Adrenal crisis

Background

• Life-threatening emergency resulting from acute cortisol deficiency
• Mortality up to 25% if untreated; rapidly fatal without intervention
• Most common cause: stress event in patient with chronic adrenal insufficiency on glucocorticoid replacement who does NOT increase dose ("stress dosing")
• Can also occur as first presentation of undiagnosed adrenal insufficiency

Causes of Adrenal Insufficiency

• Primary (adrenal gland destruction):
  • Autoimmune adrenalitis (Addison disease — most common in developed countries)
  • Infections: TB (most common worldwide), CMV, HIV, fungal
  • Bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome — meningococcemia, anticoagulation, DIC)
  • Metastatic disease, bilateral adrenalectomy
• Secondary (pituitary — ACTH deficiency):
  • Pituitary tumors, surgery, radiation, Sheehan syndrome
• Tertiary (hypothalamic — MOST COMMON overall):
  • Chronic exogenous glucocorticoid use → HPA axis suppression
  • Even short courses >2 weeks can suppress HPA axis
  • Abrupt discontinuation → adrenal crisis

Precipitants of Crisis

• Infection/sepsis (most common trigger)
• Surgery, trauma, critical illness
• Non-compliance or abrupt withdrawal of chronic steroids
• GI illness with vomiting (unable to take oral steroids)
• Emotional stress, adrenal hemorrhage

Clinical Features

• Refractory hypotension/shock — does NOT respond to IV fluids or vasopressors until cortisol replaced
• Weakness, fatigue, lethargy → obtundation → coma
• Nausea, vomiting, abdominal pain (may mimic acute abdomen)
• Fever or hypothermia
• Hypoglycemia (especially in children; cortisol is counterregulatory)
• Dehydration (cortisol deficiency + aldosterone deficiency in primary AI)
• In chronic primary AI: hyperpigmentation (increased ACTH → MSH), vitiligo, salt craving

Classic Lab Pattern

• Hyponatremia (most common electrolyte abnormality)
• Hyperkalemia (primary AI only — aldosterone deficiency; absent in secondary/tertiary)
• Hypoglycemia
• Eosinophilia (cortisol normally suppresses eosinophils)
• Metabolic acidosis, elevated BUN (dehydration)

Differential Diagnosis

• Sepsis / septic shock (most common misdiagnosis — and most common precipitant)
• Thyroid storm / myxedema coma
• Diabetic ketoacidosis
• Hypovolemic shock
• Acute abdomen (gastroenteritis, pancreatitis)
• Drug withdrawal
• Pheochromocytoma crisis

Evaluation

• Random cortisol level (draw BEFORE giving steroids if possible, but do NOT delay treatment):
  • Cortisol <3 mcg/dL: diagnostic of adrenal insufficiency
  • Cortisol 3-18 mcg/dL in acutely stressed patient: suspicious (should be elevated in stress)
  • Cortisol >18 mcg/dL in acute illness: effectively rules out AI
• ACTH level (distinguish primary vs secondary):
  • High ACTH = primary AI; Low/normal ACTH = secondary/tertiary
• BMP: hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis
• CBC: eosinophilia, lymphocytosis
• Blood glucose (POC immediately)
• TSH (concurrent hypothyroidism in autoimmune polyendocrine syndrome)
• Infectious workup: blood cultures, UA, CXR, lactate (identify precipitant)
• ACTH stimulation test (cosyntropin test): NOT needed acutely — do NOT delay treatment for this test

Management

Immediate

• Hydrocortisone 100 mg IV bolus — give immediately if suspected (even before lab confirmation)
• Then hydrocortisone 50 mg IV q6-8h (or continuous infusion 200 mg/24h)
• If hydrocortisone unavailable: dexamethasone 4 mg IV (does not interfere with subsequent cortisol testing)
• IV fluids: aggressive NS resuscitation (patients are often 2-3L volume depleted)
  • D5NS if hypoglycemic — correct hypoglycemia with D50W 25-50 mL IV
• Vasopressors if refractory hypotension (norepinephrine) — shock typically improves rapidly with steroids
• Treat precipitant: antibiotics for infection, etc.

Key Principles

• Do NOT delay steroids for diagnostic testing
• Hydrocortisone at stress doses provides both glucocorticoid AND mineralocorticoid activity (no need for separate fludrocortisone in acute phase)
• Hypotension refractory to fluids and vasopressors in a critically ill patient → think adrenal crisis
• Correct electrolytes (but hyperkalemia usually resolves with hydrocortisone and fluids)

Taper

• Once stable: taper to maintenance over 2-4 days
• Maintenance: hydrocortisone 15-25 mg/day (divided doses)
• Primary AI also needs fludrocortisone 0.05-0.1 mg PO daily (mineralocorticoid replacement)

Prevention=

• Medical alert bracelet for all patients with adrenal insufficiency
• Sick day rules: double or triple oral glucocorticoid dose during illness
• Injectable hydrocortisone at home for emergencies (patient education)
• Stress dosing prior to surgery: hydrocortisone 100 mg IV before induction

Disposition

• ICU admission for hemodynamic instability or altered mental status
• Monitored bed for less severe presentations
• Endocrinology consultation
• Serial electrolytes, glucose monitoring
• Patient and family education on stress dosing before discharge

See Also

• Adrenal insufficiency
• Myxedema coma
• Sepsis
• Shock
• Hyponatremia

References

• Bornstein SR, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. PMID 26760044
• Rushworth RL, et al. Adrenal crisis. N Engl J Med. 2019;381(9):852-861. PMID 31461595
• Puar TH, et al. Adrenal crisis: still a deadly event in the 21st century. Am J Med. 2016;129(3):339.e1-e9. PMID 26524708