What is the management of acute adrenal insufficiency?

Acute Adrenal Insufficiency: Causes and Management

Immediate Emergency Management

Administer hydrocortisone 100 mg IV bolus immediately upon clinical suspicion—this is the single most critical intervention and must never be delayed for diagnostic confirmation. 1, 2, 3

First Hour Protocol

• Draw blood for cortisol, ACTH, electrolytes, creatinine, urea, and glucose before treatment begins, but do not wait for results to initiate therapy 1, 2
• Initiate aggressive fluid resuscitation with 0.9% isotonic saline at 1 liter over the first hour to address severe volume depletion 1, 2, 3
• Begin continuous monitoring of blood pressure, heart rate, and hemodynamic status 1, 2

Ongoing Acute Management (First 24-48 Hours)

• Continue hydrocortisone at 200 mg per 24 hours as continuous IV infusion, or alternatively 50 mg IV/IM every 6 hours 1, 2
• Maintain IV fluid resuscitation with 3-4 liters total of isotonic saline or 5% dextrose in isotonic saline over 24 hours, adjusting based on hemodynamic response 1, 3
• Monitor serum electrolytes frequently to guide fluid management and avoid complications 1, 3
• Do NOT add separate mineralocorticoid (fludrocortisone) during acute crisis—high-dose hydrocortisone (≥50 mg/day) provides adequate mineralocorticoid activity 1, 2

Critical Pitfall: Dexamethasone is inadequate for primary adrenal insufficiency as it completely lacks mineralocorticoid activity 1

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Common Causes and Precipitating Factors

Primary Adrenal Insufficiency (Addison's Disease)

• Autoimmune adrenalitis accounts for ~85% of cases in Western populations 3
• Adrenal hemorrhage or thrombosis, particularly in critically ill patients 4
• Infections including tuberculosis, fungal infections, and HIV-related opportunistic infections 5
• Congenital adrenal hyperplasia (most common in children) 6
• Pharmacological inhibition from high-dose azole antifungals or etomidate 5, 7
• Surgical removal of adrenal tissue 5

Secondary Adrenal Insufficiency

• Pituitary tumors, hemorrhage, or surgery affecting corticotropin production 5
• Inflammatory/infiltrative conditions including hypophysitis, sarcoidosis, and hemochromatosis 5
• Medications suppressing corticotropin production, particularly chronic opioid use 5

Glucocorticoid-Induced Adrenal Insufficiency

• Abrupt withdrawal or rapid taper of supraphysiological glucocorticoid doses 5
• Inadequate stress-dose coverage during illness or surgery in patients on chronic steroids 8, 1

Acute Crisis Precipitants in Known Adrenal Insufficiency

• Gastrointestinal illness with vomiting/diarrhea is the most common trigger—patients cannot absorb oral medication when they need it most 1, 2, 6
• Any infection (respiratory, urinary, systemic) 1, 2, 6
• Surgical procedures without adequate steroid coverage 1, 2
• Physical trauma, myocardial infarction, or severe allergic reactions 1, 2
• Failure to increase glucocorticoid doses during intercurrent illness despite patient education 1
• Chronic under-replacement with fludrocortisone combined with low salt intake 1
• Poor medication compliance, often related to underlying psychiatric disorders 1

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Clinical Recognition

Cardinal Presenting Features

• Severe hypotension (often <90/60 mmHg) with orthostatic changes appearing before supine hypotension 1, 3
• Shock and cardiovascular collapse in severe cases 1, 2
• Severe dehydration from volume depletion 1, 2
• Gastrointestinal symptoms: severe nausea, vomiting, abdominal pain 1, 2
• Neurological manifestations: confusion, altered mental status, or coma in severe cases 1, 2
• Hyperpigmentation of skin (only in primary adrenal insufficiency due to elevated ACTH) 1

Laboratory Findings

• Hyponatremia in ~90% of cases 1, 2
• Hyperkalemia in ~50% of cases (absence does not exclude crisis) 1, 2
• Hypoglycemia, especially in children 1, 2
• Elevated creatinine and BUN from prerenal azotemia 1, 2
• Serum cortisol <250 nmol/L (<10 mcg/dL) with markedly elevated ACTH in primary adrenal insufficiency 1, 3, 5

Clinical Pearl: Consider adrenal crisis in any patient with unexplained collapse, hypotension, vomiting, or diarrhea, especially with electrolyte abnormalities 1, 3

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Supportive Care and Monitoring

• Consider ICU or high-dependency unit admission for severe cases with persistent hypotension or end-organ dysfunction 1, 2
• Provide gastric stress ulcer prophylaxis during acute illness 1, 2
• Consider low-dose heparin for thromboprophylaxis depending on severity 1, 2
• Treat precipitating conditions with appropriate antimicrobial therapy if infection suspected 1, 2
• Monitor blood glucose frequently, especially in pediatric patients who are more vulnerable to hypoglycemia 1

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Transition to Maintenance Therapy

• Taper parenteral glucocorticoids over 1-3 days to oral therapy once the precipitating illness permits and patient can tolerate oral medications 1, 2
• Resume oral hydrocortisone at double the usual dose for 48 hours after uncomplicated recovery, or up to a week following major surgery 8, 1
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg per day, as lower doses no longer provide adequate mineralocorticoid effect 1
• Transition to maintenance hydrocortisone 15-25 mg daily divided into 2-3 doses, with preference for short-acting hydrocortisone over longer-acting agents 1, 5
• Add fludrocortisone 0.05-0.3 mg daily for patients with primary adrenal insufficiency 5, 4

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Pediatric-Specific Considerations

• Initial fluid bolus: 10-20 mL/kg (maximum 1,000 mL) normal saline for hypotension 1, 2
• Hydrocortisone dosing: 2 mg/kg IV at induction, followed by weight-based continuous infusion:
  • Up to 10 kg: 25 mg/24 hours
  • 11-20 kg: 50 mg/24 hours
  • Over 20 kg prepubertal: 100 mg/24 hours
  • Pubertal: 150 mg/24 hours 8
• More frequent blood glucose monitoring is essential as children are more vulnerable to hypoglycemia 1, 2

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Prevention of Future Crises

Patient Education (Paramount to Preventing Deaths)

• Teach "sick day rules": double or triple oral glucocorticoid doses during minor illness (fever, vomiting, diarrhea) 1, 2, 9
• Prescribe emergency injectable hydrocortisone 100 mg IM and train patients/families on self-injection technique 1, 2, 5, 9
• Provide medical alert jewelry and emergency steroid card indicating diagnosis and need for immediate hydrocortisone 1, 2, 3, 9
• Ensure adequate emergency supplies are always available 2, 3, 9

Stress-Dose Coverage

• Minor procedures under general anesthesia: hydrocortisone 100 mg IV at induction, then double oral doses for 24 hours 8
• Major surgery: hydrocortisone 100 mg IV at induction, followed by 200 mg/24 hours continuous infusion, then double oral doses for 48 hours 8
• Labor and vaginal delivery: hydrocortisone 100 mg IV at onset, followed by 200 mg/24 hours infusion or 50 mg IM every 6 hours 8

Follow-Up Care

• Evaluate precipitating causes after each crisis and review patient understanding of stress dosing 2
• Investigate chronic under-replacement with mineralocorticoid and low salt intake in recurrent cases 1
• Assess for poor compliance and underlying psychiatric disorders in patients with recurrent crises 1
• Schedule annual follow-up minimum to assess health, weight, blood pressure, and electrolytes 3

Critical Warning: Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies—this can trigger adrenal crisis 1