Elevated Cortisol Levels Research Articles

Habitat complexity and predator odours impact on the stress response and antipredation behaviour in coral reef fish.

Mass coral bleaching events coupled with local stressors have caused regional-scale loss of corals on reefs globally. Following the loss of corals, the structural complexity of these habitats is often reduced. By providing shelter, obscuring visual information, or physically impeding predators, habitat complexity can influence predation risk and the perception of risk by prey. Yet little is known on how habitat complexity and risk assessment interact to influence predator-prey interactions. To better understand how prey's perception of threats may shift in degraded ecosystems, we reared juvenile Pomacentrus chrysurus in environments of various habitat complexity levels and then exposed them to olfactory risk odours before simulating a predator strike. We found that the fast-start escape responses were enhanced when forewarned with olfactory cues of a predator and in environments of increasing complexity. However, no interaction between complexity and olfactory cues was observed in escape responses. To ascertain if the mechanisms used to modify these escape responses were facilitated through hormonal pathways, we conducted whole-body cortisol analysis. Cortisol concentrations interacted with habitat complexity and risk odours, such that P. chrysurus exhibited elevated cortisol levels when forewarned with predator odours, but only when complexity levels were low. Our study suggests that as complexity is lost, prey may more appropriately assess predation risk, likely as a result of receiving additional visual information. Prey's ability to modify their responses depending on the environmental context suggests that they may be able to partly alleviate the risk of increased predator-prey interactions as structural complexity is reduced.

Hyper- and hypocortisolism: Latent profiles of diurnal cortisol underlying depressive symptoms in adolescents

A secular trend of increased depressive symptoms among adolescents and early adults has received both scientific and media attention (Office of the Surgeon General, 2021). Research on cortisol and depression has revealed the important role of the HPA axis in internalizing disorders. But evidence remains mixed regarding the direction of effects, with findings of both higher and lower levels of diurnal cortisol associated with depressive symptoms. There is a need for new approaches to study the biological underpinnings of depressive symptoms. We analyzed diurnal cortisol among 141 adolescents (Mage = 15.0; 59.7% female; 50.8% white). Latent Profile Analysis (LPA) was used to characterize cortisol rhythms identified from four daily salivary samples (at waking, 30 minutes after waking, after school, and bedtime) taken over five days. Resulting profiles were examined in relation to reported stress, depressive symptoms, and other measures of psychosocial functioning. Analyses identified two cortisol profiles associated with elevated depressive symptoms. One had the lowest average cortisol levels at each sampling time throughout the day. The other corresponded to highly elevated diurnal cortisol, with both waking and bedtime levels exceeding 0.8 μg/dL. However, they diverged in associations with other aspects of psychosocial functioning. We will present the correlates of each diurnal profile and discuss implications for longitudinal work. Both elevated and suppressed cortisol rhythms were associated with higher depressive symptoms than those among adolescents with more typical rhythms. Using LPA to characterize diurnal cortisol may allow for better understanding of youth risk for depression.

Associations between psychological distress and hair cortisol during pregnancy and the early postpartum: A meta-analysis

Pregnancy and the early postpartum signify a period of high stress. Perinatal stress can include psychological distress (PD), such as anxiety, depression, and stress, as well as neuroendocrine stress, indexed by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the production of cortisol. Elevated PD and cortisol levels during the perinatal period can have long-term implications for the mother and child. Despite knowing that PD and HPA activity during the perinatal period independently impact health and development, research to date is unclear as to the association between PD and maternal hair cortisol. The present meta-analysis included 27 studies to assess the strength of the relation between PD and hair cortisol levels during pregnancy and early postpartum. Several sample and methodological factors were assessed as moderators. Analyses were conducted using multilevel meta-analysis. The overall effect size between PD and HCC was small and not significant z = 0.044, 95% CI [-0.001, 0.089]. Moderator analyses indicated that the strength of the association between PD and hair cortisol was moderated by pregnancy status (i.e., effects were stronger in pregnant compared to postpartum samples), timing of HCC and PD measurements (i.e., effects were larger when PD was measured before HCC) and geographic location (i.e., effects were larger in North American studies). The findings advance our understanding of the link between PD and HPA activity during the perinatal period, and further underscores the need for longitudinal work to better understand this relationship during a critical developmental period.

It’s all in the hair: Changes in hair cortisol concentrations in reaction to the COVID-19 pandemic predicts post-traumatic stress symptoms in children

About 25 to 35% of victims of a traumatic event will develop post-traumatic stress disorder (PTSD). Low cortisol levels appear to be a risk factor for the development of PTSD. In adults, decreased diurnal and cumulative cortisol levels before or shortly after a traumatic event are associated with increased post-traumatic symptoms in the months thereafter. In contrast, results from the only two studies conducted in children showed that elevated diurnal cortisol levels shortly after exposure to a traumatic event are associated with more severe post-traumatic symptomatology. Given that a pandemic can induce post-traumatic stress symptoms, we investigated whether cumulative cortisol levels prior to and in the beginning stages of the COVID-19 pandemic in Quebec (Canada) predicted post-traumatic stress symptoms in children. We collected hair samples from 69 children (8-12 y/o) without history of psychopathology and exposure to a traumatic event. Cortisol levels were measured before (December 2019 - February 2020) and at the beginning of the pandemic (March 2020 - May 2020). Post-traumatic stress symptoms were assessed every 3 months between June 2020 (T1) and March 2021 (T4). The results showed that the percentage change in cumulative cortisol levels between the beginning of and prior to the pandemic predicted post-traumatic stress symptoms at T1. Specifically, a decrease in cortisol levels early in the pandemic was associated with increased post-traumatic stress symptoms. This study suggests that a decrease in cortisol in response to a stressful event may be a predisposing factor for PTSD in children.

Multivariate characterization of biochemical and physiological attributes umpires Pangasianodon hypophthalmus for a welfare-based open-water cage culture.

The striped catfish, Pangasianodon hypophthalmus, dominates in the Indian inland freshwater cage culture because of its rapid growth and adaptive feeding habits; however, suitable stocking density based on growth without compromising the health of fish is important. Furthermore, fish growth and survival are inversely proportional to stocking density. Many farmers face size differentiation and poor survival at higher stocking densities. To address the aforementioned practical issue, the current study was carried out to study the influence of different stocking densities on the growth performance of P. hypophthalmus in cages. The fingerlings of P. hypophthalmus (10.63 ± 0.27 g) were stocked in triplicate in five different stocking densities (20, 30, 40, 50, and 60 m-3), and the fishes were given commercial feed for 240 days. The outcome demonstrated that the fish stocking densities and their growth attributes were inversely related. Stocking density in the range of 20 to 40 m-3 produced the highest final weight, relative growth rate, and specific growth rate. The feed conversion ratio was significantly lower in 20, 30, and 40 m-3 than the higher densities of 50 and 60 m-3. The level of serum biochemical markers such as serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and glucose and cortisol levels elevated significantly in higher stocking densities. The muscle quality changed as crude fat and muscle pH decreased at 50 and 60 m-3, leading to a drop in drip loss and frozen leakage rate. The vital water quality parameters were found within a suitable range. According to the outcomes of principal component analysis (PCA), elevated levels of SGOT, SGPT, glucose, and cortisol were detrimental to fish growth. The stocking density of 30 m-3 had the highest benefit-cost ratio (B:C) and return on investment (RI), followed by 20 and 40 m-3. Higher economic return was achieved at lower densities (30-40 m-3). This study suggests that rearing P. hypophthalmus at stocking densities of about 30-40 m-3 could be considered as an optimum for the inland freshwater cage culture which gives the best performance in terms of growth and production in tropical reservoirs of India. The best-suited stocking density is also taken into consideration based on the characterization of multivariate biochemical and physiological attributes.

Negative feedback regulation in the hypothalamic-pituitary-interrenal axis of rainbow trout subjected to chronic social stress

The formation of dominance hierarchies in pairs of juvenile rainbow trout (Oncorhynchus mykiss) results in subordinate individuals exhibiting chronically elevated plasma cortisol concentrations. Cortisol levels reflect a balance between cortisol production, which is coordinated by the hypothalamic-pituitary-interrenal (HPI) axis in teleost fish, and negative feedback regulation and hormone clearance, which act to lower cortisol levels. However, the mechanisms contributing to the longer-term elevation of cortisol levels during chronic stress are not well established in fishes. The current study aimed to determine how subordinate fish maintain elevated cortisol levels, by testing the prediction that negative feedback and clearance mechanisms are impaired by chronic social stress. Plasma cortisol clearance was unchanged by social stress based on a cortisol challenge trial, hepatic abundance of the cortisol-inactivating enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11βHSD2), and tissue fate of labelled cortisol. The capacity for negative feedback regulation in terms of transcript and protein abundances of corticosteroid receptors in the preoptic area (POA) and pituitary appeared stable. However, changes in 11βHSD2 and mineralocorticoid receptor (MR) expression suggest subtle regulatory changes in the pituitary that may alter negative feedback. The chronic cortisol elevation observed during social subordination likely is driven by HPI axis activation and compounded by dysregulated negative feedback.

Scoping Review of the Relationship between Salivary Cortisol and Depression

Anxiety and depression are some of the most common mental disorders associated with a dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and elevated cortisol levels in the saliva. The aim of this scoping review was to synthesize all of the current information about the relationship between salivary cortisol and depression as well as address some of the shortcomings in prior research to explore its potential applications in diagnosing depression. In late July 2022, records from 2012-2022 were identified using Web of Science, PubMed, and Scopus. Unique abstracts were screened using the following criteria: (1) depression and saliva; (2) anxiety and saliva; (3) age and salivary cortisol and depression; (4) sex and salivary cortisol and depression. 4,869 records were identified across all three databases; resulting in 90 unique abstracts. 11 articles met all inclusion criteria. On balance, most studies associated the dysregulation of the HPA with depression and anxiety disorders, with a cofactor being the cortisol awakening response. Several studies also presented sex and age-related differences in salivary cortisol measures. However, there were several inconsistencies with some studies showing no age and/or sex-related differences. Furthermore, several studies also emphasized the importance of testing morning salivary cortisol as an effective method to diagnose depression and anxiety disorders. The oral microbiome may play a role in mental health disorders through changes in inflammation and cortisol levels in saliva. Our review contributes to the existing literature on the topic, highlighting gaps and strategizing the next steps.

Health Complications of Obesity

Obesity is associated with a wide range of comorbidities that transverse multiple specialties in clinical medicine. The development of these comorbidities is driven by various mechanistic changes including chronic inflammation and oxidative stress, increased growth-promoting adipokines, insulin resistance, endothelial dysfunction, direct loading and infiltrative effect of adiposity, heightened activities of the renin-angiotensin-aldosterone system and sympathetic nervous system, impaired immunity, altered sex hormones, altered brain structure, elevated cortisol levels, and increased uric acid production, among others. Some of the comorbidities might develop secondary to one or more other comorbidities. Considering the obesity-associated comorbidities in the context of the mechanistic changes is helpful in understanding these conditions and in guiding treatment and future research.

Changes in the cortisol level under the influence of physical exertion in patients with hypertension and in practically healthy individuals

Background. Today, there are difficulties with the prevention and diagnosis of early stages of hypertension, especially in active and able-bodied young people. Among the factors that potentiate an increase in blood pressure, one of the components is chronic stress, which a person often faces in modern society. The purpose of study is to evaluate and compare blood cortisol and plasma malondialdehyde content in healthy individuals and in patients with stage II hypertension before and after dosed exercises. Materials and methods. Thirty patients with stage II hypertension and 10 practically healthy persons were examined. Subjects performed two-stage physical exercises on a bicycle ergometer with an intensity corresponding to 50 and 75% of the appropriate maximum oxygen consumption of the body. The duration of the load was equal to 5 minutes at each stage with a three-minute rest between them. Blood was taken from the ulnar vein before cycling ergometry and 5 minutes after it. Blood cortisol and plasma malondialdehyde content were determined in patients before and after exercises. Results. A significant increase in cortisol content after exercises was noted in healthy individuals against the background of some decrease in patients with hypertension. It has been suggested that since people with high blood pressure already have an elevated initial level of cortisol, their threshold of stress sensitivity to physical exertion is increased. Submaximal bicycle ergometric load does not lead to an increase in blood cortisol levels in hypertensive patients. Conclusions. The background higher level of cortisol in individuals with hypertension does not increase under the influence of submaximal dosed exercises. An increase in the level of malondialdehyde can be considered a marker of the degree of stress for assessing the power of physical exertion. In view of the above, it can be stated that the activation of the sympathoadrenal system under the influence of emotional stress leads to an increase in blood pressure. There is sufficient evidence that psycho-emotional stress is a cause of white-coat hypertension and hypertension in the workplace.

High CSF cortisol levels are associated with frontal lobe and hippocampal atrophy across patients on the Alzheimer’s disease spectrum

AbstractBackgroundMultiple studies have linked high cerebrospinal fluid (CSF) cortisol levels, a frequently used biomarker of stress, with the Alzheimer’s disease (AD) pathophysiology. However, the relationship between CSF cortisol levels and AD‐related brain atrophy is not fully understood. Thus, this study sought to determine the association between CSF cortisol levels and neuroimaging biomarkers of brain structure indexed by magnetic resonance imaging (MRI) in patients across the AD spectrum.MethodsParticipants with baseline measures of CSF cortisol and structural (high‐resolution T1‐weighted) MRI (n = 300) were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The MRI scans were processed with FreeSurfer (v. 7.1.1), and the statistical analyses were performed using R (v. 4.1.1; R Core Team, 2021). We performed a region‐of‐interest (ROI) analysis using a generalized linear model (GLM), to assess the association between CSF cortisol levels and (1) volume of hippocampus, amygdala, subcortical and cortical segmentation, (2) cortical thickness and (3) surface area of cortical structures (Fig. 1). The ROI analysis was corrected by Bonferroni (p < 0.0005).ResultsCSF cortisol levels did not correlate with left hippocampal volume (p = 0.2; Fig. 2A) and mean global brain thickness (p = 0.002; Fig. 2C). However, we found a negative correlation with the volume of left fimbria (r = ‐0.20, p = 0.0003; Fig. 2B) and right superior frontal thickness (r = ‐0.21, p = 0.0003; Fig. 2D). In the regression model, only right superior frontal thickness showed significant association with CSF cortisol levels after adjusting for age (corrected R2 = 0.11, p < 0.0001). The other regions and parameters analyzed did not present significant correlations with CSF cortisol levels.ConclusionsThis cross‐sectional study found an association between elevated CSF cortisol levels and atrophy of left fimbria and right superior frontal in patients on the AD spectrum. Our findings suggest a particular vulnerability to cortisol in selected regions. To the best of our knowledge, this is the first study to assess the associations between CSF cortisol levels and ROIs from hippocampus and amygdala segmentation. Our results have potential implications for understating AD‐related brain atrophy and developing innovative therapeutic strategies.

Are hair cortisol levels dependent on hair growth rate? A pilot study in rhesus macaques

Research incorporating the analysis of glucocorticoids, specifically cortisol, in hair samples has exploded over the past 10–15 years, yet factors contributing to the accumulation of cortisol in hair are not yet fully characterized. In particular, it is not clear whether cortisol accumulation in hair is dependent on hair growth rate, a possibility raised by prior rodent studies reporting glucocorticoid-mediated inhibition of hair growth. Using rhesus macaque monkeys (Macaca mulatta), an extensively studied nonhuman primate species, the present pilot study evaluated the hypothesis that hair cortisol accumulation is inversely related to hair growth rate (i.e., slower hair growth leading to elevated cortisol levels). Hair samples were collected from 19 adult female macaques and 17 infants (9 males) 3 months apart using a shave-reshave procedure from the same site below the posterior vertex of the scalp. The second hair samples were measured to the nearest millimeter (mm) for growth rate over the previous 3 months and assayed for hair cortisol concentrations (HCCs) using enzyme immunoassay. Because of the possibility of age-related differences in hair growth rate, correlational analyses were performed separately for adults and infants to determine whether HCC values were associated with growth rate in each age group. These analyses revealed that neither group displayed a significant correlation of HCCs with hair growth. The results additionally showed that overall, adults had a faster hair growth rate than infants and, as expected from previous studies, had lower HCCs than infants. Our results suggest that higher HCCs within the non-stress range do not result from cortisol-mediated inhibition of hair growth. Moreover, similarities between humans and macaque monkeys in both HPA axis regulation and hair growth rates argue that these findings are relevant for human hair cortisol studies. Extrapolation to other species in which the features of hair growth and the relevant regulatory mechanisms are less well understood should be done with caution.

Preconception sleep quality moderates the association between preconception hair cortisol levels and mental health in pregnant women

BackgroundPoor sleep quality may elevate cortisol levels and affect prenatal mental health through altered HPA axis functioning. This study aims to examine whether subjective sleep quality during preconception moderates the association between preconception hair cortisol levels and mental health from preconception to pregnancy trimesters. MethodsWomen from a prospective cohort study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI) questionnaires during preconception (T0) and at each pregnancy trimesters (T1, T2, and T3). We analyzed 266 of these women who conceived and had fully completed measures at preconception for hair cortisol, sleep quality and either EPDS or STAI-state. Changes in EPDS and STAI-state scores were derived (i.e., T1–T0, T2–T0, T3–T0). Johnson-Neyman technique identified PSQI scores with significant moderation of cortisol on mental health. ResultsAfter adjusting for potential covariates, there was a significant positive correlation between preconception hair cortisol levels and depressive symptom at the second trimester (rs (144) = 0.22, p = 0.008), but not the first and third trimesters (all ps > 0.05). The positive association between preconception hair cortisol and change in depressive symptoms between third trimester and preconception was significant only among women with poor preconception sleep quality (PSQI ≥ 7). LimitationsSleep quality and prenatal mood were derived from self-reported questionnaires, which may be more susceptible to bias. ConclusionsThe positive association between preconception hair cortisol and change in prenatal depressive symptoms is significant among women who reported poor sleep quality during preconception. Improving preconception sleep quality can potentially mitigate the association between preconception hair cortisol and depressive symptoms during pregnancy.

Abstract #1375771: A Fluke or No? Fluconazole Treatment in a Case of Ectopic Cushing Syndrome

Cushing syndrome is characterized by elevated cortisol levels due to iatrogenic causes, pituitary tumors or from an ectopic focus. Ketoconazole has been shown to effectively decrease cortisol levels without a high risk of toxicities. Here we show a case report of a patient with ectopic Cushing syndrome treated with an alternative steroidogenesis inhibitor, fluconazole. We reported a 75-year-old male with a past medical history significant for atrial fibrillation, hypertension and obstructive sleep apnea. He was admitted to the hospital due to severe hypokalemia of 2.6 mmol/L (reference range 3.6-5.2 mmol/L), a blood sugar of 498 mg/dL (reference range 7-99 mg/dL), elevated PM cortisol levels of 66.1 mcg/dL (reference range 3-13 mcg/dL) and AM Cortisol Levels of 112 (reference range 5-25mcg/dL), thus prompting an endocrinology consult. Further examination of 24-hour urine cortisol displayed elevated levels at 11,656 mcg/24hrs (reference range 4-40 mcg/24hrs). The patient failed an 8mg dexamethasone suppression test with AM cortisol levels of 57.8 mcg/dL (5-25 mcg/dL) with a dexamethasone drug level of 2713 ng/dL (reference range >200 ng/dL), excluding elevated metabolism as cause of failed suppression. Pituitary magnetic resonance imaging showed a normal pituitary gland. Patient was started on 400mg of fluconazole daily with plans to switch to 400 mg ketoconazole in outpatient care. Outpatient positron emission tomography failed to identify the source of ACTH. Additionally, petrosal sinus sampling failed to detect altered levels of ACTH secretion. Patient was readmitted to hospital one month after original diagnosis with continued hypokalemia of 2.7 mmol/L (reference range 3.6-5.2 mmol/L) and worsening diabetic symptoms. Patient was taken off ketoconazole two weeks after prior discharge, not knowing it was temporary treatment for his Cushing’s syndrome. He was restarted on 400mg fluconazole and on day three of admission, fluconazole dose was increased to 600 mg daily (Endocrinology Metabolism case reports 2019, July 3) with cortisol levels to be monitored. On day one of admission, his AM cortisol levels were 91.5 mcg/dL (reference range 5-25 mcg/dL) and declined to 76.8 mcg/dL, 72.9 mcg/dL, 69.2 mcg/dL, 66.4 mcg/dL, and 60 mcg/dL the following days with fluconazole treatment. The patient was then discharged to outpatient follow-up with continuation of 600mg fluconazole. Within a week of the latest discharge, the patient presented to the hospital again due to an episode of atrial fibrillation. AM cortisol levels were measured to be 37.2 mcg/dL (reference range 5-25 mcg/dL), showing a 59.3% decrease since his last admission. Patient was then discharged from our care to an outpatient endocrinologist. This case shows that cortisol levels in ectopic Cushing Syndrome can be effectively lowered through fluconazole treatment. This medication has a more favorable side effect profile than other steroidogenesis inhibitors such as metyrapone and mitotane. Fluconazole monotherapy or dual therapy should be investigated further as a viable option for ectopic Cushing Syndrome therapy prior to bilateral adrenalectomy.

Abstract #1405095: PCOS Diagnosis Leading to a Delayed Diagnosis of Cushing's Disease

Polycystic ovarian syndrome (PCOS) is a common disorder affecting pre-menopausal women. Diagnostic criteria for PCOS include menstrual irregularities, biochemical or clinical hyperandrogenism and/or evidence of polycystic ovaries on ultrasound. Any 2 of the above is sufficient for a diagnosis of PCOS. However, PCOS is a diagnosis of exclusion so other pathologies should be investigated including hypercortisolemia. We present a case of Cushing's Disease in which the patient’s clinical features were previously attributed to a diagnosis of PCOS delaying appropriate intervention. A 22-year-old nulligravida woman with no significant past medical history presented to the Ob/Gyn clinic with complaints of amenorrhea and infertility. Patient noted irregular menstrual cycles since attaining menarche, she denies any headaches, galactorrhea but reported facial hirsutism and weight gain. She was initially diagnosed with PCOS but had continued amenorrhea despite treatment with medroxyprogesterone acetate. Additional work up was ordered by Gyn which noted mildly elevated Prolactin at 30.84 ng/ml. MRI head/brain subsequently ordered noted a large T2 weighted hyperintense lesion measuring 2.2 x 1.65 x 2.0 cm involving the sella with extension suggesting a pituitary macro-adenoma. Patient was referred to endocrinology for additional work up. Further evaluation showed normal repeat prolactin level with dilution study normal at 11.9 ng/ml. She was found to have secondary hypogonadism with FSH - 5.32 mIU/ml, LH- 2.1IU/L and estradiol level at < 20 pg/ml. She also had secondary hypothyroidism with TSH 0.88 mIU/ml and free T4 at 0.64 ng/dl. Morning Cortisol was at 19.13 ug/uL with baseline ACTH elevated at 127 pg/ml. This showed adequate adrenal function but concern for ACTH dependent hypercortisolemia. She had 2 failed 1 mg dexamethasone suppression test with cortisol level at 10.92 ug/uL and 20.91 ug/uL with adequate dexamethasone levels. She had 2 elevated 24-hour urine cortisol at 72ug/24hr and 81ug/24hr. She also had 2 elevated midnight salivary cortisol level at 0.338ug/dl and 0.349ug/dl. Other labs showed normal IGF-1 and normal DHEA-S. Patient was diagnosed with Cushing Disease and underwent successful transsphenoidal resection of the pituitary macroadenoma. Post operative cortisol was <2 ug/ul, she was initiated on hydrocortisone 20mg am and 10mg pm. Patient had continued monitoring for recovery of hypothalamic-pituitary-axis. A month after the surgery, patient got pregnant and was continued on her hydrocortisone and levothyroxine replacement. In our case the diagnosis and treatment of Cushing's disease was delayed due to clinical features mimicking PCOS. PCOS is a diagnosis of exclusion, and our case illustrates the importance of excluding the other endocrine pathologies, such as Cushing's disease, to prevent delaying the appropriate treatment and to mitigate the risk of increased morbidity and mortality that may be associated with them.

Studies on the contribution of PPAR Gamma to tuberculosis physiopathology.

Tuberculosis (TB) is a major health problem characterized by an immuno-endocrine imbalance: elevated plasma levels of cortisol and pro- and anti-inflammatory mediators, as well as reduced levels of dehydroepiandrosterone. The etiological agent, Mycobacterium tuberculosis (Mtb), is captured by pulmonary macrophages (Mf), whose activation is necessary to cope with the control of Mtb, however, excessive activation of the inflammatory response also leads to tissue damage. Glucocorticoids (GC) are critical elements to counteract the immunoinflammatory reaction, and peroxisome proliferator-activated receptors (PPARs) are also involved in this regard. The primary forms of these receptors are PPARϒ, PPARα, and PPARβ/δ, the former being the most involved in anti-inflammatory responses. In this work, we seek to gain some insight into the contribution of PPARϒ in immuno-endocrine-metabolic interactions by focusing on clinical studies in pulmonary TB patients and in vitro experiments on a Mf cell line. We found that TB patients, at the time of diagnosis, showed increased expression of the PPARϒ transcript in their peripheral blood mononuclear cells, positively associated with circulating cortisol and related to disease severity. Given this background, we investigated the expression of PPARϒ (RT-qPCR) in radiation-killed Mtb-stimulated human Mf. The Mtb stimulation of Mf derived from the human line THP1 significantly increased the expression of PPARϒ, while the activation of this receptor by a specific agonist decreased the expression of pro- and anti-inflammatory cytokines (IL-1β and IL-10). As expected, the addition of GC to stimulated cultures reduced IL-1β production, while cortisol treatment together with the PPARϒ agonist lowered the levels of this proinflammatory cytokine in stimulated cultures. The addition of RU486, a glucocorticoid receptor antagonist, only reversed the inhibition produced by the addition of GC. The current results provide a stimulating background for further analysis of the interconnection between PPARs and steroid hormones in the context of Mtb infection.

Tournament incentives affect perceived stress and hormonal stress responses

We conduct a laboratory experiment among male participants to investigate whether rewarding schemes that depend on work performance—in particular, tournament incentives—induce more stress than schemes that are independent of performance—fixed payment scheme. Stress is measured over the entire course of the experiment at both the hormonal and psychological level. Hormonal stress responses are captured by measuring salivary cortisol levels. Psychological stress responses are measured by self-reported feelings of stress and primary appraisals. We find that tournament incentives induce a stress response whereas a fixed payment does not induce stress. This stress response does not differ significantly across situations in which winners and losers of the tournament are publically announced and situations in which this information remains private. Biological and psychological stress measures are positively correlated, i.e. increased levels of cortisol are associated with stronger feelings of stress. Nevertheless, neither perceived psychological stress nor elevated cortisol levels in a previous tournament predict a subsequent choice between tournaments and fixed payment schemes, indicating that stress induced by incentives schemes is not a relevant criterion for sorting decisions in our experiment. Finally, we find that cortisol levels are severely elevated at the beginning of the experiment, suggesting that participants experience stress in anticipation of the experiment per se, potentially due to uncertainties associated with the unknown lab situation. We call this the novelty effect.

Cushing’s Syndrome Presenting as Nonconvulsive Status Epilepticus: A Case Report and Literature Review (P9-1.011)

<h3>Objective:</h3> NA <h3>Background:</h3> Cushing’s Syndrome (CS) may present with neuropsychiatric manifestations that can mimic autoimmune encephalitis, potentially delaying diagnosis and treatment. We present a case of CS presenting with personality changes and status epilepticus and performed a literature review describing neurological manifestations of CS. <h3>Design/Methods:</h3> A male in his 50s presented with episodic word-finding difficulties, inappropriate smiling, fatigue, cognitive decline and one episode of generalized tonic clonic seizure on levetiracetam from an outside hospital. Workup revealed thrombocytopenia, hypokalemia, hypertension, normal MRI brain and sella. Continuous electroencephalogram revealed nonconvulsive status epilepticus. Lumbar puncture demonstrated elevated protein with normal white blood cell count. He was started on high-dose IV methylprednisolone followed by IVIg for presumed autoimmune encephalitis. Autoimmune encephalitis antibodies including anti-NMDA receptor were negative. CT PET scan showed bilateral adrenal enlargement, which in the context of hypokalemia, hyperglycemia, hypertension, and thrombocytopenia was concerning for severe Cushing’s Syndrome. Methylprednisolone and anti-seizure medications were stopped. Inferior petrosal sinus sampling and cerebral angiogram were unremarkable. The diagnosis was supported by elevated random and urine cortisol levels and managed with etomidate and ketoconazole. He underwent bilateral open adrenalectomy following which he was started on oral glucocorticoids. Repeat EEG showed no ictal activity and the patient remained seizure-free. <h3>Results:</h3> Literature review utilizing PubMed identified 17 articles describing CS presenting with neuropsychiatric symptoms. The most common symptoms cited were cognitive decline (23%), psychosis (18%) and seizure (6%). Additional isolated cases cited posterior reversible encephalopathy syndrome, hypogeusia and hyposmia. Most patients had significant improvement or full recovery once CS was treated. <h3>Conclusions:</h3> Cushing’s Syndrome can present with neuropsychiatric symptoms and status epilepticus. It can be an emergency requiring prompt endocrine and surgical evaluation. Serum cortisol levels should be checked in patients presenting with acute personality changes and seizures. <b>Disclosure:</b> Dr. Cameron has nothing to disclose. Dr. Venegas has nothing to disclose. Dr. Fahad has nothing to disclose. Dr. Mathew has nothing to disclose.

Features of the relationship between the levels of regulation of hemodynamics and the activity of immune reactions in healthy and patients with coronary heart disease residents of the European North and the Arctic of the Russian Federation

Objective. To establish the features and interrelation of the levels of hemodynamics and the activity of immune reactions regulation in practically healthy people and patients with coronary heart disease living in the European North and the Arctic of the Russian Federation.Material and methods. The study included 430 people aged 21 to 55, 274 women and 156 men, living in Arkhangelsk region (Arkhangelsk, settlements of the Konosha district; 60° N.L., 40° E.L.), Murmansk region (settlements of Revda and Lovozero; 67° N.L., 34° E.L.) and the Spitsbergen archipelago (Barentsburg; 80° N.L., 10° E.L.). 244 of those were practically healthy at the time of the examination and 186 patients were diagnosed with coronary heart disease. The research included the study of hemogram, content of phenotypes of CD3+, CD4+, CD8+, CD16+, CD71+ lymphocytes, concentrations of sCD71, transferrin, IL-1β, epinephrine, norepinephrine, dopamine, Nt-pro-BNP, endothelin-1, total NO, endogenous NO2, nitrate NO3, cGMP, cAMP, antibodies to cardiolipin, antibodies to phospholipids, CEC IgM.Results. It was found that practically healthy residents of the Arctic, compared to people living in more favorable climatic conditions, are 2–2.5 times more likely to have elevated concentrations of transferrin, sCD71, dopamine, cortisol, endothelin-1 and Nt-pro-BNP, as well as autoantibodies to cardiolipids and IgM CIC in the plasma of venous peripheric blood. In patients with coronary heart disease, the frequency of elevated levels of trasferrin, endothelin-1, and cortisol in the blood is 1.5–2 times higher, and concentrations of natriuretic peptide, antiphospholipids, CIC and a free pool of transferrin receptors are 4–5 times higher than those in healthy people. The strongest correlations of all these factors with the concentration of the cardiomyocyte damage marker were found in sCD71, which confi rms the involvement of elevated concentrations of the serum transferrin receptor in the mechanisms of tissue damage.Conclusion. Hyperfunction of the cardiovascular system is provided by elevated reactions. A systematic increase in the levels of hemodynamic reactions, intercellular interactions, and integration of homeostasis regulation mechanisms provide correction of a certain stage of regulation and may lead to a reduction in reserve regulatory capabilities and excessive severity of adaptive processes.

Changes in serum cortisol levels after 10 days of overfeeding and fasting.

Chronic caloric deprivation and obesity are complicated by hypercortisolemia. The effects of acute overfeeding and fasting on circulating free cortisol levels and conversion of cortisone to free cortisol are unknown. We hypothesized that serum-free cortisol and free cortisol-to-cortisone ratio would increase after both overfeeding and fasting. This is a prospective study of 22 healthy volunteers who completed a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-wk washout. Morning free and total cortisol and free cortisone levels (LC/MS) were measured at baseline and after 10 days of each intervention. Both high-calorie feeding and fasting increased total and free cortisol and the free cortisol-to-free cortisone ratio (P = 0.001 to P = 0.046). There were sex interactions, with significant effects in men (P < 0.001), but not in women (P = 0.898 and 1.000, respectively) in subset analyses examining the effects of fasting on free cortisol and the free-to-total cortisol ratio. Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility.NEW & NOTEWORTHY Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. The effect of fasting on free cortisol levels is modified by sex. Further study is needed to determine the mechanisms driving the increases in cortisol.

A Systematic Review and Meta-Analysis of Basal and Post-Stress Circulating Cortisol Concentration in an Important Marine Aquaculture Fish Species, European Sea Bass, Dicentrarchus labrax.

European sea bass is a species characterized by high and dispersed cortisol levels. The aim of the present study was to analyze all published data on basal and post-acute stress cortisol levels in this species. For this systematic review and meta-analysis the Web of Science and Scopus databases were searched for papers reporting plasma or serum cortisol levels in E. sea bass, without language or date restrictions. Data were extracted directly for the reported results and were analyzed separately for basal and post-acute stress levels, as well their standardized mean differences (SMD) using random-effects meta-analyses. Of 407 unique records identified, 69 were eligible. Basal cortisol levels had a pooled effect of 88.7 ng mL-1 (n = 57), while post-acute stress levels were 385.9 ng mL-1 (n = 34). The average SMD between basal and post-stress was calculated to be 3.02 (n = 22). All analyses had a high between-study heterogeneity. Results for basal and post-stress levels were affected by the assay type and anesthesia prior to blood sampling. Cortisol levels in E. sea bass are higher than most studied fish species and display large heterogeneity. Application of stress led to elevated cortisol levels in all studies examined. In all cases, sources of between-studies heterogeneity were identified.