How is Hypothalamic-Pituitary (HP) axis suppression managed?

Management of Hypothalamic-Pituitary (HP) Axis Suppression

Patients with documented or suspected HPA axis suppression from glucocorticoid therapy require stress-dose hydrocortisone coverage during physiological stress (surgery, severe illness) and gradual tapering when discontinuing therapy, with the understanding that HPA suppression can persist up to 12 months after cessation. 1, 2, 3

Identifying Patients at Risk

Risk stratification is essential before implementing management strategies:

• Daily prednisolone ≥5 mg (or equivalent) for ≥4 weeks places adults at high risk for clinically significant HPA suppression, with approximately 50% developing biochemical adrenal insufficiency 2, 4
• Any glucocorticoid dose for ≥3 weeks at 20 mg/day prednisone equivalent warrants consideration of HPA suppression 1
• All routes of administration (oral, inhaled, topical, intranasal, intra-articular) can cause HPA suppression, not just systemic therapy 1, 2
• Children receiving chronic glucocorticoids are at particular risk, with adrenal insufficiency occurring in nearly all children immediately after cessation of ALL treatment protocols 5

Perioperative Management

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

Major Surgery Requiring General Anesthesia

• Adults: 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, 4
• Children: Hydrocortisone 2 mg/kg IV at induction, followed by continuous infusion: 25 mg/24h (up to 10 kg), 50 mg/24h (11-20 kg), 100 mg/24h (>20 kg prepubertal), or 150 mg/24h (pubertal) 1
• Tapering: Once stable, double usual oral doses for 48 hours, then reduce to normal doses over up to one week 1

Minor Procedures with General Anesthesia

• Children: Hydrocortisone 2 mg/kg IV/IM at induction, then double normal doses for 24 hours once enteral feeding established 1

Minor Procedures WITHOUT General Anesthesia

• Double the morning dose of hydrocortisone pre-operatively, then resume normal dosing 1

Critical caveat: The 2021 WSES guidelines note that recent evidence questions routine "push-dose" steroids for all patients, suggesting they may not be needed if patients continue their usual dosage 1. However, in the event of unexplained fluid-unresponsive hypotension perioperatively, administer hydrocortisone 100 mg IV immediately as adrenal crisis must be in the differential 1, 4

Management During Acute Illness or Stress

Stress dosing protocols based on illness severity:

Minor Illness (fever, URI, gastroenteritis)

• Double the usual oral hydrocortisone dose for 24-48 hours, then taper back to baseline 4

Severe Illness or Major Stress

• Hydrocortisone 100 mg IM/IV immediately, followed by 50-100 mg every 6-8 hours until recovered 4
• Rapid IV fluid resuscitation alongside corticosteroid administration 4

Adrenal Crisis Recognition and Treatment

• Immediate hydrocortisone 100 mg IV bolus upon recognition of crisis (hypotension, severe GI symptoms, cardiovascular collapse) 4
• Continue 50-100 mg IV every 6-8 hours for first 24-48 hours 4
• Aggressive fluid resuscitation with frequent vital sign monitoring 4

Tapering Glucocorticoid Therapy

When discontinuing chronic glucocorticoid therapy:

• Never stop abruptly due to risk of adrenal crisis 2, 3
• Gradual dose reduction in small increments at appropriate intervals until reaching the lowest effective dose 3
• For septic shock patients: Taper steroids when vasopressors are no longer required, though optimal duration remains unclear 1
• Recovery time for normal HPA activity is variable depending on dose and duration of treatment, with suppression potentially lasting up to 12 months 3, 2

Practical tapering approach from FDA labeling:

• Once disease control is established, either: (a) change to alternate-day therapy then gradually reduce the alternate-day dose, or (b) reduce daily dose to lowest effective level then switch to alternate-day schedule 3
• For patients on long-term daily steroids: Consider tripling or quadrupling the daily maintenance dose given every other day rather than just doubling if difficulty encountered 3

Ongoing Monitoring and Patient Safety

Essential safety measures for all patients with HPA suppression:

• Medical alert bracelet indicating adrenal insufficiency is mandatory 4, 6
• Emergency injectable hydrocortisone kit (100 mg IM) with training on self-administration 4, 6
• Stress dosing education: Patients must understand when to double/triple doses during illness 6
• Follow-up in 2-4 weeks after initiating replacement therapy to reassess symptoms and adjust medication 4
• Annual monitoring of weight, blood pressure, and serum electrolytes 4

Special Populations and Considerations

Septic Shock

• Do NOT use ACTH stimulation test to identify patients who should receive hydrocortisone in septic shock 1
• Continuous infusion preferred over repetitive bolus injections when using low-dose hydrocortisone 1
• Do NOT administer corticosteroids for sepsis in the absence of shock (unless history of steroid therapy or adrenal dysfunction) 1

Inhaled Corticosteroids

• Low/medium doses cause minimal HPA suppression with minimal risk of acute adrenal insufficiency 7
• Long-term high-dose inhaled steroids may result in significant suppression requiring supplementary systemic steroids during stress, especially if prior long-term systemic steroid use 7
• HPA suppression occurs at commonly prescribed doses in a dose-dependent manner 1

Topical Corticosteroids

• Infants have greater risk due to high absorption through diaper area 8
• Potent topical steroids (clobetasol propionate, diflucortolone valerate) can cause HPA suppression and Cushing's syndrome 8

Drug Interactions

• Fluconazole and similar antifungal drugs may prolong duration of adrenal insufficiency 5
• Etomidate for intubation suppresses the HPA axis and was associated with increased 28-day mortality in the CORTICUS trial 1

Common Pitfalls to Avoid

• Alternate-day dosing does NOT eliminate the risk of adrenal suppression 2
• Do NOT test adrenal function while patients are still taking glucocorticoids, as this gives false results 2
• Do NOT underestimate cumulative glucocorticoid exposure from multiple sources (topical, inhaled, oral, intra-articular) 2
• Inadequate fluid resuscitation alongside corticosteroid administration is a frequent error in crisis management 4
• Tapering too quickly before clinical stabilization increases risk of adrenal crisis 4
• HPA suppression can persist up to 12 months after discontinuation, requiring stress-dose coverage during this entire period 2, 3