Basal Cortisol Concentrations Research Articles

Early human contact and housing for pigs – part 3: ability to cope with the environment

Early experiences can have long-term impacts on stress adaptability. This paper is the last of three in a series on early experiences and stress in pigs, and reports on the effects of early human contact and housing on the ability of pigs to cope with their general environment. Using a 2 × 2 factorial design, 48 litters of pigs were reared in either a farrowing crate (FC) or a loose farrowing pen (LP; PigSAFE pen) which was larger, more physically complex and allowed the sow to move freely. Piglets were provided with either routine contact from stockpeople (C), or routine contact plus regular opportunities for positive human contact (+HC) involving 5 min of scratching, patting and stroking imposed to the litter 5 days/week from 0 to 4 weeks of age. At 4 weeks of age (preweaning), C piglets that were reared in FC had considerably lower concentrations of serum brain-derived neurotrophic factor (BDNF) than piglets from the other treatment combinations. Compared to C pigs, +HC pigs had fewer injuries at 4 weeks of age. There were no clear effects of human contact on BDNF concentrations or injuries after weaning, or on basal cortisol or immunoglobulin-A concentrations, behavioural time budgets, tear staining, growth, or piglet survival. Compared to FC piglets, LP piglets showed more play behaviour and interactions with the dam and less repetitive nosing towards pen mates during lactation. There was no evidence that early housing affected pigs’ behavioural time budgets or physiology after weaning. Tear staining severity was greater in LP piglets at 4 weeks of age, but this may have been associated with the higher growth rates of LP piglets preweaning. There was no effect of lactation housing on growth after weaning. Preweaning piglet mortality was higher in the loose system. The findings on BDNF concentrations, injuries and play behaviour suggest improved welfare during the treatment period in +HC and LP piglets compared to C and FC piglets, respectively. These results together with those from the other papers in this series indicate that positive human interactions early in life promote stress adaptability in pigs. Furthermore, while the farrowing crate environment deprives piglets of opportunities for play behaviour and sow interaction, there was no evidence that rearing in crates negatively affected pig welfare or stress resilience after weaning. Whether these findings are specific to the two housing systems studied here, or can be generalised to other housing designs, warrants further research.

Maternal Vitamin C Intake during Pregnancy Influences Long-Term Offspring Growth with Timing- and Sex-Specific Effects in Guinea Pigs.

Our previous work in guinea pigs revealed that low vitamin C intake during preconception and pregnancy adversely affects fertility, pregnancy outcomes, and foetal and neonatal growth in a sex-dependent manner. To investigate the long-term impact on offspring, we monitored their growth from birth to adolescence (four months), recorded organ weights at childhood equivalence (28 days) and adolescence, and assessed physiological parameters like oral glucose tolerance and basal cortisol concentrations. We also investigated the effects of the timing of maternal vitamin C restriction (early vs. late gestation) on pregnancy outcomes and the health consequences for offspring. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum during preconception. Pregnant dams were then randomised into four feeding regimens: consistently optimal, consistently low, low during early pregnancy, or low during late pregnancy. We found that low maternal vitamin C intake during early pregnancy accelerated foetal and neonatal growth in female offspring and altered glucose homeostasis in the offspring of both sexes at an age equivalent to early childhood. Conversely, low maternal vitamin C intake during late pregnancy resulted in foetal growth restriction and reduced weight gain in male offspring throughout their lifespan. We conclude that altered vitamin C during development has long-lasting, sex-specific consequences for offspring and that the timing of vitamin C depletion is also critical, with low levels during early development being associated with the development of a metabolic syndrome-related phenotype, while later deprivation appears to be linked to a growth-faltering phenotype.

On Primary Adrenal Insufficiency with Normal Concentrations of Cortisol - Early Manifestation of Addison's Disease.

Primary adrenal insufficiency (AI) is an endocrine disorder in which hormones of the adrenal cortex are produced to an insufficient extent. Since receptors for adrenal steroids have a wide distribution, initial symptoms may be nonspecific. In particular, the lack of glucocorticoids can quickly lead to a life-threatening adrenal crisis. Therefore, current guidelines suggest applying a low threshold for testing and to rule out AI not before serum cortisol concentrations are higher than 500 nmol/l (18 μg/dl). To ease the diagnostic, determination of morning cortisol concentrations is increasingly used for making a diagnosis whereby values of>350 nmol/l are considered to safely rule out Addison's disease. Also, elevated corticotropin concentrations (>300 pg/ml) are indicative of primary AI when cortisol levels are below 140 nmol/l (5 μg/dl). However, approximately 10 percent of our patients with the final diagnosis of primary adrenal insufficiency would clearly have been missed for they presented with normal cortisol concentrations. Here, we present five such cases to support the view that normal to high basal concentrations of cortisol in the presence of clearly elevated corticotropin are indicative of primary adrenal insufficiency when the case history is suggestive of Addison's disease. In all cases, treatment with hydrocortisone had been started, after which the symptoms improved. Moreover, autoantibodies to the adrenal cortex had been present and all patients underwent a structured national education program to ensure that self-monitored dose adjustments could be made as needed.

Associations between immune competence phenotype and stress response in sheep

Immune competence in domestic sheep is gaining more attention in genetic selection programs that seek to enhance flock immunity and animal welfare. A goal of many programs is to identify behavioral phenotypes that indicate stress-coping strength, as well as disease resilience. The current study set out to explore the relationship between immune responsiveness, physiological stress, and behavioral response among sheep that had been selected for ‘low’ (LR) or ‘high’ (HR) response to cell-mediated and antibody-mediate reactivity to a clostridial vaccine. Multiparous ewes were placed in four experiments which exposed the animals to various threats including, dog presence, human proximity, visual isolation from flock, and physical restraint. To evaluate the consistency of behavioral phenotypes, all ewes were placed in the test circuit one year later. Basal body temperature (via iButton) and serum cortisol concentrations were collected prior to and after the circuit each year. Immune group (HR vs. LR) was not found to be related to behavioral performance during the dog, human, isolation, or restraint challenge. Immune group categorization was also unrelated to pre- and post-cortisol concentrations, and the change in cortisol concentrations during testing. There was a negative relationship identified between response to visual isolation and change in cortisol response during testing, indicating that sheep which were more active or agitated during visual isolation from the flock experienced less of an increase in serum cortisol levels and were perhaps experiencing a negative, high arousal state compared to less reactive sheep (e.g., freeze behavior) (χ2(4, N=99) = 42.72, P <0.0001). There was also a post hoc, positive relationship identified between weight measurements and immune group, such that individuals with greater body weight were more likely to be in the high immune responsiveness group (P= 0.01). Specifically, for every unit increase in weight, there was a ~49% chance of being categorized in the HR group. This is relevant for selection programs because producers that seek to enhance immune responsiveness and performance may be able to select sheep that carry a greater body mass, and while not found in the present study, could lead to greater flock immunity.

Association between childhood maltreatment and adult cortisol concentrations mediated through subjective health complaints.

Lower cortisol concentrations in adulthood were repeatedly associated with more severe childhood maltreatment. Additionally, childhood maltreatment was reported to promote health risk behavior, such as smoking or alcohol consumption, and to increase the risk of mental and somatic diseases during adulthood, such as major depressive disorders or obesity. The present study investigated if health risk behavior and disease symptoms in adults mediate the associations between past childhood maltreatment and present basal serum cortisol concentrations. Data from two independent adult cohorts of the general population-based Study of Health in Pomerania (SHIP-TREND-0: N = 3,517; SHIP-START-2: N = 1,640) was used. Childhood maltreatment was assessed via the Childhood Trauma Questionnaire (CTQ). Cortisol concentrations were measured in single-point serum samples. Health risk behavior and mental and physical symptoms were used as mediators. Mediation analyses were calculated separately for both cohorts; results were integrated via meta-analyses. In mediator-separated analyses, associations between childhood maltreatment and basal serum cortisol concentrations were partly mediated by depressive symptoms (BDI-II: βindirect effect = -.011, pFDR = .017, 21.0% mediated) and subjective somatic health complaints (somatic complaints: βindirect effect = -.010, pFDR = .005, 19.4% mediated). In the second step, both mediators were simultaneously integrated into one mediation model. The model replicated the mediation effects of the subjective somatic health complaints (whole model: βindirect effect = -.014, p = .001, 27.6% mediated; BDI-II: βindirect effect = -.006, p = .163, 11.4% mediated, somatic complaints: βindirect effect = -.020, p = .020, 15.5% mediated). The results support the hypothesis that the long-lasting effects of childhood maltreatment on the stress response system are partly mediated through self-perceived disease symptoms. However, no mediation was found for health risk behavior or physically measured mediators. Mediation models with multiple simultaneous mediators pointed to a relevant overlap between the potential mediators. This overlap should be focused on in future studies.

Serial changes in the concentrations of cortisol and thyroid hormones in Beagle dogs infected with Babesia rossi

An experimental infection using Babesia (B.) rossi was performed in healthy male Beagle dogs to assess the changes in endocrine variables during disease. Two dogs were infected with a low dose (LD) of parasite inoculum (104 parasites) and three dogs were infected with a high dose (HD) (108 parasites). Basal serum cortisol, thyroxine (T4), and thyrotropin (TSH) concentrations were measured every second day. Samples were analyzed using a solid- phase, competitive chemiluminescent enzyme immunoassay (Immulyte® 2000, Siemens). Variables were compared between groups and timepoints using linear mixed models. In both groups, the median cortisol concentration increased, whilst the median T4 concentration decreased after infection, with a return towards baseline concentration post treatment. The highest cortisol and the lowest T4 concentrations were reached at 96 h and 108 h post infection, respectively, in the HD group and slightly later at 108 and 144 h post-infection, respectively, in the LD group. A higher cortisol concentration with a more rapid increase, and a lower T4 concentration with a more rapid decline, were associated with disease severity and a higher dose of parasite inoculum. The TSH concentration remained within the reference interval throughout the study period. This study illustrated the temporal changes in endocrine parameters during experimental B. rossi infection and demonstrated that cortisol and T4 tracked the severity of disease, albeit in opposite directions.

Ocean acidification alters the acute stress response of a marine fish

The absorption of anthropogenic carbon dioxide from the atmosphere by oceans generates rapid changes in seawater carbonate system and pH, a process termed ocean acidification. Exposure to acidified water can impact the allostatic load of marine organism as the acclimation to suboptimal environments requires physiological adaptive responses that are energetically costly. As a consequence, fish facing ocean acidification may experience alterations of their stress response and a compromised ability to cope with additional stress, which may impact individuals' life traits and ultimately their fitness. In this context, we carried out an integrative study investigating the impact of ocean acidification on the physiological and behavioral stress responses to an acute stress in juvenile European sea bass. Fish were long term (11 months) exposed to present day pH/CO2 condition or acidified water as predicted by IPCC “business as usual” (RCP8.5) scenario for 2100 and subjected to netting stress (fish transfer and confinement test). Fish acclimated to acidified condition showed slower post stress return to plasma basal concentrations of cortisol and glucose. We found no clear indication of regulation in the central and interrenal tissues of the expression levels of gluco- and mineralocorticoid receptors and corticoid releasing factor. At 120 min post stress, sea bass acclimated to acidified water had divergent neurotransmitters concentrations pattern in the hypothalamus (higher serotonin levels and lower GABA and dopamine levels) and a reduction in motor activity. Our experimental data indicate that ocean acidification alters the physiological response to acute stress in European sea bass via the neuroendocrine regulation of the corticotropic axis, a response associated to an alteration of the motor behavioral profile. Overall, this study suggests that behavioral and physiological adaptive response to climate changes related constraints may impact fish resilience to further stressful events.

Adult‑onset X‑linked adrenal hypoplasia congenita caused by a novel mutation in DAX1/NR0B1: A case report and literature review

Adrenal hypoplasia congenita (AHC) is a rare X-linked recessive disease caused by mutations in the nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene, which is also referred to as dosage-sensitive sex-reversal, adrenal hypoplasia congenita, in the critical region of the X chromosome, gene 1 (DAX1). This gene is expressed in the hypothalamus, anterior pituitary and steroidogenic tissues, including the gonads and adrenal cortex. Adult-onset forms of X-linked AHC are a significant cause of concern. In the present study, the case of a 21-year-old male who exhibited adrenal insufficiency and hypogonadotropic hypogonadism was described. The patient initially presented with nausea, vomiting, fatigue and dizziness. The laboratory results demonstrated that the patient had hyponatremia, a low basal cortisol concentration and increased adrenocorticotropic hormone levels. Molecular genetic examination revealed a novel frameshift mutation (c.1005delC, p.V336Cfs*36). Following steroid supplementation, the patient's vomiting, fatigue and dizziness rapidly improved. To the best of our knowledge, the present study was the first case report of adult-onset X-linked AHC with this novel frameshift mutation. Furthermore, the present study highlighted differences in the clinical presentation of adult-onset forms of X-linked AHC. This may therefore alert medical professionals to the need to perform genetic analysis for DAX1 mutations in adolescents and adults with primary adrenal insufficiency and hypogonadotropic hypogonadism.

Differences in stress response between two altitudes assessed by salivary cortisol levels within circadian rhythms in long-distance runners

There are conflicting reports regarding the efficacy of cortisol as a stress marker in altitude training due to the influence of the circadian rhythm. This study aimed to verify whether the automated measurement of salivary cortisol concentration via sequential sampling could detect the differences in exercise stress between two altitudes. We enrolled 12 elite female long-distance runners living near sea level. For the first higher-altitude camp, the runners lived at 1800 m and trained at 1700 m for 7 days. For the second lower-altitude camp, they lived at 1550 m and trained at 1300 m for 7 days. Their saliva was sequentially collected on the last 2 days during each camp which involved different intensity exercises in the morning and afternoon. The salivary cortisol concentrations were measured using electrochemiluminescence immunoassay. Before dinner, the basal salivary cortisol concentrations were significantly higher in the higher-altitude camp. The rate of change in the salivary cortisol concentration during the morning exercise was significantly higher in the higher-altitude camp than in lower-altitude camp (p = 0.028) despite the same exercise programs and intensities. Salivary cortisol level measurements during the athletes' circadian rhythms could detect the differences in acclimatization and exercise stress between two altitudes.

Serum Cortisol and Its Correlation with Leucocyte Profile and Circulating Lipids in Donkeys (Equus asinus).

Simple SummaryThere are relatively few studies investigating serum cortisol levels in donkeys. The aim of this study was to evaluate basal cortisol values in donkeys, and its physiological role on the immune system and lipid levels in relation to age and pregnancy. The results showed that age did not influence cortisol levels while pregnancy increased its concentrations. Different correlations were found between cortisol, leucocyte types, and serum triglycerides depending upon age and pregnancy state. Although correlation is, of course, not equivalent to causation, we can hypothesize that the multiple functions of cortisol on the immune system and lipid metabolism vary across donkey lifespan and are related to physiological state.The values for basal serum cortisol concentrations of horses are available in many studies. However, there are limited data about serum cortisol in donkeys. The present study aimed to determine the baseline values for serum cortisol, to evaluate the influence of age and pregnancy on its levels, and to correlate its values with leucocyte profile, serum cholesterol, and triglycerides. Serum samples were collected from 97 healthy donkeys. Cortisol was analyzed by chemo-luminescent assay. The median and the 2.5th and 97.5th percentiles of serum cortisol measured and calculated in all donkeys were 5.64, 3.40, and 10.54 µg/dL, respectively. Females (n.91) were divided into three groups: Group A (young), Group B (adult), and Group C (pregnant at the 9th–11th months). The effect of age and physiological status was investigated by the Mann–Whitney test. Group C showed significantly higher levels than Group B (p < 0.05). Significant correlations were found in Group B with monocytes (r = 0.37, p < 0.01) and triglycerides (r = 0.30, p < 0.05), and in Group C with monocytes (r = 0.79, p < 0.01), basophils (r = 0.6, p < 0.05), and neutrophil/lymphocyte ratio (r = −0.63, p < 0.05). Higher cortisol values related to late pregnancy are also found in this species. These preliminary results provide evidence for a relationship between cortisol and the immune system as well as cortisol and lipid metabolism modulated by age and pregnancy when parameters are within normal values.

Sex differences in the association between basal serum cortisol concentrations and cortical thickness

BackgroundBasal cortisol concentrations vary between men and women. Likewise, previous findings suggest stress-related cortical thickness alterations. Thus, we aimed at elucidating sex differences in the association between serum cortisol concentrations and cortical thickness. MethodsData of 2594 participants (55.55% male; mean age = 53.55 years ± 13.17 years) of the general population were used to investigate sex differences in basal serum cortisol concentrations and associations of serum cortisol concentrations with global and regional cortical thickness. The validity of the results was tested by including sex hormone concentrations as a biological and childhood maltreatment and depressive symptoms as a psychological confounder. ResultsBasal serum cortisol concentrations were higher in men than in women (β = −0.158, t(2575) = -6.852, p = 9.056e-12). Sex differences in serum cortisol concentrations were diminished by including serum concentrations of testosterone, estrone, or estradiol in the models. In men but not in women, serum cortisol concentrations were inversely associated with the global cortical thickness (men: β = −0.064, t(1412) = -3.010, p = .003; women: β = −0.016, t(1131) = -0.607, p = .544). Additionally, these effects were observed in eleven cortical regions after adjusting for multiple testing. The associations were independent of childhood maltreatment and depressive symptoms. ConclusionSex differences in serum cortisol concentrations and the association between serum cortisol concentrations and cortical thickness suggest important sex-specific effects of stress on the brain. Future studies should integrate the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis in sex-stratified analyses.

Basal cortisol concentrations related to maternal behavior during puppy development predict post-growth resilience in dogs

A prolonged stress hyporesponsive period (SHRP) due to the mother's presence may delay the timing of glucocorticoid (GC) elevation in infants, thereby reducing the excessive stress response that would affect post-growth temperament. In dogs, the SHRP has been suggested to persist until postnatal week (PW) 4; therefore, PW 5, which SHRP may be prolonged by the mother dog, may be a critical point in the developmental stage of dogs to establish stress responsiveness. We conducted a long-term survey on the development of dogs to investigate i) whether the degree of the stress response at PW 5 is determined by maternal behavior and ii) whether it can predict post-growth stress responses and temperament in dogs. As a result, the offspring of mother dogs who had more delivery experience and exhibited more maternal behavior showed higher basal cortisol concentrations at PW 5. These offspring may have acquired less fear response as an individual trait and had relatively quick adaptability, albeit with high cortisol concentrations during exposure to novel environments post-growth, suggesting that high cortisol concentrations at PW 5 are linked to resilience post-growth. Basal cortisol concentrations at PW 7 were not affected by maternal variables and were not associated with cortisol response to novel environments post-growth. GCs are essential hormones that increase the probability of survival. Therefore, the high hypothalamic pituitary adrenal activities of the mother dogs and their offspring in this study may not immediately indicate negative states, and these results prompt a reconsideration of the role of GC in organisms.

Flaxseed oil as omega-3 polyunsaturated fatty acid source modulates cortisol concentrations and social dominance in male and female guinea pigs

Flaxseed oil is an excellent source of the essential omega-3 polyunsaturated fatty acid (PUFA) alpha-linolenic acid (ALA). Omega-3 PUFAs are important neuronal components and can counteract aggressive, depressive, and anxiety-like behavior, reduce glucocorticoid (e.g. cortisol) concentrations under chronic stress but also increase acute glucocorticoid responses. As glucocorticoids per se and glucocorticoid responsiveness can modulate the establishment of dominance hierarchies, we investigated if flaxseed oil high in ALA can promote social dominance through effects on glucocorticoid concentrations. Two male and two female groups of domestic guinea pigs (n = 9 per group) were maintained on a control or a 5% (w/w) flaxseed oil diet for four weeks. Social behaviors, hierarchy indices, locomotion, and saliva cortisol concentrations were determined during basal group housing conditions and stressful social confrontations with unfamiliar individuals of the other groups. Flaxseed groups had increased basal cortisol concentrations and showed no cortisol increase during social confrontations. Cortisol concentrations in control groups significantly increased during social confrontations. Such higher cortisol responses positively affected individual hierarchy indices in control males. However, flaxseed males became dominant irrespective of cortisol concentrations. In females, the opposite was detected, namely a higher dominant status in control compared to flaxseed females. Open-field- and dark-light-tests for anxiety-like behavior revealed no pronounced differences, but flaxseed males showed the highest locomotor activity. Flaxseed oil as an ALA source sex-specifically promoted social dominance irrespective of cortisol concentrations and responses. The underlying neuronal mechanisms remain to be determined, but a sex-specific energetic advantage may have accounted for this effect.

Salivary alpha amylase and cortisol levels as stress biomarkers in children with cerebral palsy and their association with a physical therapy program

IntroductionCerebral palsy (CP) is one of the main causes of physical disabilities in childhood. There is evidence that CP children display high levels of stress, which could interfere with learning processes and interpretation of relevant sensory information during motor skills acquisition and socialization. ObjectiveThis study aims to compare basal levels of stress biomarkers (cortisol and alpha-amylase) of healthy children (HC) and children with CP, and to investigate whether a physical therapy session using the neurodevelopmental technique (NDT) interferes with these levels. MethodsA cross-sectional design was used. A total of 86 children (HC: n = 45 and CP: n = 41) with matching age, sex, socioeconomic status, and sampling time. Salivary cortisol and alpha-amylase levels were measured by means of electrochemiluminescence and spectrophotometry methods. A single saliva sample was collected in the HC group to determine basal levels. For CP group three samples were collected: a first sample was taken 20−30 min prior to the intervention, while two post-intervention samples were collected (5 and 20 min) to evaluate individual changes in salivary stress biomarkers. ResultsHigher basal cortisol concentration was found in CP children when compared to HC group. Moreover, CP children showed a significant reduction in cortisol levels 20 min after NDT intervention. No significant differences were observed in alpha-amylase values. ConclusionPresent results show that CP causes alteration in basal cortisol values at childhood and suggest that CP children respond to environmental regulatory factors such as NDT, in attempt to reduce stress.

Endocrine and metabolic responses to glucose, insulin, and adrenocorticotropin infusions in early-lactation dairy goats of high and low milk yield

This experiment aimed to examine endocrine and metabolic responses to glucose, insulin, and adrenocorticotropin (ACTH) infusions in early-lactation dairy goats of different levels of milk production (LMP). Goats were grouped as either high (HY; 4.0 L/d, n = 13) or low milk yield (LY; 2.4 L/d, n = 13). Individual milk yield (L/d) and dry matter intake (DMI; kg/d) were measured daily. Concentration (mM) of glucose, fatty acids, and β-hydroxybutyrate, percent of milk fat and protein, body weight (BW; kg), and body condition score (BCS) were assessed weekly (from 2-6 wk postpartum). An intravenous glucose tolerance test (IVGTT), an insulin tolerance test (ITT), and an ACTH stimulationtest were carried out at 43, 44, and 45 ± 0.7 d in milk, respectively. The HY goats had greater milk yield (+67%), energy-corrected milk (ECM; +70%), DMI (+28%), ratio of ECM output to metabolic BW (+67%), and feed efficiency (+25%), but lesser BCS than LY goats (2.4 vs. 2.6). The DMI (% of BW) was moderately correlated with ECM (r = 0.70) and negatively correlated with BCS (r = -0.57). At the time of the IVGTT, HY goats had lesser basal insulin and glucose than LY goats. However, results from IVGTT and ITT indicate that the sensitivity of peripheral tissues to insulin was unaffected by LMP. Compared with LY, HY goats had lesser insulin secretion (-52%) and greater insulin clearance rate (+47%) after glucose infusion. The ITT and ACTH stimulation test results show that both the growth hormone response to insulin and the cortisol response to ACTH were unaffected by LMP. Also, basal plasma concentrations of GH and cortisol were not correlated with glucose and fatty acids concentrations or any performance traits. Collectively, our results suggest that differences between HY and LY goats, concerning milk yield and feed efficiency, were probably more closely related to differences in insulin secretion and clearance than to differences in peripheral tissue responsiveness to the effects of catabolic and anabolic hormones.

Can Endocrine Dysfunction Be Reliably Tested in Aged Horses That Are Experiencing Pain?

Simple SummaryPituitary pars intermedia dysfunction (PPID) is an endocrine (secreting internally) disease of aged horses and ponies. An enlargement (hyperplasia) of the pars intermedia of the pituitary gland leads to an increased secretion of hormones, including adrenocorticotropic hormone (ACTH). The main tests for a diagnosis of PPID are the measurement of basal ACTH and the thyrotropin-releasing hormone (TRH) stimulation test, where TRH stimulates the secretion of ACTH. Since pain can also lead to elevated concentrations of ACTH, it is unclear whether horses with pain can be tested for PPID correctly. The aim of the present study was to find out whether pain caused a marked increase of ACTH can lead to a false positive result in the diagnosis of PPID. Therefore, we examined fifteen horses treated for different pain conditions, which also served as their own controls as soon as they were pain-free again. The ACTH and cortisol were measured before and after the TRH stimulation test. There was no significant difference in the ACTH concentration in horses with pain and the controls, between different pain intensities or between disease groups. Thus, measuring the basal ACTH concentration and performing the TRH stimulation test for the diagnosis of PPID seem to be possible in horses with a treated low to moderate pain condition.The aim of the present study was to evaluate (i) the effects of different intensities and types of treated pain on the basal concentrations of adrenocorticotropic hormone (ACTH) and cortisol, and (ii) the thyrotropin-releasing hormone (TRH) stimulation test, to determine whether treated pain caused a marked increase of ACTH, which would lead to a false positive result in the diagnosis of pituitary pars intermedia dysfunction (PPID). Methods: Fifteen horses with treated low to moderate pain intensities were part of the study. They served as their own controls as soon as they were pain-free again. The horses were divided into three disease groups, depending on their underlying disease (disease group 1 = colic, disease group 2 = laminitis, disease group 3 = orthopedic problems). A composite pain scale was used to evaluate the intensity of the pain. This pain scale contained a general part and specific criteria for every disease. Subsequently, ACTH and cortisol were measured before and after the intravenous application of 1 mg of TRH. Results: There was no significant difference in the basal or stimulated ACTH concentration in horses with pain and controls, between different pain intensities or between disease groups. Descriptive statistics, however, revealed that pain might decrease the effect of TRH on the secretion of ACTH. There was an increase of ACTH 30 min after TRH application (p = 0.007) in the treated pain group, but this difference could not be statistically confirmed. Measuring the basal ACTH concentration and performing the TRH stimulation test for the diagnosis of PPID seem to be possible in horses with low to moderate pain.

Prevalence and characterization of hypoadrenocorticism in dogs with signs of chronic gastrointestinal disease: A multicenter study.

BackgroundDogs with hypoadrenocorticism (HA) frequently show signs of gastrointestinal disease (SGD). The prevalence of dogs presented for chronic SGD with HA is unknown.ObjectivesThe aims of this study were to determine the prevalence of HA in dogs with chronic SGD and to identify clinical and laboratory variables for HA in this population.AnimalsOne hundred fifty‐one dogs with chronic SGD.MethodsIn this multicentered prevalence study a standardized workup was performed in prospectively enrolled dogs with SGD > 3 weeks duration. Basal serum cortisol concentration was measured in every dog with ACTH stimulation test (ACTHST) if basal serum cortisol concentration was <3 μg/dL.ResultsBasal serum cortisol concentration was <3 μg/dL in 80/151 (53%) dogs, <2 μg/dL in 42/151 (28%) dogs, and < 1 μg/dL in 9/151 (6%) dogs. In 6/151 dogs HA was diagnosed based on ACTHST (stimulated serum cortisol concentration < 2 μg/dL), a prevalence of 4%. There was no difference in history, physical examination, and laboratory variables between dogs with HA and those with other causes of chronic SGD. In 4/6 dogs with HA, there was melena or hematochezia indicating gastrointestinal blood loss. Hyperkalemia, hyponatremia, or both was not observed in any dog.Conclusion and Clinical ImportanceThe prevalence of HA among dogs with chronic SGD is higher than in the general population. Based on these results, testing adrenal function should be performed as a standard screening test in dogs with chronic SGD to differentiate between HA and chronic enteropathies.

Role of Basal Hormones on Sweat Rate and Sweat Na+ Loss in Elite Women Soccer Players.

We aimed to determine whether basal concentrations of testosterone, cortisol or the ratio testosterone/cortisol were related to sweat Na+ loss, sweat Na+ concentration ([Na+]) and sweat rate during exercise. Twenty-two female elite soccer players participated in the study. Testosterone and cortisol were measured in blood samples before exercise. Sweat samples were collected during a training session (~20°C, ~30% RH, and ~0.55 m/s of wind speed) to measure sweat [Na+]. Sweat rate was determined by considering the difference between post-and pre-body weight, along with the amount of liquid consumed. During exercise, sweat Na+ loss (0.33[0.19] g/h) and sweat rate (0.49[0.20] L/h) were related to basal testosterone concentration (1.4[0.4] pg/mL) (r=0.54; r=0.55, respectively; p<0.05), but not with basal cortisol concentration (119.2[24.2] ng/mL) nor testosterone/cortisol ratio (0.012[0.003]) (p>0.05). However, when Na+ loss was adjusted to sweat rate, no association was found between Na+ loss and testosterone (p>0.05). In addition, no differences were found between players with high vs. low Na+ loss adjusted to sweat loss in menstrual phase or intensity during exercise (p>0.05). In conclusion, these results suggest that in these specific environmental conditions, basal levels of testosterone might increase sweat rate and therefore, the amount of Na+ lost during exercise in elite women soccer players.

Novel Insights Into Effects of Cortisol and Glucagon on Nocturnal Glucose Production in Type 2 Diabetes.

The effect of physiological changes in night-time cortisol and glucagon on endogenous glucose production (EGP) and nocturnal glycemia are unknown. To determine the effects of changes in cortisol and glucagon on EGP during the night. Two overnight protocols were conducted. In Protocol 1, endogenous cortisol was blocked with metyrapone and hydrocortisone infused either at constant (constant) or increasing (variable) rates to mimic basal or physiological nocturnal cortisol concentrations. In Protocol 2, endogenous glucagon was blocked with somatostatin and exogenous glucagon was infused at either basal or elevated rates to mimic nocturnal glucagon concentrations observed in nondiabetic (ND) and type 2 diabetes (T2D) individuals. EGP was measured using [3-3H] glucose and gluconeogenesis estimated with 2H2O in all studies. Mayo Clinic Clinical Research Trials Unit, Rochester, MN, US. In Protocol 1, 34 subjects (17 ND and 17 T2D) and in Protocol 2, 39 subjects (21 ND and 18 T2D) were studied. Endogenous glucose production. EGP, gluconeogenesis, and glycogenolysis were higher with variable than with constant cortisol at 7 am in T2D subjects. In contrast, nocturnal EGP did not differ in ND subjects between variable and constant cortisol. While elevated glucagon increased EGP, glycogenolysis, and gluconeogenesis in ND, the data in T2D subjects indicated that EGP and gluconeogenesis but not glycogenolysis were higher during the early part of the night. Nocturnal hyperglucagonemia, but not physiological rise in cortisol, contributes to nocturnal hyperglycemia in T2D due to increased gluconeogenesis.

Remitted depression and cognition in HIV: The role of cortisol and inflammation

In major depressive disorder (MDD) and remitted MDD (rMDD) alterations in cortisol and inflammation are associated with cognitive difficulties, but these relationships have not been investigated in HIV. We used secondary data from a placebo-controlled, cross-over study of cognitive performance following a probe of the hypothalamic-pituitary-adrenal (HPA) axis (low dose hydrocortisone; LDH 10 mg) in 65 people with HIV (PWH; 36 women). Using placebo data, we examined sex-specific associations between two biomarkers – basal afternoon salivary cortisol and salivary inflammatory cytokines - cognition, and rMDD. Salivary cortisol and inflammatory biomarkers were sampled across the 5 -h study. The panel of inflammatory markers included interleukin (IL)-6, IL-8, IL-1β, tumor necrosis factor-(TNF)-α, CRP, interferon gamma-induced protein (IP-10), monocyte chemotactic protein (MCP)-1, monokine induced by interferon (MIG), matrix metalloproteinase MMP-9, and MMP-1. Learning, memory, attention/concentration, and executive function were assessed 30 min and 4 h after the placebo intervention; visuospatial ability was also assessed 30 min after the placebo intervention. For women but not men with HIV, basal cortisol concentrations were higher in rMDD versus noMDD groups, and related to poorer learning and memory. For men and women with HIV, basal inflammatory cytokines were higher in rMDD versus noMDD groups, but were negatively related to cognition independent of rMDD status. Cortisol and cytokines relate to cognition in PWH, but the associations depended on sex, rMDD status, and their interaction.