Cortisol Circadian Rhythm Research Articles

24 HOURS CHRONOMICS OF AMBULATORY BLOOD PRESSURE/HEART RATE IN TERMS OF ACROPHASE & HYPERBARIC INDEX IN NIGHT SHIFT NURSING PROFESSIONALS: RISK FOR CARDIOVASCULAR DISEASES

Objective: This study was aimed to investigate the effect of Light at night and Rotating night shift as risk factor for cardiovascular diseases. 24 hours chronomics of BP/HR in terms of Double amplitude, Acrophase and Hyperbaric index and its relation with circadian rhythm of salivary cortisol and 6 sulfatoxy melatonin levels in night shift nursing professional. Design and method: 56 night shift nurses, aged 20 to 40 years, performing day and night shift duties were recruited from the Trauma Center, KGMU, India, and 56 age sex matched actual day workers were also enrolled as controls. During their night and day shift duties, BP/HR were recorded by Ambulatory Blood Pressure Monitoring (ABPM) along with circadian pattern of cortisol in saliva, metalonin in urine also tested. Results: Highly significant difference was found in double amplitude (2DA) of among between night (23.10 ± 14.68) and day shift (34.27 ± 16.44) (p < 0.0005). In night shift, hyperbaric index (HBI) of mean SBP was found to be increased at 00 to 03 am (midnight) while during day shift, peak was found at 06 to 09 am. HBI of mean HR was found to be increased at 18 to 21 pm during night shift while in controls, peak was found at 09 to 12 & again 15 to 18 pm of SBP, DBP & HR. Alterations in Acrophase of BP/HR were very common among night shift workers and Ecphasia was found in few nights shift workers. Difference was found in night cortisol levels among night (4.08 ± 3.28) vs day shift (2.62 ± 2.37), while in comparison to night shift or day shift with controls (1.82 ± 1.18) these difference was significant (p < 0.05). Conclusions: Alteration in morning melatonin and Night cortisol level were found during night shift. Reverse pattern of Acrophase and HBI of BP/HR along with salivary cortisol during night shift represents desynchronization. It indicates that the circadian rhythm was disrupted during night shift and incomplete recovery occurs during day shift. It may leads to future cardio vascular diseases risk.

Evidence of persistent mild hypercortisolism in patients medically treated for Cushing's disease: the Haircush study.

Cortisol-lowering drugs may not restore a normal cortisol secretion in Cushing's disease (CD). Assess the long-term cortisol exposure in medically treated CD patients using hair-cortisol (HF) and -cortisone (HE) measurement. Multicenter prospective study. Three groups of female patients: CushMed=16 treated with a stable cortisol-lowering drug dosage and normal UFCs; CushSurg=13 cured by pituitary surgery; CushBla=15 receiving stable recommended doses of hydrocortisone following bilateral adrenalectomy. Patients were evaluated during 3 months with their usual treatments. Two late-night saliva and 24h urine samples were monthly collected in CushMed, and at study end in CushSurg and CushBla patients. A 3-cm hair sample was collected at study end in all patients. Clinical score and centralized measurement of UFC, late-night salivary cortisol (LNSF) and -cortisone (LNSE), HE, HF. Despite having almost all UFCs normalized, CushMed patients exhibited increased HE as compared to CushSurg controls (p=0.003). CushMed patients also had increased clinical score (p=0.001), UFC (p=0.03), LNSF, LNSE (p=0.0001) and variability in the latter parameters (p=0.004). CushBla patients had increased HF and HE contrasting with similar LNSE to CushSurg patients. Six of 15 CushMed patients exhibited increased HE concentrations and had increased antihypertensive drug dosage compared to CushMed patients with normal HE (p=0.05). Despite normalized UFCs, a subset of medically-treated CD patients displays an altered circadian rhythm of serum cortisol. A single HE measurement identifies chronic mild persistent hypercortisolism and could replace multiple saliva analyzes to monitor medical treatments in CD patients once UFC is normalized.

126 Time-budget and welfare indicators of stabled horses in three different stall architectures: A cross-sectional study

Keeping horses in single stalls can prevent them from performing natural behaviors leading to the development of abnormal behaviors (AB) and stereotypic behaviors (SB). Time-budget (TB) is the daily amount of time an animal engages in behavioral activities. Differences in the TB of domesticated horses compared with feral conspecifics in their natural environment can be used to reveal welfare impairment. Other measurements indicative of stress levels in horses are the cortisol circadian rhythm (CCR), and the leucocyte numbers (LN). The current study aimed to identify how 3 different stall architectures can influence the TB and physiological parameters in full-time stabled horses fed at 1.45% DMI/BW twice a day with a 34:66 grain: forage ratio. Stall types included: 1) 3.2 × 3.7m stalls with tactile contact (TC) between horses, B1; 2) 2.6 × 3.5m stalls with only visual contact (VC) between horses with outside view, B2; 3) 2.3 × 3.4m stalls with VC and outside view, B3. The horses were used for light exercise, 4 d a week. Surveillance cameras were installed in one stall per barn. Twenty-nine mixed breed horses (10 horses from B1 and B3, and 9 from B2) were randomly selected and filmed for one period of 24 h per horse. The video was analyzed with continuous sampling and the time spent in SB, AB and other activities was measured second-by-second and inserted into a spreadsheet. Blood collection wasperformed one day after de recording period at 8:00 a.m. and at 5:00 p.m. The samples were used to determine the cortisol levels, and CCR. The effects of the different stall architectures were analyzed by ANOVA and significant results compared by post hoc Tukey test. B1 had higher social interaction time (2.77% of the TB) compared with B2 (0%) and B3 (0.01%) (P = 0.020), with no other differences among barns. Restricted availability of food had a direct impact on all the horses’ TB, creating long periods of idleness (41% of the TB observing the exterior, 18% of the TB standing attentively) and fasting. The low time spent eating (204 ± 13 min) may have led horses to develop AB like bed-eating (176 ± 19 min), coprophagy (18 ± 9 min) and wood-chewing (42 ± 19 min). All horses presented SB and AB, 25% of the horses low LN, 38% of the horses had cortisol above the reference range, and 29% of the horses an altered CCR. The physiological and TB alterations along with high prevalence of SB and AB indicate that horses were in a state of chronic stress and the stalls’ architecture did not affect the horses’ capability to cope with such housing conditions. Feed restriction likely led to AB and SB.

The possible relation of ventilation ear tubes with nocturnal noise-induced discoordination of the stress response axis – Anatomical and physiological considerations

Nocturnal noise above 30 dB Leq can impact the hypothalamus–pituitaryadrenal axis and discoordinate cortisol circadian rhythms, affecting, among others, blood pressure, sleep architecture, and behavior. A physiologic middle ear-based model suggested in this article may attenuate noise during sleep, especially at low frequencies. As a significant part of gas exchange occurs viadiffusion, caused by the partial pressure gradient of gases between the middle ear cleft and submucosa capillaries, physiologically expected hypoventilation during sleep may account for hypercapnia and CO2 accumulation in the middle ear due to its rapid diffusion rate and the Eustachian tube’s relative dysfunction during sleep. Pressure on the tympanic membrane can render it less compliant, thus attenuating low-frequency noise. However, this model does not function with a perforated tympanic membrane, as in the case of children having ventilation tubes (VT) placed for otitis media with effusion. Thus, we hypothesize that children treated with VT present with cortisol circadian rhythm discoordination. We propose the evaluation of morning urine or salivary samples and arterial pressure levels along with questionnaires concerning behavioral parameters in children with VT and their comparison with the corresponding measurements of a referral population, weighted for age, endocrinology history, medications, and household noise levels. The findings mayunderline the need to reconsider therapeutic options for otitis media with effusion in selected cases by relying on more physiologically-oriented therapeutical approaches, like the endoscopic balloon Eustachian tube dilatation.

Prevalence and risk factors of sub-health and circadian rhythm disorder of cortisol, melatonin, and temperature among Chinese midwives.

This study aimed to explore the influencing factors of sub-health and circadian rhythm disorder among midwives and whether circadian rhythm disorder was associated with sub-health. A multi-center cross-sectional study was conducted among 91 Chinese midwives from six hospitals through cluster sampling. Data were collected by demographic questionnaire, Sub-Health Measurement Scale version 1.0, and circadian rhythm detection. Minnesota single and population mean cosine methods were used to analyze the rhythm of cortisol, melatonin, and temperature. Binary logistic regression, nomograph model, and forest plot were performed to identify variables associated with midwives' sub-health. There were 65 midwives with sub-health and 61, 78, and 48 midwives with non-validation of circadian rhythms of cortisol, melatonin, and temperature among 91 midwives, respectively. Midwives' sub-health was significantly related to age, duration of exercise, weekly working hours, job satisfaction, cortisol rhythm, and melatonin rhythm. Based on these six factors, the nomogram was presented with significant predictive performance for sub-health. Furthermore, cortisol rhythm was significantly associated with physical, mental, and social sub-health, whereas melatonin rhythm was significantly correlated with physical sub-health. Sub-health and circadian rhythm disorder were generally common among midwives. Nurse administrators are supposed to pay attention and take measures to prevent sub-health and circadian rhythm disorder among midwives.

Changes of adrenocorticotropic hormone rhythm and cortisol circadian rhythm in patients with depression complicated with anxiety and their effects on the psychological state of patients.

Objective: This work was to explore the rhythm of adrenocorticotropic hormone (ACTH) and cortisol in patients with depression and anxiety and their effects on mental state. In this work, with depression complicated with anxiety patients as the A-MDD group (n = 21), and depression without anxiety symptoms as the NA-MDD group (n = 21). Firstly, data features were extracted according to the electroencephalo-graph (EEG) data of different patients, and a DR model was constructed for diagnosis. The Hamilton Depression Scale 24 (HAMD-24) was employed to evaluate the severity, and the ACTH and cortisol levels were detected and compared for patients in the A-MDD group and NA-MDD group. In addition, the psychological status of the patients was assessed using the Toronto Alexithymia Scale (TAS). As a result, the AI-based DR model showed a high recognition accuracy for depression. The HAMD-24 score in the A-MDD group (31.81 ± 5.39 points) was statistically higher than the score in the NA-MDD group (25.25 ± 5.02 points) (P < 0.05). No visible difference was found in ACTH levels of patients in different groups (P > 0.05). The incidence of cortisol rhythm disorder (CRD) in the A-MDD group was much higher (P < 0.05). The differences in TAS scores between the two groups were significantly statistically significant (P < 0.01). In conclusion, the AI-based DR Model achieves a more accurate identification of depression; depression with or without anxiety has different effects on the mental state of patients. CRD may be one of the biological markers of depression combined with anxiety.

Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach.

Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level. Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature. Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBGNLME stable around 0.5 μM vs. steady increase from 0.35 to 0.8 μM for CBG PBPK). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (ΔOFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias. Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK.

Age-related and individual features of the HPA axis stress responsiveness under constant light in nonhuman primates.

The hypothalamic-pituitary-adrenal (HPA) axis is a key adaptive neuroendocrine system, dysfunction of which plays an important role in the increasing incidence of stress-dependent age-related pathology. Among the environmental factors effecting increase age-related diseases, great importance is given to disturbances of the light-dark schedule, particularly with increased illumination at night. While disruption of the light-dark schedule has long been recognized as a powerful behavioral stressor, little is known regarding stress reactivity of the HPA under constant light (CL) conditions, especially with aging and depending on the features of stress behavior. The purpose of this investigation was to study the age-related and individual features of the HPA axis response to acute stress exposure (ASE) under chronic CL in nonhuman primates that are known to differ in behavioral responsiveness to stress. Young and old female rhesus monkeys (with control standard behavior or anxiety and depression-like behavior) were exposed to CL (24h light/day, 330-400 lux for 4 to 8 weeks). Control young and old monkeys were exposed to standard lighting (SL) with natural light during the day and darkness at night. All animals were subjected to ASE (restriction of mobility for 2 hours), functional tests with corticotrophin-releasing hormone and arginine-vasopressin, and study of circadian rhythms of cortisol and pineal melatonin secretion. For the first time an inhibitory effect of CL on the reaction of the adrenal cortex to ASE was revealed in all individuals, regardless of age and preexisting behavior stress reactivity, the mechanisms of which were age-dependent: due to inhibition of the pituitary ACTH secretion in young animals and mainly not affecting the ACTH secretion in old individuals. There were no significant changes in melatonin secretion both in young and old animals. The observed CL inhibition of adrenal cortical reactivity to ASE may be useful to correct increased vulnerability to ASE observed in individuals with preexisting anxiety and depression-like stress behaviors. On the other hand, the CL induced decrease in adrenal stress reactivity of behaviorally normal animals suggests a potential risk of reducing the adaptive capacity of the organism under conditions of continuous light exposure.

PS-R03-10: CASE REPORT: CUSHING SYNDROME IN A YOUNG MALE

A 27-year-old male without any significant past medical history was advised to visit a hospital for elevated blood pressure, elevated liver enzymes, and dyslipidemia in a workplace health checkup. His body weight had increased by more than 10 kg in the last two years. He presented to our department and underwent laboratory work-up. He had bilateral lower limb pitting edema, hypokalemia, and elevation of low-density lipoprotein. No sign of dysthyroidism, renin-angiotensin-aldosterone system disorder, or increased catecholamine secretion was found. Diet and exercise therapy and calcium channel blocker did not improve his hypertension, and he suffered from lumber vertebral fracture, refractory hypokalemia, and lower leg cellulitis. He was admitted to our department for detailed examination of worsening lower limb edema. On admission, he had striae on his abdomen and legs as well as edema of both lower extremities. The endocrinological data showed high levels of adrenocorticotropic hormone (ACTH) and cortisol. Overnight 1 mg dexamethasone suppression test resulted in a non-suppression response, and his circadian rhythm of cortisol was absent. Urine cortisol level was high. These findings confirmed the diagnosis of ACTH-dependent Cushing syndrome. A contrasted magnetic resonance imaging (MRI) scan demonstrated enlargement of the pituitary gland more than 1 cm in length. Taking into account drug-resistant hypokalemia and vulnerability to infection, he was administered with metyrapone 500 mg per day until he underwent transsphenoidal hypophysectomy. The pathological findings were consistent with that of a pituitary adenoma. Postoperative MRI scan showed remnant lesions which stretch to the bilateral cavernous sinuses and the right middle cranial fossa. Although a decrease in urine cortisol was observed, the absence of a circadian rhythm of cortisol, hypertension, and hypokalemia persisted. He is now treated with somatostatin analog and craniotomy followed by gamma knife surgery is planned. Cushing syndrome should be suspected in cases of early-onset hypertension with symptoms including weight gain, hypokalemia, and bone fracture.

S-23-4: EFFECTS OF ROTATING NIGHT SHFT ON CIRCADIAN PATTERN OF AMBULATORY BLOOD PRESSURE/HEART RATE, SALIVARY CORTISOL AND SULFATOXY MELATONIN LEVELS

Objective: The present study was aimed to investigate effect of Light exposute at night on 24 hours chronomics of BP/HR in terms of Double amplitude, Acrophase and Hyperbaric index and its relation with circadian rhythm of salivary cortisol and 6 sulfatoxy melatonin in rotating night shift nursing professionals and actual day workers. Design &amp; Methods: 56 night shift nurses, aged 20 to 40 years, performing day and night shift duties were recruited from the Trauma Center, KGMU, India, and 56 age sex matched actual day workers were also enrolled as controls. BP and HR were recorded by Ambulatory Blood Pressure Monitoring (ABPM) at every 30 min intervals in day time and each hour in night time during shift duties. Results: Highly significant difference was found in double amplitude (2DA) of among between night (23.10 ± 14.68) and day shift (34.27 ± 16.44) (p &lt; 0.0005). In night shift, hyperbaric index (HBI) of mean SBP was found to be increased at 00 to 03 am (midnight) while during day shift, peak was found at 06 to 09 am. HBI of mean HR was found to be increased at 18 to 21 pm during night shift while in controls, peak was found at 09 to 12 &amp; again 15 to 18 pm of SBP, DBP &amp; HR. Alterations in Acrophase of BP/HR were very common among night shift workers and Ecphasia was found in few nights shift workers. Difference was found in night cortisol levels among night (4.08 ± 3.28) vs day shift (2.62 ± 2.37), while in comparison to night shift or day shift with controls (1.82 ± 1.18) these difference was significant (p &lt; 0.05). Conclusion: Alteration in mean morning melatonin and Increased Night cortisol level were found during night shift. Reverse pattern of Acrophase and HBI of BP &amp; HR along with salivary cortisol during night shift represents desynchronization. It indicates that the circadian rhythm was disrupted during night shift and recovery occurs during day shit.

Inhibiting nighttime melatonin and boosting cortisol increase patrolling monocytes, phagocytosis, and myelination in a murine model of multiple sclerosis

Conflicting results on melatonin synthesis in multiple sclerosis (MS) have been reported due to variabilities in patient lifestyles, which are not considered when supplementing melatonin. Since melatonin acts through its receptors, we identified melatonin receptors in oligodendrocytes (OLs) in the corpus callosum, where demyelination occurs; the subventricular zone, where neural stem/progenitor cells (NSPCs) are located; and the choroid plexus, which functions as a blood-cerebrospinal fluid barrier. Moreover, using chimeric mice, resident macrophages were found to express melatonin receptors, whereas bone marrow-derived macrophages lost this expression in the demyelinated brain. Next, we showed that cuprizone-fed mice, which is an MS model, tended to have increased melatonin levels. While we used different approaches to alter the circadian rhythm of melatonin and cortisol, only the constant light approach increased NSPC proliferation and differentiation to oligodendrocyte precursor cells (OPCs), OPCs maturation to OLs and recruitment to the site of demyelination, the number of patrolling monocytes, and phagocytosis. In contrast, constant darkness and exogenous melatonin exacerbated these events and amplified monocyte infiltration. Therefore, melatonin should not be considered a universal remedy, as is currently claimed. Our data emphasize the importance of monitoring melatonin/cortisol oscillations in each MS patient by considering diet and lifestyle to avoid melatonin overdose.

ODP639 The Occurrence and Predictors of Postoperative Adrenal Insufficiency for Patients With Subclinical Cushing's Syndrome

Abstract Objective To identify the occurrence and predictive factors of postoperative adrenal insufficiency in patients with subclinical Cushing's syndrome (SCS), and try to provide evidence for decision-making in SCS management. Methods The present retrospective analysis included 77 patients who underwent unilateral laparoscopic adrenalectomy for SCS between December 2011 and April 2021. Among them, 59 patients with complete follow-up data were included. We compared clinical characteristics of patients with and without postoperative adrenal insufficiency. The logistic regression model was used to find the potential risk factors in predicting the occurrence of postoperative adrenal insufficiency. The receiver operating characteristic (ROC) curve was used to evaluate the predictive values. Results We included 59 patients, of whom the incidence of postoperative adrenal insufficiency is 42.37%. The circadian rhythms of adrenocorticotropic hormone (ACTH) and cortisol disappeared in both two groups. Compared patients without postoperative adrenal insufficiency, patients with postoperative adrenal insufficiency were characterized by suppressed plasma ACTH level [1.11(1.11, 1.83) pmol/L vs 2.56(1.16, 4.63) pmol/L], elevated midnight cortisol level [268. 00(164. 00, 347.50) nmol/L vs 181.50(156.32, 227. 00) nmol/L] and increased cortisol level after 1 mg overnight dexamethasone suppression test (DST) [281. 00(241. 00, 396.64) nmol/L vs 172.50(144. 05, 215.25) nmol/L] (all P &amp;lt; 0. 05). Multivariate logistic regression analysis showed that the serum cortisol after a 1 mg-DST was the only independent predictive factor for the occurrence of postoperative adrenal insufficiency. The ROC curve showed that the best cut-off value of the serum cortisol after a 1 mg-DST was 233 nmol/L, with a sensitivity of 80. 00% and a specificity of 82.35%. The combination of the serum cortisol after a 1 mg-DST, plasma ACTH and midnight cortisol had the highest predictive accuracy (83. 05%). Conclusion Patients who underwent unilateral laparoscopic adrenalectomy for SCS had a risk of postoperative adrenal insufficiency. The pre-surgical assessment of the serum cortisol after a 1 mg-DST plus elevated midnight cortisol and suppressed plasma ACTH had predictive value for the occurrence of postoperative adrenal insufficiency. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

The association between circadian rhythm of cortisol and shift work regularity among midwives-A multicenter study in Southeast China.

ObjectiveThis article aims to explore the association between the trends of cortisol rhythm and the regularity of shift work among midwives.MethodsMidwives from six Southeast Chinese hospitals were recruited through cluster sampling in a multi-center cross-sectional study. Urine samples were collected half an hour after waking up, at 11:00, 19:00, and 23:00 on two consecutive days in a longitudinal cohort. The urinary cortisol was assayed by the chemiluminescence method.ResultsA total of 86 midwives were included in this study, contributing 688 cortisol samples. The midwives displayed a circadian rhythm in cortisol secretion, with zeniths in the morning and nadirs in the evening. The trend of the first day was repeated on the second day. Although the total working hours per week of the two groups, namely the regular shift group (N = 43) and the irregular shift group (N = 43), were the same, significant main effects of groups (F = 62.569, p < 0.001), time (F = 45.304, p < 0.001), and group-by-time interaction (F = 226.695, p < 0.001) were indicated through linear mixed models. The main effect of day was not statistically significant, with F = 0.105 and p = 0.746. The fluctuation range of cortisol curve in the group with irregular schedules was slightly lower than that in the group with regular schedules.ConclusionOur results may indicate that cortisol was more inhibited in midwives with irregular shift patterns than those with regular shift patterns. It is necessary to further study the relationship between cortisol rhythm and patterns of midwives' shifts in future so as to lay a foundation for hospital managers to develop a more reasonable scheduling system for midwives with the further purpose to minimize their occupational fatigue and ensure the safety of mothers and infants.

CN73 Circadian rhythms of cortisol, α-amylase and pro- / anti-inflammatory cytokines of osteosarcoma pediatric patients under chemotherapy

CN73 Circadian rhythms of cortisol, α-amylase and pro- / anti-inflammatory cytokines of osteosarcoma pediatric patients under chemotherapy

(Digital Presentation) Electrocatalytic Cortisol Tracing Smart Patch

Rapid and continuous tracking of the stress hormone cortisol's circadian rhythm is vital for diagnosing diseases related to chronic stress and adrenal gland disorders [1]. Commercial cortisol sensors relying on labeled enzyme and antibodies suffer from limited stability, lengthy reaction time, and cross-reactivity with analogous molecules [2]. To address these issues, we developed an electrocatalytic sensor using phthalocyanine (Pc) doped molecularly imprinted polymer (MIP) modified screen-printed electrodes for label-free, reagentless, sensitive, and selective electrochemical detection of cortisol. The sensor was constructed via one-step electropolymerization of conductive prepolymer in the presence of Pc and template cortisol. The controlled release of cortisol templates resulted in an MIP network embedded with Pc catalysts in the vicinity of the cortisol-specific binding cavities. The sensor directly measures the cortisol level by catalysing the reduction reaction of the cortisol captured by the cavities of the MIP. Proof of studies was performed to detect cortisol over a wide concentration range varying from 500 pM to 10 µM with high selectivity against structurally similar hormones. The facile label-free and antibody-free cortisol sensor on a wearable smart patch offers an appealing approach for selective steroid hormone detection at point-of-care testing.

The role of subclinical depressive symptomatology during the prenatal period in cortisol rhythm alterations and postpartum depression risk

IntroductionCortisol, the hormonal endpoint of Hypothalamic Pituitary Adrenal (HPA) axis, coordinates the body response in front of daily stressful situations. Disturbances in cortisol circadian rhythm have been implicated in the pathophysiology of depression and neurodevelopment lasting consequences. Although pregnancy entails a progressively increase in cortisol levels, the consequences of subclinical depression traits during pregnancy in cortisol circadian rhythm remains unclear.ObjectivesTo analyze the impact of prenatal subclinical depressive symptomatology in cortisol circadian rhythm through pregnancy and its relevance for postpartum depression risk.MethodsA cohort of 112 healthy pregnant women (Mean age±SD=32.32±4.37) of the general population was followed throughout their first pregnancy and first two months of postpartum period. Diurnal salivary cortisol curve (four measures) was obtained for every trimester; the Area Under the Curve with respect to the ground (AUCg) and with respect to the increase (AUCi) were used as measures of basal HPA axis functioning. Depressive symptomatology was assessed every pregnancy trimester and postpartum period following EPDS criteria. All the analyses were adjusted for maternal age, weight, ethnicity and socioeconomic status and sample collection’s time.ResultsPrenatal subclinical depressive symptomatology (EPDS&gt;10) was associated with a blunted cortisol rhythm during first trimester (F= 3.913,p=.011) but not during second (F=2.629, p=056) or third trimesters (F=.411,p=.724). Furthermore, a logistic regression model showed a positive association between Prenatal subclinical depressive symptomatology and the risk of postpartum depression (χ2=13.8, p&lt;.001,OR=9.6; 95%CI 2.5–35.5).ConclusionsWomen with subclinical depressive symptomatology in early pregnancy had alterations in cortisol circadian rhythmicity and a higher risk of postpartum depression.DisclosureNo significant relationships.

Effect of night-shift work on cortisol circadian rhythm and melatonin levels.

ObjectivesNight-shift work has been associated with several negative effects on worker’s health, possibly due to circadian desynchronization, sleep deprivation and suppression of nocturnal melatonin secretion including exposure to light during the work shift. The objective of this study was to evaluate the impact of fixed night-shift work versus day-shift work on the sleep-wake cycle and on the night and day levels of cortisol and melatonin.Material and MethodsSaliva samples were obtained from 36 individuals, 19 day workers (12 women and 7 men) and 17 night workers (12 women and 5 men) from a university hospital in southern Brazil, with no history of chronic diseases. Demographic and personal information were obtained through a self-administered questionnaire and sleep information by the Munich chronotype questionnaire.ResultsSalivary cortisol showed normal circadian rhythm in day- and night-shift workers, but was attenuated in night-shift workers during their working hours and on leave days. Night workers sleep fewer hours at night and have higher negative social jet lag than day workers.ConclusionIntervals between night shifts can be beneficial for the recovery of the hypothalamic-pituitary-adrenal axis, minimizing the negative effects on workers’ health, in addition to a preventive approach to aspects related to sleep hygiene and healthy life habits.

Chronotherapy based on modified-release hydrocortisone to restore the physiological cortisol diurnal rhythm

In this inspirational note, we describe the development of an endocrine chronotherapy to restore the physiological rhythm of the essential adrenal stress hormone, cortisol. The challenges included demonstrating the circadian rhythm of the drug target, creating a drug formulation that replicated that rhythm and then proving benefit in clinical trials. The physiological cortisol circadian rhythm is well defined with cortisol levels high on waking and low on going to sleep. We experimented with different formulation technologies including modified-release tablets and multi-particulates to replicate the cortisol rhythm where absent through disease. We describe the development of Efmody®, a modified-release formulation of hydrocortisone, which replicates the cortisol diurnal rhythm and improves the disease control of congenital adrenal hyperplasia, the commonest hereditary form of adrenal insufficiency. This program shows it is possible, through modified-release technology, to treat chronic endocrine diseases with physiological replacement to preserve health for life.

A fixed single meal in the subjective day prevents free-running of the human sleep-wake cycle but not of the circadian pacemaker under temporal isolation.

Effects of a fixed single meal per day were examined on the circadian pacemaker and sleep-wake cycle in subjects under temporal isolation. When the time of single meal was allowed to take at any time of day (ad-lib meal), the sleep-wake cycle as well as the circadian rhythms in plasma melatonin, cortisol, and core body temperature were significantly phase-delayed in 8 days. On the other hand, when the time of meal was fixed at 1800 h in local time (RF meal), the phase-shift of sleep-wake cycle was not significant while those of the circadian rhythms were significant. The differential effects of a fixed single meal schedule were confirmed in most individual subjects. There was no evidence for the prefeeding increase in plasma cortisol and leptin levels under the fixed single meal schedule. The plasma ghrelin level was apparently high before meal in both ad-lib and RF meal groups, which was, however, likely sculptured by a nonspecific prandial drop and gradual increase after meal intake. Single meal augmented the prandial increase of plasma insulin levels by four to five times. These findings indicate that a single meal at a fixed time of the day during the subjective day failed to prevent the human circadian pacemaker but prevented the sleep-wake cycle from free running for at least 8 days under temporal isolation, suggesting that mealtime was a potent nonphotic time cue for the human sleep-wake cycle.

Circadian Rhythm of Salivary Cortisol in Obese Adolescents With and Without Apnea: A Pilot Study.

Background and ObjectiveObstructive sleep apnea (OSA) and obesity are associated with stress system activation involving the hypothalamic-pituitary-adrenal (HPA) axis in adults, but these effects in childhood and adolescence remain unclear. We examined diurnal salivary cortisol as a measurement of the HPA axis function in obese adolescents with and without OSA and the relationships between cortisol levels, body weight, and parameters of polysomnography (PSG).MethodsAfter PSG, saliva samples were collected from obese participants (with and without OSA) and lean participants four times over a 24-h period, namely, at 7:00 h (m-sCort), 13:00 h (a-sCort), 19:00 h (e-sCort), and 23:00 h (n-sCort). An enzyme-linked immunosorbent assay (ELISA) was used to measure salivary cortisol levels. The mean values of cortisol levels and fixed-time point diurnal cortisol slope (DCS) were calculated and compared among the three study groups. Correlations between parameters were analyzed using Spearman's correlation coefficients.ResultsObese OSA participants had significantly higher e-sCort and n-sCort levels than both obese non-OSA participants and lean controls. However, m-sCort and a-sCort in these patients had a pronounced upward trend. M-sCort was significantly correlated with both the lowest oxygen saturation (SpO2) and time with SpO2 <90%. Moreover, in the obese OSA group, DCS was significantly flatter than in the other two groups. The a-sCort in obese non-OSA participants was significantly higher than that in the lean control group and, surprisingly, was positively correlated with the apnea/hypopnea index. Additionally, m-sCort was related to body weight.ConclusionThis study provided further evidence for alterations in diurnal cortisol production in obese adolescents, which may indicate a chronically stressed HPA axis. However, there were significant differences in salivary cortisol parameters between participants with and without OSA. Furthermore, patients with OSA had more associations between time-point cortisol levels and OSA-related indices. Nonetheless, this research is a pilot study, and further investigations are necessary.