cortisol stress response in participants with low InterSC, including a slow salivary cortisol response during the acute stress reactivity phase and a small overall acute salivary cortisol response. However, this blunting effect was not observed with high InterSC participants, indicating that high InterSC buffered the blunting effect of HCC on the acute salivary cortisol stress response. In conclusion, this study provided new insights into how InterSC is associated with the hypothalamus-pituitary-adrenal axis stress system and revealed the dual-faceted role of InterSC for acute salivary cortisol stress and HCC.

Hormones, stress, and heart disease in transgender women with HIV in LITE Plus.

INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of death among transgender women and people with HIV. Exogenous estrogen and psychosocial stressors are known risk factors for CVD. Yet, few studies have used biomarkers to examine the role of stress in CVD risk among transgender women with HIV (TWHIV). This analysis examined whether stress moderates relationships between gender-affirming hormone therapy (GAHT) duration and CVD risk among TWHIV. METHODS: This cross-sectional analysis of baseline data from an observational cohort of 108 Black and Latina TWHIV in Boston, New York, and Washington, DC, enrolled December 2020 - June 2022, measured socio-demographics, medical diagnoses, medications, smoking history, and perceived stress via interviewer-administered surveys. Physiological stress was measured with 14 biomarkers to calculate allostatic load indices (ALI). Forty participants provided saliva samples used to calculate cortisol awakening response and cortisol daily decline. The 2018 American College of Cardiology revised pooled cohort equation estimated 10-year CVD risk. Data were analyzed in 2024. RESULTS: GAHT duration was positively associated with CVD risk scores in bivariate regression. In multivariable linear regression models (adjusting for age, income, education), only age and ALI remained significantly associated with CVD risk scores [ß 1.13, CI: 1.05, 1.21]. No stress measure significantly interacted with GAHT duration to affect CVD risk scores. In visual plots, GAHT duration increased CVD risk scores only for TWHIV experiencing the highest ALI. CONCLUSIONS: Stress plays an important role in CVD in TWHIV. More research is needed on non-GAHT factors, which influence CVD health among transgender women.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

PURPOSE: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. METHODS: A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. RESULTS: After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. CONCLUSION: The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

A novel model using leukocytes to differentiating mild autonomous cortisol secretion and non-functioning adrenal adenoma.

BACKGROUND: Mild autonomous cortisol secretion (MACS) accounts for a significant proportion of adrenal incidentaloma. Current endocrinological screening tests for MACS are complex, particularly in areas with limited medical resources. This study aimed to develop a diagnostic tool based on leukocyte-related parameters to differentiate between MACS and non-functioning adrenal adenoma (NFA). METHODS: Inthis retrospective case-control study, propensity score-matching was used to select 567 patients from a cohort of 1108 patients (201 MACS, 907 NFA). External validation cohort included 52MACS and 48 NFA from two hospitals, which did not overlap with the modeling cohort patients. Leukocyte-related parameters were evaluated, and the diagnostic efficacy of each parameter was assessed by calculating Youden's J index (J) and the area under the curve (AUC). The study population was divided into training and testing samples using a 10-fold cross-validation method. Machine learning (ML) and classification and regression tree (CART) model were established. RESULTS: After propensity score matching, 567 patients were enrolled, including 197 MACS and 370 NFA. With the exception of basophil percentage, all other parameters differed significantly between the two groups. Lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, and basophil percentage were lower in the MACS group compared to the NFA group. Eosinophils percentage demonstrated the highest AUC (0.650), with a sensitivity of 51.3% and specificity of 73.2%. The ML model, based on multiple parameters,exhibited better performance in diagnosing MACS (sensitivity 76%, specificity 77.4%, and AUC 0.818). A clinically usable CART model achieved an AUC of 0.872, with a sensitivity of 95% and a specificity of 75.7%.  In the validation cohort, the prediction accuracy of the ML model and the CART model were 0.784 and 0.798, respectively. CONCLUSION: TheCART diagnostic model, constructed based on leukocyte-related parameters, could assist clinicians in distinguishing between MACS and NFA.

Assessing the psychobiological demands of high-fidelity training in pre-hospital emergency medicine.

BACKGROUND: Individuals who provide critical emergency care mount rapid psychobiological responses when faced with an incident. These responses are adaptive and ensure resources at time of demand; however, frequent activation with minimal opportunity for recovery can have negative consequences for health and wellbeing. Monitoring individuals in real emergency situations would provide an understanding of their stress responses during the provision of critical care; however, this presents logistical challenges. An alternative is to assess individuals during high-fidelity training scenarios. This is the first comprehensive assessment of psychobiological responding during continuous high-fidelity training in pre-hospital emergency medicine. METHODS: A sample of doctors and paramedics (N = 27) participated during 10 days of training and a weekend of no activities. Training involved the acquisition of human factors, non-technical and surgical skills, and their application in complex high-fidelity scenarios including road-traffic accidents, firearms incidents, and swift water rescue operations. On each day participants reported levels of state, cognitive, and somatic anxiety, and self-confidence following waking and before sleep, and their anticipated (at wake) and experienced (before sleep) demands of the day. Saliva samples were obtained each day for assessment of diurnal cortisol indices and the Cortisol Awakening Response (CAR). Garmin smartwatches were worn throughout for the collection of heart rate and HRV-derived stress. RESULTS: There were significant (p < 0.001) differences across days for state, cognitive, and somatic anxiety; self-confidence; anticipated and experienced demands; aggregated measures of heart rate and HRV-derived stress; levels of cortisol at waking (p = 0.002) and for the CAR (p < 0.001). Measures of psychobiological responding during training were distinct from the weekend and the highest levels of psychobiological responding occurred on days characterised by greater anticipated and experienced demands. DISCUSSION: This high-fidelity training is typical of the day-to-day requirements of emergency services and these observations are representative of functioning during real-life critical care emergencies. Increased responding during times of demand is adaptive; however, frequent and sustained responding increases allostatic load and is a contributor to burnout. As burnout is a significant concern in emergency medicine, this study identifies patterns of responding and recovery that may impact upon longer-term health and wellbeing.

Maternal stress and the early embryonic microenvironment: investigating long-term cortisol effects on bovine oviductal epithelial cells using air-liquid interface culture.

The oviduct epithelium is the initial maternal contact site for embryos after fertilization, offering the microenvironment before implantation. This early gestation period is particularly sensitive to stress, which can cause reduced fertility and reproductive disorders in mammals. Nevertheless, the local impact of elevated stress hormones on the oviduct epithelium has received limited attention to date, except for a few reports on polyovulatory species like mice and pigs. In this study, we focused on the effects of chronic maternal stress on cattle, given its association with infertility issues in this monoovulatory species. Bovine oviduct epithelial cells (BOEC) differentiated at the air-liquid interface (ALI) were stimulated with 250 nmol/L cortisol for 1 or 3 weeks. Subsequently, they were assessed for morphology, bioelectrical properties, and gene expression related to oviduct function, glucocorticoid pathway, cortisol metabolism, inflammation, and apoptosis. Results revealed adverse effects of cortisol on epithelium structure, featured by deciliation, vacuole formation, and multilayering. Additionally, cortisol exposure led to an increase in transepithelial potential difference, downregulated mRNA expression of the major glucocorticoid receptor (NR3C1), upregulated the expression of cortisol-responsive genes (FKBP5, TSC22D3), and significant downregulation of oviductal glycoprotein 1 (OVGP1) and steroid receptors PGR and ESR1. The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells, indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine. The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2, an enzyme controlling the cellular capacity to metabolise cortisol. These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.

The Interactive Effects of Rejection and Rumination on Diurnal Cortisol among Adolescent Girls: A Preliminary Daily Diary Study.

Background: The perseverative cognition hypothesis stipulates that rumination (repetitive, passive, uncontrollable negative thinking) prolongs the experience of a stressor which impacts stress physiology. In line with this hypothesis, we proposed that in response to real-life experiences of social rejection, adolescent girls who ruminate would show a blunted diurnal cortisol slope the next day relative to girls who do not ruminate. We also examined the effects of social rejection and rumination on waking cortisol levels and the cortisol awakening response. Method: Participants were (n = 50) adolescent girls (mean age = 13.30, SD = 2.34) who varied on psychiatric risk and provided saliva samples 4 times a day for 3 days, as well as, daily diary reports of social rejection and rumination. A lagged multilevel model was utilized to examine the interactive effects of rejection and rumination on diurnal cortisol. Results: There was a significant interaction between social rejection and rumination. Specifically, rumination following social rejection was associated with a flatter diurnal cortisol slope. In the absence of rumination, social rejection was marginally associated with a steeper diurnal cortisol slope. The effects for waking cortisol levels and the cortisol awakening response were null. Conclusion: Findings support the perseverative cognition hypothesis and suggest that cognitive mechanisms such as rumination can impact stress physiology.

Higher hair cortisol levels associated with previous cardiovascular events and cardiovascular risks in a large cross-sectional population study.

BACKGROUND: Stress is today a common feature of patients seeking medical care and a growing public health issue in society. A method has been developed to measure biological chronic stress by Hair Cortisol Concentrations (HCC). This biomarker, for chronic stress, captures information about cumulative cortisol levels over the course of several months. Long-term stress might be one of the factors contributing to the onset of cardiovascular conditions and also affecting different risk factors. The aim of this study was to analyse the association between Hair Cortisol Concentrations and previous cardiovascular diseases and cardiovascular risk factors. METHODS: The method of measuring chronic stress by Hair Cortisol Concentration was applied in a large Swedish national observational cross-sectional study. A population-based random sample of N = 4,821 Swedish middle-aged men and women was analysed for hair cortisol levels in relation to diagnosed previous cardiovascular diseases and biologically measured cardiovascular risk factors. RESULTS: Long-term stress, measured by hair cortisol, was significantly associated with the classical cardiovascular risk factors hypertension and high cholesterol, but not smoking. Those with elevated HCC levels also had a significantly increased pre-history of myocardial infarction, type 2 diabetes, atrial fibrillation and by-pass surgery, but not regarding stroke, angina pectoris or sleep apnoea. Higher HCC was significantly associated (p < 0.001) with Body mass index and waist circumference, but only for females. HCC was also associated with the risk markers leukocytes, and high-sensitivity CRP, indicating a possible linkage between HCC and inflammation and hypothetically also the bodily immune defense. No association was found between perceived stress and HCC. CONCLUSIONS: An overall conclusion of our results is that health care should put more emphasis on patients reporting that they have been exposed to long term stress. Altogether, these analyses of Hair cortisol levels in a large middle-aged population show that chronically elevated cortisol levels represent a relevant and significant factor associated with cardiovascular diseases and classical cardiovascular risk factors.

A systematic review of associations between hormone levels in hair and peripartum depression.

Peripartum depression is a global health concern, characterized by mood disturbances inclusive of pregnancy through up to 12-months postpartum. Hormones play a vital role in pregnancy maintenance, fetal development, and labor and delivery and change significantly as a function of pregnancy and childbirth. However, such life sustaining changes may have consequences related to risk for peripartum depression. To date, most studies that have examined hormones in relation to peripartum depression have focused on blood or saliva sampling approaches, though hair analysis offers unique information on trajectories of hormone concentrations over more sustained periods of time (i.e., over months). The aim of this systematic review was to provide a comprehensive review of the association between hair measures of hormones (i.e., cortisol, progesterone, estrogen, and testosterone) and depression during the peripartum period. Forty-one studies were identified for inclusion. A majority of studies reported statistically null associations. Between-person studies varied widely in reported direction and magnitude of hair hormone-depression associations, most likely attributable to a wide range of methodological approaches including timing of assessments and sample size. Studies using within-person approaches observed positive coupling of cortisol concentration and symptoms across time. Most studies focused exclusively on cortisol. We recommend future research consider both stress and reproductive hormones, prioritize within-person change in hormone levels given this is a period of dramatic change, and include contextual (e.g., social support, adverse and benevolent childhood experiences, physical and psychiatric conditions) features that may modify both changes in hormones and the association between hormone levels and depression in the peripartum period.

Temperature, dietary lipids, and Aeromonas hydrophila modulate self-protection mechanisms in pacu Piaractus mesopotamicus Holmberg 1887.

Water temperature has a direct influence on several physiological processes in fish. This study investigated the effects of the exposure of pacu (Piaractus mesopotamicus) to 10 days of reduced temperature in stress and innate immune and antioxidant systems, all of which are involved in energy mobilization. Two groups of fish, fed a control diet or a diet with a higher lipid level, were exposed for 10 days to 16°C and then inoculated with Aeromonas hydrophila bacterin. Samples were taken before and after 5 and 10 days of exposure. The results showed that the low temperature (16°C) was a stressor, increasing cortisol levels. Higher levels of cortisol were seen in fish with more body fat, especially at 16°C, compared to those fed control diet. The immune system was enhanced by low temperature that activated the hemolytic activity of the complement system (HAC50) and lysozyme after 10 days of exposure in fish with more body fat. Bacterin inoculation, regardless of temperature and body fat, impaired the respiratory activity of leukocytes, but the complement system activity remained at the levels seen before cold activation. Similarly, lysozyme remained at the levels seen before cold activation, showing later activation. Furthermore, soon after inoculation (at 3 and 6 h), bacterin induced oxidative stress that decreased at 24 h when the concentration of reduced glutathione (GSH) showed lower levels, suggesting that GSH was consumed to attenuate the oxidative stress. Pacu was resilient to the reduced temperature, displaying protective responses to the stressful condition using lipids to modulate these responses.

Myosteatosis and sarcopenia are linked to autonomous cortisol secretion in patients with aldosterone-producing adenomas.

Patients with adrenal aldosterone-producing adenomas (APA) face elevated cardiovascular risks, especially when cortisol is co-secreted, yet the impact on muscle health remains unclear. Myosteatosis, characterized by fatty infiltration into muscles, is linked to cardiometabolic diseases and decreased survival. We aimed to investigate the association between autonomous cortisol secretion (ACS) in APA and muscle quantity and quality. In this study, we analyzed data from 228 APA patients undergoing laparoscopic adrenalectomy between 2009 and 2024, assessing muscle composition via computed tomography. Intermuscular adipose tissue (IMAT), skeletal muscle area and density, visceral and subcutaneous adipose tissue area at L3 were measured. Comparisons were made between ACS and non-ACS groups. We found that among 228 patients, 76 (33.3%) had ACS. Those with ACS exhibited significantly higher IMAT area (P = 0.042) and lower skeletal muscle area (P = 0.002) and density (P < 0.001). Multivariable regression confirmed ACS positively associated with IMAT area and negatively associated with skeletal muscle area and density. At 1-year follow-up, ACS patients (n = 15) experienced decreased IMAT area (P = 0.001) and increased skeletal muscle area (P = 0.031) post-adrenalectomy, while those without ACS (n = 29) showed no IMAT change but increased visceral (P < 0.001) and subcutaneous (P = 0.008) adipose tissue area. In summary, myosteatosis and sarcopenia are linked to ACS in APA patients, and these parameters improve following adrenalectomy.

Association between resting heart rate and low natural killer cell activity: a cross-sectional study.

Resting heart rate (RHR), a simple physiological indicator, has been demonstrated to be associated with inflammation and even metabolic disorders. This study aimed to investigate whether RHR is associated with natural killer cell activity (NKA) in a large population of healthy adults using a novel assay to measure NKA. This cross-sectional study included 7,500 subjects in the final analysis. NKA was estimated by measuring the amount of interferon-gamma (IFN-γ) released by activated natural killer cells; low NKA was defined as IFN-γ level <500 pg/mL. Subjects were categorized into four groups according to RHR as follows: C1 (≤ 60 bpm), C2 (60-70 bpm), C3 (70-80 bpm), and C4 (≥ 80 bpm). Individuals with higher RHR exhibited poorer metabolic and inflammatory profiles, with the prevalence of low NKA being highest in the highest RHR category. Compared with C1 as reference, the fully adjusted odd ratios (ORs) [95% confidence intervals (CIs)] for low NKA were significantly higher in C3 (OR: 1.37, 95% CI: 1.08-1.75) and C4 (OR: 1.55, 95% CI: 1.20-2.00). In addition, RHR was shown to exert indirect effects on NKA upon consideration of the mediation effect of serum cortisol in path analysis. Our findings confirm a significant link between elevated RHR and low NKA, and suggest the usefulness of RHR, a simple indicator reflecting increased sympathetic nervous system activity and stress, in predicting reduced immune function.

Social Context in Stress and Autism: Comparing Physiological Profiles Across Two Social Paradigms in Youth with and without Autism Spectrum Disorder.

Background: The social world is often stressful for individuals with autism spectrum disorder (ASD). Research shows youth with ASD demonstrate physiological hyperreactivity to some social stressors (e.g., interaction) but not others (e.g., evaluation); therefore, this study examined diagnosis (ASD or typical development (TD)), social context, perceived anxiety, and physiological responsivity across multiple stress systems; namely, the hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS). Method: This study examined 244 ten-to-thirteen-year-olds with ASD (N = 140) or TD (N = 104). Physiological responses, measured by salivary cortisol, heart rate (HR), and respiratory sinus arrhythmia (RSA), were assessed before and after a social evaluative threat paradigm (Trier Social Stress Test; TSST) and social interaction (Trier Social Stress Test- Friendly; TSST-F). Mediation models examined the relationships between anxiety, diagnosis, and physiology. Results: Significant three-way interactions were observed for cortisol (p=0.007) and HR (p=0.002), suggesting diagnostic groups respond differently across context and time points. There was no significant interaction for RSA (p=0.149), although ASD youth had significantly lower RSA overall (p=0.038). State and trait anxiety did not mediate the relationship between diagnosis and physiology (all p>0.05). Conclusions: Findings emphasize the critical role of context and a multisystem approach in examination of physiological social stress in youth with ASD. Results provide a foundation to elucidate unique response patterns across physiological systems to more precisely identify those with heightened physiological arousal across social contexts. It is proposed that future identification of subtypes may ultimately inform approaches for enhancing social engagement.