By: Casey Carr, MD

• Adrenal insufficiency occurs when there is a disruption between the hypothalamic-pituitary-adrenal axis; adrenal crisis is a life threatening condition that occurs when the adrenal cortex is unable to produce appropriate stress hormones in response to severe physiologic stress.
• The main categories of adrenal insufficiency are primary (PAI), secondary (SAI), and tertiary (TAI).
• The most common cause of primary adrenal insufficiency in developed countries is autoimmune – Addison’s disease.
• Addison’s disease is most common in women in their fourth to sixth decades of life
• The most common cause of secondary and tertiary adrenal insufficiency is the abrupt cessation of prolonged glucocorticoid therapy.
• Approximately 50% of patients with PAI will have an adrenal crisis in their lifetime
• The most commonly precipitating causes of adrenal crisis are fever, gastrointestinal illness, surgery, and strenuous activity. Ischemia can also be a precipitate however.

• Cardiovascular: increases contractility and the vascular response to vasoconstrictors
• Endocrine: inhibits insulin secretion, promotes peripheral insulin resistance, increases epinephrine synthesis
• Inflammatory: causes demargination of granulocytes, suppresses adhesion, reduces circulating eosinophils and lymphocytes
• Metabolism: stimulates gluconeogenesis, promotes lipolysis, induces muscle protein catabolism, increases glucose during stress

• The hallmark of adrenal crisis is hypotension and shock refractory to fluid resuscitation and vasopressors.
• Accompanying this hemodynamic instability will be nonspecific symptoms including abdominal pain, nausea, vomiting, weakness, and confusion
• See table and full reference below for differentiating characteristics between Primary Adrenal Insufficiency, Secondary Adrenal Insufficiency, and Tertiary Adrenal Insufficiency

• Treatment should be started empirically before receiving the results of confirmatory laboratory testing
• Hydrocortisone is the drug of choice, as it provides both glucocorticoid and mineralocorticoid effects
• A thorough search for precipitating cause should also be undertaken
• Also will need to correct electrolyte abnormalities, concurrent endocrinopathies, coagulopathy.
• Empiric antibiotics may also be given depending on patients presentation
• Treatment regime: fluid resuscitation (D5NS or normal saline boluses), hydrocortisone (100 mg bolus followed by daily doses of 100 mg divided two to three times per day), and glucose replacement (D50 as necessary). Vasopressors may also be necessary, if not already started
• All forms of adrenal insufficiency exhibit a deficiency of cortisol
• For critically ill patients in the emergency department, random serum cortisol levels above 34 mcg/dL generally exclude AI; levels below below 15 mcg/dL suggest adrenal crisis (in a patient in severe shock)
  

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References:

Tuccy, V et al. “The Clinical Manifestations, Diagnosis, and Treatment of Adrenal Emergencies”. Emergency Medicine Clinics of North America. 2014; 32: 465-84