What are the diagnostic criteria and immediate treatment for adrenal crisis?

Adrenal Crisis Diagnostic Criteria and Immediate Treatment

Adrenal crisis is a clinical diagnosis requiring immediate treatment with hydrocortisone 100 mg IV bolus and 0.9% saline 1 L over the first hour—never delay therapy for diagnostic confirmation. 1

Clinical Diagnostic Criteria

Cardinal Presenting Features

• Cardiovascular collapse: Severe hypotension (often <90/60 mmHg), shock, and profound dehydration are hallmark features requiring immediate recognition 1, 2
• Gastrointestinal symptoms: Severe nausea, vomiting, abdominal pain, and diarrhea occur in the majority of cases 1, 2
• Neurological manifestations: Altered mental status ranging from confusion and lethargy to obtundation and coma in severe cases 1, 3
• Constitutional symptoms: Profound malaise, fatigue, muscle pain/cramps, and weakness 1, 2

Laboratory Findings (Do Not Wait for Results)

• Hyponatremia: Present in approximately 90% of cases, though its absence does not exclude the diagnosis 1, 3
• Hyperkalemia: Found in only ~50% of patients—absence cannot rule out adrenal crisis 1, 3
• Hypoglycemia: More common in children but can occur in adults 1
• Elevated creatinine/BUN: Reflects prerenal azotemia from volume depletion 1, 3
• Serum cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH: Diagnostic of primary adrenal insufficiency in acute illness 1, 3

Critical Pitfall to Avoid

• Never rely on electrolyte abnormalities alone—10-20% of patients may have normal electrolytes or only mild abnormalities at presentation 1, 3

Immediate Emergency Treatment Protocol (First Hour)

Step 1: Simultaneous Glucocorticoid and Fluid Resuscitation

• Administer hydrocortisone 100 mg IV bolus immediately upon clinical suspicion—this dose saturates 11β-hydroxysteroid dehydrogenase type 2 to provide both glucocorticoid and mineralocorticoid activity 1, 2
• Begin 0.9% isotonic saline infusion at 1 L over the first hour to address profound volume depletion 1, 2
• If IV access cannot be rapidly established, give hydrocortisone 100 mg IM as an acceptable backup route 1

Step 2: Obtain Diagnostic Blood Samples (But Do Not Delay Treatment)

• Draw blood for serum cortisol, ACTH, electrolytes (sodium, potassium), creatinine, urea, and glucose before administering hydrocortisone if feasible 1, 3
• Treatment must proceed immediately without waiting for laboratory results—mortality increases with delayed intervention 1, 2

Ongoing Management (First 24-48 Hours)

Continued Glucocorticoid Administration

• Continue hydrocortisone 200 mg per 24 hours as continuous IV infusion (preferred method) 1, 2
• Alternative regimen: Hydrocortisone 50 mg IV or IM every 6 hours (total 200 mg/day) if continuous infusion is unavailable 1, 2

Fluid Management

• Provide total of 3-4 L isotonic saline or 5% dextrose-in-saline over 24-48 hours with frequent hemodynamic monitoring to avoid fluid overload 1, 2
• Monitor serum electrolytes frequently to guide fluid management and detect complications 1, 2

Supportive Care

• Admit to ICU or high-dependency unit for patients with persistent hypotension or severe presentation 1, 2
• Provide gastric stress ulcer prophylaxis to reduce risk of stress-related GI bleeding 1, 2
• Administer low-dose heparin prophylaxis for venous thromboembolism prevention 1, 2
• Treat precipitating infections promptly with appropriate antimicrobial therapy—infections are the most common trigger 1, 2
• Monitor blood glucose frequently, especially in pediatric patients who are more vulnerable to hypoglycemia 1

Critical Management Pitfall

• Do not add separate mineralocorticoid (fludrocortisone) during acute crisis—high-dose hydrocortisone (≥50 mg/day) provides adequate mineralocorticoid activity 1

Common Precipitating Factors to Investigate

• Gastrointestinal illness with vomiting/diarrhea: Most frequent trigger (prevents oral medication absorption) 1, 2
• Any type of infection: Respiratory, urinary, or systemic infections 1, 2
• Surgical procedures without adequate steroid coverage 1, 2
• Physical trauma or injuries 1, 2
• Medication non-compliance or failure to increase glucocorticoid doses during illness 4, 5
• Myocardial infarction and severe allergic reactions 1
• Medications that accelerate cortisol clearance (anticonvulsants, rifampin) without dose adjustment 1

Transition to Maintenance Therapy

• Taper parenteral glucocorticoids over 1-3 days once the precipitating illness permits and oral intake is tolerated 1, 2
• Re-introduce fludrocortisone only after hydrocortisone dose falls below 50 mg per day—lower doses no longer provide sufficient 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

Prevention of Future Crises

Patient Education (Paramount to Preventing Deaths)

• Teach patients to double or triple oral glucocorticoid doses during minor illness, fever, or physical stress 1, 4
• Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training for severe illness or inability to take oral medications 1, 6, 7
• Provide medical alert jewelry and emergency steroid card to trigger stress-dose corticosteroids by emergency personnel 1, 6, 7

Common Causes of Recurrent Crises to Address

• Chronic under-replacement with fludrocortisone combined with low salt consumption 1
• Poor compliance with mineralocorticoid therapy 1
• Inadequate patient education despite prior instruction—documented instances exist where patients receive little or no education 1
• Underlying psychiatric disorders affecting medication adherence 1

Special Population Considerations

• Pediatric patients: Initial fluid bolus 10-20 mL/kg (maximum 1,000 mL) normal saline; more frequent blood glucose monitoring required 1
• Obstetric patients: Hydrocortisone 100 mg at onset of labor, then 200 mg per 24 hours IV infusion (or 50 mg IM every 6 hours) until after delivery 1
• Patients on immune checkpoint inhibitors: At particular risk during rapid corticosteroid tapers after treatment of hypophysitis 1