Snapshot A 26-year-old woman is brought to the emergency room after collapsing at her workplace. Per her coworker, the patient caught a cold yesterday and was complaining of a headache all day. The coworker mentions that she stopped taking her medication for her rheumatoid arthritis because of this. Her temperature is 103°F (39.4°C), blood pressure is 86/54 mmHg, pulse is 124/min, and respirations are 12/min. A physical examination demonstrates an unconscious patient with a positive Brudzinski sign. (Infection-induced adrenal crisis) Introduction Clinical definition acute, life-threatening medical emergency characterized by the loss of adrenal function (e.g., low levels of cortisol) Epidemiology Demographics most commonly occur in patients with primary adrenal insufficiency due to the characteristic volume depletion and hypotension resulting mainly from mineralocorticoid deficiency Risk factors primary adrenal insufficiency chronic glucocorticoid use ETIOLOGY Pathogenesis there is always an acute stressor or cause of adrenal insufficiency in patients with adrenal crisis chronic primary adrenal insufficiency occurs in patients with serious infection or other major stress (e.g., surgery) glucocorticoid and/or mineralocorticoid insufficient dosing may occur in patients with known primary/secondary adrenal insufficiency can be due to insufficient doses failure to take more glucocorticoid during infection or major illness persistent vomiting/diarrhea leading to decreased absorption acute glucocorticoid withdrawal includes oral and inhaled medications occurs in patients who are abruptly withdrawn from glucocorticoid therapy acute adrenal gland destruction bilateral hemorrhage (e.g., Waterhouse-Friderichsen syndrome associated with meningococcemia) bilateral infarction (e.g., heparin-induced thrombocytopenia) trauma acute causes of secondary/tertiary adrenal insufficiency pituitary infarctions Presentation Symptoms fever abdominal or flank pain anorexia, nausea, or vomiting confusion or disorientation severe lethargy syncope Physical exam skin and mucosal hyperpigmentation (if Addison disease) hypotension or shock imaging Computed tomography (CT) may demonstrate bilateral adrenal injury, hemorrhage, or infarction Studies Diagnostic testing diagnostic approach diagnosis is based on clinical presentation and confirmed (following initial treatment) with an endocrine evaluation studies serum cortisol concentration (e.g., morning serum cortisol) best initial test low serum cortisol (e.g., < 5 ug/dL) strongly suggests adrenal insufficiency plasma ACTH concentration and stimulation test indicated following initial treatment for differentiating the cause of adrenal insufficiency levels will vary depending on the type of adrenal insufficiency plasma aldosterone and renin levels will have low aldosterone levels, renin levels will vary depending on the cause chemistry panel hyperkalemia hyponatremia Differential Sepsis distinguishing factors will not have the significant electrolyte imbalances seen in adrenal crisis Treatment Treatment of patients should not be delayed while diagnostic tests are performed First-line IV fluids volume replacement as patients are hypovolemic 1-3L of 0.9% saline or 5% dextrose in 0.9% saline within the first 12-24 hours glucocorticoid replacement e.g., dexamethasone or hydrocortisone to give initial bolus, then maintenance dose of 50 mg every 8 hours mineralocorticoid replacement not indicated in the acute setting as its effects take several days in patients with known primary adrenal insufficiency or significant hyperkalemia, hydrocortisone can be given for its mineralocorticoid activity Complications Coma Death