Cortisol Dynamics Research Articles

Evaluation of Cushing's disease remission after transsphenoidal surgery based on early serum cortisol dynamics

To evaluate the ability of post-transsphenoidal pituitary surgery (TSS) serum cortisol levels (s-cortisol) to predict surgical remission and recurrence of Cushing's disease (CD). One hundred and three patients with CD from a tertiary referral centre were prospectively analysed over 6·0 ± 4·8 years of follow-up. Twenty patients received perioperative glucocorticoids as routine care and had s-cortisol measured 10-12 days after TSS (Protocol I). Eighty-six patients (91 surgeries) had s-cortisol measured at 6, 12, 18, 24, 48 h, and 10-12 days after TSS, and received glucocorticoids only in case of adrenal insufficiency (Protocol II). Remission [clinical signs and symptoms of adrenal insufficiency (or hypocortisolism) plus cortisol <3 μg/dl on the 1-mg overnight test (OT) and/or normal free urinary cortisol] during follow-up. Recurrence was defined as loss of remission criteria at least 1 year after TSS. The remission rate after first TSS was 80%; 8% had recurrence. An s-cortisol nadir ≤3·5 μg/dl within 48 h after TSS had sensitivity of 73%, specificity and positive predictive value (PPV) of 100% and negative predictive value (NPV) of 60% and an s-cortisol nadir ≤5·7 μg/dl within 10-12 days of TSS had specificity and PPV of 100% and sensitivity of 91% NPV of 78% for CD remission. At hospital discharge, the s-cortisol nadir within 48 h after TSS was already able to predict surgical remission for some patients, and the s-cortisol nadir within 10-12 days of TSS was able to predict cohort-wide surgical remission.

Cortisol dynamics and endothelin-1/nitric oxide ratio are associated with clinical vasospasme

Background: Cortisol dynamics in serum might be related to clinical vasospasm, also known as delayed ischemic neurological deficits (DIND). Two vasoactive substances that play a role in pathophysiology of DIND are endothelin-1 (ET1) and nitric oxide (NO), both are proved associated with cortisol. This study aimed to know how cortisol play a role on ET1/NO ratio and its relationship to DIND. Methods: This was a prospective cohort study for the first 14 days after aneurysmal subarachnoid hemorrhage (SAH). Patients with inclusion criteria will be enrolled for blood test before surgery, and post-operative day 2, 4, 7, and 10 (between 8:00-9:00 AM). The blood tests were performed for cortisol, ACTH, CBG, NO, and ET1. Free cortisol is calculated with Coolens equation. Logistic regression was used to see the interaction model and its scale. Bivariate analysis (corelation) was used to see the relationship between total cortisol, free cortisol, NO, ET1, and clinical vasospasm (DIND). Results: Forty-four patients are enrolled into this study (20 male; 24 females). Mean age is 52.02 years (52.02 ± 11.23). There were 29 patients (66%) within&nbsp; DIND group and 15 patients Non-DIND as the control group. The mean of cortisol level shown is significantly higher in DIND group (35.99 ± 14.24) µg/dL compared to Non-DIND group (19.57 ± 6.19) µg/dL, p &lt; 0.001. The mean of free cortisol level was significantly higher in DIND group (2.06 ± 1.094) µg/dL compared to non-DIND group (0.838 ± 0.365 µg/dL; p &lt; 0.001). The Scatter Plot graph show that correlation of cortisol with ET1/NO ratio started increasing on day 4 and became stronger on day 10. Conclusion: Cortisol is associated with DIND following aneurysmal SAH, probably through its role in keeping the balance between ET1 and NO level. (Med J Indones. 2013;22:161-6. doi: 10.13181/mji.v22i3.585)

AB0027 Impact of additional genetic markers of rheumatoid arthritis on pattern of functional stress responses

BackgroundGrowing evidence supports the hypothesis that alteration of the stress response and interactions between the autonomic nervous system, the hypothalamus-pituitary-adrenal axis and the immune system contributes to the pathogenesis of...

Distinguishing normal, depressive and PTSD cortisol dynamics in humans through mathematical modelling

Distinguishing normal, depressive and PTSD cortisol dynamics in humans through mathematical modelling

Cortisol, obesity, and the metabolic syndrome: A cross‐sectional study of obese subjects and review of the literature

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome. To evaluate these relationships, we performed a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers and reviewed the previous literature.Overweight and obese subjects had at least two other features of Cushing’s syndrome. They underwent measurements representing cortisol dynamics (24h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol and weight from 60 healthy volunteers were analyzed.No subject had Cushing’s syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P< 0.0001), and correlated with waist circumference (WC) in men (rs=0.28, P=0.02) and systolic BP in women (rs=0.24, P =0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (rs=− 0.31, P=0.01) and HOMA-IR (rs=−0.31, P=0.01) in men and systolic (rs=0.18, P= 0.02) and diastolic BP (rs=0.20, P=0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or metabolic syndrome.

Hair cortisol, stress exposure, and mental health in humans: A systematic review

The deleterious effects of chronic stress on health and its contribution to the development of mental illness attract broad attention worldwide. An important development in the last few years has been the employment of hair cortisol analysis with its unique possibility to assess the long-term systematic levels of cortisol retrospectively. This review makes a first attempt to systematically synthesize the body of published research on hair cortisol, chronic stress, and mental health. The results of hair cortisol studies are contrasted and integrated with literature on acutely circulating cortisol as measured in bodily fluids, thereby combining cortisol baseline concentration and cortisol reactivity in an attempt to understand the cortisol dynamics in the development and/or maintenance of mental illnesses. The studies on hair cortisol and chronic stress show increased hair cortisol levels in a wide range of contexts/situations (e.g. endurance athletes, shift work, unemployment, chronic pain, stress in neonates, major life events). With respect to mental illnesses, the results differed between diagnoses. In major depression, the hair cortisol concentrations appear to be increased, whereas for bipolar disorder, cortisol concentrations were only increased in patients with a late age-of-onset. In patients with anxiety (generalized anxiety disorder, panic disorder), hair cortisol levels were reported to be decreased. The same holds true for patients with posttraumatic stress disorder, in whom - after an initial increase in cortisol release - the cortisol output decreases below baseline. The effect sizes are calculated when descriptive statistics are provided, to enable preliminary comparisons across the different laboratories. For exposure to chronic stressors, the effect sizes on hair cortisol levels were medium to large, whereas for psychopathology, the effect sizes were small to medium. This is a first implication that the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in the development and/or maintenance of psychopathology may be more subtle than it is in healthy but chronically stressed populations. Future research possibilities regarding the application of hair cortisol research in mental health and the need for multidisciplinary approaches are discussed.

Cortisol dynamics are associated with electrocardiographic abnormalities following the aneurysmal subarachnoid hemorrhage

Context:Electrocardiographic (ECG) abnormalities are common following subarachnoid hemorrhage (SAH). It probably represents cardiovascular stress after SAH.Aims:The purpose of this study was to assess cortisol dynamics in relation to the ECG abnormality and disease course of SAH.Settings and Design:The study follows a consecutive cohort of aneurysmal SAH patients, who underwent surgery within 72 hours of onset, and they were followed up for 10 days.Materials and Methods:Serum cortisols, cortisol-binding globulin (CGB), adenocorticotropic hormone were measured (between 08.00-09.00 hours) preoperatively and then on postoperative days (PODs) 2, 4, 7, and 10. Electrocardiographs (ECG) were recorded on initial assessment and after surgery on daily basis in ICU. ECG abnormalities will be followed up by measurement of cardiac troponin T to quantify the myocyte necrosis.Statistical Analysis Used:Logistic regression analysis using commercial available software STATA 9.Results:A total of 44 patients (20 M and 24 F) were eligible for the cohort analysis. Average patient age is 52.02 years (52.02 ± 11.23), and 86% (6/44) arrived with World Federation of Neurosurgical Society Scale grade 3 or better. The ECG abnormality was found in 10 cases (22.7%), but the abnormal TnT (>1 μg/l) were found in eight cases, and two cases contribute to the mortality. The ECG abnormalities are significantly associated with total cortisol on day 4 (P < 0.05) and free cortisol on day 2 (P = 0.0065).Conclusions:Elevated levels of morning cortisol within the first four days after surgery are associated with the ECG abnormality.

A phenomenological model for circadian and sleep allostatic modulation of plasma cortisol concentration

Both circadian rhythmicity and sleep play significant roles in the regulation of plasma cortisol concentration by the hypothalamo-pituitary-adrenal (HPA) axis. Numerous studies have found links between sleep and changes in cortisol concentration, but the implications of these results have remained largely qualitative. In this article, we present a quantitative phenomenological model to describe the effects of different sleep durations on cortisol concentration. We constructed the proposed model by incorporating the circadian and sleep allostatic effects on cortisol concentration, the pulsatile nature of cortisol secretion, and cortisol's negative autoregulation of its own production and validated its performance on three study groups that experienced four distinct sleep durations. The model captured many disparate effects of sleep on cortisol dynamics, such as the inhibition of cortisol secretion after the wake-to-sleep transition and the rapid rise of cortisol concentration before morning awakening. Notably, the model reconciled the seemingly contradictory findings between studies that report an increase in cortisol concentration following total sleep deprivation and studies that report no change in concentration. This work provides a biomathematical approach to combine the results on the effects of sleep on cortisol concentration into a unified framework and predict the impact of varying sleep durations on the cortisol profile.

ВОЗРАСТНАЯ ДИНАМИКА СОДЕРЖАНИЯ ГОРМОНОВ В ПЕРИФЕРИЧЕСКОЙ КРОВИ У ТЕЛОК ПРИ РАЗНЫХ ТЕХНОЛОГИЯХ ВЫРАЩИВАНИЯ

To study age dynamics of cortisol, triiodothyronine, thyroxine, oestradiol and progesterone levels, the parameters were tested in the Black-and-White heifers of different ages (from birth to 18 months) kept in an industrial environment and at private farms. The cattle from private farms was characterized by earlier onset of pubertal hormonal activity of the ovaries in comparison with commercial animals. Cortisol levels were higher in heifers from commercial facilities as compared to those of private farms indicating more stressful conditions for them. Our study demonstrated that breeding technology has a great importance for development of the endocrine system and perhaps for future productivity and fertility in cattle.

Modeling Cortisol Dynamics in the Neuro-endocrine Axis Distinguishes Normal, Depression, and Post-traumatic Stress Disorder (PTSD) in Humans

Cortisol, secreted in the adrenal cortex in response to stress, is an informative biomarker that distinguishes anxiety disorders such as major depression and post-traumatic stress disorder (PTSD) from normal subjects. Yehuda et al. proposed a hypothesis that, in humans, the hypersensitive hypothalamus-pituitary-adrenal (HPA) axis is responsible for the occurrence of differing levels of cortisol in anxiety disorders. Specifically, PTSD subjects have lower cortisol levels during the late subjective night in comparison to normal subjects, and this was assumed to occur due to strong negative feedback loops in the HPA axis. In the present work, to address this hypothesis, we modeled the cortisol dynamics using nonlinear ordinary differential equations and estimated the kinetic parameters of the model to fit the experimental data of three categories, namely, normal, depressed, and PTSD human subjects. We concatenated the subjects (n = 3) in each category and created a model subject (n = 1) without considering the patient-to-patient variability in each case. The parameters of the model for the three categories were simultaneously obtained through global optimization. Bifurcation analysis carried out with the optimized parameters exhibited two supercritical Hopf points and, for the choice of parameters, the oscillations were found to be circadian in nature. The fitted kinetic parameters indicate that PTSD subjects have a strong negative feedback loop and, as a result, the predicted oscillating cortisol levels are extremely low at the nadir in contrast to normal subjects, albeit within the endocrinologic range. We also simulated the phenotypes for each of the categories and, as observed in the clinical data of PTSD patients, the simulated cortisol levels are consistently low at the nadir, and correspondingly the negative feedback was found to be extremely strong. These results from the model support the hypothesis that high stress intensity and strong negative feedback loop may cause hypersensitive neuro-endocrine axis that results in hypocortisolemia in PTSD.

Modulation of hypothalamic–pituitary–interrenal axis function by social status in rainbow trout

Juvenile rainbow trout (Oncorhynchus mykiss) form stable dominance hierarchies when confined in pairs. These hierarchies are driven by aggressive competition over limited resources and result in one fish becoming dominant over the other. An important indicator of low social status is sustained elevation of circulating cortisol levels as a result of chronic activation of the hypothalamic–pituitary–interrenal (HPI) axis. In the present study it was hypothesized that social status modulates the expression of key proteins involved in the functioning of the HPI axis. Cortisol treatment and fasting were used to assess whether these characteristics seen in subordinate fish also affected HPI axis function. Social status modulated plasma adrenocorticotropic hormone (ACTH) levels, cortisol synthesis, and liver glucocorticoid receptor (GR) expression. Plasma ACTH levels were lower by approximately 2-fold in subordinate and cortisol-treated fish, consistent with a negative feedback role for cortisol in modulating HPI axis function. Although cortisol-treated fish exhibited differences in corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) mRNA relative abundances in the preoptic area and telencephalon, respectively, no effect of social status on CRF or CRF-BP was detected. Head kidney melanocortin 2 receptor (MC2R) mRNA relative levels were unaffected by social status, while mRNA relative abundances of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage (P450scc) enzyme were elevated in dominant fish. Liver GR2 mRNA and total GR protein levels in subordinate fish were lower than control values by approximately 2-fold. In conclusion, social status modulated the functioning of the HPI axis in rainbow trout. Our results suggest altered cortisol dynamics and reduced target tissue response to this steroid in subordinate fish, while the higher transcript levels for steroid biosynthesis in dominant fish leads us to propose an adaptive role for responding to subsequent stressors.

Endogenous cortisol is associated with functional connectivity between the amygdala and medial prefrontal cortex

Whether glucocorticoids mediate medial prefrontal cortex (mPFC) regulation of the amygdala in humans remains unclear. In the current study we investigated whether cortisol levels under relatively stress-free circumstances are related to amygdala resting-state functional connectivity with the mPFC. Resting-state fMRI data were acquired from 20 healthy male participants. Salivary cortisol was sampled at multiple times throughout the experiment. The cortisol area under the curve increase (AUCi) was calculated as a measure of cortisol dynamics. Next, seed based correlations were employed on the resting-state fMRI data to reveal regions of amygdala functional connectivity related to variations in cortisol AUCi. The resulting statistical maps were corrected for multiple comparisons using cluster based thresholding (Z>2.3, p<.05). Two regions in the mPFC showed decreasing negative functional connectivity with the amygdala when a lesser decrease in cortisol AUCi was observed: the perigenual anterior cingulate cortex and medial frontal pole (BA10). Although we initially showed a relation with cortisol AUCi, it seemed that the baseline cortisol levels were actually driving this effect: higher baseline cortisol levels related to stronger negative functional connectivity with the mPFC. Endogenous cortisol levels may modulate amygdala functional connectivity with specific regions in the mPFC, even under relatively stress-free circumstances. Our results corroborate previous findings from both animal and human studies, suggesting cortisol-mediated regulation of the amygdala by the mPFC. We propose that through this feedback mechanism the stress response might be adjusted, pointing to the putative role of cortisol in modulating stress- and, more generally, emotional responses.

Coexistence of Growth Hormone-Secreting Pituitary Adenoma and Intracranial Meningioma

A 60-year-old woman was referred to our centre for evaluation of Acromegaly. Serum GH level was 60 ng/ml and remained unchanged after OGTT (75 g). Thyroid functions revealed normal TSH and T4 cortisol dynamics showed stimu-lated cortisol of 11 g/dl. MRI revealed pituitary macroadenoma associated with a frontal men ingioma ,JMS 2011;14(2):75&#x0D;

The association between cortisol dynamics and the course of aneurysmal subarachnoid hemorrhage

Context:One of aneurysmal subarachnoid hemorrhage complication is delayed ischemic neurological deficits (DIND). It is postulated that cortisol dynamics might be associated with the severity of this complication.Aims:The goal of the study is to investigate whether the peak of morning serum cortisol levels are associated with the severity of its complication during the course of the disease.Settings and Design:This is a prospective cohort study conducted from January 2009 to June 2011, at our institution.Materials and Methods:The study follows a consecutive cohort of patients for 14 days after the aneurysmal subarachnoid hemorrhage. Serum cortisols, cortisol binding globulin, adenocorticotrophic hormone (ACTH) were measured pre operatively and then on post operative days (POD) 2, 4, 7, and 10. Blood was drawn to coincide with peak cortisol levels between 08.00-09.00 hours. Neurological examinations were conducted at least twice daily and patient outcome were graded according to modified Ranklin Scale. DIND was defined by a decrease in the Glasgow Coma Scale of two or more points compared to the status on POD 1.Statistical Analysis:All the results were analyzed using statistical software, Statistical Package for Social Sciences (SPSS v61; SPSS, Inc., Chicago, IL). Logistic regression analysis was used to compare the relationship between the variables.Results:Thirty six consecutive patients are collected, but only 28 patients (12 M and 16 F) were eligible for the cohort analysis. Average patient age is 50.75 years old (50.75±12.27), and more than 50% (15/28) arrived with World Federation of Neurologic Surgeons grade 3 or better. Elevated total cortisol levels of more than 24 mg/dl on day 2, 4, and 10 were associated with DIND, and the most significant being on day 4 (P=0.011). These patients also had a higher grade on the modified Ranklin scale of disability.Conclusions:This study shows that the elevated levels of morning total cortisol in the serum are associated with the onset of DIND during the disease course, and it's also associated with bad outcomes.

Salivary Cortisol Increases After Bariatric Surgery in Women

Cortisol increases have been associated with psychological and physiological stress; however, cortisol dynamics after weight loss (bariatric) surgery have not been defined. Obese participants not using exogenous glucocorticoids were eligible to participate. Female participants (n=24) provided salivary cortisol samples at bedtime, upon awakening the following morning, and 30 min after awakening before, and at 6 or 12 months after bariatric surgery. The Medical Outcomes Study Short Form-12 version 2 questionnaire regarding health-related quality of life was also completed. Preoperatively, mean body mass index was 45.1±8.1 kg/m2. Mean late night (1.8±1.1 nmol/l), awakening (10.7±7.4 nmol/l), and after-awakening (11.5±7.9 nmol/l) salivary cortisol values were within normal ranges. The cortisol awakening response (mean 21.1±79.7%, median 13.7%) was at the low end of normal. Preoperatively, participants had lower mental and physical health-related quality of life scores than US adult norms (p<0.001). Salivary cortisol was not correlated with measures of health-related quality of life. Mean BMI decreased over time (p<0.001) and participants experienced improved physical and mental health-related quality of life (p≤0.011). Postoperative late night salivary cortisol was not different from preoperative values. Awakening and after-awakening cortisol levels were higher than preoperative values (15.3±7.7 nmol/l, p=0.013; 17.5±10.2 nmol/l, p=0.005; respectively), but the cortisol awakening response was not changed (mean 26.7±66.2%; median 7.8%). Morning salivary cortisol increased at long-term follow-up after bariatric surgery. Although self-evaluated mental and physical health improved after surgery, the cortisol awakening response is at the low end of normal, which may indicate continued physiological stress.

Ultradian Cortisol Pulsatility Encodes a Distinct, Biologically Important Signal

ContextCortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.ObjectiveDetermination of the biological consequences of ultradian cortisol pulsatility.DesignA novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined. In addition, effects on glucocorticoid receptor (GR) expression levels and phosphorylation, as a potential mediator, were measured.ResultsPulsatile cortisol caused a significant reduction in cell survival compared to continuous exposure of the same cumulative dose, due to increased apoptosis. Comprehensive analysis of the transcriptome response by microarray identified genes with a differential response to pulsatile versus continuous glucocorticoid delivery. These were confirmed with qRT-PCR. Several transcription factor binding sites were enriched in these differentially regulated target genes, including CCAAT-displacement protein (CDP). A CDP regulated reporter gene (MMTV-luc) was, as predicted, also differentially regulated by pulsatile compared to continuous cortisol delivery. Importantly there was no effect of cortisol delivery kinetics on either GR expression, or activation (GR phosphoSer211).ConclusionsCortisol oscillations exert important effects on target cell gene expression, and phenotype. This is not due to differences in cumulative cortisol exposure, or either expression, or activation of the GR. This suggests a novel means to regulate GR function.

Alleviation of cyclic heat stress in broilers by dietary supplementation of mannan-oligosaccharide and Lactobacillus-based probiotic: Dynamics of cortisol, thyroid hormones, cholesterol, C-reactive protein, and humoral immunity

Heat stress (HS), one of the major problems of tropical and subtropical countries, adversely affects the production performance of poultry. Keeping this in view, the present study was designed to investigate some of the biological markers of HS in broilers as modulated by dietary supplementation of mannan-oligosaccharide (MOS) and a Lactobacillus-based probiotic (LBP), either alone or in combination. Two hundred fifty 1-d-old-chicks were randomly divided into 5 groups. From d 22, the birds were either kept at the thermoneutral zone (TN) or exposed to HS to the conclusion of study, d 42. Birds were fed either a corn-based basal diet (TN and HS groups) or the same diet supplemented with 0.5% MOS (HS-MOS group), 0.1% LBP (HS-LBP group), or their combination. Birds were immunized against Newcastle disease virus on d 4 (intraocular; live attenuated) and d 20 (drinking water; live attenuated) and infectious bursal disease virus on d 8 (intraocular; live intermediate strain) and d 24 (drinking water; live attenuated). Birds were killed on d 42 to collect serum for determination of cortisol, thyroid hormones, cholesterol, C-reactive protein, and postvaccinal antibody titers. Results revealed that dietary supplementations decreased (P < 0.05) the serum cortisol and cholesterol concentrations and increased (P < 0.05) thyroxine concentration compared with the HS group without affecting triiodothyronine concentration. The percentage of the C-reactive protein-positive birds was higher (P < 0.05) in the HS group compared with the TN group. Dietary supplementations improved humoral immunity against Newcastle disease virus and infectious bursal disease virus during HS. In conclusion, dietary supplementation of either MOS or LBP alone or in combination can reduce some of the detrimental effects of HS in broilers.

Dynamics of social and energetic stress in wild female chimpanzees

Stress hormone measurements can reinforce and refine hypotheses about the costs of particular contexts or behaviors in wild animals. For social species, this is complicated because potential stressors may come from the physical environment, social environment, or some combination of both, while the stress response itself is generalized. Here, we present a multivariate examination of urinary cortisol dynamics over 6 years in the lives of wild female chimpanzees in the Kanyawara community of Kibale National Park, Uganda. We hypothesized that chimpanzee socioecology provides strong indications of both energetic and social stress to females, but that the salience of these stressors might vary over a female's life history in accordance with their changing reproductive costs and social interactions. Using linear mixed models, we found that urinary cortisol levels increased significantly with age but were also elevated in young immigrants to the community. Across reproductive states, cycling, non-estrous females had relatively low cortisol compared to lactating, estrous, or pregnant females. Aggression from males led to higher cortisol levels among estrous females, frequent targets of aggressive sexual coercion. In contrast, energetic stress was most salient to lactating females, who experienced higher cortisol during months of low fruit consumption. Low dominance rank was associated with increased cortisol, particularly during the energetically demanding period of lactation. The effects of female conflict were felt widely, even among those who were the primary aggressors, providing further evidence that long-term resource competition, while apparently muted, exerts a far-reaching impact on the lives of chimpanzee females.

Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis

The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.

Cortisol Dynamics in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage: Associations with Disease Severity and Outcome

The purpose of this study was to assess cortisol dynamics in the acute phase after aneurysmal subarachnoid hemorrhage (SAH) and to set the parameters of cortisol release in relation to the severity of illness and outcome. In 22 consecutive patients with aneurysmal SAH, cortisol, corticosteroid binding globulin, interleukin-6, and adrenocorticotrophic hormone were measured immediately after hospital admission (t(0)), 7 days (t(1)) later, and at least 14 days later (t(2)). Additionally, diurnal profiles of cortisol secretion were assessed at t(1) and t(2), and area under the curve (AUC) was computed for calculated free serum cortisol (CFSC). In this study, normal diurnal CFSC profiles were associated with a significantly shorter ICU-stay, less complications, and a more favorable outcome than abnormal diurnal profiles. AUC and 8 a.m. cortisol were not related to clinical course or outcome. It is concluded that cortisol secretion patterns are associated with the severity and outcome of SAH. For an appraisal of the hypothalamo-pituitary-adrenal axis in SAH patients, single cortisol measurements are insufficient.