Acute Adrenal Insufficiency (Adrenal Crisis)

How to Cite This Chapter: Rodríguez-Gutiérrez R, Husein N, 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 July 22, 2024.
Last Updated: July 27, 2020
Last Reviewed: July 27, 2020
Chapter Information

Definition, Etiology, PathogenesisTop

Adrenal crisis is a life-threatening clinical syndrome caused by acute severe cortisol deficiency. It may be the presenting manifestation of previously undiagnosed adrenal insufficiency or may occur in:

1) Patients with chronic adrenal insufficiency:

a) In the presence of pathologic physiologic or psychological precipitant/stress, without administration of an appropriate additional dose of a glucocorticoid (the most frequent cause).

b) As a result of diminished supplemental glucocorticoid absorption due to diarrhea or vomiting.

c) As a result of increased glucocorticoid metabolism related to certain drugs (eg, phenytoin, barbiturates, mitotane, rifampin [INN rifampicin], ketoconazole) or hyperthyroidism.

2) Patients with adrenal injury caused by trauma, hemorrhage in the course of disseminated intravascular coagulation (DIC) (eg, in sepsis), heparin-induced thrombocytopenia (HIT), anticoagulant treatment, or eclampsia, as well as in the case of sudden discontinuation of long-term treatment with glucocorticoids (exogenous 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. This concept of critical illness–related corticosteroid insufficiency (CIRCI) is controversial, but the diagnosis is likely if 2 criteria are met: change <9 microg/dL in baseline cortisol levels at 60 minutes after cosyntropin use (IV administration of 250 microg) and a random plasma cortisol level <10 microg/dL. Our approach is, depending on the perceived urgency, to wait for the results or to treat pending results. Use of glucocorticoids in sepsis: see Sepsis and Septic Shock.

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.

3) A septic workup (screen) may reveal an infectious etiology (urinary tract infection, pneumonia, and other sources).

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


Adrenal crisis is a life-threatening condition requiring immediate treatment.

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, starting immediately after collection of blood samples for key biochemical (glucose, sodium, potassium, creatinine) and hormonal (cortisol, adrenocorticotropic hormone [ACTH]) tests, as well as for microbiologic 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, then taper over 2 to 3 days as the situation improves. Treatment of patients with septic shock: see Sepsis and Septic Shock.

2) Volume expansion with crystalloids or colloids to treat hypovolemia (including 10% 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.

4) Prevention of venous thromboembolism (VTE) as dictated by the patient’s status.

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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