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Endocrine Reviews Jun 2020The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need... (Review)
Review
The past decade has seen several critical advances in our understanding of hypothalamic-pituitary-adrenal (HPA) axis regulation. Homeostatic physiological circuits need to integrate multiple internal and external stimuli and provide a dynamic output appropriate for the response parameters of their target tissues. The HPA axis is an example of such a homeostatic system. Recent studies have shown that circadian rhythmicity of the major output of this system-the adrenal glucocorticoid hormones corticosterone in rodent and predominately cortisol in man-comprises varying amplitude pulses that exist due to a subhypothalamic pulse generator. Oscillating endogenous glucocorticoid signals interact with regulatory systems within individual parts of the axis including the adrenal gland itself, where a regulatory network can further modify the pulsatile release of hormone. The HPA axis output is in the form of a dynamic oscillating glucocorticoid signal that needs to be decoded at the cellular level. If the pulsatile signal is abolished by the administration of a long-acting synthetic glucocorticoid, the resulting disruption in physiological regulation has the potential to negatively impact many glucocorticoid-dependent bodily systems. Even subtle alterations to the dynamics of the system, during chronic stress or certain disease states, can potentially result in changes in functional output of multiple cells and tissues throughout the body, altering metabolic processes, behavior, affective state, and cognitive function in susceptible individuals. The recent development of a novel chronotherapy, which can deliver both circadian and ultradian patterns, provides great promise for patients on glucocorticoid treatment.
Topics: Adrenocorticotropic Hormone; Animals; Bodily Secretions; Circadian Rhythm; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Secretory Pathway
PubMed: 32060528
DOI: 10.1210/endrev/bnaa002 -
Psychoneuroendocrinology Sep 2017Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been... (Meta-Analysis)
Meta-Analysis Review
Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r=0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r=0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health.
Topics: Circadian Rhythm; Emotions; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mental Health; Pituitary-Adrenal System; Saliva; Stress, Psychological
PubMed: 28578301
DOI: 10.1016/j.psyneuen.2017.05.018 -
Current Cardiology Reports Aug 2019This review focuses on the concentration of cortisol in human hair as a biomarker of chronic stress in cardiovascular disease (CVD). We outline the cardiovascular... (Review)
Review
PURPOSE OF REVIEW
This review focuses on the concentration of cortisol in human hair as a biomarker of chronic stress in cardiovascular disease (CVD). We outline the cardiovascular consequences of cortisol excess and provide a comprehensive overview of recent studies investigating the relationship of hair cortisol with CVD. In addition, clinical implications and limitations of the evidence are discussed, together with directions for future research.
RECENT FINDINGS
Hair cortisol may be a reliable biomarker of chronic stress since it provides quantification of total cortisol secreted into hair over several weeks. A growing body of evidence suggests that elevated hair cortisol levels are associated with both the incidence of CVD and poorer recovery and treatment outcomes. Moreover, increased hair cortisol concentration has been linked with established cardiometabolic risk factors for CVD including high blood pressure, diabetes, and adiposity. Hair cortisol is a promising biomarker of chronic cortisol excess which may contribute to both the pathogenesis and prognosis of CVD. However, the current evidence relies on small-scale cross-sectional studies. Further research adopting longitudinal designs across larger samples of CVD patients and healthy participants is required to inform the development of novel evidence-based interventions.
Topics: Biomarkers; Cardiovascular Diseases; Chronic Disease; Hair; Humans; Hydrocortisone; Saliva; Stress, Physiological; Stress, Psychological
PubMed: 31471749
DOI: 10.1007/s11886-019-1208-7 -
BMB Reports Apr 2015Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual's adaptive... (Review)
Review
Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual's adaptive response to environmental demands. However, chronic, excessive stress causes cumulative negative impacts on health outcomes through "allostatic load". Thus, monitoring the quantified levels of long-term stress mediators would provide a timely opportunity for prevention or earlier intervention of stress-related chronic illnesses. Although either acute or chronic stress could be quantified through measurement of changes in physiological parameters such as heart rate, blood pressure, and levels of various metabolic hormones, it is still elusive to interpret whether the changes in circulating levels of stress mediators such as cortisol can reflect the acute, chronic, or diurnal variations. Both serum and salivary cortisol levels reveal acute changes at a single point in time, but the overall long-term systemic cortisol exposure is difficult to evaluate due to circadian variations and its protein-binding capacity. Scalp hair has a fairy predictable growth rate of approximately 1 cm/month, and the most 1 cm segment approximates the last month's cortisol production as the mean value. The analysis of cortisol in hair is a highly promising technique for the retrospective assessment of chronic stress.
Topics: Adrenal Glands; Allostasis; Animals; Biomarkers; Blood Pressure; Circadian Rhythm; Data Mining; Endocrine System; Heart Rate; Humans; Hydrocortisone; Metabolomics; Stress, Physiological; Stress, Psychological
PubMed: 25560699
DOI: 10.5483/bmbrep.2015.48.4.275 -
Frontiers in Endocrinology 2021Cyclic Cushing's syndrome (also known as intermittent or periodic) is a disease characterized by periods of transient hypercortisolemia shifting into periods of normo-... (Review)
Review
Cyclic Cushing's syndrome (also known as intermittent or periodic) is a disease characterized by periods of transient hypercortisolemia shifting into periods of normo- and/or hypocortisolemia. Diagnosis of cyclic Cushing's syndrome is based on at least three periods of confirmed hypercortisolemia interspersed by two periods of normocortisolemia. Cyclic Cushing's syndrome is one of the greatest challenges in modern endocrinology due to its diverse clinical picture, unpredictable duration and frequency of phases, and various etiologies. We discuss a diagnostic algorithm for periodic hypercortisolemia with special regard to hair cortisol analysis and desmopressin stimulation test which both seem to be helpful in finding the correct answer.
Topics: Animals; Cushing Syndrome; Hair; Humans; Hydrocortisone
PubMed: 33967962
DOI: 10.3389/fendo.2021.658429 -
Physical Therapy Dec 2014Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to...
Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to facilitate treatment, prevent chronic disability, and improve quality of life.
Topics: Adaptation, Psychological; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pain; Pituitary-Adrenal System; Stress, Physiological; Stress, Psychological
PubMed: 25035267
DOI: 10.2522/ptj.20130597 -
Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal).Journal of Veterinary Internal Medicine 2013This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on...
This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on the history and physical examination. Endocrine tests should be performed only when clinical signs consistent with HAC are present. None of the biochemical screening or differentiating tests for hyperadrenocorticism are perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has heightened over time. Thus, case presentation is more subtle. Due to the changes in manifestations as well as test technology the Panel believes that references ranges should be reestablished. The role of cortisol precursors and sex hormones in causing a syndrome of occult hyperadrenocorticism remains unclear.
Topics: Adrenocortical Hyperfunction; Animals; Consensus; Dog Diseases; Dogs; Female; Hydrocortisone; Male
PubMed: 24112317
DOI: 10.1111/jvim.12192 -
Endocrinology and Metabolism (Seoul,... Aug 2022Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose.... (Review)
Review
Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose. Comprehensive assays have been developed to determine the levels of bioactive free cortisol and their clinical and analytical efficacies have been extensively discussed because the level of total cortisol is affected by changes in the structure or circulating levels of corticoid-binding globulin and albumin, which are the main reservoirs of cortisol in the human body. Antibody-based immunoassays are routinely used in clinical laboratories; however, the lack of molecular specificity in cortisol assessment limits their applicability to characterize adrenocortical function. Improved specificity and sensitivity can be achieved by mass spectrometry coupled with chromatographic separation methods, which is a cutting-edge technology to measure individual as well as a panel of steroids in a single analytical run. The purpose of this review is to introduce recent advances in free cortisol measurement from the perspectives of clinical specimens and issues associated with prospective analytical technologies.
Topics: Adrenal Insufficiency; Humans; Hydrocortisone; Prospective Studies; Saliva
PubMed: 35982612
DOI: 10.3803/EnM.2022.1549 -
The Journal of Clinical Endocrinology... May 2008The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.
OBJECTIVE
The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.
PARTICIPANTS
The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.
CONSENSUS PROCESS
Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments.
CONCLUSIONS
After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.
Topics: Cushing Syndrome; Dexamethasone; Evidence-Based Medicine; Humans; Hydrocortisone; Saliva
PubMed: 18334580
DOI: 10.1210/jc.2008-0125 -
Epigenomics Dec 2022To describe exon-1 methylation and cortisol levels in newborns. Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5,...
To describe exon-1 methylation and cortisol levels in newborns. Preterm ≤1500 g and full-term infants were included. Samples were collected at birth and at days 5, 30 and 90 (or at discharge). 46 preterm and 49 full-term infants were included. Methylation was stable over time in full-term infants (p = 0.3116) but decreased in preterm infants (p = 0.0241). Preterm infants had higher cortisol levels on the fifth day, while full-term infants showed increasing levels (p = 0.0177) over time. Hypermethylated sites in at birth and higher cortisol levels on day 5 suggest that prematurity, reflecting prenatal stress, affects the epigenome. Methylation decrease over time in preterm infants suggests that postnatal factors may modify the epigenome, but their role needs to be clarified.
Topics: Female; Humans; Infant; Infant, Newborn; Pregnancy; DNA Methylation; Epigenesis, Genetic; Hydrocortisone; Infant, Premature; Receptors, Glucocorticoid
PubMed: 36861354
DOI: 10.2217/epi-2022-0444