How should I acutely treat an adult with primary adrenal insufficiency presenting in adrenal crisis?

Acute Management of Adrenal Crisis in Adults with Primary Adrenal Insufficiency

Immediately administer hydrocortisone 100 mg IV bolus and begin rapid infusion of 0.9% isotonic saline at 1 liter over the first hour—treatment must never be delayed for diagnostic confirmation. 1, 2, 3

Immediate Emergency Management (First Hour)

Glucocorticoid Administration:

• Give hydrocortisone 100 mg IV bolus immediately upon clinical suspicion 1, 2, 3
• This high dose saturates 11β-hydroxysteroid dehydrogenase type 2, providing both glucocorticoid and essential mineralocorticoid activity 2, 3
• If IV access cannot be rapidly established, administer hydrocortisone 100 mg IM as an acceptable backup 3, 4

Fluid Resuscitation:

• Initiate aggressive volume expansion with 0.9% isotonic saline at 1 liter over the first hour 1, 2, 3
• This addresses the severe volume depletion and hypotension that characterize adrenal crisis 2, 3

Laboratory Workup (Do Not Delay Treatment):

• Draw blood for serum cortisol, plasma ACTH, electrolytes (sodium, potassium), creatinine, urea, and glucose before administering hydrocortisone if feasible 2, 3
• Critical caveat: Never postpone treatment while awaiting laboratory results—mortality increases with delayed intervention 1, 3
• Obtain blood cultures and infection workup, as infections are the most common precipitant 3

Ongoing Management (First 24-48 Hours)

Continued Glucocorticoid Therapy:

• Administer hydrocortisone 200 mg per 24 hours as continuous IV infusion (preferred method) 2, 3, 5
• Alternative regimen: hydrocortisone 50 mg IV or IM every 6 hours (total 200 mg/day) if continuous infusion is not feasible 1, 3
• Evidence note: A 2020 pharmacokinetic study demonstrated that continuous IV infusion is superior to intermittent bolus administration for maintaining cortisol concentrations in the range observed during major stress 5

Fluid Management:

• Continue isotonic saline infusion at a slower rate, delivering a total of 3-4 liters over 24-48 hours 2, 3, 6
• Monitor hemodynamics frequently (blood pressure, heart rate) to prevent fluid overload 2, 3
• Check serum electrolytes frequently to guide fluid management 3

Supportive Care:

• Provide gastric stress ulcer prophylaxis 2, 3
• Consider low-dose heparin for DVT prophylaxis depending on severity of illness 3
• Treat any precipitating infections promptly with appropriate antimicrobial therapy 3
• Monitor blood glucose frequently, especially in pediatric patients who are more vulnerable to hypoglycemia 3

Critical Care Considerations:

• Admit patients with persistent hypotension, shock, or end-organ dysfunction to ICU or high-dependency unit 2, 3

Important Clinical Pitfalls to Avoid

Do Not Add Separate Mineralocorticoid During Acute Crisis:

• High-dose hydrocortisone (≥50 mg per day) provides adequate mineralocorticoid activity 3
• Fludrocortisone should only be restarted when hydrocortisone dose falls below 50 mg per day during the taper 3

Do Not Use Dexamethasone:

• Dexamethasone lacks mineralocorticoid activity and is inadequate for primary adrenal insufficiency 3

Do Not Attribute Persistent Fever Solely to Infection:

• Persistent pyrexia may be due to adrenal insufficiency itself, not just sepsis 3
• Steroid supplementation should not be reduced while the patient remains febrile 3

Transition to Maintenance Therapy

Tapering Strategy:

• Taper parenteral glucocorticoids over 1-3 days to oral therapy once the precipitating illness permits and patient can tolerate oral medications 2, 3, 6
• Resume oral hydrocortisone at double the usual dose for 48 hours after uncomplicated recovery 2
• Reintroduce fludrocortisone 50-200 μg once daily when hydrocortisone dose falls below 50 mg per day 3, 6

Standard Maintenance Dosing:

• Hydrocortisone 15-25 mg daily divided into 2-3 doses (e.g., 10 mg morning, 5 mg midday, 2.5 mg afternoon) 6, 7
• Fludrocortisone 0.05-0.3 mg daily for primary adrenal insufficiency 6, 7

Common Precipitating Factors to Investigate

The most frequent triggers for adrenal crisis include:

• Gastrointestinal illness with vomiting/diarrhea (most common) 3, 6, 8
• Any type of infection 3, 6, 8
• Surgical procedures without adequate steroid coverage 3, 6
• Physical trauma or injuries 3, 6
• Medication non-compliance or inadequate dose adjustment during illness 3, 8
• Myocardial infarction and severe allergic reactions 3

Prevention of Future Crises

Patient Education:

• Teach "sick day rules": double or triple oral glucocorticoid doses during minor illness 2, 3
• Prescribe emergency injectable hydrocortisone 100 mg IM and train patients/families on self-injection technique 2, 3, 7
• Ensure patients wear medical alert identification jewelry and carry a steroid emergency card 1, 6

Evaluate Recurrent Crises:

• Assess for chronic under-replacement with fludrocortisone combined with low salt consumption 3
• Investigate poor medication compliance and underlying psychiatric disorders 3
• Consider medications that accelerate cortisol clearance requiring dose adjustment 3

Critical mortality data: Despite available treatments, adrenal crisis carries a mortality rate of 0.5 per 100 patient-years, making prevention through education paramount 8