What are the causes of postoperative adrenal insufficiency?

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From the Guidelines

Post-operative adrenal insufficiency is most commonly caused by the abrupt discontinuation of long-term exogenous corticosteroid therapy, which suppresses the hypothalamic-pituitary-adrenal (HPA) axis, as well as other factors such as direct surgical manipulation of the adrenal glands, severe stress from major surgery, and certain medications like etomidate. The causes of post-operative adrenal insufficiency can be categorized into several key areas, including:

  • Abrupt discontinuation of long-term exogenous corticosteroid therapy, such as prednisone, dexamethasone, or hydrocortisone, which can suppress the HPA axis 1
  • Direct surgical manipulation of the adrenal glands, such as during adrenalectomy, or pituitary surgery that damages ACTH production 1
  • Severe stress from major surgery, which can unmask previously undiagnosed adrenal insufficiency 1
  • Bilateral adrenal hemorrhage, which can occur in critically ill post-operative patients, especially those on anticoagulants, and can rapidly destroy adrenal function 1
  • Medications like etomidate, an induction agent, which can temporarily inhibit cortisol synthesis 1
  • Patients with sepsis or critical illness, who may develop critical illness-related corticosteroid insufficiency 1

The management of post-operative adrenal insufficiency typically involves stress-dose steroids, such as hydrocortisone 100mg IV every 8 hours, with gradual taper based on clinical response, along with treating the underlying cause when possible 1. It is essential to identify patients at risk of adrenal insufficiency and provide adequate glucocorticoid supplementation during the peri-operative period to prevent adrenal crisis 1.

From the FDA Drug Label

Corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted

The causes of postoperative adrenal insufficiency include:

  • HPA axis suppression due to corticosteroid use
  • Drug-induced secondary adrenocortical insufficiency Key factors that contribute to this condition are:
  • Sudden withdrawal of treatment
  • Inadequate gradual reduction of dosage
  • Stress occurring after discontinuation of therapy 2

From the Research

Causes of Postoperative Adrenal Insufficiency

  • Adrenal dysfunction can occur in high-risk postoperative patients, particularly those requiring vasopressor therapy after adequate volume resuscitation 3
  • Surgical trauma can induce overwhelming inflammatory responses, leading to sepsis and organ dysfunction, which can cause postoperative relative adrenal insufficiency 4
  • The use of exogenous glucocorticoid therapy can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to tertiary adrenal insufficiency 5
  • Autoimmune adrenalitis, the most common cause of primary adrenal insufficiency, may be associated with other autoimmune disorders 5
  • Hypothalamic or pituitary pathology can also lead to secondary adrenal insufficiency 5

Risk Factors

  • Age > 55 years 3
  • Postoperative hypotension requiring vasopressors 3
  • Major surgical trauma 4
  • Use of exogenous glucocorticoid therapy 5
  • Autoimmune disorders 5

Clinical Presentation

  • Chronic fatigue, weight loss, and vulnerability to infection 5
  • Inability to cope with acute illness or infection, which can precipitate life-threatening adrenal crisis 5
  • Postoperative complications, such as systemic inflammatory response syndrome (SIRS) and organ dysfunction 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Surgical trauma-induced adrenal insufficiency is associated with postoperative inflammatory responses.

Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 2007

Research

Adrenal insufficiency: Physiology, clinical presentation and diagnostic challenges.

Clinica chimica acta; international journal of clinical chemistry, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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