Changes In Cortisol Levels Research Articles

A Study to Assess Changes in Cortisol Level and Heart Rate Variability between Fixed Duty and Shift Duty Health Care Providers in a Tertiary Care HospitalA Cross-Sectional Study

Introduction: Increased demand of service 24 hours around the clock has divided the workers into 2 domains as “Fixed duty” and “Shift duty”. Personals associated with shift duty are increasing in numbers day by day. Shift duty or more specifically night duty is associated with increased stress which results in high morbidity and decrease in work efficiency. Cortisol hormone and Heart Rate Variability (HRV) are useful parameters to determine the effects of stress. Aim: To find any change in cortisol levels, HRV, Athens score among the fixed duty and shift duty healthcare providers. Materials and Methods: A descriptive cross-sectional comparative study was conducted in a tertiary care hospital at Kolkata between July, 15th to Sept, 15th 2021. Predesigned and pretested questionnaire was made and ethical clearance was taken from institutional IEC. Then after taking consent total 120 (60 fixed duty and 60 shift duty) healthcare providers were recruited for the study. Subjects of the study filled up a questionnaire {including Athens Insomnia Scale (AIS)}. After applying exclusion criteria (any cardiovascular, neurological, psychological, sleep disorder) 120 health individuals were taken five minutes short-term HRV (time and frequency domain) recording in supine posture and 4 PM blood sample (for cortisol) were obtained from the participants which was further analysed in Chemiluminescence Immunoassay (CLI). Data was analysed in SPSS version 20.0. Statistical tests like student t-test, Cron bach’s alpha and chi-square tests were applied significant p<0.05 (95% CI). Results: After analysis, shift duty workers showed a significant (p<0.001, Odd’s 10.706) higher chance of having insomnia (Athens score >6) than fixed duty workers. Blood test showed that shift duty workers had significantly high evening cortisol level than fixed duty workers (p= 0.036). The time domain of HRV showed that the parameters like Standard Deviation all NN interval (SDNN) (p=0.001), Mean HR (p=0.037), RMSSD (p <0.001), NN50 (p=0.006), pNN50 (p=0.002) were significantly different in the two groups. Whereas the frequency domain of HRV showed that HF power was lower and LF power (p=0.002), LF/HF ratio (p <0.001) were significantly higher in shift duty workers. Conclusion: The study showed that shift duty workers had comparatively higher stress levels resulting in significantly high sympathetic drive and increased risk of insomnia. This can be associated with morbidity and ill health in the shifting duty workers.

Food-dependent Cushing's syndrome due to unilateral adrenocortical adenoma with cortisol secretion without ACTH elevation detected in peripheral blood by the CRH test: a case report.

We report an extremely rare case of a 61-year old woman with food-dependent Cushing's syndrome (FDC) due to unilateral adrenocortical adenoma (UAA) with cortisol (CORT) secretion without ACTH elevation detected in peripheral blood by the CRH test. She was on oral medications for hypertension and depression, and presented weight gain, general fatigue, muscle weakness, and hypokalemia. Despite the fact that the diurnal variation of ACTH was always suppressed, a diurnal variation in CORT was observed, in the form of low levels in the early morning and high levels in the afternoon. An increase in CORT was shown in a 75 g-oral glucose tolerance test (OGTT) and in a mixed meal tolerance test, but no change in CORT levels was seen in intravenous glucose tolerance tests. Elevated CORT levels were observed in response to intravenous injection of CRH, although ACTH levels were always below the measured sensitivity. Laparoscopic left adrenalectomy was performed, which resulted in postoperative improvement in potassium and ACTH levels and disappearance of the CORT secretory response in the OGTT. Clear expression of glucose-dependent insulinotropic polypeptide receptor (GIPR), CRH and CRH receptor 2 (CRHR2) were confirmed in the surgically-resected UAA specimen by molecular and immunohistochemical analyses, suggesting the involvement of not only GIPR, but also CRH and CRHR2 in FDC.

The effect of acute stress on spatial selectivity in dual-stream emotion induced blindness: The role of cortisol and spontaneous frontal EEG theta/beta ratio.

The current study explored the effect of acute stress on dual-stream emotion induced blindness (EIB). We focused on spatially localised target processing induced by stress, as well as the role of cortisol and the frontal EEG theta/beta ratio (TBR). Eight-minutes spontaneous EEG data were recorded first. After performing a Trier Social Stress Test (TSST) or a corresponding control task a week apart, the participants completed a dual-stream EIB task. Changes in cortisol levels over time were likewise recorded. We found that stress promoted the target processing in the same stream location as the distractor, eliminating the spatial-localisation effect. Cortisol and frontal TBR positively and negatively, respectively, predicted a reduced spatially localised target detection induced by stress following negative distractors. Overall, acute stress apparently reduced the dual-stream EIB due to the effective allocation of limited resources. Further, the role of cortisol associated with better target detection was more specific to the negative distractor condition and partially disassociated from the general stress response. Cortisol levels and frontal TBR independently predicted the spatially localised processing, suggesting differentiated influence paths of trait and state factors on target detection following emotional distractors.

Non-randomized controlled trial examining the effects of livestock on motivation and anxiety in patients with chronic psychiatric disorders.

Patients with chronic schizophrenia exhibit negative symptoms, including decreased work motivation. Animal-assisted therapy programs have been reported to benefit such patients; hence, there is a possibility that sheep-rearing, rather than conventional employment training, may motivate these patients. Therefore, we investigated the effects of a one-day experiential learning program of sheep-rearing on the work motivation and anxiety of patients with chronic schizophrenia. Fourteen patients were included in a non-randomized controlled trial conducted between August 2018 and October 2018. The patients' participation in the sheep-rearing experiential learning (one day; intervention day) and normal day care (one day; control day) programs were compared. The salivary cortisol and testosterone levels and State-Trait Anxiety Inventory (STAI) scores of the patients were analyzed. The patients' salivary testosterone was significantly higher on the intervention day (p = 0.04) than on the control day (p = 0.02). Their salivary cortisol was lower on the control day than on the intervention day, although the difference was not significant. Regression analysis was performed based on the change in salivary cortisol levels and STAI-Trait scores (p = 0.006), and a regression equation was established. The study revealed that participation in sheep-rearing may have promoted the testosterone production but did not increase anxiety in patients with schizophrenia. Additionally, regression equations for salivary cortisol levels in such patients may provide information on individual differences in anxiety levels.

THE EFFECTIVENESS OF GUIDED IMAGERY ON DEPRESSION AND CORTISOL LEVELS IN COLON RECTAL CANCER PATIENTS

Background: Depression in colon rectal cancer patients can inhibit the healing process, increasing the morbidity and mortality. Purpose of the study: This study aims to determine the effectiveness of guided imagery on the level of depression and cortisol. Guided imagery is a relaxation and comfort therapy that can provide a calm effect. Guided imagery is performed by guiding the patient in imagining a beautiful and comfortable place. Research Method: This study uses experimental design. The study sample consist of 52 patients with colon rectal cancer who undergo the treatment. Depression levels and examination of cortisol levels are carried out before and after the intervention. Guided imagery is given to 26 people in the intervention group, and 26 people in the control group for the standard care. Data analysis using independent t-test and dependent t-test if the data is normally distributed. Results: The use of Guided Imagery therapy can reduce the average level of depression in CRC patients but does not show changes in cortisol levels in patient's body.

Effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles of diabetic and non-diabetic patients with low back pain.

We aimed to investigate the effect of repeated transforaminal epidural low-dose dexamethasone injections on glucose profiles and pituitary-adrenal axis functions of diabetic and non-diabetic patients with low back pain. A total of 28 patients (ten diabetic [DM group] and 18 non-diabetic patients [non-DM group]) with low back pain were followed-up. Transforaminal epidural low-dose dexamethasone (1.65mg) injections were repeated every 7-14days for 8weeks. Fasting blood sugar (FBS), hemoglobin A1c (HbA1c), morning plasma adrenocorticotropin (ACTH), and cortisol levels were measured at baseline and during the 8-week follow-up period. There were no significant changes in FBS and HbA1c levels between baseline and 8-week follow-up period in both DM and non-DM groups (difference in FBS [95% confidence Interval, CI]: -0.6mg/dL [-6.4, 5.1], p = 0.83 in the non-DM group, -0.2mg/dL [-26.2, 25.8], p = 0.99 in the DM group; difference in HbA1c [95% CI] -0.02% [-0.1, 0.1], p = 0.69 in the non-DM group, 0.04% [-0.3, 0.4], p = 0.79 in the DM group). There were no significant longitudinal changes in ACTH and cortisol levels (ACTH, p = 0.38 [baseline vs. 8week], p = 0.58 [non-DM vs. DM]; cortisol, p = 0.52 [baseline vs. 8week], p = 0.90 [non-DM vs. DM]). Repeated transforaminal epidural low-dose dexamethasone injections provided no significant elevations in blood glucose or suppression of the pituitary-adrenal axis for two months from the first injection in both diabetic and non-diabetic patients. Our results indicate the intermediate-term safety of repeated transforaminal epidural low-dose dexamethasone injections with regard to the effect on glucose profile and pituitary-adrenal axis functions.

"Following the Breath:" A Trauma-Informed Intervention for Educator Wellness in Rural Montana.

Given the prevalence of mental health issues for both educators and adolescents in rural Montana, this project is designed to help mitigate the impact of stressors by providing coping strategies linked to improvements in overall mental health outcomes for teachers, which may ultimately lead to improved co-regulation of students and classroom climate. The immediate goal of this pilot study was to measure physical and mental health outcomes of educators resulting from a remotely-delivered trauma-informed yoga intervention. Findings suggest improvements in participants' depression and anxiety levels, trauma symptoms, sleep quality, and non-significant changes in heart rate variability and cortisol levels.

Changes in the Serum Concentration Levels of Serotonin, Tryptophan and Cortisol among Stress-Resilient and Stress-Susceptible Individuals after Experiencing Traumatic Stress

Stress is a common response to many environmental adversities. However, once dysregulated, this reaction can lead to psychiatric illnesses, such as post-traumatic stress disorder (PTSD). Individuals can develop PTSD after exposure to traumatic events, severely affecting their quality of life. Nevertheless, not all individuals exposed to stress will develop psychiatric disorders, provided they show enhanced stress-resilience mechanisms that enable them to successfully adapt to stressful situations and thus avoid developing a persistent psychopathology. The study involved 93 participants. Of them, 62 comprised a study group and 31 comprised a control group. The aim of the study was to assess serotonin, cortisol and tryptophan concentration levels in subjects with PTSD (stress-susceptible; PTSD-SS) and in healthy individuals (stress-resilient; PTSD-SR), who had experienced a traumatic event but fully recovered after the trauma. The subjects were between 18 and 50 years of age (mean 35.56 ± 8.26 years). The serum concentration levels of serotonin, cortisol and tryptophan were measured with an ELISA kit. It was found that the serotonin, tryptophan and cortisol concentration levels were consistent with the features of both PTSD-SR and PTSD-SS patients. It was reported that the mean cortisol concentration levels increased more significantly in the PTSD-SS group than in the PTSD-SR group, versus those in the control group. Similarly, the PTSD-SS group was found to show a larger decrease in the mean serotonin concentration levels than the PTSD-SR group, versus those in the control group. No significant changes were found in the tryptophan concentration levels between the study groups, versus those in the control group. These findings can be useful when attempting to improve resilience in individuals using neuropharmacological methods. However, it is necessary to conduct more cross-sectional studies that would address different types of negative stress to find out whether they share common pathways.

Moderators of ayahuasca's biological antidepressant action.

The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

Metabolic and hormonal changes after laparoscopic sleeve gastrectomy in pediatric population: An observational study.

Despite the growing popularity of laparoscopic sleeve gastrectomy (SG) for managing severe obesity in children, adolescents, and adults, there is a paucity of studies reporting the effects of SG on metabolic and hormonal outcomes in pediatric populations. In this single-centre, retrospective study, we assessed nutritional biomarkers (hemoglobin, ferritin, iron profile, Vitamin B12, Vitamin D, and calcium), glucose homeostasis indicators (C-peptide, HbA1C, and random blood glucose), blood lipids (triglycerides and cholesterol components), hormones involved in the hypothalamic-pituitary-adrenal axis (cortisol and adrenocorticotropic hormone), and thyroid hormones (T3, T4, thyroid-stimulating hormone, and parathyroid hormone) preoperatively and 12-month after SG in children aged 5-15 years. This study included 64 adolescents (mean age = 11.2 ± 2.3 years) who underwent laparoscopic SG. Significant reduction in circulatory C-peptide (-62.1%; p = 0.005), HbA1C (-10.9%; p = 0.001), random blood glucose (-15.4%; p = 0.036), and triglycerides (-39.4%; p = 0.003) were observed postoperatively at 12 months compared to baseline. Although we did not observe any changes in cortisol levels, adrenocorticotropic hormone levels declined significantly by -40.9% postoperatively (p = 0.033). However, cholesterol components, thyroid hormones, and nutritional biomarkers remained unchanged from baseline. Consistent with prior literature, our study demonstrates improvement or resolution of diabetes and hypertriglyceridemia in the year following SG. However, given that blood cholesterol components, nutritional biomarkers, and thyroid profiles remained unchanged warrants long-term monitoring of nutritional, metabolic, and endocrine factors in adolescents undergoing laparoscopic SG. To the best of our knowledge, this is the first study reporting the effects of SG on thyroid and hypothalamic-pituitary-adrenal axis hormones in pediatric populations.

Behavioral and physiological response to inequity in bonobos (Pan paniscus).

Inequity aversion (IA), the affective, cognitive, and behavioral response to inequitable outcomes, allows individuals to avoid exploitation and therefore stabilizes cooperation. The presence of IA varies across animal species, which has stimulated research to investigate factors that might explain this variation, and to investigate underlying affective responses. Among great apes, IA is most often studied in chimpanzees. Here, we investigate IA in bonobos, a reputedly tolerant and cooperative species for which few IA studies are available. We describe how bonobos respond to receiving less preferred rewards than a partner in a token exchange task. We show that bonobos respond to receiving less preferred rewards by refusing tokens and rewards, and by leaving the experimental area. Bonobos never refused a trial when receiving preferred rewards, and thus showed no advantageous IA. We also investigate the variability in the disadvantageous IA response on a dyadic level, because the level of IA is expected to vary, depending on characteristics of the dyad. Like in humans and chimpanzees, we show that the tolerance towards inequity was higher in bonobo dyads with more valuable relationships. To study the affective component of IA, we included behavioral and physiological measures of arousal: a displacement behavior (rough self-scratching) and changes in salivary cortisol levels. Both measures of arousal showed large variability, and while analyses on rough self-scratching showed no significant effects, salivary cortisol levels seemed to be lower in subjects that received less than their partner, but higher in subjects that received more than their partner, albeit that both were not significantly different from the equity condition. This suggests that although overcompensated bonobos showed no behavioral response, they might be more aroused. Our data support the cooperation hypothesis on an interspecific and intraspecific level. They show inequity aversion in bonobos, a reputedly cooperative species, and suggest that the variability in IA in bonobos can be explained by their socioecology. Most successful cooperative interactions happen between mothers and their sons and among closely bonded females. The limited need to monitor the partners'investment within these dyads can result in a higher tolerance towards inequity. We therefore suggest future studies to consider relevant socioecological characteristics of the species when designing and analyzing IA studies.

Metabolic biological markers for diagnosing and monitoring the course of tuberculosis

The international biomedical community has been currently facing a need to find a simple and most accessible type of analysis that helps to diagnose tuberculosis (TB) with the maximum reliability even before the onset of clinical manifestations. Tuberculosis results in more deaths than any other pathogen, second only to pneumonia caused by the SARS-CoV-2 virus, but the majority of infected people remain asymptomatic. In addition, it is important to develop methods to distinguish various forms of tuberculosis infection course at early stages and to reliably stratify patients into appropriate groups (persons with a rapidly progressing infection, chronic course, latent infection carriers). Immunometabolism investigates a relationship between bioenergetic pathways and specific functions of immune cells that has recently become increasingly important in scientific research. The host anti-mycobacteria immune response in tuberculosis is regulated by a number of metabolic networks that can interact both cooperatively and antagonistically, influencing an outcome of the disease. The balance between inflammatory and immune reactions limits the spread of mycobacteria in vivo and protects from developing tuberculosis. Cytokines are essential for host defense, but if uncontrolled, some mediators may contribute to developing disease and pathology. Differences in plasma levels of metabolites between individuals with advanced infection, LTBI and healthy individuals can be detected long before the onset of the major related clinical signs. Changes in amino acid and cortisol level may be detected as early as 12 months before the onset of the disease and become more prominent at verifying clinical diagnosis. Assessing serum level of certain amino acids and their ratios may be used as additional diagnostic markers of active pulmonary TB. Metabolites, including serum fatty acids, amino acids and lipids may contribute to detecting active TB. Metabolic profiles indicate about increased indolamine 2.3-dioxygenase 1 (IDO1) activity, decreased phospholipase activity, increased adenosine metabolite level, and fibrous lesions in active vs. latent infection. TB treatment can be adjusted based on individual patient metabolism and biomarker profiles. Thus, exploring immunometabolism in tuberculosis is necessary for development of new therapeutic strategies.

Abnormal cortisol profile during psychosocial stress among patients with schizophrenia in a Chinese population

Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and pre- and post-task saliva samples were collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule and Positive and Negative Syndrome Scale. The results showed (1) that the cortisol response and negative emotions in patients with schizophrenia differed significantly from those in healthy volunteers, (2) there were significant interactions between the sampling time and diagnosis for saliva cortisol levels, (3) there were significant interactions between the scoring time and diagnosis for the negative affect score of the PANAS, and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. These findings indicated an abnormal cortisol profile in patients with schizophrenia, which might be a biological characteristic of the disease.

RF01 | PMON168 Hedgehog-Induced Somatostatin Receptor Expression is Inhibited by the Activation of the Glucocorticoid Receptor Signaling Pathway in Human Pituitary Adenoma Organoids

Abstract Background Cushing's disease (CD) is an endocrine disorder caused by an ACTH-secreting pituitary adenoma that is associated with increased morbidity and mortality. Because somatostatin inhibits pituitary ACTH secretion, the somatostatin receptor subtypes (SSTR) 2 and 5 have been targets of medical therapies for CD. The SSTR5 is most consistently and strongly expressed in corticotroph pituitary tumors but the SSTR dynamics in CD during treatment and responses to cortisol level changes are far from being understood. Studies in adult stomach demonstrated that the Hedgehog (Hh) signaling pathway is critical for the regulation of somatostatin and SSTR signaling. While Hh signaling is known to be essential during the embryonic development of the pituitary and in the adult gland, the mechanism by which Hh signaling regulates SSTR expression in CD is unknown. Hypothesis Activation of glucocorticoid receptor (NR3C1, GR) results in the inhibition of Hh transcription factor GLI1 leading to reduced SSTR expression. Methods We developed a human pituitary adenoma organoid model (hPITOiPSC) from induced pluripotent stem cells treated with the glucocorticoid receptor (GR) antagonist mifepristone, and co-treated them with or without SSTR agonists pasireotide or octreotide. In a separate series of experiments, the role of Hh transcription factor GLI1 was identified using hPITOiPSC treated with mifepristone with or without GANT61 (GLI inhibitor) or ketoconazole (Smoothened, SMO inhibitor). CRISPR-Cas9 gene editing of hPITOiPSC pituitary organoids were used to model the development of pituitary corticotroph adenomas in the presence of BRAF, USP48 and USP8 mutations. Human pituitary adenoma tissue harvested fresh during pituitary surgery was used to generate pituitary corticotroph subtype adenoma organoids (hPITOs). Dose responses using standard of care drugs were performed using the hPITOs. Results 1) At baseline SSTR2 was abundantly expressed within hPITOiPSC. Mifepristone induced significant increases in ACTH secretion and POMC expression that correlated with induced SSTR2 and 5. Mifepristone-induced SSTR2 and 5 expression was significantly inhibited in the presence of GANT61, whereas SMO inhibitor ketoconazole had a minimal effect on mifepristone-induced SSTR2/5, POMC expression and ACTH secretion. Dexamethasone alone significantly inhibited both GLI1 and SSTR2 and 5. 2) While pituitary organoids that were differentiated from control iPSCs (iPSCCtrl) expressed all major hormone-producing cell lineages, there was a significant increase in ACTH expression with loss of PIT1, GH, FSH, LH and PRL in iPCSs expressing mutated BRAF, USP48 and USP8. Organoids expressing a mutation in BRAF had significantly higher SSTR2 expression levels compared to controls. 3) HPITOs generated from pituitary adenomas of CD patients showed differential organoid responses to pasireotide, mifepristone, and ketoconazole. Conclusion Within pituitary adenomas, the SSTR is a transcriptional target of Gli1, and this response is blocked by the activation of the GR. These data form the basis of combination therapy for CD with mifepristone and pasireotide. Presentation: Saturday, June 11, 2022 1:37 p.m. - 1:42 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Comparison of dorsal penile nerve block alone and in combination with lidocaine–prilocaine cream in neonates undergoing circumcision: a randomized controlled study

BackgroundSuboptimal neonatal circumcision analgesia causes a significant stress response. There is continued search for more effective analgesia for neonatal circumcision. We aimed to determine whether lidocaine–prilocaine cream (LPC) prior to...

ODP618 The profile of patients with ACTH-secreting pituitary adenomas and subclinical pituitary apoplexy

Abstract Background Subclinical hemorrhage or necrosis of pituitary adenomas (PAs), often defined as subclinical pituitary apoplexy (SPA), presents in up to 20% of all PAs and is more common in large prolactinomas. SPA in corticotropinomas in patients with Cushing disease (CD) is not common and the clinical and biochemical characteristics of patients with CD and SPA are not known. Subjects and methods: Pediatric patients with confirmed CD diagnosed between 2005-2021 with available MRI images before any surgical intervention were included in the study (n= 171). SPA diagnosis was based on MRI findings. Although MRI sequences and machines were not same for all patients and varied over time, the results were based on possible signs of hemorrhage on the available images, but smaller areas of bleeding or necrosis may have been missed. Statistical analyses were performed with Wilcoxon signed-rank test, chi-square or Fisher's exact test, and Cox proportional hazard as appropriate. Results are shown as median [Q1, Q3], count (percentage) and odds ratio (OR) (95% confidence intervals, 95%CI). Results Out of 171 patients, 12 patients (7%) were found to have imaging characteristics of possible hemorrhage or intratumor infarct. Patients with and without SPA were similar in age (median age: 12.5 years [10.6, 15.6] in SPA group vs 13.1 years [10.6, 15.4] in non-SPA group, p= 0.95) and gender distribution (n of female= 5 (41.7%) in SPA group vs 89 (56%) in non-SPA group, p= 0.51). Patients with SPA had shorter duration of disease as noted by changes in their growth chart parameters (median duration: 1. 0 year [1. 0, 2. 0] in SPA group vs 2.5 years [1.5, 3. 0] in non-SPA group, p= 0. 014). Morning and midnight cortisol and 24hour urinary cortisol levels were similar in both groups, but patients with SPA had higher levels of morning ACTH (60.8 pg/mL [43.5, 80.3]) compared to patients without SPA (39.8 pg/mL [28.5, 53.4], p=0. 017). Change of cortisol and ACTH levels during CRH stimulation test were similar between the two groups, but patients with SPA had lower suppression of cortisol after overnight high dose (8mg or weight-based equivalent) dexamethasone suppression test (58. 0% [-85.4, -49.7]) compared to patients without SPA (85.8 [-90.5, -76.8], p= 0. 035). Specifically, patients with SPA had lower chance of passing the threshold of 69% that it suggestive of pituitary source of hypercortisolemia compared to patients without SPA (OR: 0.18, 95%CI: 0. 03-0.95). The odds of remission after surgery and the risk of recurrence after initial remission did not differ based on the presence of SPA. Conclusion Patients with CD and sings of hemorrhage or necrosis in their tumor may present with different characteristics on their biochemical evaluation which should be considered during their diagnostic workup, especially in the setting of a discordant dexamethasone suppression test. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Peripartum prolactin and cortisol level changes. A prospective pilot study.

Although the role of prolactin and cortisol in the human lactation process seems to be undisputed, the changes in postpartum serum concentrations in mothers make data interpretation difficult. To determine the factors that possibly influence these hormones, we examined a group of patients who were admitted to the Gynecology-Obstetrics Clinical Hospital in Poznań for labor induction and/or in the active phase of the first labor period. The serum levels of cortisol and prolactin were assessed in these full-term pregnant women during admission to labor, in the third stage of labor, and on the second day postpartum. The prolactin and cortisol levels were also measured in the umbilical cord for the assessment of newborn babies. The results showed a significant relationship between maternal age and the level of prolactin measured before childbirth and fluctuations in cortisol level with respect to labor duration. In addition, we observed a strong correlation between the level of prolactin assessed before childbirth and the pH and base excess of the umbilical cord artery. Most importantly, a correlation was noted between breastfeeding within 2 hours after the labor and the level of cortisol measured after childbirth. We observed a significant correlation between a summarized labor duration and maternal and umbilical cord cortisol levels measured right after the labor. The fact of breastfeeding within 2 hours after the labor strongly correlated with lower levels of maternal cortisol as well as a cortisol level in umbilical cord blood and it suggests that immediate initiation of breastfeeding reduces stress level for both, mother and newborn.

Application of Felid Hair for Non-Invasive Tracking of Animal Reproductive Status and Adrenal Activity.

Simple SummaryHair can be a useful matrix to examine the hormonal status of an animal, although it is difficult to correlate the results to a specific time point. We measured seasonal changes in cortisol and testosterone levels in four feline species with different breeding strategies. Both hormones showed annual dynamic fluctuations, which coincided with the reproductive traits of the studied species. Seasonal increases in testosterone were observed in three seasonal breeders (lynx, Amur wildcat and domestic cat) but not in caracal, an aseasonal species, which sustained high testosterone levels over the whole year. Sexual differences in testosterone level were found for these species only during the mating season, when testosterone levels were higher in males than in females. Cortisol levels increased during the mating period, and in caracal an increase in cortisol was associated with the transfer of animals to smaller cages.Hair can be a useful matrix to examine the hormonal status of an animal, although it is difficult to correlate the results to a specific time point. The aim of this study was to evaluate seasonal changes in cortisol and testosterone levels in the hair of four feline species (lynx, Lynx lynx, n = 8; Amur wildcat, Prionailurus bengalensis euptilurus, n = 8; caracal, Caracal caracal, n = 6 and domestic cat, Felis catus, n = 17) with different breeding strategies. Animals of both sexes were sampled over the year, once per season (every three months), and the concentrations of hair testosterone and cortisol were measured by EIA. Both hormones showed annual dynamic changes, which coincided with the reproductive seasonality of the studied species. Sexual differences in testosterone level were found only during the mating season (spring for lynx and Amur wildcats, spring–summer for domestic cats), when testosterone levels were higher in males than in females. Cortisol levels were higher in males than in females in domestic cats and Amur wildcat, but also only during the mating season. Seasonal increases in testosterone were observed in three seasonal breeders (lynx, Amur wildcat and domestic cat) but not in caracal, which had high testosterone levels over the whole year. In lynx and Amur wildcat, it decreased sharply in the summer. Cortisol levels increased during the mating period in domestic cat males and lynx of both sexes; in caracal, an increase in cortisol was related to the transfer of animals to smaller winter cages. Measurements of steroids in hair can provide a reliable method for evaluating the reproductive status and the activity of the hypothalamus–pituitary–adrenal axis in several felid species.

A safety and pharmacodynamic study of the highly selective aldosterone synthase inhibitor PB6440 in the cynomolgus monkey

Abstract Background Aldosterone is an important mediator of hypertension, particularly resistant hypertension, heart failure, and chronic kidney disease. PB6440 is a potent inhibitor of aldosterone synthase (CYP11B2) with high selectivity over the closely related enzyme CYP11B1. In previous studies in cynomolgus monkeys, PB6440 exhibited excellent oral bioavailability and a marked suppression of aldosterone synthesis at doses as low as 1 mg/kg/day. Importantly, no effect was observed on cortisol production nor significant changes noted in plasma concentrations of the steroid precursors 11-deoxycortisol or deoxycorticosterone (DOC), which are dependent on CYP11B1 activity. The purpose of the current study was to assess the safety and pharmacodynamics of higher doses of PB6440 in the cynomolgus monkey in order to determine a therapeutic index prior to initiation of studies in humans. Methods Male and female cynomolgus monkeys (2/sex/dose group) were administered 0, 10, 30 or 100 mg/kg PB6440 once-daily for 14 days by oral gavage. Assessment of safety was based on mortality, clinical observations, body weights, and clinical and anatomic pathology. Blood samples were also collected for pharmacodynamic analysis, including aldosterone, cortisol, 11-deoxycortisol, DOC, and ACTH. Results PB6440 was well tolerated at all doses. There were no deaths and no reports of clinical observations at any dose level. Mild decreases in body weight were observed in PB6440-treated animals, which were likely due to the diuretic effects of the compound. PB6440 caused an increase in adrenal weights which was associated with hypertrophy of the adrenal zona fasciculata, a finding which has previously been observed with other aldosterone synthase inhibitors. PB6440 led to marked declines in basal aldosterone levels of −97%, −97% and −98% from baseline at 10, 30 and 100 mg/kg/day, respectively, at 24-hours following the final dose. Despite these clear declines in circulating aldosterone levels, no meaningful changes in cortisol, 11-deoxycortisol, DOC, or ACTH levels were observed, supporting lack of CYP11B1 inhibition. PB6440 led to expected decreases in plasma sodium (up to 7 nmol/L at the high dose). No effect on plasma potassium levels were observed at any dose level. Conclusions PB6440 was well tolerated in the cynomolgus monkey at doses that are much higher than needed for potent aldosterone suppression based on previous studies. At the highest dose level tested (100 mg/kg), which led to a 98% reduction in basal aldosterone levels, no evidence of significant CYP11B1 inhibition was observed. The absence of an increase in plasma potassium in the presence of a plasma sodium decline merits further study. Thus, PB6440 is a highly selective novel aldosterone synthase inhibitor for the potential treatment of hypertension, heart failure, and chronic kidney disease in humans. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): PhaseBio Pharmaceuticals Inc.

Fitness consequences of chronic exposure to different light pollution wavelengths in nocturnal and diurnal rodents

Use of artificial at night (ALAN) exposes the world to continuously increasing levels and distribution of light pollution. Our understanding of the adverse effects of ALAN is based mostly on observational or laboratory studies, and its effects are probably underestimated. Demonstration of direct experimental fitness consequences of ALAN on mammals is missing. We studied the effects of chronic light pollution at different wavelengths on fitness and glucocorticoid hormone levels under semi-natural conditions in two closely related species: the nocturnal common spiny mouse (Acomys cahirinus) and the diurnal golden spiny mouse (Acomys russatus). Our results clearly demonstrate the adverse effects of ALAN exposure on the fitness of both nocturnal and diurnal species, manifested by changes in cortisol levels and reproductive timing, reduced reproductive output and reduced survival, which differed between species and wavelengths. In A. russatus exposure to blue ALAN had the strongest effect on fitness, followed by white and yellow ALAN exposure. In A. cahirinus the results are more complex and suggest it suffered from the combined effects of ALAN and competition. Our research shows that light pollution presents a real threat to both nocturnal and diurnal species, affecting the species fitness directly and through interspecific interactions. Worryingly, these effects are probably not limited to spiny mice. The clear adverse effects we documented, as well as the differences between wave lengths, contribute to our ability to present science-based recommendations to decision makers regarding the use of artificial light at night. Such information and guidelines are highly important nowadays when lighting systems are being replaced to promote energy efficiency.