Cortisol Circadian Rhythm Research Articles

Aircraft noise exposure and saliva cortisol in the DEBATS longitudinal study

IntroductionAlthough aircraft noise is known to impact human health, the biological pathway is still unclear. One of the possible pathway is that aircraft noise exposure may induce a modification of the cortisol circadian rhythm. However, only a few studies have examined the association between this exposure and cortisol levels.ObjectivesThis longitudinal study conducted in France aimed to investigate the association between aircraft noise exposure and saliva cortisol levels.MethodsThe DEBATS study included 1,244 participants living near three French major airports. In 2013, 2015 and 2017, these participants responded to a face-to-face questionnaire administered at their home by a trained interviewer and collected two saliva samples: the first one immediately after awakening (when the cortisol level is usually high) and the second one just before going to bed (when the cortisol level is usually the lowest). ELISA kits were used to determine morning and evening cortisol levels in saliva for the 1,115 participants who followed the protocol and did not use any medication that could modify cortisol levels. Outdoor aircraft noise levels were estimated at each home address using noise maps. To estimate the associations between noise levels and cortisol levels (morning, evening, relative daily variation), linear mixed models were used with a subject-specific random intercept and adjusted on potential confounders.ResultsA 10 dB(A) increase in the day-evening-night (Lden) level was associated with decreased relative daily variation of cortisol (exp(β)=0.77; 95% confidence interval: 0.70-0.85), higher evening cortisol levels (exp(β)=1.16; 95% CI: 1.08-1.23) and unchanged morning levels (exp(β)=0.95; 95% CI: 0.90-1.00).DiscussionThe results of this study support the hypothesis that aircraft noise exposure was associated with flattened diurnal cortisol rhythm across the day, indicating a possibly disturbed hypothalamus-pituitary-adrenal axis regulation.

Clinical features and outcomes of surgical versus conservative management in patients with subclinical Cushing's syndrome

Objective: To examine the clinical characteristics and metabolic features of subclinical Cushing's syndrome (SCS), and determine the effects of surgical or conservative approaches on the hormone levels and metabolic comorbidities in patients with SCS, thereby providing the evidence for decision-making in SCS management. Methods: A total of 56 consecutive SCS patients were selected in Drum Tower Hospital Affiliated to Nanjing University Medical School between 2010 and 2018, with 41 patients undergoing surgical treatment and 15 patients receiving conservative therapy. Meanwhile, 56 and 68 cases of sex-and age-matched patients diagnosed as nonfunctional adrenal adenoma (NFA) and adrenal Cushing's syndrome (CS) were included respectively. Clinical characteristics of patients in different groups were compared. Hormone levels and metabolic comorbidities were also observed during follow-up. Results: There were 56 SCS patients, including 15 males and 41 females, with an age of (52.0±12.6) years. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in CS and SCS groups. Compared to NFA group, patients with SCS were characterized by suppressed plasma ACTH level [2.40 (1.11, 4.33) pmol/L vs 4.23 (2.74, 6.26) pmol/L], elevated midnight cortisol level [(240±121) nmol/L vs (59±8) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test [(241±130) nmol/L vs (34±12) nmol/L] (all P<0.01). The derangement of ACTH-cortisol axis was more obvious in CS patients compared to SCS patients. The prevalence of hypertension, glucose intolerance, dyslipidemia and osteopenia/osteoporosis were higher in SCS patients compared to NFA patients (75.0% vs 41.1%, 33.9% vs 12.5%, 62.5% vs 28.6%, 35.7% vs 8.9%, all P<0.05). The 24-hour urine free cortisol correlated positively with systolic blood pressure, glycated hemoglobin A1c (HbA1c) and fasting blood glucose in SCS patients (r=0.335, 0.562 and 0.463, respectively, all P<0.05). In the surgical group, body weight, body mass index (BMI) and blood pressure decreased significantly after surgery (all P<0.05). Glucose intolerance/diabetes mellitus improved in 6 of 9 patients, BMI of 4 of 11 overweight/obesity patients normalized, and hypertension in 54.5% of patients (12/22) showed improvement after surgery. However, no alterations of hormone levels and metabolic parameters were observed in conservatively-managed patients. Conclusions: Patients with SCS are characterized by mild autonomous cortisol secretion and increased risk of metabolic comorbidities. Compared with conservative management, hormone abnormalities were corrected and metabolic abnormalities were improved in some SCS patients after surgery.

Are the thyroid and adrenal system alterations linked in depression?

BackgroundDisturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently found in major depression. Given that glucocorticoids may inhibit thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion, it has been hypothesized that hypercortisolemia could lead to HPT axis abnormalities. So far, data on interactions between the HPA and HPT axes in depression remain inconclusive. MethodsIn order to investigate this issue, we examined circadian rhythms of serum TSH and cortisol (sampled at 4 -hly intervals throughout a 24 -h span), TSH responses to 0800 h and 2300 h protirelin (TRH) tests and cortisol response to dexamethasone suppression test (DST) in 145 unmedicated inpatients meeting DSM-IV criteria for major depressive disorder (MDDs) and 25 healthy hospitalized control subjects (HCs). ResultsThe secretion of TSH and cortisol exhibited a significant circadian rhythm both in HCs and MDDs. However, compared to HCs, MDDs showed: 1) reduced TSH mesor and amplitude values; 2) blunted 2300 h-ΔTSH and ΔΔTSH values (i.e. differences between 2300 h and 0800 h TRH-TSH responses); and 3) increased cortisol mesor and post-DST cortisol values. DST nonsuppresssors (n = 40, 27 %) showed higher cortisol mesor than DST suppressors (n = 105, 73 %). There was no difference between DST suppressors and nonsuppressors in their TSH circadian parameters and TRH-TSH responses. In addition, cortisol values (circadian and post-DST) were not related to TRH test responses. ConclusionOur results do not confirm a key role for hypercortisolemia in the HPT axis dysregulation in depression.

Clinical characteristics of primary aldosteronism with concurrent adrenal Cushing's syndrome

Objective: To analyze and summarize the clinical characteristics of primary aldosteronism (PA) with concurrent adrenal Cushing's syndrome (ACS). Methods: The clinical, imaging and pathological data of 87 patients with PA admitted to Peking University First Hospital from January 1st, 2013 to December 31th, 2016 were reviewed. There were 45 males (51.7%) and 42 females (48.3%) with an average age of (52.7±10.5) years (range: 15-70 years). According to whether they were diagnosed with ACS, the patients were divided into PA with concurrent ACS group (n=11) and pure PA group (n=55). The clinical characteristics of PA with concurrent ACS were summarized. Results: Ten of the eleven patients in PA with concurrent ACS group were diagnosed with subclinical ACS. Compared with these in pure PA group, the patients in PA with concurrent ACS group were older [(55.6±9.1) years vs (48.4±10.2) years, P=0.033], with larger diameters of adrenal tumors [(2.3±1.6) cm vs (1.4±0.6) cm, P=0.015], higher serum cortisol levels in the circadian rhythm [158 (92, 217) nmol/L vs 71 (43, 128) nmol/L at 0∶00, P=0.004], lower plasma adrenocorticotropic hormone (ACTH) levels in the circadian rhythm [0.80 (<0.22, 1.45) pmol/L vs 4.40 (2.58, 5.93) pmol/L at 8∶00, P<0.001; 0.25 (<0.22, 0.91) pmol/L vs 2.03 (0.74, 3.69) pmol/L at 16∶00, P<0.001;<0.22 (<0.22, 0.44) pmol/L vs 1.27 (<0.22, 2.66) pmol/L at 0∶00, P<0.001], and higher serum cortisol levels after 1 mg overnight dexamethasone suppression test [95 (73, 142) nmol/L vs 30 (22, 41) nmol/L, P<0.001]. Unilateral adrenalectomy was performed in 31 patients, of whom 3 patients in PA with concurrent ACS group (3/8) and 3 patients in pure PA group (3/23) presented with adrenal insufficiency and received glucocorticoid replacement therapy after adrenalectomy. Conclusions: PA with concurrent ACS is not rare in PA patients, which are mainly complicated with subclinical ACS and easily misdiagnosed. It is recommended that elderly PA patients with large adrenal tumors should be screened for ACS by means of cortisol and ACTH circadian rhythm and 1 mg overnight dexamethasone suppression test. Postoperative adrenal insufficiency is prone to occur in those patients, who should be followed up closely after adrenalectomy, and receive glucocorticoid replacement therapy in time.

The relationship between the daily stress and the circadian rhythm of cortisol: Intraindividual changes after 4 weeks and 8 weeks

The relationship between the daily stress and the circadian rhythm of cortisol: Intraindividual changes after 4 weeks and 8 weeks

Timed physical exercise does not influence circadian rhythms and glucose tolerance in rotating night shift workers: The EuRhythDia study

Objectives:Night shift workers are at cardiometabolic risk due to circadian misalignment. We investigated whether infrequent exercise before each night shift that intentionally would not improve physical performance improves glucose tolerance and 24-h blood pressure profiles and synchronizes circadian rhythms of melatonin and cortisol in rotating night shift workers.Methods:A total of 24 rotating night shift workers (mean age, 35.7 ± 11.8 years) were randomized to exercise or no intervention. Workers in the exercise group performed 15.2 ± 4.5 exercise sessions within 2 h before each night shift. Before and after 12 weeks of exercise intervention and 12 weeks after the intervention, spiroergometry, oral glucose tolerance testing and 24-h blood pressure profiles were performed. Plasma melatonin and cortisol levels were measured in 3-hourly intervals during one 24-h period on each study day.Results:Exercise did not significantly change serum glucose nor insulin levels during oral glucose tolerance testing. Timed physical exercise had no effect on physical performance, nor did it change the circadian rhythms of melatonin and cortisol or influence 24-h blood pressure profiles.Conclusion:Physical exercise before each night shift at a low intensity level that does not improve physical performance does not affect circadian timing, glucose tolerance or 24-h blood pressure profiles in rotating night shift workers.

Assessment of exercise-induced stress by automated measurement of salivary cortisol concentrations within the circadian rhythm in Japanese female long-distance runners

BackgroundOvertraining syndrome, caused by prolonged excessive stress, results in reduced performance and cortisol responsiveness in athletes. It is necessary to collect saliva samples sequentially within circadian rhythm for assessing exercise stress by measuring cortisol concentrations, and automated cortisol measurements using electrochemiluminescence immunoassay (ECLIA) may be useful for measuring a large number of saliva samples. In this study, we evaluated the appropriate use of cortisol-based exercise stress assessment within the circadian rhythm, which may diagnose and prevent overtraining syndrome in athletes.MethodsWe collected saliva and sera from 54 healthy participants and analyzed the correlation between salivary cortisol concentrations measured by ECLIA and enzyme-linked immunosorbent assay (ELISA) or serum cortisol analysis. We also collected saliva continuously from 12 female long-distance runners on 2 consecutive days involving different intensities and types of exercise early in the morning and in the afternoon and measured salivary cortisol concentrations using ECLIA. Each exercise intensity of runners was measured by running velocities, Borg Scale score, and rate of change in the pulse rate by exercise.ResultsECLIA-based salivary cortisol concentrations correlated positively with those detected by ELISA (ρ = 0.924, p < 0.001) and serum cortisol (ρ = 0.591, p = 0.001). In long-distance runners, circadian rhythm of salivary cortisol, including the peak after waking and the decrease promptly thereafter, were detected on both days by continuous saliva sampling. The rates of change in salivary cortisol concentrations were significantly lower after an early morning exercise than after an afternoon exercise on both days (day 1, p = 0.002, and day 2, p = 0.003). In the early morning exercise, the rate of change in salivary cortisol concentration was significantly higher on day 1 than on day 2 (p = 0.034), similar to a significant difference in running velocities (p = 0.001).ConclusionsOur results suggest that automated ECLIA-based salivary cortisol measurements are able to detect the athletes’ circadian rhythm and compare the exercise stress intensities at the same times on different days, even in the early morning, possibly leading to the prevention of overtraining syndrome.

Salivary cortisol levels during Ramadan fasting in hydrocortisone-treated secondary adrenal insufficiency patients.

Patients with adrenal insufficiency have difficulties in fasting during the month of Ramadan with an increased risk of complications. Cortisol levels are unknown in these patients. The objective of this study was to assess the daily cortisol profile in hydrocortisone-treated patients with secondary adrenal insufficiency (SAI) and healthy controls during a fasting day. A cross-sectional matched case-control study on 50 hydrocortisone-treated SAI patients and 69 controls who are used to fast. Clinical and therapeutic data were collected. Five salivary samples for cortisol measurement were collected throughout a fasting day of the third week of Ramadan 2019. Salivary cortisol levels were significantly higher on awakening, at midnight and before the predawn meal in patients compared with controls. The circadian cortisol rhythm was disrupted in patients. The area under the salivary cortisol level versus time curve (AUC) was lower than the 2.5th percentile of the controls in one patient (2.5%) and higher than the 97.5th percentile in 23 patients (59%) who were considered overtreated. Age ≥ 35 years was independently associated with overtreatment (adjusted odds ratio = 12.0; 95% CI (2.0-70.4); p = 0.006). Seven patients broke their fasting for a complication compared with no one of the controls (p = 0.001). No factor was associated with this risk. Salivary cortisol levels were high in fasting hydrocortisone-treated SAI patients with a disruption of the circadian rhythm.

Evidence for disruption of diurnal salivary cortisol rhythm in childhood obesity: relationships with anthropometry, puberty and physical activity

BackgroundThe aim of this study was to examine the characteristics of diurnal cortisol rhythm in childhood obesity and its relationships with anthropometry, pubertal stage and physical activity.MethodsThirty-five children with obesity (median age: 11.80[interquartile range 10.30, 13.30] and median BMI z-score: 3.21[interquartile range 2.69, 3.71]) and 22 children with normal weight (median age: 10.85[interquartile range 8.98, 12.13] and median BMI z-score: − 0.27[interquartile range − 0.88, 0.35]) were recruited. Saliva samples were collected at 08:00, 16:00 and 23:00 h. Cortisol concentrations at 3 time points, corresponding areas under the curve (AUCs) and diurnal cortisol slope (DCS) were compared between the two groups. Anthropometric measures and pubertal stage were evaluated, and behavioural information was obtained via questionnaires.ResultsChildren with obesity displayed significantly lower cortisol08:00 (median [interquartile range]: 5.79[3.42,7.73] vs. 8.44[5.56,9.59] nmol/L, P = 0.030) and higher cortisol23:00 (median [interquartile range]: 1.10[0.48,1.46] vs. 0.40[0.21,0.61] nmol/L, P < 0.001) with a flatter DCS (median [interquartile range]: − 0.29[− 0.49, 0.14] vs. -0.52[− 0.63, 0.34] nmol/L/h, P = 0.006) than their normal weight counterparts. The AUC increased with pubertal development (AUC08:00–16:00:P = 0.008; AUC08:00–23:00: P = 0.005). Furthermore, cortisol08:00 was inversely associated with BMI z-score (β = − 0.247, P = 0.036) and waist-to-height ratio (WHtR) (β = − 0.295, P = 0.027). Cortisol23:00 was positively associated with BMI z-score (β = 0.490, P<0.001), WHtR (β = 0.485, P<0.001) and fat mass percentage (FM%) (β = 0.464, P<0.001). Absolute values of DCS were inversely associated with BMI z-score (β = − 0.350, P = 0.009), WHtR (β = − 0.384, P = 0.004) and FM% (β = − 0.322, P = 0.019). In multivariate analyses adjusted for pubertal stage and BMI z-score, Cortisol08:00, AUC08:00–16:00 and absolute values of DCS were inversely associated with the relative time spent in moderate to vigorous intensity physical activity (P < 0.05). AUC16:00–23:00 was positively associated with relative non-screen sedentary time and negatively associated with sleep (P < 0.05).ConclusionsThe disorder of diurnal salivary cortisol rhythm is associated with childhood obesity, which is also influenced by puberty development and physical activity. Thus, stabilizing circadian cortisol rhythms may be an important approach for childhood obesity.

Welfare benefits after the implementation of slow-feeder hay bags for stabled horses

Horse confinement is a common practice worldwide. However, preventing horses from grazing and denying them social interaction can compromise their welfare and lead to undesirable consequences. Considering the hypothesis that increasing the forage consumption time can lead to improved welfare, the objective of this study was to verify the effect of the implementation of a slow-feeder hay bag on the ethogram, motor activity, heart rate, and cortisol circadian rhythm (CCR) of stabled horses. Seven healthy horses were kept exclusively in individual stalls and fed pelleted feed, alfalfa hay, and Tifton hay. Horses were evaluated before the experiment and for 10 days foraging through a slow-feeder hay bag. The horses were monitored for 24 hours for ethogram and forage consumption time evaluations. The CCR was calculated by the percentage variance between the morning and afternoon serum concentration. A variation of 30% or less was indicative of poor welfare. The effect of time over the variables was verified by paired Student's t or Student-Newman-Keuls tests (P < 0.05). The inclusion of hay bags increased the alfalfa ingestion time by 87% (P = 0.006). At the end of the study, coprophagia stopped in three of four horses and the mean (±SD) time spent performing abnormal behaviors decreased from 130.6 (±168.8) to 86 (±140) min (P = 0.02). The mean CCR variation increased from 26% (±24) to 58% (±9) (P = 0.006), with an incidence of four horses with abnormal CCR at the baseline and none at the end of the experiment. The motor activity was reduced from 574 (±126) to 306 (±167) steps per day (P = 0.05) and the heart rate did not vary. In conclusion, the adoption of a slow-feeder bag, an available and low-cost device, was effective in improving the welfare of stabled horses.

PK/PD modeling of 5-hydroxytryptophan (5-HTP) challenge test with cortisol measurement in serum and saliva.

This research was planned to build a Pharmacokinetic/Pharmacodynamic (PK/PD) model of 5‐hydroxytryptophan (5‐HTP) challenge study including a circadian rhythm component of cortisol and to predict serum cortisol based on saliva cortisol. Data from three 5‐HTP challenge studies in healthy volunteers were collected. Serum 5‐HTP, saliva, and serum cortisol were sampled as PK and PD marker. The population PK/PD modeling approach was applied. A baseline model of serum cortisol was built to assess the circadian rhythm before a pharmacodynamic model was used to evaluate the drug effect of the 5‐HTP on cortisol. Finally, linear and power function relationships were tested to predict serum cortisol based on saliva cortisol. The PK of 5‐HTP could be described using a one‐compartment model with a transit compartment. The typical value for clearance was 20.40 L h−1 and showed inter‐study variability. A cosine function was chosen and properly described the circadian rhythm of serum cortisol. A linear approximation model was applied to fit the 5‐HTP PD effect on cortisol data with a slope of 4.16 ng mL−1 h. A power function provided a better description than a linear function to relate the saliva and serum cortisol. In conclusion, a circadian rhythm component was built in the PK/PD model of the 5‐HTP challenge test which could better improve the understanding of the stimulating effect on HPA with cortisol change. After the 5‐HTP challenge, saliva cortisol correlated well with serum cortisol and was predictable by a population PK‐PD model.

Couples’ behavior during conflict in the lab and diurnal cortisol patterns in daily life

The current study tested whether positive and negative behaviors exhibited by couples during conflict interactions assessed in the laboratory are associated with individuals’ diurnal cortisol patterns (i.e., circadian rhythms in cortisol across the course of the day) outside of the lab. Participants (N = 82) provided a total of 18 salivary cortisol samples over a 3-day period and came into the lab with their spouse to engage in two ten-minute dyadic conflict discussions. These videotaped interactions were coded to assess the intensity with which couples displayed various positive behaviors (e.g., humor, affection) and negative behaviors (e.g., defensiveness, frustration) during the conflict discussions. Multi-level modeling was used to examine the associations between couples’ positive and negative behavior during conflict discussions and diurnal cortisol patterns in daily life. Results showed links between overall positive, but not negative, behaviors and diurnal cortisol patterns. Individuals who experienced more positive behaviors with their partner during the conflict discussion showed a steeper (“healthier”) cortisol slope across the day in their daily lives. Exploratory analyses investigating the association between specific positive and negative behaviors and diurnal cortisol revealed that affection and scorn were associated with diurnal cortisol patterns in daily life. This research advances our understanding of the impact of social relationships on physical health from a biopsychosocial perspective and has implications for understanding how the ways in which couples resolve conflict are linked to health-related biological processes in daily life.

The diagnosis and treatment of adrenocortical carcinoma in pregnancy: a case report

BackgroundPregnancy complicated with adrenocortical carcinoma (ACC) is a sporadic syndrome that is characterized by hypertension, uncontrolled hypokalemia, severe heart failure, premature delivery and other adverse effects. The clinical presentation of adrenocortical carcinoma is vague and nonspecific, it is challenging to identify complications of pregnancy with adrenocortical carcinoma. Here we present a case of adrenocortical carcinoma during pregnancy. We describe how to distinguish secondary hypertension from other conditions and the importance of timely detection and treatment of such patients.Case presentationA 22-year-old woman 30 weeks pregnant was hospitalized with uncontrolled hypertension and hypokalemia. An ultrasound examination of the right adrenal gland revealed a large mass. She underwent transabdominal adrenalectomy, and histopathology from the sample removed revealed an adrenocortical carcinoma. Five days after surgery, the patient had a premature rupture of the fetal membranes and gave birth to a newborn girl via vaginal delivery at 32 weeks of gestation. The newborn was transferred to the neonatal pediatrics ward, and the woman started receiving chemotherapy.ConclusionsPregnancy with adrenocortical carcinoma is a rare condition. This case alerts the obstetricians that analysis of hypertension, hypokalemia, the plasma level and circadian rhythm of plasma cortisol provides a strategy to diagnose adrenocortical carcinoma during pregnancy.

Effect of mild obstructive sleep apnea in mountaineers during the climb to Mount Aconcagua.

Objectiveto compare mountaineers with and without asymptomatic sleep apnea (OSA) before the ascent and to study high altitude-related sleep disorders, its interaction with metabolic, neuroendocrine and immunological components.Material and MethodsDuring an expedition to Mount Aconcagua, researchers assessed the respiratory polygraphy (RP), clinical condition and inflammatory parameters, and rhythm of cortisol secretion in mountaineers sleeping at different altitude camps.Results8 athletes (4 women), 36 years old (25-51) participated. Baseline and final BMI were; 23.6 (20.9-28.7) and 22.77 (20.9-27.7), respectively: p<0.01. 40 valid RP recordings were analyzed. At 746 m.a.s.l. (baseline), only 2 mountaineers presented mild asymptomatic OSA. The OSA group presented baseline apnea-hypopnea index (AHI) values between 5-15 events per hour, which evidence a mild respiratory sleep disorder with AHI increased by altitude depending of central apneas and hypopneas (p<0.05) as high altitude periodic breathing pattern but no increase in obstructive apneas (p<0.01). The circadian rhythm of cortisol was maintained in all cases in which they had not received treatment with dexamethasone and their values increased with the altitude reached. Increased systolic blood pressure was observed in the OSA group.ConclusionIn a context of hypobaric hypoxia, individuals with pre-existing asymptomatic OSA are prone to experiencing lower oxygen saturations and clinical deterioration.

The circadian rhythms of cortisol: Modelling their role in regulating homeostasis and personalized resilience and adaptation

The hypothalamic-pituitary-adrenal (HPA) axis orchestrates the physiological response stress. Moreover, the HPA axis exhibits prominent circadian activity and synchronizes peripheral circadian clocks to daily environmental cycles, thereby promoting homeostasis. Persistent disruption of homeostatic glucocorticoid circadian rhythmicity due to chronic stress exposure is correlated with the incidence of various pathological conditions including depression, diabetes and cancer. Allostatic habituation of the HPA axis can therefore confer fitness advantages by preventing the sustained dysregulation of glucocorticoid-responsive signaling pathways. However, such allostatic adaptation results in a physiological cost (allostatic load) that might impair the homeostatic stress-responsive and synchronizing functions of the HPA axis. We use mathematical modeling to characterize specific chronic stress-induced allostatic adaptations in the HPA network. We predict the existence of multiple personalized regulatory strategies enabling the maintenance of homeostatic glucocorticoid rhythms, while allowing for flexible HPA response characteristics. We show that this regulatory variability produces a trade-off between the stress-responsive and time-keeping properties of the HPA axis. Finally, allostatic regulatory adaptations are predicted to cause a time-of-day dependent sensitization of the acute stress response and impair the entrainability of the HPA axis

Stress, the cortisol awakening response and cognitive function.

There is evidence that stress-induced disruption of the circadian rhythm of cortisol secretion, has negative consequences for brain health. The cortisol awakening response (CAR) is the most prominent and dynamic aspect of this rhythm. It has complex regulatory mechanisms making it distinct from the rest of the cortisol circadian rhythm, and is frequently investigated as a biomarker of stress and potential intermediary between stress and impaired brain function. Despite this, the precise function of the CAR within the healthy cortisol circadian rhythm remains poorly understood. Cortisol is a powerful hormone known to influence cognition in multiple and complex ways. Studies of the CAR and cognitive function have used varied methodological approaches which have produced similarly varied findings. The present review considers the accumulating evidence linking stress, attenuation of the CAR and reduced cognitive function, and seeks to contextualize the many findings to study populations, cognitive measures, and CAR methodologies employed. Associations between the CAR and both memory and executive functions are discussed in relation to its potential role as a neuroendocrine time of day signal that synchronizes peripheral clocks throughout the brain to enable optimum function, and recommendations for future research are provided.

Diurnal Patterns for Cortisol, Cortisone and Agouti-Related Protein in Human Cerebrospinal Fluid and Blood.

Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconverted by 11ß-HSD1, have not been characterized in humans. To conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol and cortisone in CSF and examine their relationships to changes in AgRP. Stored CSF and plasma samples were obtained from 8 healthy subjects who served as controls for a sleep study. CSF was collected every 2h for 36h via indwelling lumbar catheter; plasma was collected every 2h. There was a diurnal rhythm for cortisol and cortisone in CSF that closely followed the plasma rhythm by 2 h with peak and nadir levels at 0900h and 0100h. The ratio of cortisol (active) to cortisone (inactive) in CSF was 48% higher at the peak versus nadir. There was a diurnal rhythm for AgRP in plasma that was out of phase with the cortisol rhythm. There was a less distinct diurnal rhythm for AgRP in CSF that oscillated with a similar phase as cortisol. There is a robust diurnal rhythm for cortisol and cortisone in CSF. Diurnal changes were noted for AgRP that are related to the cortisol changes. It remains to be determined if AgRP mediates adverse metabolic effects associated with disruption of the cortisol circadian rhythm.

The Influence of Psychocurative on Cortisol Level, Anxiety, and Quality of Life in Advanced Stage Cervical Cancer Patients

Every year, there are 500.000 new cases and more than 250.000 deaths caused by cervical cancerworldwide. Cervical cancer patients faced physical and psychological problems several times that it activate stress mechanism such as hypothalamus-pituitary-adrenal (HPA) axis. These recurrent activations caused HPA axis disruption and adverse clinical effects. Several symptoms of endocrine stress response are the change of circadian cortisol rhythm. Cortisol is known as a stress hormone that involves an organism's response to stress and anxiety that influence the quality of life. This research aims to analyze the differences among serum cortisol level, anxiety, and quality of life in cervical cancer patients before and after psychocurative intervention in obstetrics and gynecology wards and polyclinic in RSUD Dr. Moewardi Surakarta. This research is an experimental double-blind randomized controlled clinical trial pre-test post-test group design study. The subjects were advance stage (IIB-IV)cervical cancer patients. The subjects were randomly chosen into fifteen subjects that given standard therapy and psychocurative, while the other fifteen subjects as a control only got standard therapy. Data were obtained from measurement of serum cortisol level, anxiety questionnaire DASS 42 and WHO quality of life questionnaire. Data were analyzed using SPSS 21 using difference test. The difference mean test result of cortisol serum level, anxiety, quality of life from the controlled group and uncontrolled group showed a significant difference (p &lt; 0.05). In conclusion, psychocurative is significant to reduce cortisol level, anxiety, and improve the quality of life in advanced stage cervical cancer patients.

Salivary cortisol levels as a biomarker for severity of withdrawal in opioid-exposed newborns.

Scoring tools used to quantify withdrawal in infants with neonatal abstinence syndrome (NAS) are often confounded by subjective measurements. This study assessed salivary cortisol as an objective biomarker of withdrawal severity in opioid-exposed newborns. A prospective study was conducted in 25 full-term opioid-exposed newborns monitored for NAS. Morning and evening salivary cortisol levels were collected starting within 48 h post birth until initiation of pharmacologic treatment for withdrawal (Pre-Treatment) or when the infant was discharged without pharmacotherapy (No Treatment). Cortisol levels in the Pre-Treatment group (n = 11) were significantly higher within the first week of life (median 1.74 µg/dl) than in the No Treatment group (n = 11; median 0.72 µg/dl; P = 0.003); three infants had inadequate saliva volume for cortisol assay. Cortisol significantly decreased after 72 h post birth among infants discharged without pharmacotherapy (≤72 h median 1.25 µg/dl; ≥72 h median 0.58 µg/dl; P = 0.022), whereas cortisol remained elevated for infants subsequently treated for severity of withdrawal. No cortisol circadian rhythm was observed for either group. Salivary cortisol in opioid-exposed newborns may provide an index of stress and help identify infants who will have more severe clinical presentation of NAS. Such a biomarker would allow risk stratification for early treatment and discharge decisions.

Circadian rhythm of glucocorticoid administration entrains clock genes in immune cells: A DREAM trial ancillary study

Conventional glucocorticoid (GC) therapy in adrenal insufficiency (AI) does not fully mimic the endogenous cortisol circadian rhythm, and this may adversely affect long-term health. In the recent DREAM trial (Dual Release Hydrocortisone vs. Conventional Glucocorticoid Replacement in Hypocortisolism) patients with AI showed an atypical inflammation, with more classic monocytes and impaired innate immune responses. Treatment with once-daily modified-release hydrocortisone improved circulating immune cell profiles and reduced infections compared to standard GC replacement therapy.