Acute Adrenal Insufficiency (Adrenal Crisis)

How to Cite This Chapter: Rodríguez-Gutiérrez R, Mancillas-Adame LG, Gonzalez-Nava V, Dorsey-Treviño EG, Bednarczuk T, Płaczkiewicz-Jankowska E, Kasperlik-Załuska AA. Acute Adrenal Insufficiency (Adrenal Crisis). McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed September 30, 2020.
Last Updated: January 26, 2018
Last Reviewed: August 7, 2019
Chapter Information

Definition, Etiology, PathogenesisTop

Adrenal crisis is a life-threatening clinical syndrome caused by acute severe cortisol deficiency. It may occur in:

1) Patients with chronic adrenal insufficiency in case of stress without administration of an appropriate additional dose of hydrocortisone (the most frequent cause). Adrenal crisis may be the presenting manifestation of previously undiagnosed adrenal insufficiency.

2) Patients with adrenal injury caused by trauma, hemorrhage in the course of disseminated intravascular coagulation (DIC) (eg, in sepsis), anticoagulant treatment, or eclampsia, as well as in the case of sudden discontinuation of long-term treatment with glucocorticoids (secondary adrenal insufficiency).

3) Critically ill patients with severe diseases due to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis with concomitant tissue insensitivity to glucocorticoids and a severe inflammatory reaction.

Clinical Features and Natural HistoryTop

Prodromal symptoms: Loss of appetite, nausea, muscle pain, and malaise.

Symptoms of impending crisis: Increasing weakness, influenza-like muscle pain, abdominal pain, nausea, gradual blood pressure decrease. These may be accompanied by elevated body temperature caused by cytokines released in cortisol deficit.

Symptoms of crisis: Severe weakness, altered mental status, vomiting, diarrhea; blood pressure decrease and tachycardia; shock.

In patients with adrenal crisis caused by DIC in the course of sepsis, particularly of meningococcal etiology, the symptoms of acute adrenal insufficiency are accompanied by extensive cutaneous hemorrhages (Waterhouse-Friderichsen syndrome). In critically ill patients with severe diseases, the key symptom is a blood pressure drop not responding to fluid resuscitation and vasopressor drugs. It may be accompanied by symptoms of sepsis or acute respiratory failure.

Diagnostic Tests

1. Laboratory tests:

1) Biochemical tests may reveal hyperkalemia, hyponatremia, and hypoglycemia.

2) Hormone tests reveal low basal serum cortisol levels (<138 nmol/L [5 microg/dL]). There is no need for stimulation tests as the adrenal crisis is a stimulation per se.

2. Imaging studies depend on the suspected cause of adrenal crisis.


The goal of treatment is to correct the deficits of cortisol, fluids, and glucose; correct electrolyte disturbances; and control the infection or other underlying condition that may have precipitated the crisis.

1. Treatment of acute adrenal insufficiency after collection of blood samples for key biochemical (glucose, sodium, potassium, creatinine) and hormonal (cortisol, adrenocorticotropic hormone [ACTH]) tests, as well as for microbiological studies where appropriate:

1) Hydrocortisone: Immediately administer 100 mg IV followed by 200 mg over 24 hours as an IV infusion or 50 mg IV every 4 to 6 hours. When blood pressure and heart rate return to normal, administer 50 mg IV or IM every 6 hours. Treatment of patients with septic shock: see Sepsis and Septic Shock.

2) Volume expansion with crystalloids or colloids to treat hypovolemia (including glucose solutions in case of low serum glucose levels). A reasonable starting point is a 1-L bolus with further doses according to the precipitating condition and individual patient requirements.

3) Treatment of hyponatremia: Monitor the patient closely. The type and volume of administered fluids depend on the fluid balance, severity of electrolyte disturbances, cardiovascular and renal status, and body weight. Also see Hyponatremia.

2. Treatment of impending adrenal crisis: Early administration of IV hydrocortisone 100 mg can halt the development of adrenal crisis. Ensure appropriate hydrocortisone replacement, correct for possible electrolyte disturbances, and treat the underlying condition.


Appropriate treatment of adrenal crisis is life-saving but the prognosis may be affected by underlying conditions that precipitated the crisis.

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