Effects of combined postweaning social isolation and ketamine administration on schizophrenia-like behaviour in male Sprague Dawley rats.

The pathophysiology behind negative and cognitive symptoms of schizophrenia is not well understood, thus limiting the effectiveness of treatment on these symptoms. Developing reliable animal model of schizophrenia is vital to advance our understanding on the neurobiological basis of the disorder. Double hit is used to refer to the use of two schizophrenia inducing interventions viz ketamine exposure and social isolation. In this study we aim to investigate the robustness of double hit model of schizophrenia in inducing negative and cognitive symptoms of schizophrenia. On postnatal day (PND) 23, thirty-two male Sprague Dawley rats were randomly grouped into four equal groups as follows: group housed + saline (GH), group housed + ketamine (GHK), isolated + saline (SI), and isolated + ketamine (SIK). A single ketamine dose (16 mg/kg) was administered 3 times a week for four weeks. Isolated animals were housed singly throughout the study. The following behavioural tests were carried out: elevated plus maze, three chamber social interaction, resident intruder tests, and novel object recognition (NOR). The SIK group exhibited high anxiety levels, with increased ACTH, corticosterone and norepinephrine concentration when compared to the other groups. The SIK animals also presented with reduced social interaction and decreased oxytocin concentration. SIK rats were more aggressive towards a juvenile intruder but had low testosterone concentration. The SIK group or double hit model showed impaired visual learning and memory and increased expression of proinflammatory cytokines. This suggest that the double hit model is more robust in inducing negative and cognitive symptoms of schizophrenia than each treatment alone.

Hypercorticosteronemia induces hyperphagia and obesity in human growth hormone transgenic rats.

Hyperphagia and subsequent obesity are important public health issues due to the associated risks of developing serious diseases. Certain stressors play a major role in the development of hyperphagia. In previous studies, we established a line of human growth hormone transgenic (TG) rats that exhibit hyperphagia and obesity from a young age. We recently demonstrated that voluntary running on a running wheel alleviates hyperphagia in TG rats. Wheel running provides environmental enrichment for rodents and plays a role in relieving stress. These results suggested that stress is the major factor inducing hyperphagia in TG rats. Thus, in the present study, we evaluated activation of the hypothalamus-pituitary-adrenal axis. TG rats showed bilateral enlargement of adrenal glands and hypercorticosteronemia, although their hypothalamic CRH level was comparable to that of wild-type (WT) rats. The ACTH-immunoreactive area was larger and the serum ACTH level in the dark phase was higher in TG rats than in WT rats. Adrenalectomy reduced the food intake of TG rats to a level comparable to that in WT rats, and supplying glucocorticoids recurred hyperphagia in TG rats. These treatments did not affect the food intake of WT rats. Rearing TG rats under group housing prevented hyperphagia and hypercorticosteronemia. These results suggest that glucocorticoids are appetite stimulants, and that TG rats exhibit increased sensitivity to the appetite-stimulating effect of glucocorticoids.

Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

Sex-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats.

BACKGROUND: Adolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies. METHODS: Male and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus. RESULTS: The main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females. CONCLUSIONS: This study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.

[Clinical case of plurihormonal pituitary adenoma (STH/ACTH/TSH/FSH/LH-secreting), diagnostic pitfalls].

According to numerous studies, the most common pituitary tumors are prolactinomas, reaching 60% of all clinically significant adenomas, the next in order are non-functional pituitary adenomas, somatotropinomas, corticotropinomas and thyrotropinomas. Plurigormonal tumors occur in less than 1% of all pituitary adenomas. The most common form of mixed secretion adenoma in this patient population, derived from the Pit-1 cell line, produces various combinations of hormones: growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH). This article presents a patient with a plurihormonal two-component pituitary macroadenoma with a rare and exceptional combination of secreted hormones - GH / adrenocorticotropic hormone (ACTH) / TSH / follicle-stimulating hormone (FSH) / luteinizing hormone (LH) with minimal nonspecific clinical manifestations such as diabetes mellitus and poorly controlled arterial hypertension.

Cushing's Syndrome: Rapid Evidence Review.

Cushing's syndrome is a rare, multisystemic disease caused by chronic exposure to supraphysiologic levels of cortisol. Prolonged hypercortisolism is associated with significant multisystem morbidity and mortality and decreased quality of life. Diagnosis of Cushing's syndrome is often delayed by several years due to its insidiously progressive course, diverse clinical presentation, overlap of symptoms with many common conditions, and testing complexity. Exogenous glucocorticoid use must be excluded as the primary etiology. Excessive endogenous cortisol production can be caused by an overproduction of adrenocorticotropic hormone (ACTH) through pituitary tumors or ectopic sources (ACTH-dependent cases), or it can be caused by autonomous cortisol overproduction by the adrenal glands (ACTH-independent cases). The recommended diagnostic approach includes appropriate screening, confirmation of hypercortisolism, and determination of etiology. First-line treatment is surgical removal of the source of cortisol overproduction. Lifelong posttherapy monitoring is required to treat comorbidities and detect recurrence.

Assessing the effects of ex vivo hormonal exposure on oxidative responses in equine leukocytes: A preliminary study.

Breed differences exist between horses and ponies in circulating concentrations of several hormones, notably ACTH and insulin. These hormones regulate stress and metabolic responses, but in other species, they also impact leukocyte oxidant responses. The effects of these hormones on equine leukocytes have not been evaluated to date. If equine leukocytes are similarly regulated, breed differences in increased plasma hormone concentrations or altered sensitivity to them at the leukocyte level could result in breed-related differences in oxidant responses or oxidative status. The objective of this study was therefore to determine the effects of ex vivo exposure to adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), insulin, or leptin on reactive oxygen species (ROS) production from leukocytes isolated from horses and ponies. We hypothesized that ACTH, α-MSH, insulin, and leptin would alter oxidant responses from equine leukocytes in a breed specific manner. Blood was collected from 10 apparently healthy Quarter horses and seven Welsh ponies for isolation of neutrophils and peripheral blood mononuclear cells (PBMCs) via density gradient centrifugation. Cells were incubated with media (negative control), microbial antigens (positive control), or ACTH, α-MSH, leptin, or insulin for two hours. Induced ROS production was quantified with a previously validated fluorometric assay. Data was compared within groups by comparing a stimulant within a group (horses or ponies) to baseline, between groups by comparing horse response to pony response, and among stimulants using one- and two-way, repeated measures ANOVA (P<0.05). There was no significant effect of breed on basal, microbial-induced, or hormone-induced ROS production from neutrophils (P=0.465) or PBMCs (P=0.749), but in neutrophils, a significant interaction between breed and stimulant was present (P=0.037). ROS production from PBMCs from horses after hormone exposure did not differ from cells exposed to media only (P=0.1520-0.8180). Similarly, neither leptin nor insulin exposure significantly induced ROS production from PBMCs from ponies (P= 0.2645 and 0.4678 respectively), but exposure to ACTH or α-MSH induced a significant increase in ROS production (P=0.0441 and 0.0440 respectively) compared to unstimulated cells. Hormones that vary in availability among breeds may induce ex vivo pro-oxidant responses in equine leukocytes, but specific effects are breed-, leukocyte type-, and hormone-dependent. Breed differences in hormonally induced leukocyte ROS production may warrant further investigation in the context of circulating oxidative stress and how this might relate to future disease risk.

Androgens Suppress Corticosteroid Binding Globulin in Male Mice, Affecting the Endocrine Stress Response.

Biological sex affects the activity of the hypothalamus-pituitary-adrenal (HPA) axis. However, how androgen deprivation affects this axis remains largely unknown. In this study, we investigated the effect of androgen status on different components of the HPA axis in male mice. Two weeks of androgen deprivation did not affect total plasma corticosterone levels but led to increased pituitary ACTH levels. Stress-induced total plasma corticosterone levels were increased, whereas the suppression of corticosterone after dexamethasone treatment under basal conditions was attenuated. Androgen-deprived mice displayed a 2-fold increase in plasma levels of corticosteroid binding globulin (CBG). A similar increase in CBG was observed in global androgen receptor knock-out animals, compared to wild-type littermates. Androgen deprivation was associated with a 6-fold increase in CBG mRNA in the liver and enhanced transcriptional activity at CBG regulatory regions, as evidenced by increased H3K27 acetylation. We propose that the induction of CBG as a consequence of androgen deprivation, together with the unaltered total corticosterone levels, results in lower free corticosterone levels in plasma. This is further supported by mRNA levels of androgen-independent GR target genes in the liver. The reduction in negative feedback on the HPA axis under basal condition would suffice to explain the enhanced stress reactivity after androgen deprivation. Overall, our data demonstrate that, in mice, tonic androgen receptor activation affects CBG levels in conjunction with effects on gene expression and HPA-axis reactivity.

Adrenocorticotropic Hormone-Secreting Pituitary Microadenoma Presenting with Acute Psychosis, Delirium and Paroxysmal Sympathetic Hyperactivity.

Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are known to be associated with behavioural changes but acute presentation including psychosis and delirium are less common. We report the case of a 42-year-old female patient with a known medical history of hypertension and diabetes mellitus, presenting with acute onset behavioural changes suggestive of psychosis to a tertiary care centre in Muscat, Oman in 2022. Further evaluation revealed an ACTH dependent Cushing's disease with a pituitary microadenoma. The patient was admitted for endoscopic resection of the adenoma. During the peri-operative period, she experienced worsening of psychosis in addition to delirium. She also developed episodes of unresponsiveness, posturing, severe diaphoresis and dyspnoea accompanied by tachycardia and hypertension which were managed with midazolam and levetiracetam. A seizure work-up and computed tomography brain scan were unremarkable. At follow-up, she showed full resolution of symptoms with good blood pressure and glycaemic control.

Hypoadrenocorticism in cats: a 40-year update.

PRACTICAL RELEVANCE: Addison's disease is a very rare condition in cats, with only approximately 40 cases documented in the past 40 years since it was first described in 1983. CLINICAL CHALLENGES: While canine hypoadrenocorticism is a well-recognised disorder with clear diagnostic and treatment guidelines, feline hypoadrenocorticism remains a challenge because of its rarity and waxing and waning clinical signs. Furthermore, empirical treatment with corticosteroids, resulting in clinical improvement, contributes to delays in achieving the diagnosis and initiating treatment. Feline hypoadrenocorticism is diagnosed with an adrenocorticotropic hormone (ACTH) stimulation test; a low resting cortisol concentration with an inadequate or absent response to synthetic ACTH is diagnostic. Various ACTH stimulation-testing protocols are reported in published cases, with the majority using three time-limited blood samples. This can be limiting clinically, depending on cats' clinical presentation and behaviour at the veterinary practice and tolerance for procedures. Long-term treatment, similar to canine hypoadrenocorticism, consists of oral corticosteroids, with several formulations licensed in the UK, and mineralocorticoids (desoxycorticosterone pivalate), of which the only available formulation (Zycortal; Dechra) is licensed for dogs and its safety has not been assessed in cats. GLOBAL IMPORTANCE: Feline hypoadrenocorticism occurs worldwide. Although no breed, sex or age association has been reported, cats aged <6 years are overrepresented.

Patterns of hormonal changes in hypophysitis by immune checkpoint inhibitor.

BACKGROUND/AIMS: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events, including endocrine dysfunctions, which can have serious consequences on patient health and quality of life. The clinical course and characteristics of immune-related hypophysitis (irH) are not well established. This study aimed to analyze the clinical course and characteristics of irH. METHODS: This single-center, retrospective study analyzed data from electronic medical records of Asan Medical Center, spanning January 2017 through June 2021. It included adult patients with solid tumors who underwent thyroid and adrenal function tests, along with gonadotropin and/or growth hormone evaluations, following the initiation of ICI treatment within the same period. The study explored the clinical characteristics of ICI-treated patients with and without irH, the incidence of irH, the time to irH onset, and the associated hormonal changes. RESULTS: Twenty-one patients were included in this analysis. Clinical characteristics did not differ significantly between the irH (n = 13) and non-irH (n = 8) groups. Deficiency rates in the irH group were 23.1% for thyroid-stimulating hormone (n = 3), 76.9% for adrenocorticotropic hormone (n = 10), 61.5% for gonadotropin (n = 8), and 15.4% for growth hormone (n = 2). The overall incidence was 0.9 per person-year, with 6-month and 1-year cumulative incidences of 38.8% and 57.1%, respectively. The median time from ICI initiation to irH diagnosis was 7.7 months. Time to levothyroxine replacement was shorter in the irH group. CONCLUSION: The findings provide evidence that could facilitate the prediction of ICI-induced irH based on clinical course and characteristics.

Analysis of the therapeutic effect of pestle needle and EEG biofeedback and methylphenidate in the treatment of attention-deficit/hyperactivity disorder.

This research aimed to analyze the therapeutic effect of the pestle needle combined with electroencephalogram (EEG) biofeedback and methylphenidate in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children. Seventy-eight children with ADHD were selected and randomized into a control group and an observation group (n = 39 each). The control group received EEG biofeedback and methylphenidate treatment, whereas the observation group received pestle needle therapy on this basis. Both groups received continuous treatment for 3 mo. The clinical efficacy, scores of Conners Parents Symptom Questionnaire (PSQ), Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), and Pittsburgh Sleep Quality Index (PSQI), EEG θ/ß changes in values, serum indicators such as adrenocorticotropic hormone (ACTH) and cortisol (CORT), and incidence of adverse reactions were compared in the two groups. The total effective rate of the observation group was 92.31% (36/39), which was higher than the control group's 69.23% (27/39) (P < 0.05). After treatment, reduced PSQ scores, PSQI scores, EEG θ/ß values, and ACTH levels and elevated IVA-CPT and CORT levels were observed in both groups; the observation group had the best improvement effect after treatment (P < 0.05). Pestle needle combined with EEG biofeedback and methylphenidate in the treatment of ADHD children can elevate the IVA-CPT score, improve EEG waves and sleep quality, regulate serum indicators such as ACTH and CORT, reduce behavioral problem scores, and have high efficacy and safety.NEW & NOTEWORTHY The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can elevate the IVA-CPT score. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can improve EEG waves. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can improve sleep quality. The pestle needle combined with EEG biofeedback and methylphenidate in ADHD children can regulate serum indicators.

Alterations in the Hypothalamic-Pituitary-Adrenal Axis as a Response to Experimental Autoimmune Encephalomyelitis in Dark Agouti Rats of Both Sexes.

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system, usually diagnosed during the reproductive period. Both MS and its commonly used animal model, experimental autoimmune encephalomyelitis (EAE), exhibit sex-specific features regarding disease progression and disturbances in the neuroendocrine and endocrine systems. This study investigates the hypothalamic-pituitary-adrenal (HPA) axis response of male and female Dark Agouti rats during EAE. At the onset of EAE, Crh expression in the hypothalamus of both sexes is decreased, while males show reduced plasma adrenocorticotropic hormone levels. Adrenal gland activity is increased during EAE in both males and females, as evidenced by enlarged adrenal glands and increased StAR gene and protein expression. However, only male rats show increased serum and adrenal corticosterone levels, and an increased volume of the adrenal cortex. Adrenal 3ß-HSD protein and progesterone levels are elevated in males only. Serum progesterone levels of male rats are also increased, although testicular progesterone levels are decreased during the disease, implying that the adrenal gland is the source of elevated serum progesterone levels in males. Our results demonstrate a sex difference in the response of the HPA axis at the adrenal level, with male rats showing a more pronounced induction during EAE.

The impact of ACTH levels on neurotransmitters and antioxidants in patients with major depressive disorder: A novel investigation.

BACKGROUND: The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. METHODS: Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7-65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. RESULTS: Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. LIMITATIONS: The sample size is small. CONCLUSION: MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity.

High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 dams.

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Stress Response to Winter Warfare Training: Potential Impact of Location.

INTRODUCTION: Winter warfare training (WWT) is a critical component of military training that trains warfighters to operate effectively in extreme environments impacted by snow and mountainous terrain. These environmental factors can exacerbate the disruption to the hormone milieu associated with operating in multi-stressor settings. To date, there is limited research on the physiological responses and adaptations that occur in elite military populations training in arduous environments. The purpose of this study was to quantify hormone responses and adaptations in operators throughout WWT. MATERIALS AND METHODS: Participants engaged in baseline laboratory metrics at their home station, Fort Carson, located in Colorado (CO) prior to WWT, for one week in Montana (MT) and one week in Alaska (AK). WWT periods were separated by approximately one month. Blood was collected upon wake at baseline (CO) and on the first and last day of WWT at each location (MT and AK). Plasma was analyzed for stress, metabolic, and growth-related hormones via enzyme-linked immunoassay (ELISA). Sleep quality was assessed via the Pittsburg Sleep Quality Index (PSQI) at baseline (CO) and on the first day of training in MT and AK. Cognitive function was evaluated using the Defense Automated Neurobehavioral Assessment (DANA) at baseline (CO) and on the first and last day of WWT in both MT and AK. RESULTS: Fourteen US Army operators in 10th Special Forces Group (SFG) Operational Detachment participated in winter warfare training (WWT; age: 31.5 years; 95%CI[28.1, 34.3]; height: 180.6 cm; 95%CI[177.3, 183.4]; weight: 87.4 kg.; 95%CI[80.6, 97.7]; body fat: 18.9%; 95%CI[13.7, 23.1]; male: n=13; female: n=1). Plasma adrenocorticotropic hormone (ACTH) levels increased from baseline (19.9 pg/mL; 95%CI[8.6, 24.2])  to pre-WWT (26.9 pg/mL; 95%CI [16.2, 37]; p=0.004), decreased from pre-  (26.9 pg/mL; 95%CI [16.2, 37]) to post-WWT in MT (22.3 pg/mL; 95% CI [8, 23.7]; p=0.004;), and increased from pre-  (25 pg/mL; 95%CI[ 28.4) to post-WWT (36.6 pg/mL; 95%CI [17.9, 48.9]) in AK (p=0.005). Plasma cortisol levels decreased from pre- (174 ng/mL; 95%CI[106.2, 233.6])  to post-WWT (94.5 ng/mL; 95%CI[54.8, 101.7]) in MT (p=0.001) and, conversely, increased from pre- (123.1 ng/mL; 95%CI[97.5, 143.9]) to post-WWT  (162.8 ng/mL; 95%CI[128, 216.7]) in AK (p<0.001). Alterations in growth-related hormones (insulin-like growth factor 1 [IGF-1], insulin-like growth factor binding protein 3 [IGFBP-3],  and sex hormone binding globulin [SHBG]) were observed throughout WWT (p<0.05). The Total Testosterone / Cortisol ratio (TT / CORT; molar ratio) was lower pre-WWT in MT (0.04; 95%CI[0.01,0.04) compared to baseline in CO (0.07; 95%CI[0.04, 0.07]; p=0.042). Triiodothyronine (T3) levels increased from pre-  (101.7 ng/dL; 95%CI[93.7, 110.4]) to post-WWT  (117.8 ng/dL; 95%CI[105.1, 129.4]) in MT (p=0.042). No differences in sleep quality were reported between locations (CO, MT, and AK). Alterations in cognitive function were exhibited between locations and during WWT in both MT and AK (p<0.05). CONCLUSIONS: Over the course of WWT, elite operators experienced alterations in stress, metabolic, and growth-related hormones, as well as cognitive performance. The increase in stress hormones (i.e., ACTH and cortisol) and reduction in cognitive performance following training in AK are suggestive of heightened physiological strain, despite similarities in physical workload, self-reported sleep quality, and access to nutrition. The variation in hormone levels documented between MT and AK may stem from differences in environmental factors, such as lower temperatures and harsh terrain. Further research is warranted to provide more information on the combined effects of military training in extreme environments on operator health and performance.

Calculated Right Adrenal Vein Aldosterone Levels in Patients Undergoing Adrenal Vein Sampling: The Potential to Lateralize Despite Unsuccessful Selection of the Right Adrenal Vein.

PURPOSE: The aim of this study was to use calculated aldosterone level in the right adrenal vein (RAV) (cAldoRAV) rather than measured level for identifying the dominant side of aldosterone secretion in patients with primary aldosteronism undergoing adrenocorticotropic hormone-stimulated adrenal venous sampling (AVS). MATERIALS AND METHODS: Patients with primary aldosteronism who had successful AVS (selectivity index, >3) were studied. Based on the assumption that cortisol production from both adrenal glands is equal, aldosterone level in the RAV was calculated using the data from the left adrenal vein and inferior vena cava. The aldosterone level in the left adrenal vein (AldoLAV) compared with the cAldoRAV (AldoLAV:cAldoRAV ratio) was then used to determine the dominant side of aldosterone secretion compared with standard AVS interpretation using lateralization index (LI). LI ≥4 indicated unilateral disease, and LI ≤3 indicated bilateral disease. The LI between 3 and 4 was diagnosed as indeterminate. RESULTS: Sixty-eight patients with concordant results between AVS and adrenal imaging study (32 were left-sided, 22 were right-sided, and 14 were bilateral) were selected for studying diagnostic performance. The AldoLAV:cAldoRAV ratio with the cutoff values of ≥3 and ≤0.33 could identify unilateral diseases (left-sided and right-sided disease, respectively) with 92.6% sensitivity and 100% specificity. CONCLUSIONS: The calculated AldoLAV:cAldoRAV ratio can determine the dominant side of aldosterone secretion with high sensitivity and specificity when compared with standard AVS interpretation of measured levels. It provides an option for identification of unilateral and bilateral disease in select patients in whom right adrenal vein selection is unsuccessful.

Stability of adrenocorticotropic hormone in whole blood samples: effects of storage conditions.

Introduction: Adrenocorticotropic hormone (ACTH) is a peptide secreted by pituitary gland that plays an important role in regulating cortisol secretion. Its determination is difficult because of instability in whole blood. Several factors that influence ACTH stability in blood before analysis have been identified: temperature, hemolysis, time to centrifugation and presence of protease inhibitors. Published results on ACTH whole blood stability seem contradictory. Materials and methods: We performed a stability study in 10 healthy volunteers. Three different conditions were tested: ethylenediaminetetraacetic acid (EDTA) at 4 °C, EDTA + aprotinin at 4 °C, EDTA + aprotinin at room temperature. Stability was evaluated for 8 hours. Adrenocorticotropic hormone measurements and hemolysis index were performed respectively on Cobas e602 and c701 (Roche Diagnostics, Mannheim, Germany). We compared percentage deviations with total change limit using a threshold of 7.5%. Results: We showed that ACTH is stable 8 hours with EDTA at 4 °C, 4 hours with EDTA + aprotinin at 4 °C and 2 hours with EDTA + aprotinin at 22 °C. Conclusions: Aprotinin does not appear to give ACTH greater stability but can be used without exceeding 4 hours at 4 °C. Refrigerated pouch transport also seems to be more appropriate for ACTH in whole blood.

Effects of chronic stress on rat heart function following regional ischemia: a sex-dependent investigation.

Chronic psychological stress is a recognized, yet understudied risk factor for heart disease, with potential sex-specific effects. We investigated whether chronic stress triggers sex-dependent cardiac dysfunction in isolated Wistar rat hearts subjected to ischemia-reperfusion injury. The experimental cohort underwent 1 h of daily restraint stress for 4 wk versus matched controls, followed by euthanasia (sodium pentobarbital) and heart excision for ex vivo perfusion. Blood analysis revealed sex-specific alterations in stress hormones and inflammatory markers. When compared with controls, chronic restraint stress (CRS) males displayed decreased plasma brain-derived neurotrophic factor (BDNF) levels (P < 0.05), whereas CRS females exhibited elevated plasma adrenocorticotropic hormone (ACTH) (P < 0.01) and reduced corticosterone (P < 0.001) alongside lower serum estradiol (P < 0.001) and estradiol/progesterone ratio (P < 0.01). Of note, CRS females showed increased serum cardiac troponin T (P < 0.05) and tumor necrosis factor-α (TNF-α) (P < 0.01) with suppressed interleukin (IL)-1α, IL-1ß, IL-6, and IL-10 levels (P < 0.05) when compared with controls. Ex vivo Langendorff perfusions revealed that CRS female hearts displayed impaired postischemic functional recovery for baseline stroke volume (SV, P < 0.01), work performance (P < 0.05), aortic output (AO, P < 0.05), coronary flow (CF, P < 0.01), and overall cardiac output (CO, P < 0.01) when compared with matched controls and CRS males (P < 0.05). Our findings reveal intriguing sex-specific responses at both the systemic and functional levels in stressed hearts. Here, the dysregulation of stress hormones, proinflammatory state, and potential underlying cardiomyopathy in females following the stress protocol renders them more prone to damage following myocardial ischemia. This study emphasizes the importance of incorporating sex as a biological variable in cardiac research focusing on stress-related cardiomyopathy.NEW & NOTEWORTHY Although chronic psychological stress is a risk factor for cardiovascular diseases, the underlying mechanisms remain poorly understood. This study revealed that chronic restraint stress resulted in systemic changes (dysregulated stress hormones, proinflammatory state) and potential cardiomyopathy in females versus controls and their male counterparts. The stressed female hearts also displayed reduced functional recovery following ex vivo ischemia-reperfusion. This highlights the importance of incorporating sex as a biological variable in cardiac research.

Glucocorticoid alleviates hypothalamic nerve injury via remodeling HPA axis homeostasis in stressed rats.

Excessive stress can exceed the adjustment ability of body and cause injury and dysfunction, while elucidation of the mechanism and prevention measures of stress-related injury are still insufficient. The present study was to observe the effect of glucocorticoid (GC) on stress-induced hypothalamic nerve injury and elucidate the potential mechanism. The present study intended to establish a chronic restraint stress rat model for follow-up study. Open field test and elevated plus maze test were used to observe behavioral changes of stress rats; Enzyme-linked immunosorbent assay (ELISA) was used to detect changes in the levels of hypothalamus-pituitary-adrenal (HPA) axis-related hormones and inflammatory factors in hypothalamus; toluidine blue staining was used to observe pathological changes of hypothalamus. The results showed that stress rats showed obvious anxiety-like behaviors, the levels of HPA axis-related hormones and inflammatory factors showed abnormal fluctuations, and morphological results showed significant nerve injury in hypothalamus. Low-dose GC treatment significantly improved behavioral changes, alleviated hypothalamic nerve injury, and restored hypothalamic levels of inflammatory factors, serum levels of GC, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) and GC level in adrenal cortex of stressed rats, while GC receptor (GR) inhibitor, CRH receptor inhibitor, and adrenalectomy reversed the ameliorative effects of low-dose GC. Our study clarified that low-dose GC can restore stress coping ability by reshaping the homeostasis of the HPA axis, thus alleviating behavioral abnormalities and hypothalamic nerve injury in stressed rats.