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Adrenal Crisis

October 30, 2019

Written by Thomas Davis

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Adrenal crisis is increasing in frequency and can masquerade as something as seemingly benign as gastroenteritis. Read this summary to update your knowledge on the diagnosis and management of acute adrenal insufficiency.

Why does this matter?
Adrenal insufficiency is something you are going to see. Spot it; treat it; and save a life.

Crisis Averted

What defines adrenal crisis?
Adrenal crisis is an acute deterioration in health associated with either hypotension (SBP < 100) or relative hypotension (drop in SBP > 20mmHg from baseline) with symptoms and blood pressure that resolve within 1-2 hours of parenteral glucocorticoid administration. If symptoms do not resolve with steroids, a coexisting illness should be considered (e.g. sepsis).
If there is no hemodynamic compromise, this is called “symptomatic adrenal insufficiency” or “incipient adrenal crisis.” Don’t ignore these patients either.

What is the physiology of adrenal crisis?
Cortisol has a 90-minute half-life. Therefore, symptoms can start abruptly. Without the suppressive effects of cortisol, cytokines exert their influence unchecked. They cause an inflammatory surge leading to fever, vomiting, bodily pains, postural dizziness, and ultimately hypotension and mental status changes.

What precipitates adrenal crisis?

  • Infection

  • Surgery or other physical stress

  • Immune checkpoint inhibitors (e.g. melanoma treatment)

  • Medicines

    • CYP3A4 inducers (e.g. phenytoin, carbamazepine) increase risk of adrenal crisis on initiation of medication because they increase hydrocortisone metabolism. More steroids are needed to compensate for the faster metabolism.

    • CYPA3A4 inhibitors (e.g. HIV medicines, -azoles, clarithyromycin) increase risk of adrenal crisis on discontinuation of medicine. While on the medicine, metabolism slows down. On discontinuation, metabolism is sped up.

How is adrenal crisis treated?

  • Steroids:

  • Give hydrocortisone 100mg IV bolus. Then 50mg q6hrs. Once the patient responds, taper down to the patient’s normal oral dose in 2-3 days.

    1. Hydrocortisone is the preferred drug. But if not available, other steroids (dexamethasone, methylprednisolone, prednisone) can be given.

    2. Fludrocortisone is not necessary if giving more than 50mg of hydrocortisone every 24 hrs.

  • IV fluids

  • Give normal saline or D5NS. Remember, these patients have a tendency towards hyponatremia so this is one of the few times you should avoid lactated Ringer’s.


  • 3×3: During a mild febrile illness, patients should take an oral stress dose of steroids (e.g. triple dose of home steroids for 3 days).

  • Home injections: Self-injecting hydrocortisone 100mg IM (or SQ if not obese) is recommended for vomiting and/or diarrhea.

How are children different?

  • In children, adrenal crisis is defined by either:

    • Hemodynamic compromise (hypotension or sinus tachycardia)

      1. Marked electrolyte abnormality not explained by another illness (e.g. hyponatremia, hyperkalemia, hypoglycemia)

    • Hypoglycemia is more common in children than in adults.

Adrenal Crisis. N Engl J Med. 2019 Aug 29;381(9):852-861. doi: 10.1056/NEJMra1807486.

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