What is the feedback loop mechanism of the adrenal glands?

From the Guidelines

The adrenal feedback loop is a complex neuroendocrine system that regulates stress responses, immune function, and metabolism, and its disruption can lead to significant hormonal imbalances and health problems, particularly in patients with adrenal insufficiency, who are at risk of adrenal crisis and require stress doses of hydrocortisone during the peri-operative period, as recommended by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.

Key Points

• The hypothalamic-pituitary-adrenal (HPA) axis is a self-regulating mechanism that maintains appropriate cortisol levels throughout the day, with natural peaks in the morning and gradual decline toward evening, aligning with our circadian rhythm.
• Disruptions to this feedback loop can occur from chronic stress, medications like corticosteroids, or conditions such as Cushing's syndrome (excessive cortisol) or Addison's disease (insufficient cortisol), leading to significant hormonal imbalances and health problems.
• Patients taking physiological replacement doses of corticosteroids for either primary or secondary adrenal insufficiency are at significant risk of adrenal crisis and must be given stress doses of hydrocortisone during the peri-operative period, as recommended by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.
• The guidelines recommend that hydrocortisone 100 mg by intravenous (i.v.) injection should be given at induction of anaesthesia in adult patients with adrenal insufficiency from any cause, followed by a continuous infusion of hydrocortisone at 200 mg.24 h-1, until the patient can take double their usual oral glucocorticoid dose by mouth 1.

Management of Adrenal Insufficiency

• Patients with adrenal insufficiency require stress doses of hydrocortisone during the peri-operative period to prevent adrenal crisis, as recommended by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.
• The guidelines recommend that patients with a long-standing diagnosis of adrenal insufficiency are often well informed about their disease, and anaesthetists should enquire closely about the patient’s history of glucocorticoid self-management, any previous episodes of adrenal crisis, and how practised they are at medication adjustments for illness, injury, or postoperative recovery 1.
• Best practice is to collaborate as far as possible with the patient’s endocrinologist when planning scheduled surgery, and when caring for postoperative patients, as recommended by the guidelines from the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology UK 1.

From the Research

Adrenal Insufficiency and Feedback Loop

• Adrenal insufficiency is a condition where the adrenal glands do not produce adequate amounts of hormones, such as cortisol and aldosterone 2, 3.
• The feedback loop of the adrenal glands involves the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the production of cortisol and other hormones 4.
• In primary adrenal insufficiency, the adrenal glands are damaged, while in secondary adrenal insufficiency, the pituitary gland is affected, and in tertiary adrenal insufficiency, the HPA axis is suppressed by exogenous glucocorticoid therapy 4.

Glucocorticoid Replacement Therapy

• Glucocorticoid replacement therapy is the standard treatment for adrenal insufficiency, involving twice- or thrice-daily dosing with a glucocorticoid, such as hydrocortisone 2, 3.
• However, this treatment has been shown to have limitations, including increased morbidity and mortality, and a failure to replicate the natural circadian rhythm of cortisol release 3.
• New slow-release hydrocortisone formulations may help to improve the physiological cortisol plasma profile and reduce the impact of over-replacement on cardiovascular risk factors and glucose metabolism 2.

Adrenal Crisis and Prevention

• Adrenal crisis is a life-threatening emergency that can occur in patients with adrenal insufficiency, often precipitated by infections, physical stress, or forgetting to take glucocorticoid medication 5.
• Prevention of adrenal crisis involves patient education on stress dosing and parenteral glucocorticoid administration, as well as carrying a steroid dependency alert card and wearing a medical alert bracelet 5.
• Improved patient and clinician education, as well as measures to facilitate parenteral hydrocortisone self-administration, are central to the management of adrenal crisis 5.

Glucocorticoid-Induced Adrenal Insufficiency

• Glucocorticoid-induced adrenal insufficiency (GI-AI) can occur as a result of suppression of the HPA axis by exogenous glucocorticoid therapy 6.
• Factors affecting the risk of GI-AI include the duration and dose of glucocorticoid therapy, as well as individual susceptibility 6.
• A careful approach to glucocorticoid tapering and patient counseling are necessary to assure a successful taper and prevent GI-AI 6.