How to treat Hypothalamic-Pituitary-Adrenal (HPA) axis suppression?

Treatment of HPA Axis Suppression

For patients with established HPA axis suppression, the cornerstone of management is physiologic glucocorticoid replacement with hydrocortisone, typically 15-25 mg daily in divided doses (mimicking diurnal rhythm with higher morning doses), combined with stress-dose protocols during illness or surgery, patient education on emergency management, and medical alert identification. 1

Identifying Patients Requiring Treatment

• Patients taking daily prednisolone ≥5 mg (or equivalent) for ≥4 weeks are at high risk, with approximately 50% developing biochemical adrenal insufficiency requiring intervention 1
• Any glucocorticoid dose ≥20 mg/day prednisone equivalent for ≥3 weeks warrants consideration of HPA suppression 2, 1
• All routes of administration (oral, inhaled, topical, intranasal, intra-articular) can cause clinically significant HPA suppression requiring treatment 1, 3, 4, 5
• HPA suppression can persist up to 12 months after discontinuation of chronic glucocorticoid therapy, requiring ongoing stress-dose coverage during this entire period 1, 6

Acute Management: Suspected Adrenal Crisis

When adrenal crisis is suspected, immediate treatment takes precedence over diagnostic confirmation:

• Administer hydrocortisone 100 mg IV bolus immediately, followed by 50-100 mg IV every 6-8 hours 1, 7
• Initiate aggressive fluid resuscitation with 3-4 L of isotonic saline or 5% dextrose in isotonic saline at approximately 1 L/hour initially 7
• For children undergoing major surgery, give hydrocortisone 2 mg/kg IV at induction followed by continuous infusion 1
• Clinical diagnosis should take precedence over laboratory confirmation—do not delay treatment while waiting for test results 7

Perioperative Stress-Dose Management

For patients on chronic steroids or with steroid use in the past year undergoing major surgery:

• Hydrocortisone 100 mg IV at induction, followed by 50-100 mg IV every 6-8 hours for 24-48 hours, then taper to maintenance dose over 5-10 days 1
• Recent evidence suggests that patients continuing their usual dosage may not require routine "push-dose" steroids if they remain hemodynamically stable 2, 1
• However, in the event of unexplained fluid-unresponsive hypotension immediately prior/during/after surgery, administer 100 mg hydrocortisone IV push immediately 2

Important caveat: While some centers have moved away from routine stress dosing, the risk of adrenal crisis carries significant mortality, and stress-dose administration appears to carry minimal risk compared to the consequences of untreated adrenal insufficiency 2

Management During Acute Illness or Physiologic Stress

Severity-based approach:

• Minor illness (fever, URI): Double the usual oral hydrocortisone dose for 24-48 hours, then taper back to baseline 1
• Moderate illness (stable vital signs but concerning symptoms): Oral hydrocortisone at 2-3 times maintenance dose (typically 30-75 mg/day in divided doses) 7
• Severe illness or major stress: Hydrocortisone 100 mg IM/IV immediately, followed by 50-100 mg every 6-8 hours until recovered 1, 7

Tapering Glucocorticoid Therapy to Prevent/Minimize HPA Suppression

When discontinuing chronic glucocorticoid therapy:

• Gradual dose reduction in small increments at appropriate intervals until reaching the lowest effective dose 1, 6
• If the drug is to be stopped after long-term therapy, withdraw gradually rather than abruptly 6
• Adrenocortical insufficiency may result from too rapid withdrawal and may be minimized by gradual reduction 6
• For septic shock patients, taper steroids when vasopressors are no longer required 1

Critical pitfall: Tapering too quickly before clinical stabilization increases the risk of adrenal crisis 1

Ongoing Monitoring and Patient Safety Measures

Mandatory patient safety interventions:

• Medical alert bracelets indicating adrenal insufficiency are mandatory 1
• Emergency injectable hydrocortisone kits with training on self-administration 1
• Stress dosing education covering when to double or triple doses 1
• Follow-up in 2-4 weeks after initiating replacement therapy 1
• Monitor carefully for recurrence of inflammation and signs of adrenal insufficiency after stopping corticosteroids 2

Special Considerations and Common Pitfalls

Alternate-day dosing does NOT eliminate risk:

• Alternate-day prednisolone dosing does not eliminate the risk of adrenal suppression 1, 8
• Even single morning doses can carry suppressive effects into the following day when pharmacologic doses are used 6

Monitoring after discontinuation:

• Corticosteroid-induced adrenal suppression is duration-dependent; patients receiving longer courses (>14 days) are particularly likely to benefit from a taper and evaluation of HPA axis function 2
• Recovery time for normal HPA activity is variable depending upon dose and duration of treatment—during this time the patient is vulnerable to any stressful situation 6

Inadequate fluid resuscitation alongside corticosteroid administration is a frequent error in crisis management 1

Testing limitations:

• HPA axis testing does not directly predict the possibility of perioperative hypotension or clinical manifestation and therefore should not guide treatment decisions 2
• Testing for adrenal function should not be performed while patients are still taking prednisolone, as this can give false results 8