How should I work up adrenal insufficiency from chronic prednisone use in a 63-year-old man with hypotension, hypoglycemia, and Crohn's disease treated with infliximab?

Workup of Glucocorticoid-Induced Adrenal Insufficiency in Acute Crisis

This patient is presenting with an adrenal crisis from glucocorticoid-induced adrenal insufficiency and requires immediate treatment with IV hydrocortisone 100 mg followed by continuous hydrocortisone replacement, not diagnostic workup—the diagnosis is already established by the clinical presentation and cortisol response to treatment. 1

Immediate Management (Priority Over Workup)

Since cortisol improved after administration at 30 minutes and 1 hour, this patient has already received appropriate acute treatment. The key now is:

• Continue stress-dose hydrocortisone: 100 mg IV bolus followed by 50 mg IV every 6 hours or 200 mg/24 hours continuous infusion until hemodynamically stable 2, 3
• Aggressive IV fluid resuscitation: 0.9% saline to correct hypotension and hypoglycemia 4
• Dextrose administration: For hypoglycemia correction
• Monitor electrolytes: Check for hyponatremia (common) and hyperkalemia 3

Diagnostic Workup (After Stabilization)

Initial Laboratory Assessment

The diagnostic workup should have been done before glucocorticoid administration, but since treatment was appropriately prioritized, obtain these when stable:

Morning (8 AM) baseline labs 2:

• Serum cortisol: Will be artificially elevated from treatment, but document baseline once off stress dosing
• ACTH (corticotropin): Expected to be low or low-normal in glucocorticoid-induced AI (distinguishes from primary AI where ACTH is elevated) 2
• DHEAS: Expected to be low or low-normal 2
• Electrolytes: Hyponatremia common; hyperkalemia suggests primary AI (unlikely here) 3

Key Diagnostic Considerations

Glucocorticoid-induced AI is diagnosed clinically in this case based on 1:

• Chronic prednisone use >3-4 weeks at supraphysiologic doses (>5 mg prednisone equivalent)
• Classic presentation: hypotension, hypoglycemia, and response to glucocorticoid administration
• The 2024 European/Endocrine Society guidelines define risk as doses >4-6 mg prednisone for >3-4 weeks 1

Do NOT perform ACTH stimulation testing acutely 2:

• Only indicated if morning cortisol is intermediate (5-10 µg/dL) after recovery
• Not needed when clinical diagnosis is clear
• Measure cortisol before and 60 minutes after cosyntropin 250 µg only if diagnostic uncertainty exists after acute phase

Special Considerations for This Patient

Crohn's Disease on Infliximab

Critical infection risk assessment 5:

• Infliximab increases infection risk, particularly in patients ≥65 years (this patient is 63)
• Screen for occult infections that may have precipitated the crisis:
  • Chest X-ray for pneumonia
  • Urinalysis and culture
  • Blood cultures if febrile
  • Consider tuberculosis screening if not previously done
• The combination of chronic glucocorticoids + infliximab significantly increases serious infection risk 5

Precipitating Factors to Investigate

Six patients in the European registry developed adrenal crisis from glucocorticoid dose reduction 1. Determine:

• Was prednisone recently tapered or stopped?
• Any intercurrent illness, surgery, or physical stress?
• Crohn's flare requiring increased metabolic demand?

Long-Term Management Plan

Transition to Maintenance Therapy

Once stable, transition to:

• Hydrocortisone 15-25 mg daily (divided doses: 10 mg morning, 5 mg afternoon, 5 mg evening) OR
• Prednisone 3-5 mg daily (single morning dose) 2

No mineralocorticoid replacement needed (fludrocortisone) since this is secondary/glucocorticoid-induced AI, not primary AI 2

Recovery Assessment

Recent 2026 data shows HPA axis recovery is driven by tapering itself 6:

• Each 1 mg prednisolone reduction increases cortisol by ~49 nmol/L
• 42% of patients who successfully discontinued had nadir morning cortisol <150 nmol/L
• Current guideline thresholds may be too conservative
• Structured, symptom-led tapering is safe even with very low cortisol values

Patient Education (Critical)

Provide immediately 2, 7:

• Injectable hydrocortisone 100 mg for home use
• Training for self/family administration
• Steroid emergency card
• Sick-day rules: Double or triple dose during illness, vomiting, surgery, dental procedures
• Instructions to seek emergency care if unable to take oral medications

Common Pitfalls to Avoid

1. Delaying treatment for diagnostic testing: Adrenal crisis is life-threatening; treat first, diagnose later 4, 3

2. Assuming low-dose or short-term steroids are safe: Even <5 mg prednisone for <4 weeks can suppress the HPA axis 8, 9

3. Stopping stress-dose steroids too quickly: Taper only after complete hemodynamic stability and resolution of precipitating illness

4. Forgetting infection screening in immunosuppressed patients: Infliximab + chronic steroids create high infection risk 5

5. Inadequate patient education: ~50% of AI patients experience adrenal crisis after diagnosis due to inadequate stress-dosing education 7

6. Over-reliance on ACTH stimulation testing: The 2026 study shows physiological dose tapering itself enables HPA recovery; routine Synacthen testing is not supported 6