Basal Plasma Cortisol Research Articles

A simple ultraperformance liquid chromatography mass spectrometry method for the determination of cortisol level in sea bass plasma

A simple, precise, and rapid ultra-performance liquid chromatography method for cortisol quantification in sea bass plasma, based on LC-ESI-UHR-QqTOF-MS, was optimised using tolperisone as internal standard. Sea bass plasma samples containing cortisol were spiked with tolperisone as internal standard and extracted with acetonitrile. Samples were vortexed and centrifuged at 15,000g for 10 min at 4 °C. The final extract, diluted in ammonium formate (1:1), was injected in the LC-ESI-UHR-QqTOF-MS system for analysis. Mass spectrometry acquisition parameters were set using positive ionisation mode over a m/z range from 150 to 2200. Cortisol and tolperisone were detected and quantified at m/z 363.21 and 246.18, respectively, in an Auto MS (MS/MS) mode. The detection and quantification limits of cortisol in sea bass plasma were 0.01 and 0.02 μg/mL, respectively. The mean extraction recovery of cortisol was of 99.1 ± 4.0 %. The within- and between-day precision presents a relative standard deviation (RSD) below 2.9 % and 5.3, respectively. Furthermore, the effect of four different diets (fish feed 1–4) in the basal and stress-induced plasma cortisol levels of sea bass was also assessed.

Effect of Maternal High Fat Diet on the Hypothalamus-Pituitary-Adrenal Gland (HPA) Axis of the Offspring in Sheep

Maternal consumption of a high fat diet (HFD) during pregnancy is associated with metabolic dysfunction and altered HPA axis function in the offspring. These effects are well established in species with short gestation length (e.g., rodents), but less established in species with longer gestation periods more comparable with humans. The objective of the study was to determine the effect of maternal HFD on basal and stimulated cortisol secretion in the offspring at 16 weeks of age in sheep. All experiments were approved by the Institutional Animal Care and Use Committee at Cal Poly Pomona. Pregnant ewes were assigned to control (n=3) and HFD (n=3) groups. The control group was fed farmers best complete ewe and ram pellets. The HFD group was fed the same diet with an additional 30% rumen protected fat (Megalac, Volac Wilmar Feed Ingredients Ltd). After birth lambs were weaned at 12 weeks of age and given free access to control pellet diet with grains. To assess adrenal cortisol secretion at 16 weeks, lambs were infused intravenously with adrenocorticotropic hormone (ACTH; 2 ug/kg cortrosyn in 1 mL saline). Blood samples (1 mL) were taken through the jugular catheter at −30, −15, and 0 min (immediately before) and 5, 15, 30, 60, 90, and 120 min after ACTH administration for measurement of plasma cortisol by ELISA. Data were analyzed by two-way repeated measures ANOVA with a Tukey posthoc test. Basal plasma cortisol tended to be higher in HFD (32±8 ng/mL) than control (13±3 ng/mL) lambs, but this did not reach statistical significance. Plasma cortisol was higher than baseline from 15 to 90 minutes after ACTH administration in all lambs (p<0.05). The increment in plasma cortisol was higher in HFD than control lambs from 15-90 minutes (p<0.05). Accordingly, the maximum increase in plasma cortisol at 60 minutes and was higher in HFD (245±8 ng/mL) than control lambs (121±50 ng/mL p<0.05). These preliminary data suggest that maternal consumption of a high fat diet during pregnancy may increase basal and stimulated activity of the HPA axis in sheep. The study was funded by a Strategic Interdisciplinary Research Grant (SIRG) at California State Polytechnic University, Pomona. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Activated Wake Systems in Narcolepsy Type 1.

Narcolepsy type 1 (NT1) is assumed to be caused solely by a lack of hypocretin (orexin) neurotransmission. Recently, however, we found an 88% reduction in corticotropin-releasing hormone (CRH)-positive neurons in the paraventricular nucleus (PVN). We assessed the remaining CRH neurons in NT1 to determine whether they co-express vasopressin (AVP) to reflect upregulation. We also systematically assessed other wake-systems, since current NT1 treatments target histamine, dopamine, and norepinephrine pathways. In postmortem tissue of people with NT1 and matched controls, we immunohistochemically stained and quantified neuronal populations expressing: CRH and AVP in the PVN, and CRH in the Barrington nucleus; the key neuronal histamine-synthesizing enzyme, histidine decarboxylase (HDC) in the hypothalamic tuberomammillary nucleus (TMN); the rate-limited-synthesizing enzyme, tyrosine hydroxylase (TH), for dopamine in the mid-brain and for norepinephrine in the locus coeruleus (LC). In NT1, there was: a 234% increase in the percentage of CRH cells co-expressing AVP, while there was an unchanged integrated optical density of CRH staining in the Barrington nucleus; a 36% increased number of histamine neurons expressing HDC, while the number of typical human TMN neuronal profiles was unchanged; a tendency toward an increased density of TH-positive neurons in the substantia nigra compacta; while the density of TH-positive LC neurons was unchanged. Our findings suggest an upregulation of activity by histamine neurons and remaining CRH neurons in NT1. This may explain earlier reports of normal basal plasma cortisol levels but lower levels after dexamethasone suppression. Alternatively, CRH neurons co-expressing AVP neurons are less vulnerable. ANN NEUROL 2023;94:762-771.

Water temperature explains part of the variation in basal plasma cortisol level within and between fish species.

Within the thermal tolerance range of fish, metabolism is known to escalate with warming. Rapid thermic changes also trigger a series of physiological responses, including activation of the stress axis, producing cortisol. Fish have adapted to their environment by producing a low level of plasmatic cortisol when unstressed (basal), so that thriving in their natural temperature should not impact their basal cortisol levels. Yet, surprisingly, little is known on how temperature affects cortisol within and between fish species. Here, we conducted a phylogenetic meta-analysis to (1) test whether temperature can explain the differences in basal cortisol between species and (2) evaluate the role of temperature on differences in cortisol levels between individuals of a same species. To do this, we retrieved basal plasma cortisol data from 126 studies, investigating 33 marine and freshwater fish species, and correlated it to water temperature. Intra-species variability in basal plasma cortisol levels was further investigated in two species: the European sea bass Dicentrarchus labrax and the Nile tilapia Oreochromis niloticus. Factors such as life stage, sex and weight were also considered in the analyses. Overall, our phylogenetic analysis revealed a clear positive correlation between basal cortisol level and the temperature at which the fish live. The role of temperature has also been confirmed within D. labrax, while it failed to be significant in O. niloticus. In this paper, the influence of habitat, life stage, sex and weight on basal plasma cortisol levels is also discussed. Since some abiotic parameters were not included in the analysis, our study is a call to encourage scientists to systematically report other key factors such as dissolved oxygen or salinity to fully depict the temperature-cortisol relationship in fishes.

The developmental consequences of early adverse care on infant macaques: A cross-fostering study

Early life adversity/stress (ELA/ELS), particularly adverse caregiving experiences such as child maltreatment (MALT), is a main risk factor for psychopathology, including psychiatric disorders such as anxiety, depression, ADHD, and substance abuse. Yet how these alterations unfold during development and the underlying mechanisms remain poorly understood, as it is difficult to prospectively and longitudinally study early developmental phases in humans, and nearly impossible to disentangle postnatal caregiving effects from heritable traits. This study examined the specific effects of “nurture” (maternal care) versus “nature” (heritable, biological maternal factors) on nonhuman primate infant socioemotional, stress neuroendocrine, and physical development. For this we used a translational and naturalistic macaque model of infant maltreatment by the mother with randomized assignment at birth to either mothers with a history of maltreating their infants (MALT group, n = 22) or to competent mothers (Control group, n = 20). Over the first 6 months of life (roughly equivalent to 2 years in humans), we examined the development of the mother-infant relationship, as well as infants’ social behavior and emotional reactivity. In parallel, we assessed hypothalamic-pituitary-adrenal (HPA) axis function longitudinally, using measures of hair cortisol accumulation, and basal morning plasma cortisol. We identified broad impairments in maternal care exhibited by MALT foster mothers, beyond maltreatment (physical abuse, rejection) events, suggesting that MALT foster mothers provide an overall lower quality of care to their infants compared to Controls. MALT infants exhibited alterations in their initiations and breaks of proximity towards their mothers, as well as heightened emotional reactivity in comparison to Controls. Most striking are the HPA axis findings, with MALT infants showing higher levels of plasma cortisol across the first 6 postnatal months as well as higher hair cortisol accumulation from birth through month 6 (a signature of chronic stress) than Controls. No caregiving effects were detected on physical growth, which ruled out confounding effects of maternal nutrition, metabolism, etc. Taken together, these results suggest that the developmental trajectory of MALT and Control infants is different, marked by heightened levels of emotional reactivity, increased HPA activity and alterations in mother-infant interactions in MALT animals. These findings appear to be due to specific effects of postnatal maternal care, and not to biological/ behavioral traits inherited from the mother, or due to prenatal programming caused by prenatal stress, as the cross-fostering design controlled for these potential factors. However, we also detected a couple of interesting biological effects suggesting heritable transmission of some phenotypes. The prolonged HPA axis activation during the first 6 postnatal months of life is expected to have long-term consequences for brain, physiological, and behavioral development in MALT offspring.

Pituitary function after transsphenoidal surgery including measurement of basal morning cortisol as predictor of adrenal insufficiency.

IntroductionPatients with pituitary adenomas undergoing transsphenoidal surgery require pre- and post-surgery examination of pituitary hormones. There is currently no consensus on how to evaluate the adrenal axis post-surgery. The aims of this study were to investigate factors that may predict postoperative adrenal insufficiency (AI) and to investigate the overall effect of transsphenoidal surgery on pituitary function.MethodsOne hundred and forty-three consecutive patients who had undergone transsphenoidal surgery for pituitary adenomas were included. Data on tumour size, pituitary function pre-surgery, plasma basal cortisol measured within 48 h post-surgery and pituitary function 6 months post-surgery were collected. Patients with AI prior to surgery, perioperative glucocorticoid treatment, Cushing’s disease and no re-evaluation after 1 month were excluded (n = 93) in the basal cortisol analysis.ResultsLow plasma basal cortisol post-surgery, tumour size and previous pituitary surgery were predictors of AI (all P < 0.05). A basal cortisol cut-off concentration of 300 nmol/L predicted AI 6 months post-surgery with sensitivity and negative predictive value of 100%, specificity of 81% and positive predictive value of 25%. New gonadal, thyroid and adrenal axis insufficiencies accounted for 2, 10 and 10%, respectively. The corresponding recovery rates were 17, 7 and 24%, respectivelyConclusionTranssphenoidal surgery had an overall beneficial effect on pituitary endocrine function. Low basal plasma cortisol measured within 48 h after surgery, tumour size and previous surgery were identified as risk factors for AI. Measurement of basal cortisol post-surgery may help to identify patients at risk of developing AI.

Non-Fasting Hypoglycemia Secondary to Opioid Induced Adrenal Insufficiency: A Case Report

Abstract Background: A patient on chronic methadone therapy presented following a suicide attempt, was noted to have recurrent episodes of non-fasting symptomatic hypoglycemia and was diagnosed with opioid induced adrenal insufficiency (OIAI). Opioid induced endocrinopathies are underappreciated, particularly in the midst of a growing opioid epidemic in the United States. We believe this is the first reported clinical case of OIAI associated with non-fasting hypoglycemia. Clinical Case: A 33-year-old female with history of depression and heroine abuse on methadone therapy presented after a suicide attempt by methadone overdose. Home medications included 170mg of methadone daily for the past 5 years. She was afebrile, heart rate of 68, blood pressure 102/72, respiratory rate of 10, oxygen saturation 92%. On exam she was lethargic with altered mental status and had pinpoint pupils. Labs showed a normal complete blood count and metabolic panel. Urine toxicology was positive for methadone. Clinical picture improved temporarily after Narcan administration however 1 hour later she was confused again, with a fingerstick glucose of 50mg/dL and she was admitted to ICU for monitoring. In the ICU she continued to be lethargic with dizziness, nausea and headaches. She continued to have approximately 4 spontaneous episodes of hypoglycemia per day, despite having a good appetite and increased parenteral glucose administration. Blood pressure continued to be marginal, ranging from 85–100/50–60. There was no obvious source of infection. Urine sulfonylurea screen was negative. Investigations showed a morning cortisol of 2.23 ug/dL. A 250 µg ACTH stimulation test showed an inadequate response. The am basal plasma cortisol was 2.25 ug/dL with 15.28 ug/dL and 15.13 ug/dL at 30 and 60 minutes respectively (6.20–19.40ug/dL). She was diagnosed with hypoglycemia secondary to OIAI. Given the patient’s critical condition she was initially started on stress dose of hydrocortisone 80mg every 8 hours. Attempts to down titrate the methadone dose were unsuccessful. Patient’s symptoms improved and hypoglycemia subsided. She was discharged home on hydrocortisone 10mg qam &amp; 5 mg qpm and she was continued on Methadone 170mg daily. Conclusion: OIAI is an under-recognized clinical entity with potentially serious adverse outcomes. Currently, 3% to 4% of US adults receive long-term opioid treatment. OIAI is present in 9—29% of individuals on chronic opioids. Opioids act through suppression of the HPA axis, primarily at the level of the hypothalamus, mediated through either delta or kappa receptors leading to a decrease in ACTH and cortisol secretion. Management should include decreasing and ideally discontinue opioids, along with glucocorticoid replacement until documented recovery of the HPA axis. Reference: Reference: (1)Donegan, Diane et al. Opioid-Induced Adrenal Insufficiency. Mayo Clin. Proc. 2018 93(7), 937–944.

Cushing\u2019s disease due to a pituitary adenoma as a component of collision tumor: A case report and review of the literature

BackgroundThe coexistence of two morphologically different tumors attached to each other creates a very rare type of tumor called a collision tumor. Collision tumors containing pituitary adenoma–sellar meningioma have only been described in four cases to date; we discuss a fifth case harboring a collision tumor comprising a pituitary corticotroph adenoma and a sellar meningioma in the same anatomic position.Case presentationA 34-year-old Caucasian woman presented with menstrual irregularity, severe weakness of the proximal muscles, and 10–15 kg weight gain within a year. Basal plasma cortisol and adrenocorticotrophic hormone levels were 17.7 mg/dL and 58 pg/mL, respectively. Her diurnal cortisol rhythm was impaired (plasma cortisol at 23:00, 18.2 mg/dL) and after a 48-hour, 2-mg dexamethasone suppression test, plasma cortisol level was 13.6 mg/dL. The results were consistent with a diagnosis of Cushing’s syndrome. We then performed a nocturnal 8-mg dexamethasone suppression test and the suppression of cortisol was not greater than 50% (21.4 to 19.3). A pituitary magnetic resonance imaging revealed a tuberculum sellae meningioma arising from within the sellar region. An operation was chosen in order to examine whether the tumor was an adrenocorticotrophic hormone/corticotropin-releasing hormone-secreting lesion or if there were any microadenomas that could be observed during the operation. Via an extended endoscopic endonasal approach the meningioma was resected successfully. Unexpectedly, our patient complained of nausea and vomiting postoperatively. Plasma cortisol was 2.6 mg/dL and orally administered hydrocortisone treatment was initiated immediately. Histopathological examination revealed that the tumor generally consisted of a pituitary corticotroph adenoma infiltrated by meningioma. Our patient maintained hydrocortisone treatment for 11 months. At the latest visit, she had lost 12 kg, and her hypertension, menstrual irregularity, and weakness of the proximal muscles had disappeared. Her mental and physical wellbeing were restored.ConclusionsTo the best of our knowledge, this is the first report of Cushing’s disease due to a pituitary corticotroph adenoma adjacent to a meningioma. Even if a high-dose dexamethasone suppression test fails to suppress basal cortisol level, the importance of considering a suprasellar/sellar meningioma a possible component of a collision tumor presenting as adrenocorticotrophic hormone-dependent Cushing’s syndrome is highlighted here.

Corticosteroid-Induced Adrenal Insufficiency in Africa: Report of Nine Cases at the Internal Medicine/Endocrinology-Diabetology Department of Pikine NHC

Introduction: Prolonged corticosteroid therapy is labeled as the main cause of corticotropic adrenal insufficiency. However, the current frequency of this complication remains unknown. The objective of our study was to assess its epidemiologic, diagnostic, therapeutic, and evolutionary aspects of our practice. Methodology: A 60-month retrospective study was performed from May 2014 to April 2020 in the Pikine National Hospital Centre. Data were obtained from the medical records of patients with corticosteroid-induced adrenal insufficiency. Epidemiologic, diagnostic, therapeutic, and evolutionary parameters, and data related to corticotherapy were recorded. Patients with basal plasma cortisol levels Results: Medical records were obtained from nine patients, comprising six women and three men. The mean age of the patients was 48 years. Long-term corticosteroid therapy was used for self-medication in six patients and artificial bleaching in the remaining three patients. Betamethasone was the most commonly used drug in four patients, followed by clobetasol in three patients. Corticotropic insufficiency was revealed as a result of acute decompensation in five patients. All patients presented with a pseudo-cushingoid pattern. Diagnosis of corticotropic adrenal insufficiency was confirmed by measuring basal plasma cortisol levels of Conclusion: Post-corticosteroid therapy adrenal insufficiency remains a concern in our practice and is favoured by the non-compliance of providing rules by pharmacies and the parallel drug market.

30-Year-Old Woman With Intractable Vomiting

30-Year-Old Woman With Intractable Vomiting

SAT-218 Hypothalamic-Pituitary-Gonadal (HPG) and Hypothalamic-Pituitary-Adrenal (HPA) Axis Responsiveness in Women and Men during 29 Weeks of Basic Military Training

Exercise-associated endocrinopathy in athletes has been attributed to low energy availability (EA). We hypothesized this would be relevant to British Army Officer training, which involves arduous exercise and non-exercise stressors. We aimed to explore changes in LH, FSH and cortisol responsiveness in women and in a smaller cohort of men over 29 weeks of basic military training. We studied fifty-six Officer Cadets (age 24.4 ± 2.5 years, 47 female: combined contraceptive pill users (CCP, n=14), progestogen-only users (PROG, n=16), and non-contraceptive and intrauterine device users (NONE, n=17)) on entering (week (w)1) and completing (w29) training. Body composition was measured by DXA and average monthly hair cortisol by LC-MS. A combined low dose 10µg GnRH and 1.0µg ACTH-(1-24) test was performed with LH, FSH and cortisol measured by LC-MS at baseline, 20, 30 and 60 mins. For cortisol analyses, PROG and NONE groups were considered seperately (as PROG/NONE), due to CCP increasing CBG. Weight increased in both women and men over the training period (mean ±SD, 64.4 ±7.4 kg vs 65.3 ±7.2 kg, p=0.05 and 84.5 ±7.4 kg vs 87.0 ±9.1 kg, p=0.02, respectively), comprising increased fat but not lean mass. Menstrual cyclicity in NONE was unchanged. Training blunted the peak LH- and FSH-foldwise response to GnRH in women (median [IQR] 5.74 [3.23, 19.7] vs 3.44 [2.62, 6.51], p=0.002 and 1.65 [1.37, 2.37] vs 1.39 [1.25, 1.77], p=0.005, respectively) but not men (4.28 [2.92, 4.73] vs 3.29 [2.34, 5.78], p=0.5 and 1.46 [1.30, 1.56] vs 1.34 [1.21, 1.51], p=0.6, respectively). Hair cortisol was higher in women than men over the 3 months before training (median (IQR) 7.71 (3.85, 16.0) pg/mg vs 3.53 (2.95, 5.89) pg/mg, p<0.0001) and remained higher in women in the final 3 months of training (8.18 (3.61, 10.37) vs 3.38 (2.38, 5.79) pg/mg, p=0.001). Basal cortisol tended to be lower among PROG/NONE than males in w1 (177 ± 91.9 vs 313 ±92.9 nmol/l, p=0.08), but increased by w29 in PROG/NONE but not men (to 259 ±103 nmol/l; p=0.003 vs to 246 ±187 nmol/l; p=0.4, respectively). Cortisol response to ACTH was blunted in PROG/NONE (peak foldwise increase 3.83 ±1.5 vs 2.84 ±1.0, p=0.048) but was unchanged in men (2.96 ±0.9 vs 2.46 ±0.9, p=0.3). No significant cortisol changes were seen in CCP.The elevated hair cortisol in women may represent greater anticipatory response than men. Hair and basal plasma cortisol increased in women compared to men in response to training, though LH, FSH and cortisol responsiveness in women was blunted. While our findings are broadly in accord with previous reports of exercise and training-associated pituitary and adrenal suppression, our novel finding is that this was not associated with evidence of low EA in our population. We propose endocrine changes in arduous training reflect complex interactions of sex and stressors with the HPA and HPG axes.

Impact of physical or sexual childhood abuse on plasma DHEA, DHEA-S and cortisol in a low-dose dexamethasone suppression test and on cardiovascular risk parameters in adult patients with major depression or anxiety disorders

While the impact of childhood trauma on basal and dynamic cortisol regulation has widely been studied, the most abundant steroid hormones dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S have received little attention in this context. One-hundred in-door patients suffering from major depression or an anxiety disorder filled in the Childhood Trauma Questionaire. A low dose dexamethasone suppression test (DST) measuring DHEA, DHEA-S and cortisol was performed. Furthermore, various cardiovascular risk parameters were measured. Forty-six percent of the patients reported a history of substantial physical or sexual childhood abuse. However, no significant differences in plasma DHEA or DHEA-S emerged in the DST between the traumatised group and the remaining patients. Basal plasma cortisol was significantly lower in the childhood trauma group. No impact of childhood trauma history on cardiovascular risk factor profile was detected. Current limited data about DHEA or DHEA-S in patients with childhood trauma are equivocal. Further study using more sophisticated assessment of trauma history and simultaneously measuring a multitude of putative biomarkers of traumatization are needed.

Effects of Chronic Intraperitoneal Curcumin Administration on Tissue‐Specific Inflammation in a Murine Model of Systemic Lupus Erythematosus

Chronic inflammation has been implicated in the pathogenesis of hypertension and our lab uses a model of systemic lupus erythematosus (SLE) to study this relationship. SLE is an autoimmune disorder that primarily affects reproductive age women, and there is a high prevalence of renal injury and hypertension in patients with the disease. In addition, SLE is associated with diminished autonomic (vagal) tone and dysregulated neuroendocrine/neuroimmune mechanisms—one example being the hypothalamic‐pituitary‐adrenal (HPA) axis, which can be activated by the afferent vagus nerve and whose impairment results in inadequate basal plasma cortisol that can promote chronic inflammation in SLE. Curcumin, the active component of the spice turmeric that is thought to have anti‐inflammatory properties, activates vagal afferents via TRPA1 channels. Therefore, we hypothesize that chronic curcumin administration increases HPA axis function and heightens cortisol release in SLE, and that this protects against tissue‐specific inflammation. Previous studies in our laboratory demonstrated that chronic intraperitoneal administration paradoxically increased inflammatory markers in the renal cortex and medulla, as well as the spleen. Because these results could potentially be due to repeated peritoneal injection, we repeated the study and focused on inflammation in other organs that are major sites of the reticuloendothelial system: the liver and lungs. Thirty‐week old female SLE (NZBWF1) and control (NZW) mice (n = 4–5 mice/group) were administered curcumin (50 mg/kg in sesame oil; i.p. injections) or vehicle daily for 28 days. Mice were euthanized at the end of the study and livers and lungs were harvested. Liver tumor necrosis factor (TNF)‐a (pro‐inflammatory cytokine measured by Western blot and normalized to total protein) was not significantly elevated in SLE mice in relation to control mice (3.0e6 ± 1.7e6 vs 1.1e6 ± 1.5e5; p = 0.560), but was increased in curcumin‐treated SLE mice (6.1e6 ± 1.3e6; p = 0.028). Lung TNF‐a was elevated in SLE mice compared to controls (1.3e7 ± 1.3e6 vs 7.7e6 ± 2.0e5; p = 0.004), while curcumin treatment did not alter its expression in SLE mice (1.3e7 ±1.3e6; p = 0.941). Lung IL‐10 (anti‐inflammatory cytokine) was not significantly elevated in SLE mice in relation to control mice (2.1e7 ± 3.0e6 vs 2.2e7 ± 5.5e6; p = 0.825), but was increased in curcumin‐treated SLE mice (3.6e7 ± 5.0e6; p = 0.010). The results indicate that chronic intraperitoneal curcumin administration produced differential responses: inflammatory effects in the liver (just as in the kidney and spleen) and anti‐inflammatory effects in the lung. Taken together, the damage caused by curcumin on abdominal organs counter the prevailing theory of curcumin's protective actions. Our findings suggest that daily peritoneal curcumin administration may be injurious due to the relative lack of a protective fibrous peritoneum overlying the kidneys, spleen and liver.Support or Funding InformationFunded by AHA grants 14SDG18320033 (KWM), 16PRE29910012 (GSP), and UNTHSC Intramural FundingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adrenal cortex reactivity in dairy cows differs between lactational stages and between different feeding levels

Changes in ACTH challenge test characteristics in dairy cows changing their physiological status at different lactational stages and different feeding levels were not investigated in terms of repeatability yet. In 23 multiparous Holstein cows (10 cows fed a sole fresh herbage diet without concentrate, 13 cows fed with concentrate), three ACTH challenge tests were performed: once during pregnancy shortly prior to drying off (T1), and in week 3 (T2) and 8 (T3) after parturition. Test characteristics were correlated to performance and metabolic parameters: DMI, BW, energy balance (EB), plasma concentrations of free fatty acids (NEFA) and beta-hydroxybutyrate (BHB). Basal plasma cortisol concentrations were higher at T1 compared with T2 and T3 (p<.05). The adrenal cortex sensitivity (expressed as total AUC (AUCt ) of cortisol response after ACTH application) was lowest at T2 compared with T1 and T3 (p<.05). Ranking of the individual animals' responses was not repeatable between time points of the ACTH tests. Enhancing the energy deficiency during early lactation by omission of concentrate did not affect baseline cortisol concentrations in plasma, but decreased peak height at T2 (p<.05). Baseline plasma cortisol concentrations were positively correlated with cortisol peak values after ACTH application, previous lactation performance, milk yield and BW (p<.05). The AUCt was positively correlated with baseline cortisol concentrations, EB and DMI. Cortisol release after ACTH injection was lower in animals with high plasma concentrations of NEFA, BHB and with higher contents of fat and free fatty acids in milk (p<.05). Cortisol peak height after ACTH administration was higher in cows with a more positive EB, higher DMI and lower plasma concentrations of NEFA and BHB. In summary, cortisol responses to ACTH challenges in this study were not repeatable in dairy cows changing their physiological status.

1128 OmniGen-AF® reduces basal plasma cortisol as well as cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone and vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions

1128 OmniGen-AF® reduces basal plasma cortisol as well as cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone and vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions

Relationship between diabetes mellitus and hypothalamic-pituitary-adrenal axis: A systematic review

Objective To provide objective evidences for early screening of the hypothalamic-pituitary-adrenal(HPA)axis function in diabetic patients, the relationship between HPA axis function and diabetes mellitus was systematically reviewed. Methods PubMed, Ovid, Embase, Web of science Databases were retrieved from articles reporting the relationship between HPA axis function and diabetes mellitus. Meta-analysis were carried out by Stata 12.0 software for heterogeneity test and data merged among articles for the inclusion and exclusion criteria. Results Our meta-analysis showed the following results: Compared with control group, the basal plasma cortisol level in total diabetes group, T1DM group, T2DM group, diabetes patients(with or without chronic complications)combined with hypertension was significantly higher. Compared with control group, postdexamethasone cortisol level was markedly higher in diabetes group. There was no significant difference in 24 h urinary free cortisol(24h UFC)and ACTH levels between diabetes group and control group. Our qualitative evaluation shows the following results: the differences of awaking salivary cortisol and cortisol awakening response(CAR)between the two groups were inconsistent among all included studies. Most studies showed that CAR was lower in diabetic patients. Conclusion The present analysis has demonstrated that HPA axis dysfunction exists along with diabetes mellitus, and diabetic comorbidity may further worsen the HPA axis dysfunction. (Chin J Endocrinol Metab, 2016, 32: 668-673) Key words: Diabetes mellitus; Hypothalamic-pituitary-adrenal axis; Cortisol; 24 h urinary cortisol; Cortisol awakening response

Effect of Intensive Training on Mood With No Effect on Brain-Derived Neurotrophic Factor.

Monitoring mood state is a useful tool for avoiding nonfunctional overreaching. Brain-derived neurotrophic factor (BDNF) is implicated in stress-related mood disorders. To investigate the impact of intensified training-induced mood disturbance on plasma BDNF concentrations at rest and in response to exercise. Eight cyclists performed 1 wk of normal (NT), 1 wk of intensified (INT), and 1 wk of recovery (REC) training. Fasted blood samples were collected before and after exercise on day 7 of each training week and analyzed for plasma BDNF and cortisol concentrations. A 24-item Profile of Mood State questionnaire was administered on day 7 of each training week, and global mood score (GMS) was calculated. Time-trial performance was impaired during INT (P = .01) and REC (P = .02) compared with NT. Basal plasma cortisol (NT = 153 ± 16 ng/mL, INT = 130 ± 11 ng/mL, REC = 150 ± 14 ng/ml) and BDNF (NT = 484 ± 122 pg/mL, INT = 488 ± 122 pg/mL, REC = 383 ± 56 pg/mL) concentrations were similar between training conditions. Likewise, similar exercise-induced increases in cortisol and BDNF concentrations were observed between training conditions. GMS was 32% greater during INT vs NT (P < .001). Consistent with a state of functional overreaching (FOR), impairments in performance and mood state with INT were restored after 1 wk of REC. These results support evidence for mood changes before plasma BDNF concentrations as a biochemical marker of FOR and that cortisol is not a useful marker for predicting FOR.

Adrenal insufficiency in patients on long-term opioid analgesia.

Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain. Cross-sectional study of chronic pain patients on long-term opioid analgesia. Patients attending tertiary chronic pain clinics at the Western General Hospital, Edinburgh, treated with long-term opioid analgesia (n = 48) with no recent exposure to exogenous glucocorticoids. Four patients (8·3%) had basal morning plasma cortisol concentrations below 100 nmol/l, of whom three failed to achieve a satisfactory cortisol response to exogenous ACTH1-24 stimulation (peak cortisol >430 nmol/l). Basal cortisol was positively associated with age (R = 0·398, P = 0·005) and negatively associated with BMI (R = -0·435, P = 0·002). Suppression of the hypothalamic-pituitary-adrenal axis is present in a clinically significant proportion of chronic pain patients treated with opioid analgesia. Studies of larger populations should be conducted to better define the prevalence and potential clinical consequences of adrenal insufficiency in this context.

Low dose aspirin like analgesic and anti-inflammatory activities of mono-hydroxybenzoic acids in stressed rodents

AimsTo compare analgesic and anti-inflammatory activities of aspirin and mono-hydroxybenzoic acids after their daily oral doses. Main methodsEfficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also. Key findingsAlthough stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid. SignificanceObservations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid.

Relations between plasma oxytocin and cortisol: The stress buffering role of social support

Stress responses in humans can be attenuated by exogenous oxytocin administration, and these stress-buffering properties may be moderated by social factors. Yet, the influence of acute stressors on circulating endogenous oxytocin levels have been inconsistent, and limited information is available concerning the influence of social support in moderating this relationship. In the current investigation, undergraduate women (N = 67) were assessed in the Trier Social Stress Test (TSST) with either social support available from a close female friend or no social support being available. An additional set of women served as controls. The TSST elicited marked elevations of state anxiety and negative emotions, which were largely attenuated among women who received social support. Furthermore, baseline oxytocin levels were inversely related to women's general feelings of distrust, as well as basal plasma cortisol levels. Despite these associations, oxytocin levels were unaffected by the TSST, and this was the case irrespective of oral contraceptive use or estrogen levels. In contrast, plasma cortisol elevations were elicited by the psychosocial stressor, but only in women using oral contraceptives, an effect that was prevented when social support was available. Taken together, these data provisionally suggest that changes in plasma oxytocin might not accompany the stress attenuating effects of social support on cortisol levels. Moreover, as plasma oxytocin might not reliably reflect brain oxytocin levels, the linkage between oxytocin and prosocial behaviors remains tenuous.