Adrenal Insufficiency



  • Inadequate hydrocortisone secretion to meet body's stress requirement
  • Adrenal deficiency:
    • Inadequate cortisol
    • Unresponsive to stimulation with adrenocorticotropic hormone (ACTH)
  • Functional hypoadrenalism:
    • Inadequate cortisol
    • Partial response to stimulation with ACTH
  • Addisonian crisis (acute adrenal insufficiency):
    • Life-threatening emergency
    • Precipitated by intensification of:
      • Chronic adrenal insufficiency
      • Acute adrenal hemorrhage
      • Rapid steroid withdrawal
      • Treatment of hypothyroidism with unrecognized adrenal disease
      • Steroid-dependent patient under stress owing to pregnancy, surgery, trauma, infection, or dehydration


Primary Adrenal Failure
  • Adrenal dysgenesis/impaired steroidogenesis:
    • Congenital hypoplasia
    • Allgrove syndrome:
      • ACTH resistance
      • Achalasia
      • Alacrima
    • Glycerol kinase deficiency:
      • Psychomotor retardation
      • Hypogonadism
      • Muscular dystrophy
  • Congenital adrenal hyperplasia:
    • 21-hydroxylase deficiency accounts for 95% of cases
  • Aldosterone synthetase deficiency
  • Mitochondrial disease
  • Adrenal destruction:
    • Autoimmune:
      • Autoimmune polyglandular syndrome types 1 and 2 (alopecia universalis, chronic mucocutaneous candidiasis, hypoparathyroid, thyroid autoimmunity, diabetes, celiac disease, pernicious anemia)
      • Adrenoleukodystrophy
    • Infectious:
      • Granulomatous: TB
      • Protozoal and fungal: Histoplasmosis, coccidioidomycosis, and candidiasis
      • Viral: Cytomegalovirus, herpes simplex virus, and HIV
      • Bacterial
      • Fungal
    • Metastatic tumor
    • Infiltration:
      • Sarcoid
      • Hemochromatosis
      • Amyloidosis
      • Iron depletion
  • Bilateral adrenalectomy
  • Hemorrhage:
    • Sepsis: Particularly meningococcemia (Waterhouse–Friderichsen syndrome), Pseudomonas infection
    • Birth trauma/anoxia
    • Pregnancy
    • Seizures
    • Anticoagulants
    • Rhabdomyolysis
  • Pharmacologic inhibition:
    • Etomidate
    • Herbal medications
    • Ketoconazole
    • Metyrapone
    • Suramin

Secondary Adrenal Failure
  • Pituitary insufficiency
  • Sepsis
  • Head trauma
  • Hemorrhage
  • Infarction (Sheehan syndrome)
  • Infiltration: Neoplasm, amyloid, sarcoid, and hemochromatosis
  • ACTH deficiency
  • Pharmacologic: Glucocorticoid administration, herbal medications

Tertiary Adrenal Failure
  • Hypothalamus insufficiency
  • Sepsis
  • Infiltrative: Neoplasm, amyloid, sarcoid, and hemochromatosis
  • Head trauma


Signs and Symptoms

  • Symptoms:
    • Depression
    • Weakness, tiredness, fatigue
    • Anorexia
    • Abdominal pain (can mimic acute abdomen)
    • Nausea or vomiting
    • Salt craving
    • Postural dizziness
    • Muscle or joint pains
    • Dehydration (found in primary adrenal insufficiency only)
  • Signs:
    • Fever or hypothermia
    • Mental status changes
    • Hypotension (<110 mm Hg systolic)
    • Tachycardia
    • Orthostatic BP changes or frank shock
    • Weight loss
    • Goiter
    • Hypogonadism
    • Hyperkalemia
    • Hypercalcemia
    • Sodium depletion
    • Azotemia
    • Eosinophilia
    • Hyperpigmentation (found in primary adrenal insufficiency only)
    • Vitiligo
  • Addisonian crisis:
    • Hypotension and shock
    • Hyponatremia
    • Hyperkalemia
    • Hypoglycemia

Essential Workup

  • Lab confirmation of diagnosis not possible in emergency department
  • Adrenal crisis: Life-threatening condition:
    • High degree of suspicion should prompt initiation of therapy before definitive diagnosis.
  • Plasma cortisol level <20 μg/dL accompanied by shock suggests adrenal insufficiency.
  • Stat electrolytes:
    • Potassium, sodium
  • BUN, creatinine:
    • Elevated owing to dehydration
  • Serum glucose levels may be low.

Diagnostic Tests and Interpretation

  • CBC with differential:
    • Anemia
    • Eosinophilia
    • Lymphocytosis
  • Arterial blood gases:
    • Hypoxemia
    • Acidosis
  • Cosyntropin stimulation test:
    • Adrenal deficiency:
      • Random serum cortisol <20 μg/dL (while stressed)
      • ACTH stimulation unresponsive
    • Functional hypoadrenalism:
      • Random serum cortisol = 20 μg/dL (while stressed)
      • 60 min post ACTH stimulation <30 μg/dL or delta cortisol (60 min – baseline) = 9 μg/dL
  • Normal anion gap metabolic acidosis due to aldosterone deficiency
  • Search for underlying infection

  • Look for infection or edema

Diagnostic Procedures/Other
  • Evaluate for electrolyte disturbances

Differential Diagnosis

  • Sepsis
  • Shock (any cause)
  • Acute abdominal emergency


Initial Stabilization/Therapy

  • Airway, breathing, and circulation management (ABCs)
  • Cardiac monitor
  • BP support for hypotension:
    • Normal saline (0.9%) IV fluids 500 mL–1 L (peds: 20 mL/kg) bolus
    • Avoid pressors (if possible):
      • May precipitate dysrhythmias
  • Supplemental oxygen to meet metabolic needs
  • Correct hyperthermia:
    • Initiate cooling measures.

Ed Treatment/Procedures

  • Glucocorticoid replacement:
    • IV hydrocortisone or dexamethasone immediately
    • Use IM route if no IV access
    • Dexamethasone will not interfere with results of cosyntropin stimulation tests.
  • Volume expansion:
    • NS (0.9%) or D5NS at rate of 500–1,000 mL/hr for 1st 3–4 hr
    • Care should be taken to note patient's age, volume, and cardiac and renal function.
  • For hypoglycemia:
    • D50W
  • Treat life-threatening dysrhythmias secondary to hyperkalemia with calcium, bicarbonate, and insulin/glucose.
  • Identification and correction of underlying precipitant
  • Should see BP improvement within 4–6 hr of therapy


  • Dexamethasone: 6–10 mg (peds: 0.15 mg/kg per dose) q12h
  • Dextrose: 50–100 mL D50 (peds: 2 mL/kg of D10 over 1 min) IV
  • Hydrocortisone: 100 mg (peds: 1–2 mg/kg per dose) IV q6h
  • Insulin (regular): 10 U by IV push (for hyperkalemia)
  • Sodium bicarbonate: 1–2 mEq/kg IV (for hyperkalemia)

Ongoing Care


Admission Criteria
  • All patients with acute adrenal insufficiency
  • ICU admission for patients with unstable or potentially unstable cases

Discharge Criteria
  • Normal lab evaluation with treated adrenal insufficiency
  • Should speak with endocrinologist before discharge with chronic patients

Follow-Up Recommendations

  • Should have primary care physician follow-up within a few weeks depending on symptoms.
  • May benefit from endocrinology referral.

Pearls and Pitfalls

  • Acute adrenal insufficiency is a life-threatening emergency, and treatment should not be delayed in the ED while waiting for definite lab diagnosis.
  • Cancer of any type can present with adrenal insufficiency; the most common being lung, melanoma, and breast.
  • The benefit from steroids for relative adrenal insufficiency in septic shock is limited to the treatment of shock refractory to vasopressive (mortality benefit and clinical effect is questionable).
  • The clinical consequence of a single dose of etomidate for rapid sequence intubation is controversial. Studies do show biochemical adrenal suppression which must be weighed against agents with other undesirable properties while performing a critical, life-saving procedure.

Additional Reading

  • Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin N Am. 2006;35:767–775.
  • Kwon KT, Tsai VW. Metabolic emergencies. Emerg Med Clin N Am. 2007;25:1041–1060.
  • Maxime V, Lesur O, Annane D. Adrenal insufficiency in septic shock. Clin Chest Med. 2009;30:17–27.  [PMID:19186278]
  • Taub YR, Wolford RW. Adrenal insufficiency and other adrenal oncologic emergencies. Emerg Med Clin N Am. 2009;27:271–282.
  • Tuuri R, Zimmerman D. Adrenal insufficiency in the pediatric emergency department. Clin Pediatr Emerg Med. 2009;10:260–271.
  • Williams RH, Melmed, S, eds. Williams Textbook of Endocrinology 12th ed. Philadelphia, PA: Elsevier/Saunders, 2011.

See Also

Cushing Syndrome



  • 255.41 Glucocorticoid deficiency
  • 255.5 Other adrenal hypofunction


  • Primary adrenocortical insufficiency
  • Addisonian crisis
  • Unspecified adrenocortical insufficiency


  • 386584007 adrenal cortical hypofunction (disorder)
  • 373662000 Primary adrenocortical insufficiency (disorder)
  • 363732003 Addison's disease (disorder)


Rita K. Cydulka
Joseph P. Tagliaferro

© Wolters Kluwer Health Lippincott Williams & Wilkins

Adrenal Insufficiency is a sample topic from the 5-Minute Emergency Consult.

To view other topics, please or .

Emergency Central is a collection of disease, drug, and test information including 5-Minute Emergency Medicine Consult, Davis’s Drug, McGraw-Hill Medical’s Diagnosaurus®, Pocket Guide to Diagnostic Tests, and MEDLINE Journals created for emergency medicine professionals. .