From the Guidelines
Glucocorticoids play a crucial role in regulating the body's stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis, and their administration should be based on the patient's current daily dose rather than supra-physiologic "stress dosing" to minimize risks of hemodynamic instability and infection. When considering the role of glucocorticoids in stress response regulation, it's essential to understand their mechanism of action. Glucocorticoids, such as cortisol, are produced by the adrenal cortex in response to adrenocorticotropic hormone (ACTH) released by the pituitary gland, which is itself stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus 1. This cascade is triggered by the detection of a stressor, leading to the mobilization of energy resources, reduction of inflammation, and suppression of non-essential functions to prepare the body for a "fight or flight" response.
Key aspects of glucocorticoid function in stress response include:
- Mobilizing energy resources through gluconeogenesis and the breakdown of proteins and fats
- Reducing inflammation
- Suppressing non-essential functions like reproduction and growth
- Enhancing cardiovascular function
- Providing negative feedback to the hypothalamus and pituitary to terminate the stress response once the threat has passed
The administration of glucocorticoids, especially in patients undergoing surgery, such as total hip or total knee arthroplasty, should be guided by evidence-based recommendations. According to the 2017 American College of Rheumatology guideline 1, patients with rheumatic diseases like RA, SpA, AS, PsA, or SLE who are already on glucocorticoids should continue their current daily dose rather than receiving supra-physiologic "stress doses" to avoid unnecessary risks. This approach is supported by low-quality RCT evidence and observational trials that suggest no significant hemodynamic difference between continuing the current daily glucocorticoid dose and administering "stress-dose steroids" 1.
In the context of infection risk, the guideline also considers the threshold for immunosuppression, which is defined by the Centers for Disease Control and Prevention as 20 mg/day of prednisone for at least 2 weeks 1. Therefore, when managing patients on glucocorticoids, especially those with rheumatic diseases, it's crucial to balance the benefits of glucocorticoid therapy in regulating stress response with the potential risks, such as hemodynamic instability and infection, by adhering to evidence-based guidelines and individualizing patient care.
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. Key points are:
- Glucocorticoids are used for replacement therapy in adrenocortical deficiency states.
- They have anti-inflammatory effects and cause metabolic effects.
- They modify the body's immune responses. However, the labels do not explicitly describe the role of glucocorticoids in regulating stress response. 2 3
From the Research
Glucocorticoids and Stress Response
- Glucocorticoids play a crucial role in regulating the stress response, with their signaling being fundamental in healthy stress coping and in the pathophysiology of stress-related diseases 4.
- The surge in glucocorticoid hormone secretion after stress needs to be tightly controlled, with characteristics like peak height, curvature, and duration depending on the nature and severity of the challenge 5.
- Glucocorticoids help in regulating stress response by:
- Enhancing the organism's resistance to stress 6
- Modulating the actions of numerous intercellular mediators, including established hormones, prostaglandins, and other arachidonic acid metabolites 6
- Suppressing the body's normal reactions to stress, preventing those reactions from overshooting and themselves threatening homeostasis 6
- Permitting, stimulating, or suppressing an ongoing stress-response, or being preparative for a subsequent stressor 7
Mechanisms of Glucocorticoid Action
- Glucocorticoids interact closely with other biomolecules, such as inflammatory cytokines, monoamines, and some monoamine-metabolizing enzymes 4.
- The activity of enzymes involved in glucocorticoid metabolism, such as cytochrome P450 (CYP) and 11-β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 2 (11βHSD2), plays a crucial role in regulating glucocorticoid effects 4.
- Glucocorticoids also regulate glucose homeostasis by promoting gluconeogenesis in liver, decreasing glucose uptake and utilization in skeletal muscle and white adipose tissue, and modulating the function of pancreatic α and β cells 8.
Importance of Glucocorticoid Regulation
- Proper glucocorticoid responses to stress are critical for adaptation, and the tight control of baseline and stress-evoked glucocorticoid secretion are important constituents of an organism's resilience 5.
- Dysregulation of glucocorticoid metabolism and signaling can contribute to the development and course of stress-related diseases, such as post-traumatic stress disorder (PTSD) and other stress-related disorders 4, 5.