When should stress dose steroids be used in patients at risk of adrenal insufficiency?

When to Use Stress Dose Steroids

Stress dose steroids should be administered to patients with known or suspected adrenal insufficiency during periods of physiological stress, including surgery, trauma, critical illness, and severe medical conditions to prevent potentially life-threatening adrenal crisis.

Identifying Patients at Risk

Patients who require stress dose steroids include:

• Primary adrenal insufficiency (Addison's disease)
• Secondary adrenal insufficiency due to:
  • Pituitary disease/hypophysitis
  • Long-term exogenous steroid use (prednisolone ≥5 mg daily or equivalent)
  • Recent withdrawal from chronic steroid therapy (within past year)
• Patients on immune checkpoint inhibitors with adrenal insufficiency 1

Stress Dose Steroid Protocols

Minor Stress (e.g., minor illness with fever, minor procedures)

• Double the usual maintenance dose of oral glucocorticoids
• No additional mineralocorticoid required
• Return to normal dosing when stress resolves (usually within 2-3 days)

Moderate Stress (e.g., moderate illness, outpatient procedures)

• Hydrocortisone 30-50 mg total daily dose (or prednisone 20 mg daily) 1
• Continue maintenance mineralocorticoid if applicable
• Taper to maintenance dose after 2 days

Severe Stress (e.g., major surgery, trauma, critical illness)

• Intravenous hydrocortisone 100 mg at induction of anesthesia/onset of stress 1
• Followed by continuous IV infusion of hydrocortisone 200 mg over 24 hours 1, 2
• Continue until patient can take oral medications, then taper to maintenance dose over 5-7 days 1
• Maintain normal saline hydration (at least 2L) 1

Specific Clinical Scenarios

Surgery

• Major surgery: Follow severe stress protocol above
• Minor surgery under local anesthesia: Routine dentistry and minor procedures generally do not require supplementation 3
• Day case surgery: Can proceed with appropriate coverage, ensure adequate recovery before discharge 1

Labor and Delivery

• Hydrocortisone 100 mg IV at onset of active labor
• Followed by continuous infusion or 50 mg IM every 6 hours until after delivery 1

Intensive Endurance Exercise

• Consider supplemental glucocorticoids and mineralocorticoids before intensive endurance events 4

Immune-Related Adverse Events (irAEs)

For patients on immune checkpoint inhibitors:

• Grade 1-2 symptoms: Consider holding immunotherapy until stabilized on replacement hormones 1
• Grade 3-4 symptoms: Hold immunotherapy, provide IV stress dose steroids, and hospitalize if necessary 1

Administration Considerations

• Preferred route in severe stress: Continuous IV infusion provides the most stable cortisol levels and best mimics physiologic stress response 2
• Alternative routes when IV infusion not available: IM injection or IV bolus every 6 hours 1
• Dexamethasone is inadequate for primary adrenal insufficiency as it lacks mineralocorticoid activity 1
• Always start corticosteroids before thyroid hormone replacement to avoid precipitating adrenal crisis 1

Common Pitfalls and Caveats

1. Failure to recognize adrenal insufficiency - Watch for unexplained hypotension, hyponatremia, hyperkalemia, and hypoglycemia
2. Inadequate stress dosing - Err on the side of higher doses during acute stress
3. Premature discontinuation - Continue stress dosing until stress resolves completely
4. Omitting patient education - All patients should:
   • Carry a steroid emergency card/medical alert bracelet
   • Understand "sick day rules" for self-adjusting doses
   • Have emergency injectable hydrocortisone available
5. Forgetting mineralocorticoid replacement - Patients with primary adrenal insufficiency require fludrocortisone (0.05-0.1 mg daily) 1
6. Drug interactions - Be cautious with medications that may affect steroid metabolism (CYP3A4 inducers) 1

Remember that short-term high-dose steroid administration carries minimal risk compared to the potentially fatal consequences of adrenal crisis. When in doubt, administer stress dose steroids, as there are no significant adverse consequences from short-term coverage 1.