Elevated Cortisol Levels Research Articles

Divergent Associations of Slow-Wave Sleep versus Rapid Eye Movement Sleep with Plasma Amyloid-Beta.

Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20-68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100 minutes previously (all t values > |3|, p values < 0.003). Older participants showed higher amyloid-beta-40 levels. Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. ANN NEUROL 2024;96:46-60.

Effects of antidepressant on FKBP51 mRNA expression and neuroendocrine hormones in patients with panic disorder

ObjectiveThe purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD).MethodsSeventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment.ResultsAt baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01).ConclusionsThe results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

The impact of maternal psychopathology on psychomotor development trajectories in infants born after a threatened preterm labour from 6 to 30 months of age

IntroductionThreatened preterm labor (TPL) represents an adverse prenatal event that can impact maternal mental health in the long term. Additionally, this prenatal event can disrupt fetal neurodevelopment, primarily during the third trimester of pregnancy when neuronal connections in the fetus are established. Indeed, infants born following TPL exhibit delayed communication and socio-individual skills at 6 months of age, regardless of prematurity. Furthermore, maternal mental health during the postpartum period can also influence the offspring’s psychomotor development.ObjectivesThe aim of this study is to examine the impact of maternal psychopathology on psychomotor development trajectories in infants born after a TPL from 6 to 30 months of age.MethodsThis prospective cohort study recruited 117 mother–child pairs who suffered from a TPL. Psychomotor assessment was performed at 6 and 30 months of age using the communication and socio-individual subscales of Ages &amp; Stages Questionnaires for psychomotor development. A regression model was carried out, including gestational age at birth, maternal anxiety trait, maternal history of psychological traumas, prenatal and postnatal maternal depression, anxiety, and cortisol as well as parenting stress as predictors.ResultsIncreased communication delays were associated with higher maternal anxiety levels (p &lt; 0.001), elevated maternal depression scores (p= .0003), and increased cortisol levels (p = .004) during postpartum. Similarly, elevated cortisol levels after 6 months postpartum were predictive of increased Personal-Social delays (p = .0018).ConclusionsMaternal postpartum psychopathology was the main determinant of the course of psychomotor developmental disturbances. Therefore, infants born after TPL, whose mothers display postpartum psychopathology, should be identified and considered for psychological treatment to improve psychomotor delays in infants.Disclosure of InterestNone Declared

Cortisol as a Target for Treating Mental Disorders: A Promising Avenue for Therapy.

Cortisol, commonly known as the "stress hormone," plays a critical role in the body's response to stress. Elevated cortisol levels have been associated with various mental disorders, including anxiety, depression, and post-traumatic stress disorder. Consequently, researchers have explored cortisol modulation as a promising avenue for treating these conditions. However, the availability of research on cortisol as a therapeutic option for mental disorders is limited, and existing studies employ diverse methodologies and outcome measures. This review article aimed to provide insights into different treatment approaches, both pharmacological and non-pharmacological, which can effectively modulate cortisol levels. Pharmacological interventions involve the use of substances, such as somatostatin analogs, dopamine agonists, corticotropin-releasing hormone antagonists, and cortisol synthesis inhibitors. Additionally, non-pharmacological techniques, including cognitivebehavioral therapy, herbs and supplements, transcranial magnetic stimulation, lifestyle changes, and surgery, have been investigated to reduce cortisol levels. The emerging evidence suggests that cortisol modulation could be a promising treatment option for mental disorders. However, more research is needed to fully understand the effectiveness and safety of these therapies.

Variations in thyroid hormone levels in endangered St. Lawrence Estuary belugas: Potential linkage with stress and organohalogen contaminant exposure

The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and their metabolites reverse T3 and 3,5-diiodothyronine [3,5-T2]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T4, rT3 and 3,5-T2. Specifically, there was a weak significant negative association between T4 and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T3 and Σ34PBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.

Relationship of Endometriosis with Cortisol and Thyroid Function in Young Working Females

Objective: The study was focused to evaluate the role of endometriosis in development of hypothyroidism in working females subjected to chronic stress. Study Design: cross sectional study. Settings: This research was conducted at department of Gynecology &amp; Obstetrics, The University of Lahore Teaching Hospital, Lahore. Duration: The research was completed in from February 2023 to February 2024. Methods: Serum samples of fifty-five endometriosis patients and fifteen controls were analyzed for T3, T4, TSH, cortisol and estrogen levels by using ELISA kits. Results: The levels of TSH in patient’s serum is (1.02±0.168mIU/L) as related to control (3.08±1.090 mIU/L) were lower in females with endometriosis. Serum estrogen levels in endometriosis patients (67.07±5.54 pg/ml) were higher than normal controls (21.07±3.66pg/ml). Elevated levels of serum cortisol (27.25±3.27) than normal values (11.19±4.18) in endometriosis patients were observed. Thyroid problems may result from this imbalance. Furthermore, there is a change in the quantity of thyroid hormones (T3 and T4) in endometriotic cells. Production of T4 rose whereas that of T3 fell. Thus, our research shows that endometriosis increases the risk of thyroid malfunction and hormone imbalance in women. Conclusion: We came to the conclusion that thyroid hormone contributes to endometriosis because endometrial cells are sensitive to changes in TSH. The thyroid gland and its related hormone concentrations described a varied picture between healthy subjects and patients of endometriosis. Moreover, thyroid hormones and estrogen are found to play their significant roles in the disease.

Serial Diurnal Salivary Cortisol Profiles in 667 Pregnant Women-Association With Cardiometabolic Complications.

Maternal obesity, hypertensive pregnancy disorders, and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce. We (1) examined maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications. Women in the InTraUterine sampling in early pregnancy (ITU) study (n = 667) provided 7 salivary cortisol samples from awakening to bedtime up to 3 times during pregnancy (median gestational week 19.3, 25.7, and 38.1; n = 9356 samples). Changes in cortisol awakening response (CAR) and diurnal slope (indicative of HPA axis activity) and their associations with maternal body mass index (BMI), hypertensive pregnancy disorders and GDM were examined using linear mixed models. The CAR declined in 60% to 67% of women, and the diurnal slope attenuated from early to late pregnancy (b = 0.006; P = .001). Higher BMI was associated with less decline in CAR (b = 0.031; P = .0004) and less attenuation in diurnal slope from early to late pregnancy (b = -0.001; P = .006). Hypertensive pregnancy disorders and GDM were not significantly associated with diurnal cortisol profiles. The attenuation in CAR and diurnal slope support HPA axis hyporesponsivity during pregnancy. Less attenuation of both markers in women with a higher BMI may indicate reduced adaption of the HPA axis to pregnancy, presenting a mechanistic link to offspring health outcomes.

Blood-based assessment of oxidative stress, inflammation, endocrine and metabolic adaptations in eventing horses accounting for plasma volume shift after exercise.

After submaximal exercise, blood values of eventing horses show physiological reactions. This prospective longitudinal study investigated blood parameters in 20 elite eventing horses before and after two-four-star cross-country rides. Using a mixed model adjusting for plasma volume shift, we assessed exercise-dependent parameters and compared blood values with reference ranges for healthy horses at rest. Following exercise, cortisol, triiodothyronine (T3) and thyroxine (T4) showed short-term increases, and superoxide-dismutase showed a small short-term increase. Hepatic values showed short-term (haemoglobin [HGB], globulins) or sustained increases (bilirubin, glutamate dehydrogenase, alanine aminotransferase). Digestion-related parameters showed small short-term increases (α-amylase, triglycerides) or decreases (cholesterol, DGGR-lipase), apparent through plasma shift adjustment. Zinc decreased in the short term, and iron showed a delayed decrease. White blood cell count increased persistently after training, whereas serum amyloid A remained unchanged. Exercised eventing horses had consistently elevated HGB and cortisol levels 10 and 30min after submaximal exercise, exceeding the reference ranges for healthy horses at rest. Exercise activates the hypothalamic-pituitary-adrenocortical and hypothalamic-pituitary-thyroid axes. Antioxidant activity was observed. Increased energy requirements led to the mobilization of energy reserves, and a sustained increase in liver enzymes indicated hepatocellular injury. Mild haemolysis suggested increased muscle metabolism, whereas signs of inflammation were subtle. Further research is needed to identify which horses deviate from mean values.

It’s all in the hair: Association between changes in hair cortisol concentrations in reaction to the COVID-19 pandemic and post-traumatic stress symptoms in children over time

After exposure to a stressful/traumatic event, some individuals will develop post-traumatic stress symptoms (PTSS). In adults, low cortisol levels appear to be a risk factor for the development of PTSS. Indeed, both lower pre-trauma cortisol levels and low cortisol levels in the aftermath of a traumatic event have been associated with greater PTSS. In contrast, studies conducted in children showed that elevated cortisol levels shortly after trauma exposure are associated with more severe post-traumatic stress symptomatology. The few studies that have examined how pre-trauma cortisol levels predict PTSS in children have found no effect. Given that a pandemic can induce PTSS in certain individuals, we investigated whether cortisol secretion prior to and in the early stages of the COVID-19 pandemic in Quebec (Canada) predicted PTSS in children. In June 2020, we collected a hair sample from 71 children (8–15 y/o, M = 11.65; 54.93% girls) without a history of psychopathology or exposure to previous traumatic events. Hair samples allowed us to derive cumulative measures of cortisol levels for the months prior to (from mid-December 2019 to mid-March 2020) and at the beginning of the pandemic (from mid-March 2020 to mid-June 2020). PTSS were assessed every 3 months between June 2020 (T1) and March 2021 (T4). The results showed that a greater increase in hair cortisol at the beginning of the pandemic predicted less PTSS at T1, with an increase in these symptoms over time. This study highlights the utility of using hair cortisol during future chronic stressful events to better understand its association with the evolution of distress.

Cushing's Syndrome in Pregnancy Secondary to Adrenocortical Adenoma: A Case Series and Review.

To present a case series of Cushing's syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes. We describe five pregnant women with CS, detailing clinical presentations and laboratory findings. Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas. Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease

Congenital heart disease (CHD) is the most common birth defect, and up to 50% of infants with CHD require cardiovascular surgery early in life. Current clinical practice often involves thymus resection during cardiac surgery, detrimentally affecting T-cell immunity. However, epidemiological data indicate that CHD patients face an elevated risk for infections and immune-mediated diseases, independent of thymectomy. Hence, we examined whether the cardiac defect impacts thymus function in individuals with CHD. We investigated thymocyte development in 58 infants categorized by CHD complexity. To assess the relationship between CHD complexity and thymic function, we analyzed T-cell development, thymic output, and biomarkers linked to cardiac defects, stress, or inflammation. Patients with highly complex CHD exhibit thymic atrophy, resulting in low frequencies of recent thymic emigrants in peripheral blood, even prior to thymectomy. Elevated plasma cortisol levels were detected in all CHD patients, while high NT-proBNP and IL-6 levels were associated with thymic atrophy. Our findings reveal an association between complex CHD and thymic atrophy, resulting in reduced thymic output. Consequently, thymus preservation during cardiovascular surgery could significantly enhance immune function and the long-term health of CHD patients.

High platelet adrenergic activity and concomitant activation of the pituitary/medullar axis as alarming laboratory parameters in ACS survivors-the STRESS-AMI study.

Kinetics of stress-related biological parameters were determined in acute coronary syndrome (ACS) patients undergoing complex cardiovascular rehabilitation. We determined platelet functionality in the absence/presence of a selective alpha-2 adrenergic receptor inhibitor, atipemazole parallel with salivary cortisol levels at enrolment, and at 3- and 12-months follow-up in 75 ACS patients with percutaneous coronary intervention. Pharmacological/non-pharmacological secondary prevention methods have been efficiently applied. Baseline aggregometry indicated platelet hyperactivity, decreasing gradually and being significantly reduced late, at 12 months (p < 0.05). Cortisol levels followed similar kinetics (p < 0.05). Baseline epinephrine-induced aggregations (EIA) significantly correlated with most of the other platelet agonists, even at subsequent time-points. Patients with upper-quartile EIA at enrolment (EIA-UQ) had significantly higher ADP- and collagen-induced aggregations at enrolment, at 3- and 12-months follow-up as well, indicating that high adrenergic response in the acute phase is accompanied by general platelet hyperactivity and predicts sustained platelet activation. In the EIA-UQ group higher cardiac biomarker release, elevated C-reactive protein and cortisol levels, and lower baseline left ventricular ejection fraction were detected.Atipemazole significantly reduced platelet aggregation induced by several platelet agonists, being most potent and comparable to full in vitro P2Y12 inhibition on collagen-induced aggregations (p < 0.05), indicating that catecholamines might serve as promt/long-term modulators of platelet function. Despite effective CCR programme and dual antiplatelet therapy, prolonged activation of sympathetic neuroendocrine system and general platelet hyperactivity can be detected up to one year in ACS patients with high adrenergic platelet activity. Moreover, initial high adrenergic activity is accompanied by clinical parameters associated to increased cardiovascular risk, therefore early identification of these patients might support complex optimal long-term therapy.

The Relationship between Iron Markers, Cortisol and Insulin Resistance in Gestational Diabetes Mellitus

Background: Gestational diabetes mellitus (GDM) is a significant metabolic disorder occurring during pregnancy, associated with serious maternal and fetal complications if left untreated. The global prevalence of GDM emphasizes the urgent need for research into its pathogenesis and contributing factors, including hormonal changes, insulin resistance, and the role of iron metabolism. Objective: The aim of this study was to investigate the relationship between iron markers (hemoglobin, serum iron, and serum ferritin), cortisol, insulin resistance (measured by HOMA-IR), and the development of GDM in pregnant women between 24 and 28 weeks of gestation. Methods: This analytical cross-sectional study included 150 pregnant women, divided into GDM and non-GDM groups based on oral glucose tolerance test results. Iron markers, cortisol, fasting plasma glucose, insulin, and HOMA-IR levels were measured. Data analysis was performed using SPSS version 25, employing descriptive and inferential statistics, including the Mann-Whitney U test for non-normally distributed variables. Results: Women with GDM exhibited significantly higher mean levels of hemoglobin (12.41±0.68 g/dl), serum iron (19.57±1.14 μmol/L), serum ferritin (25.92±2.58 ng/ml), cortisol (451.32±25.20 nmol/L), fasting plasma glucose (6.83±0.46 mmol/L), insulin (12.50±1.72 μU/mL), and HOMA-IR (3.83±0.78) compared to non-GDM participants (p&lt;0.001 for all comparisons). These findings underscore the pronounced biochemical and hormonal alterations associated with GDM. Conclusion: The study identified a significant association between elevated levels of iron markers, cortisol, and insulin resistance with the development of GDM. These findings suggest that monitoring these parameters during pregnancy could be crucial for the early detection and management of GDM. Individualized iron supplementation strategies may be necessary to prevent iron overload and minimize GDM risk.

Prenatal exposure to social adversity and infant cortisol in the first year of life

Exposure to social adversity has been associated with cortisol dysregulation during pregnancy and in later childhood; less is known about how prenatal exposure to social stressors affects postnatal cortisol of infants. In a secondary analysis of data from a longitudinal study, we tested whether a pregnant woman’s reports of social adversity during the third trimester were associated with their infant’s resting cortisol at 1, 6, and 12 months postnatal. Our hypothesis was that prenatal exposure to social adversity would be associated with elevation of infants’ cortisol. Measures included prenatal survey reports of social stressors and economic hardship, and resting cortisol levels determined from infant saliva samples acquired at each postnatal timepoint. Data were analyzed using linear mixed effects models. The final sample included 189 women and their infants (46.56% assigned female sex at birth). Prenatal economic hardship was significantly associated with infant cortisol at 6 months postnatal; reports of social stressors were not significantly associated with cortisol at any time point. Factors associated with hardship, such as psychological distress or nutritional deficiencies, may alter fetal HPA axis development, resulting in elevated infant cortisol levels. Developmental changes unique to 6 months of age may explain effects at this timepoint. More work is needed to better comprehend the complex pre- and post-natal physiologic and behavioral factors that affect infant HPA axis development and function, and the modifying role of environmental exposures.

Behavioral and neurophysiological effects of buspirone in healthy and depression-like state juvenile salmon.

A proportion of farmed salmon in seawater show a behaviorally inhibited, growth stunted profile known as a depression-like state (DLS). These DLS fish are characterized by chronically elevated serotonergic signaling and blood plasma cortisol levels and the inability to react further to acute stress, which is suggestive of chronic stress. In this study, we characterize the neuroendocrine profile of growth stunted freshwater parr and confirm that they show a DLS-like neuroendocrine profile with a blunted cortisol response and no serotonergic increase in response to acute stress. Furthermore, we attempted to reverse this DLS-like profile through pharmacological manipulation of the serotonin (5-HT) system with buspirone, an anxiolytic medication that acts as a serotonin receptor agonist (i.e., decreases serotonergic signaling). We found that while buspirone decreases anxiolytic-type behavior in healthy fish, no quantifiable behavioral change was found in DLS-like fish. However, there was a physiological effect of diminished basal serotonergic signaling. This suggests that at the physiological level, buspirone appears to reverse the neuroendocrine DLS profile. With a deeper understanding of what causes DLS profiles and growth stunting in juvenile fish, steps can be taken in terms of husbandry to prevent repeated stressors and the formation of the DLS profile, potentially reducing losses in aquaculture due to chronic stress.

Adrenocorticotropic hormone Secreting Olfactory Neuroblastoma producing Ectopic Cushing&amp;rsquo;s Syndrome

Olfactory neuroblastoma is a rare sinonasal tumour of neuroendocrine type arising from olfactory neuroepithelium. Cushing`s syndrome is a clinical entity occurring due to elevated serum cortisol levels which is commonly due to exogenous steroids. Ectopic ACTH giving rise to endogenous Cushing’s syndrome requires vigilant evaluation in recognition of ectopic site. This syndrome gives rise to multitude of metabolic derangements with high morbidity which warrants early evaluation and management.

Acute and Long-Term Changes in Blood-Borne Biomarkers in Response to Dynamic Standing in Nonambulant Children With Cerebral Palsy.

To investigate acute and long-term changes in hormonal and inflammatory biomarkers in nonambulant children with cerebral palsy in response to dynamic standing exercise. Fourteen children with severe cerebral palsy were recruited. Anthropometrics and body composition measures were obtained. Physical activity levels before the study were assessed using hip-worn accelerometry. All children underwent a 30-minute dynamic standing exercise using the Innowalk standing aid. Respiratory data during exercise were collected using indirect calorimetry. Blood samples were collected before and after exercise. Blood samples were also obtained after two 16-week exercise protocols, in a resting state. Hormonal and inflammatory metabolites were measured from blood serum/plasma, and acute and long-term changes in biomarker levels were assessed using Wilcoxon signed-rank tests. Of the 14 children at baseline, all had slightly/moderately/severely elevated C-reactive protein and cortisol levels. C-reactive protein levels were decreased following a 30-minute bout of dynamic standing (before exercise: 53mg/L [interquartile range: 40-201]; after exercise: 39mg/L [interquartile range: 20-107]; P = .04). We show that several hormonal and inflammatory biomarkers are dysregulated in children with cerebral palsy. Our preliminary results from a small, but deep-phenotyped prospective cohort indicate acute and long-term alterations of several biomarkers in response to exercise.

Chronic cortisol stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain.

The hypothalamus is a key integrating center that is involved in the initiation of the corticosteroid stress response, and in regulating nutrient homeostasis. Although cortisol, the principal glucocorticoid in humans and teleosts, plays a central role in feeding regulation, the mechanisms are far from clear. We tested the hypothesis that the metabolic changes to cortisol exposure signal an energy excess in the hypothalamus, leading to feeding suppression during stress in fish. Rainbow trout (Oncorhynchus mykiss) were administered a slow-release cortisol implant for 3 days, and the metabolite profiles in the plasma, hypothalamus, and the rest of the brain were assessed. Also, U-13C-glucose was injected into the hypothalamus by intracerebroventricular (ICV) route, and the metabolic fate of this energy substrate was followed in the brain regions by metabolomics. Chronic cortisol treatment reduced feed intake, and this corresponded with a downregulation of the orexigenic gene agrp, and an upregulation of the anorexigenic gene cart in the hypothalamus. The U-13C-glucose-mediated metabolite profiling indicated an enhancement of glycolytic flux and tricarboxylic acid intermediates in the rest of the brain compared with the hypothalamus. There was no effect of cortisol treatment on the phosphorylation status of AMPK or mechanistic target of rapamycin in the brain, whereas several endogenous metabolites, including leucine, citrate, and lactate were enriched in the hypothalamus, suggesting a tissue-specific metabolic shift in response to cortisol stimulation. Altogether, our results suggest that the hypothalamus-specific enrichment of leucine and the metabolic fate of this amino acid, including the generation of lipid intermediates, contribute to cortisol-mediated feeding suppression in fish.NEW & NOTEWORTHY Elevated cortisol levels during stress suppress feed intake in animals. We tested whether the feed suppression is associated with cortisol-mediated alteration in hypothalamus metabolism. The brain metabolome revealed a hypothalamus-specific metabolite profile suggesting nutrient excess. Specifically, we noted the enrichment of leucine and citrate in the hypothalamus, and the upregulation of pathways involved in leucine metabolism and fatty acid synthesis. This cortisol-mediated energy substrate repartitioning may modulate the feeding/satiety centers leading to the feeding suppression.

Unveiling the hidden impact: Subclinical hypercortisolism and its subtle influence on bone health.

In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward-looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

Prednisolone-Induced Cushing's syndrome: A case report

Objective: Prednisolone, a frequently prescribed corticosteroid, is linked to diverse adverse effects, including Cushing's syndrome. Material and Methods: This report details a case of prednisolone-induced Cushing's syndrome in a 6-year-old girl diagnosed with Acute Disseminated Encephalomyelitis (ADEM). Prednisolone was administered to manage inflammation associated with ADEM. Subsequent to the tapering of prednisolone, the patient exhibited progressive weight gain, facial rounding, fatigue, and muscle weakness. Clinical examination revealed classic manifestations of Cushing's syndrome, including central obesity, moon facies, and proximal muscle weakness. Laboratory analysis confirmed elevated serum cortisol levels and suppressed adrenocorticotropic hormone (ACTH), confirming exogenous Cushing's syndrome induced by prednisolone. The patient's prednisolone dosage was gradually reduced under careful medical supervision. Regular follow-ups were conducted to monitor symptoms, weight fluctuations, and hormonal levels. With the decrease in prednisolone dosage, the patient's symptoms showed gradual improvement. Results and conclusion: Prednisolone-induced Cushing's syndrome arises as a recognized complication of corticosteroid therapy, primarily characterized by the suppression of the hypothalamic-pituitary-adrenal axis. Early awareness of this adverse effect is pivotal for prompt identification and management. This case emphasizes the significance of vigilant monitoring and judicious use of prednisolone to mitigate adverse effects like Cushing's syndrome. Swift recognition, dose adjustments, and a gradual tapering of corticosteroids play a crucial role in effectively managing this condition for optimal patient outcomes.