What are the management strategies for patients at risk of Hypothalamic-Pituitary-Adrenal (HPA) axis suppression, particularly those taking long-term corticosteroids like prednisone?

Management of HPA Axis Suppression in Patients on Long-Term Corticosteroids

Patients taking prednisolone ≥5 mg daily (or equivalent) for ≥1 month are at significant risk for HPA axis suppression and require stress-dose corticosteroid coverage during surgery, severe illness, or major physiological stress to prevent potentially fatal adrenal crisis. 1, 2

Identifying At-Risk Patients

Risk threshold criteria:

• Adults: Prednisolone ≥5 mg daily for ≥4 weeks places approximately 50% at risk for biochemical adrenal insufficiency 2, 3
• Children: Hydrocortisone-equivalent dose of 10-15 mg/m² daily for ≥1 month 1
• All routes of administration (oral, inhaled, topical, intranasal, intra-articular) can cause clinically significant HPA suppression, not just systemic therapy 1, 2, 3

Critical timing consideration: HPA suppression can persist up to 12 months after discontinuation of chronic corticosteroid therapy, requiring stress-dose coverage throughout this entire recovery period 2, 4

Perioperative Stress-Dose Management

For major surgery in adults with confirmed or suspected HPA suppression:

• At induction: Hydrocortisone 100 mg IV bolus 1, 2
• Maintenance: Continuous infusion of hydrocortisone 200 mg/24 hours (preferred for safety) OR 50-100 mg IV every 6-8 hours 1, 2
• Duration: Continue until patient can take double their usual oral dose, typically 24-48 hours for uncomplicated surgery 1
• Taper: Reduce to maintenance dose over 5-10 days for major/complicated procedures 1

For children undergoing major surgery:

• Hydrocortisone 2 mg/kg IV at induction, followed by continuous infusion or four-hourly boluses 1, 2
• Monitor blood glucose frequently as children are more vulnerable to glycemic instability 1

Important caveat: Recent evidence suggests that hemodynamically stable patients continuing their usual corticosteroid dosage may not require routine "push-dose" steroids, but if unexplained fluid-unresponsive hypotension occurs perioperatively, immediately administer hydrocortisone 100 mg IV push 2

Management During Acute Illness or Non-Surgical Stress

For minor illness (fever, URI, gastroenteritis):

• Double the usual oral hydrocortisone dose for 24-48 hours, then taper back to baseline 2

For severe illness or major stress (high fever, vomiting, trauma):

• Hydrocortisone 100 mg IM/IV immediately 2
• Follow with 50-100 mg every 6-8 hours until recovered 2
• Critical: Provide rapid IV fluid resuscitation alongside corticosteroid administration—inadequate fluid resuscitation is a frequent error in crisis management 2

When in doubt, give corticosteroids: There are no long-term adverse consequences of short-term glucocorticoid administration, but untreated adrenal crisis carries significant mortality risk 1, 2

Tapering Chronic Glucocorticoid Therapy

Gradual dose reduction is mandatory to allow HPA axis recovery:

• Reduce in small increments at appropriate intervals until reaching the lowest effective dose 2
• Patients receiving corticosteroids >14 days are particularly likely to benefit from tapering and HPA axis evaluation 2
• Do not abruptly discontinue prednisolone due to risk of adrenal crisis 3
• Tapering too quickly before clinical stabilization increases adrenal crisis risk 2

FDA warning: Adrenocortical insufficiency may result from too rapid withdrawal and this relative insufficiency may persist for up to 12 months after discontinuation; hormone therapy must be reinstituted during any stressful situation in this period 4

Alternative-day dosing consideration: Alternate-day prednisolone does NOT eliminate the risk of adrenal suppression, though it may reduce it 3, 4

Ongoing Monitoring and Patient Safety Measures

Mandatory patient safety interventions:

• Medical alert bracelet indicating adrenal insufficiency 2
• Emergency injectable hydrocortisone kit with training on self-administration 2
• Stress dosing education: Patients must know to double their dose during minor illness, use emergency injection if vomiting/unable to take oral medication, and seek immediate medical attention for severe illness, trauma, or surgery 5

Follow-up: Reassess 2-4 weeks after initiating replacement therapy 2

Monitor for signs of adrenal insufficiency: Hypotension (particularly postural), weight loss, fatigue, nausea, hypoglycemia, and electrolyte abnormalities (hyponatremia, hyperkalemia) 5

Special Populations and Route-Specific Considerations

Inhaled corticosteroids:

• Can cause dose-dependent HPA suppression 1, 3
• High-dose inhaled corticosteroids (≥1500 mcg beclomethasone equivalent daily) cause HPA suppression in approximately 20% of patients, particularly with prolonged use 6
• Fluticasone propionate causes 4.4 times more HPA suppression per microgram than flunisolide 7

Topical corticosteroids:

• Physiologic adrenal suppression can occur as early as 1-2 weeks with class I-IV topical corticosteroids 8
• Pathologic adrenal suppression is extremely rare when used within safety guidelines 8

Primary vs. secondary adrenal insufficiency:

• Dexamethasone is NOT adequate for primary adrenal insufficiency as it lacks mineralocorticoid activity 1
• Primary adrenal insufficiency requires both glucocorticoid and mineralocorticoid (fludrocortisone) replacement 5

Common Pitfalls to Avoid

Critical errors in management:

• Do not test HPA axis function while patients are still taking prednisolone—this yields false results 3
• Do not assume HPA axis recovery after only one week off steroids—recovery typically takes months 5
• Do not forget mineralocorticoid replacement (fludrocortisone) if treating primary adrenal insufficiency 5
• Do not rely on HPA axis testing to guide perioperative treatment decisions—testing does not predict perioperative hypotension or clinical manifestations 2
• Account for all glucocorticoid sources—patients may be using over-the-counter or prescribed corticosteroids from multiple sources (topical, inhaled, etc.) with additive suppressive effects 3

Risk factors for HPA suppression:

• Previous requirement for long-term systemic corticosteroids 6
• Increasing duration of high-dose therapy 6
• Doses ≥20 mg/day prednisone equivalent for ≥3 weeks 2