Cortisol Area Under The Curve Research Articles

Multiple adrenocortical steroid response to administration of exogenous adrenocorticotropic hormone to hospitalized foals.

BackgroundThe hypothalamic‐pituitary‐adrenal axis regulates the response to sepsis‐associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal.ObjectiveTo investigate the response of multiple adrenocortical steroids to administration of ACTH in foals.AnimalsHospitalized (n = 34) and healthy (n = 13) foals.MethodsIn this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 μg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta0‐30 were calculated for each hormone.ResultsThe AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α‐OH‐progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta0‐30 for cortisol and 17α‐OH‐progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 μg/dL/h, P < .05), suggesting adrenocortical dysfunction.Conclusion and Clinical ImportanceThe 17α‐OH‐progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.

Relationship between Meditation and Waking Salivary Cortisol Secretion among Long-Term MBSR Instructors

Background: A potential relationship between long-term meditation practice and stress reduction remains virtually unexplored. The purpose of this study was to characterize stress using salivary waking cortisol in a group of long-term meditators with training in the Mindfulness-Based Stress Reduction (MBSR) program. Materials and Methods: Four salivary cortisol samples were collected from meditators (n = 84) during the first hour of awakening. The waking cortisol rhythm was summarized using cortisol area under the curve (AUC) with respect to increased secretion above baseline (AUC_I) and cortisol AUC above ground (above zero, AUC_G); data on meditation duration and depth, perceived stress, and other covariates were collected via self-reported questionnaire. Results: Individuals in the highest quartile of years meditating (> 26 years) had statistically significantly elevated AUC_G values (p = 0.01) as compared to individuals in the lowest quartile of years meditating (≤10 years). This relationship was more pronounced among individuals waking at or before 6: 30 a.m. Conclusions: Overall, an increasing number of years of meditation practice was related to a higher waking cortisol response. These intriguing findings warrant additional exploration, as the stress response can be complex.

Cortisol and trait anxiety as relevant factors involved in memory performance in people with drug-resistant epilepsy

People with drug-resistant epilepsy are exposed to unpredictable and uncontrollable seizures, which can be considered as a chronic stress condition. Additionally, these patients present memory deficits and a high prevalence of depression and anxiety. Cortisol, the main stress hormone, has a modulatory role on memory in healthy individuals and patients with emotional disorders, but its role in memory and emotional processes remains unclear in people with epilepsy. This study analyzes the differences in cortisol levels in people with epilepsy with high and low memory performance, and the relationships among cortisol levels, epilepsy-related factors, memory, anxiety, and depression. Fifty-two adults with drug-resistant epilepsy underwent a neuropsychological evaluation, in which nine saliva samples were collected to analyze the ability of the hypothalamic–pituitary–adrenal axis to descend in accordance with the circadian rhythm. Cortisol area under the curve (AUC) was computed to study the global cortisol changes. Patients with low immediate and delayed memory performance and left-hemisphere focus showed higher cortisol levels. Additionally, patients with low memory scores had higher cortisol AUC, and therefore slower declining levels in the afternoon. Memory performance was negatively related to the cortisol AUC and trait anxiety, being both reliable predictors of memory performance, especially in patients with left-hemisphere focus. These results suggest that memory deficits in people with drug-resistant epilepsy may be influenced by exposure to cortisol derived from chronic stress. Additionally, trait anxiety could contribute to increasing the vulnerability to stress.

Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy

BackgroundAdverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women. MethodsPhysically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26 weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22–34 weeks gestation; plasma interleukin-6 (IL-6), interleukin-1β (IL-1β), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated. ResultsForty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q = 5.7 × 10^−13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-α and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p = 0.03) and eicosapentaenoic acid (EPA) (p = 0.05). DiscussionOur findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of ω-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.

Diurnal Cortisol Concentrations and Growth Indexes of 12- to 48-Month-Old Children From Mexico City.

Early life cortisol plays an important role in bone, muscle, and fat mobilization processes, which could influence body composition, affecting anthropometric indicators such as weight and height. To explore the association between diurnal cortisol levels and growth indexes in children from 12 to 48 months of age. This study includes data from 404 children from the Programming Research in Obesity, Growth, Environment and Social Stressors Mexican birth cohort. Cortisol was measured in eight saliva samples collected at four time points during the day (from wakeup to bedtime), over 2 days, when the child was either 12, 18, or 24 months old. Total daytime cortisol levels were calculated by averaging the area under the curve (AUC) for the 2 days. Height and weight were measured from 12 to 48 months of age. Growth indexes were constructed according to z scores following World Health Organization standards: weight-for-age z score (Z-WFA), height/length-for-age z score, weight-for-height/length z score (Z-WFH), and body mass index-for-age z score (Z-BMIFA). Mixed models were used to analyze the association between cortisol AUC quartiles and growth indexes. Cortisol showed an inverted U-shaped association with the four growth indexes. Compared with the first quartile, all quartiles had a positive association with indexes that include weight, with the second quartile having the strongest association, resulting in an average change of β (95% CI) 0.38 (0.13-0.64) for Z-WFA, 0.36 (0.10-0.62) for Z-WFH, and 0.43 (0.17-0.69) for Z-BMIFA. Results suggest that early life daytime cortisol levels, as a reflection of hypothalamic-pituitary-adrenal axis development, might influence growth in early infancy.

Evaluation of a laparoscopically assisted ovariectomy technique in cats.

To describe a laparoscopically assisted ovariectomy (LAO) technique in the cat with a bipolar vessel sealing device (BVSD) or suture ligation and to compare the outcomes to open ovariohysterectomy (OO). Randomized prospective study ANIMALS: Healthy, adult, sexually intact female cats (n = 30). Ten cats were assigned to each group: LAO with BVSD (group A), LAO with ligation (group B), and OO with ligation (group C). Surgical times and complications were assessed. Serum glucose and cortisol were measured prior to surgery and at 1, 2, 4, 6, 12, and 24 hours after surgery. Pain was scored by using an interactive visual analog scale (IVAS) at 0, 1, 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours after surgery. Rescue analgesia was provided when IVAS score was 4 or more. Physiological and serum values and IVAS scores were compared among groups with area under the curve (AUC) by using a 1-way ANOVA. Surgical time was shortest for group C (19.1 ± 5.2 minutes; P < .0002); there was no significant difference between groups A (27.7 ± 6.6 minutes) and B (33.2 ± 8.2 minutes). All procedures were completed successfully. No significant differences among groups were found in IVAS scores (P = .36), rescue analgesia (P = .22), glucose AUC (P = .53), or cortisol AUC (P = .27). The LAO technique was accomplished as described in all cats with no complications or failures. Pain scores were not different from cats undergoing OO. LAO can be performed efficiently to maximize the benefits of minimally invasive surgery and is amenable to clinical practice.

Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder.

Eating late in the day is common, and stress can induce eating. Little is understood about how time of day and stress interact to affect appetite and thereby body weight. These may be particularly important influences in binge eaters, who tend to binge in the evening, and in response to stress. Obese participants with (n=16) and without (n=16) binge eating disorder (BED) participated in two identical test protocols beginning either in the morning or the afternoon (AM condition/PM condition), each following an 8 h fast. For each protocol, they first received a standardized liquid meal (0900/1600 hours), then a stress test (Socially Evaluated Cold Pressor Test, 1110/1810 hours), and then a multi-item ad libitum buffet meal (1140/1840 hours) while rating appetite and stress and having blood drawn for hormone measures. Appetite at baseline was greater in the PM than in the AM condition (higher hunger, lower fullness). Following the liquid meal, area under the curve (AUC) values for hunger and ghrelin were greater and AUC values for peptide YY lower in the PM than in the AM condition. Only those with BED showed lower fullness AUC in the PM condition, as well as a pattern of higher initial PM and lower initial AM ghrelin. Following the stress test, cortisol and ghrelin increased in both the AM and PM conditions, but higher ghrelin AUC and lower cortisol AUC were observed in the PM condition. Again, only participants with BED showed lower fullness AUC in the PM condition. Buffet meal intake was similar across groups and conditions but those with BED reported greater loss of control and binge resemblance than those without. Afternoon/evening may be a high-risk period for overeating, particularly when paired with stress exposure, and for those with binge eating.

A matter of perception: Perceived socio-economic status and cortisol on the island of Utila, Honduras.

Numerous studies link low objective and subjective socioeconomic status (SES) to chronic activation of the hypothalamic pituitary adrenal (HPA) axis. Here, we examine associations between objective and subjective SES and diurnal salivary cortisol, a primary HPA component, as well as demographic and ecological predictors associated with SES perceptions and changes in diurnal cortisol. Participants were residents (age 18-79, n = 61) of Utila, a Honduran island where economic disparities are overt and geographically contained. Objective SES was measured as a composite of income, education, and occupation. Subjective SES was measured with a MacArthur ladder and a perceived lifestyle discrepancy (PLD) scale. Salivary cortisol was collected three times per day for two days. Questions addressing demographic, social, and household characteristics were assessed as predictors of PLD. Assessed independently, objective SES (P = .06) and PLD (P = .003) were associated with the steepness of diurnal cortisol changes, while PLD was also associated with higher cortisol area under the curve (AUC) (P = .036). Modeled together, only PLD predicted diurnal slope and AUC. PLD was associated with household sanitation, immigration status, food scarcity, objective SES, and owing money. Only access to sanitation and owing money had direct associations with cortisol that were not mediated by PLD. For adults on Utila, perceptions of unmet need outweigh other social and economic status factors in predicting cortisol AUC and slope. In addition, the unmediated effects of access to sanitation and owing money on cortisol suggest that these distinct aspects of inequality are important to consider when seeking to understand how inequality can impact HPA function.

Personality, Cortisol, and Cognition in Non-demented Elderly Subjects: Results from a Population-Based Study.

Certain personality traits, in particular higher neuroticism, have been associated, on one hand, with elevated cortisol levels, and on the other hand, with poorer cognitive performance. At the same time, several studies highlighted the association between high cortisol and poor cognitive functioning. Here, we hypothesized that increased cortisol may be associated with poorer cognition and with certain personality traits (mainly high neuroticism), and that personality might explain the association between cortisol and cognition. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a population-based study involving residents of Lausanne, Switzerland. Salivary cortisol samples (upon waking, 30 min after waking, at 11 am and at 8 pm) along with cognitive and personality measures were obtained from 643 non-demented participants aged at least 65. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI). We examined the links between the cortisol Area under the Curve (AUC), the Clinical Dementia Rating Sum of Boxes (CDRSOB) and the NEO-FFI scores. No association was found between personality traits and the CDRSOB or the MMSE score, controlling for age, sex, depression, education and BMI. However, the executive functioning domain z-score was negatively associated with agreeableness (p = 0.005; slope = -0.107 [-0.181; -0.033]) and openness (p = 0.029; slope = -0.081 [-0.154; -0.008]) after controlling for age, sex, depression, education and BMI. The CDRSOB score was positively associated with the cortisol AUC after controlling for age, sex, BMI, education and depression, (p = 0.003; slope = 0.686 [0.240; 1.333]). This association remained significant after controlling for personality traits and for the interaction between personality traits and the cortisol AUC (p = 0.006; slope = 0.792 [0.233; 1.352]. High agreeableness and openness might be associated with poorer executive performance in later life. Increased cortisol may be associated with both specific personality traits (high extraversion, low openness) and worse cognitive performance. Increased salivary cortisol does not mediate the relationship between personality traits and cognitive impairment.

Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study among Lausanne residents. Salivary cortisol samples were obtained from 796 nondemented subjects aged at least 65. A neuropsychological battery was used to assess cognitive performance and determine the Clinical Dementia Rating Sum of Boxes (CDRSOB). Lifetime life events and their subjective impact were assessed using a validated questionnaire. The total impact of life events was associated neither with cortisol area under the curve (AUC) nor with CDRSOB nor with any cognitive domain performance. The CDRSOB was associated with the cortisol AUC, controlling for age, sex, body mass index, education and depressive symptoms (p = 0.003; B = 0.686 [0.240; 1.333]; r = 0.114). This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.

Salivary Cortisol and Cortisone do not Appear to be Useful Biomarkers for Monitoring Hydrocortisone Replacement in Addison's Disease.

Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l-1 vs. 37.49 (27.41-52.00) nmol*min*l-1; p=0.098, respectively], whereas the peak cortisol Cmax was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l-1 vs. 227.73 (200.10-280.52) nmol*min*l-1; p≤ 0.001, respectively], and peak cortisone Cmax was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement.

Sex differences in morning cortisol in youth at ultra-high-risk for psychosis

Research suggests abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function play an important role in the pathophysiology of psychosis. However, there is limited research on the biological stress system in young people at ultra high risk (UHR) for psychosis. Morning cortisol levels are particularly relevant to study in this context, as these markers reflect HPA regulation. This is the first examination of sex differences in morning cortisol levels in UHR individuals. Twenty-eight UHR and 22 matched healthy control participants were assessed in respect to symptoms and had home-based collection of salivary cortisol over three time points in the morning. It was predicted that the UHR participants would exhibit lower morning cortisol levels and lower cortisol would be associated with greater symptomatology (i.e. higher positive, negative, and depressive symptoms). Additionally, sex differences in morning cortisol levels were explored based on recent evidence suggesting that sex differences may play an important role in the exacerbation of psychosis. While there were no group differences in morning salivary cortisol secretion, there was a sex by time interaction among UHR individuals, such that only UHR males exhibited flat cortisol levels across two hours after awakening, whereas UHR females had a pattern of cortisol secretion similar to healthy controls, even among medication-free individuals (F=6.34, p=0.004). Cortisol AUC (area under the curve) across the three time points had a trend association (medium effect size; r=0.34, p=0.08) with depressive, but not positive or negative, symptom severity. These results stress the importance of considering sex differences in the psychosis-risk period, as they improve understanding of pathogenic processes.

Repeated salivary daytime cortisol and onset of mood episodes in offspring of bipolar parents.

BackgroundDifferences in cortisol secretion may differentiate individuals at high compared to low genetic risk for bipolar disorder (BD) and predict the onset or recurrence of mood episodes. The objectives of this study were to determine if salivary cortisol measures are: (1) different in high-risk offspring of parents with BD (HR) compared to control offspring of unaffected parents (C), (2) stable over time, (3) associated with the development of mood episode onset/recurrence, and (4) influenced by comorbid complications.MethodsFifty-three HR and 22 C completed salivary cortisol sampling annually for up to 4 years in conjunction with semi-structured clinical interviews. The cortisol awakening response (CAR), daytime cortisol [area under the curve (AUC)], and evening cortisol (8:00 p.m.) were calculated.ResultsThere were no differences in baseline CAR, AUC and evening cortisol between HR and C (p = 0.38, p = 0.30 and p = 0.84), respectively. CAR, AUC and evening cortisol were stable over yearly assessments in HR, while in Cs, evening cortisol increased over time (p = 0.008), and CAR and AUC remained stable. In HR, AUC and evening cortisol increased the hazard of a new onset mood disorder/recurrence by 2.7 times (p = 0.01), and 3.5 times (p = 0.01), respectively, but this was no longer significant after accounting for multiple comparisons.ConclusionsSalivary cortisol is stable over time within HR offspring. However, between individuals, basal salivary cortisol is highly variable. More research is needed, with larger samples of prospectively studied HR youth using a more reliable method of cortisol measurement, to determine the potential role of cortisol in the development of mood disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s40345-016-0053-5) contains supplementary material, which is available to authorized users.

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean±SD age: 34±8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30min, at bedtime) and the average of 4 weekly 24-h urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: (1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and (2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r=0.61, p=0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-h UFC and HCC did not reach statistical significance (r=0.30, p=0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r=0.84, p<0.001), followed by 24-h UFC (week-to-week: r’s between 0.59 and 0.68, ps<0.05) and then integrated salivary cortisol concentrations (week-to-week: r’s between 0.38 and 0.61, p’s between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period.

Dysregulation Of The Hypothalamic-Pituitary-Adrenal Axis Increases Central Body Fat Accumulation In Males Affected By Diabetes Mellitus And Late-Onset Hypogonadism

Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH). Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered. The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 [interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 [interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 [P<.001]; β = 1.156 [P<.001]; β = -7.675 [P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH. Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.

Cortisol, life events and cognition in non-demented subjects: A population-based study

BackgroundOlder people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis. Many studies highlighted the possible deleterious effects of elevated cortisol on cognition, assuming a likely role of stressful events. Yet, very few studies actually examined these assumed links between life events, cortisol and cognition.ObjectiveTo examine associations between salivary cortisol, cognition and life events in a population of non-demented old individuals.MethodsA cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study involving 6733 Lausanne residents. Salivary cortisol samples (upon waking, 30 minutes after waking, at 11 am and at 8 pm) were obtained from 799 non-demented participants aged at least 60.Life events, activities of daily life along with depressive symptoms were assessed using a standardized questionnaire. A comprehensive neuropsychological test battery was used to determine the Clinical Dementia Rating (CDR).For multiple comparisons, P values were adjusted (P′) according to Holm-Bonferroni's method.ResultsCortisol at 11 am and cortisol area under the curve (AUC) were positively correlated with CDR sum of boxes (CDRSOB) scores (P′ = 0.035; Rho = 0.097 and P′ = 0.024; Rho = 0.110, respectively). The association between cortisol AUC and CDRSOB remained significant after controlling for age, sex, body mass index, education, smoking and depression (P = 0.001; β = 0.001; R2 change = 0.016).The number and the total impact of life events were associated neither with cortisol nor with CDRSOB.ConclusionsElevated cortisol was associated with poorer cognitive functioning yet independently of life events. This suggests that the increased cortisol associated with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Influence of the hypothalamic–pituitary–adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism

Background and aimsFunctional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic–pituitary–adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Methods and resultsFourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. ConclusionsFH may determine a worsening of the metabolic profile in DM-associated hypogonadism.

Improvement of anthropometric and metabolic parameters, and quality of life following treatment with dual-release hydrocortisone in patients with Addison's disease.

In patients with Addison's disease (AD), a dual-release preparation of hydrocortisone (Plenadren, PLEN) has been demonstrated to maintain cortisol levels in a more physiological range than conventional glucocorticoid therapy, and to exert positive effects. This study aimed to assess variations of anthropometric, metabolic, and hormonal parameters in patients with AD after switching from conventional hydrocortisone (HC) treatment to PLEN. In nineteen AD patients (15 F and 4 M, age 27-65 years) treated with HC 20 mg/day thrice daily, body weight, BMI, waist circumference, fasting glucose, HbA1c, serum lipids, plasma renin activity, electrolytes, and blood pressure were evaluated at baseline, and 1, 3, 6, and 12 months after switching from HC to PLEN. At baseline, and after 1 and 12 months of PLEN, blood ACTH and cortisol (at 0800 h at fasting, and 30, 60, 90, 120, and 240 min after drug ingestion), and health-related quality of life (HRQoL), using 30-AddiQoL questionnaire, were evaluated. During PLEN, waist and serum lipid progressively decreased. After 12 months of PLEN, a significant difference was observed in waist circumference (P = 0.007), HbA1c (P = 0.002), total and LDL-cholesterol levels (P < 0.05). ACTH levels at 240 min and the area under the curve (AUC) were lower (P < 0.05) during PLEN than HC, while cortisol peaks and AUC were similar. 30-AddiQoL total score also improved (P = 0.04) during PLEN. In AD patients, PLEN reduces central adiposity, and improves glucose and metabolism parameters and HRQoL.

Bidirectional psychoneuroimmune interactions in the early postpartum period influence risk of postpartum depression.

More than 500,000 U.S. women develop postpartum depression (PPD) annually. Although psychosocial risks are known, the underlying biology remains unclear. Dysregulation of the immune inflammatory response and the hypothalamic-pituitary-adrenal (HPA) axis are associated with depression in other populations. While significant research on the contribution of these systems to the development of PPD has been conducted, results have been inconclusive. This is partly because few studies have focused on whether disruption in the bidirectional and dynamic interaction between the inflammatory response and the HPA axis together influence PPD. In this study, we tested the hypothesis that disruption in the inflammatory-HPA axis bidirectional relationship would increase the risk of PPD. Plasma pro- and anti-inflammatory cytokines were measured in women during the 3rd trimester of pregnancy and on Days 7 and 14, and Months 1, 2, 3, and 6 after childbirth. Saliva was collected 5 times the day preceding blood draws for determination of cortisol area under the curve (AUC) and depressive symptoms were measured using the Edinburgh Postpartum Depression Survey (EPDS). Of the 152 women who completed the EPDS, 18% were depressed according to EDPS criteria within the 6months postpartum. Cortisol AUC was higher in symptomatic women on Day 14 (p=.017). To consider the combined effects of cytokines and cortisol on predicting symptoms of PPD, a multiple logistic regression model was developed that included predictors identified in bivariate analyses to have an effect on depressive symptoms. Results indicated that family history of depression, day 14 cortisol AUC, and the day 14 IL8/IL10 ratio were significant predictors of PPD symptoms. One unit increase each in the IL8/IL10 ratio and cortisol AUC resulted in 1.50 (p=0.06) and 2.16 (p=0.02) fold increases respectively in the development of PPD. Overall, this model correctly classified 84.2% of individuals in their respective groups. Findings suggest that variability in the complex interaction between the inflammatory response and the HPA axis influence the risk of PPD.

Effect of sucrose consumption on serum insulin, serum cortisol and insulin sensitivity in migraine: Evidence of sex differences

The aim of this study was to compare the effect of sucrose on biomarkers of energy metabolism and utilization in migrainous men and women. A total of 20 participants (7=Migraine (female), 5=Migraine (male), 8=Non-migraine control) submitted to an oral sucrose tolerance test (OSTT), which required them to fast for 15h overnight and then ingest 75g sucrose dissolved in 175g water at 9 AM the next morning. Blood sampling for the assessment of serum insulin, serum cortisol and plasma glucose was conducted upon arrival at 0900h and then at regular 15-min intervals across a 150-min period. Comparison of insulin sensitivity indexes that rely on fasting glucose and insulin data failed to find evidence of insulin resistance in migraineurs or controls. Prior to sucrose consumption the level of fasting serum cortisol at 0-min on average was significantly higher in migraineurs. However, no significant group differences in the level of fasting serum insulin and plasma glucose at 0-min were noted. Following sucrose consumption: the level of serum insulin was significantly higher in female migraineurs; the level of serum cortisol was significantly higher in male migraineurs; glucose/insulin (G/I) ratio was significantly higher in male migraineurs at 135-min and 150-min; insulin/cortisol (I/C) ratio was significantly different with the I/C ratio lower in male migraineurs and higher in female migraineurs; area under the curve (AUC) insulin was significantly different across groups with AUC insulin lower in male migraineurs and higher in female migraineurs; and AUC cortisol was significantly higher in male migraineurs. It was concluded that the effect of sucrose on biomarkers of energy metabolism and utilization in male and female migraineurs is not the same. Therefore, the factors underlying migraine pathogenesis in men and women may also be different.