From the Guidelines
Glucocorticoids play a crucial role in regulating the body's stress response by modulating the hypothalamic-pituitary-adrenal (HPA) axis, and their administration should be tailored to the individual's specific needs, rather than relying on "stress dosing" in patients with rheumatic conditions undergoing surgery, as evidenced by the 2017 American College of Rheumatology guideline 1. The HPA axis is activated in response to stress, leading to the release of adrenocorticotropic hormone (ACTH) and subsequent production of cortisol, which prepares the body to handle stress by increasing blood glucose levels, suppressing non-essential immune functions, and mobilizing energy stores.
- Key aspects of glucocorticoid regulation of stress response include:
- Increasing blood glucose levels through gluconeogenesis
- Suppressing non-essential immune functions
- Reducing inflammation
- Mobilizing energy stores from fat and protein
- Enhancing cardiovascular function by increasing blood pressure and heart rate The use of glucocorticoids in regulating stress response is supported by the 2017 American College of Rheumatology guideline, which recommends continuing the current daily dose of glucocorticoids in adult patients with rheumatic conditions undergoing surgery, rather than administering perioperative supra-physiologic glucocorticoid doses 1.
- This approach is based on low-quality RCT evidence and observational trials, which suggest that there is no significant hemodynamic difference between patients given their current daily glucocorticoid dose and those receiving "stress-dose steroids" 1. It is essential to consider the individual's specific needs and the potential risks associated with glucocorticoid use, such as infection risk, which is a concern in patients receiving glucocorticoids at doses of 20 mg/day of prednisone or equivalent for at least 2 weeks 1.
From the FDA Drug Label
Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.
The answer to how glucocorticoids help in regulating stress response is not directly addressed in the provided drug labels. The FDA drug label does not answer the question.
From the Research
Role of Glucocorticoids in Stress Response
Glucocorticoids play a crucial role in regulating the stress response, and their effects can be categorized into several actions:
- Permissive actions: allowing other facets of the stress response to emerge efficaciously 2
- Suppressive actions: preventing the stress response from being pathologically overactivated 3, 2
- Stimulatory actions: actively stimulating the stress response 2
- Preparative actions: preparing the body for a subsequent stressor 2
Mechanisms of Glucocorticoid Action
The mechanisms of glucocorticoid action in stress response involve:
- Modulation of intercellular mediators, including hormones, prostaglandins, and bioactive peptides 3
- Regulation of glucose homeostasis, including promotion of gluconeogenesis and inhibition of glucose uptake and utilization 4
- Regulation of glycogen metabolism, including increase of glycogen storage in liver and permissive role for catecholamine-induced glycogenolysis in skeletal muscle 4
- Modulation of the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin 4
Effects of Glucocorticoids on Stress-Related Disorders
Glucocorticoids have been implicated in the development and course of stress-related disorders, including:
- Post-traumatic stress disorder (PTSD) 5, 6
- Depression and anxiety disorders 6
- Coronary heart diseases and systemic chronic inflammatory diseases 6
- The role of inflammation in these disorders is complex, and decreased glucocorticoid signaling and/or levels may lead to unchecked inflammatory reactions 6
Glucocorticoid Metabolism and Signaling
Glucocorticoid metabolism and signaling involve:
- Metabolism by cytochrome P450 (CYP) and 11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2) 5
- Interaction with other biomolecules, including inflammatory cytokines, monoamines, and monoamine-metabolizing enzymes 5
- Dynamic cross-talk between glucocorticoids, monoamines, and their metabolizing enzymes, which may contribute to the development and course of stress-related disorders 5