Addisonian Crisis

Article Author:
Kimberly Rathbun
Article Author:
Minhthao Nguyen
Article Editor:
Mayank Singhal
3/20/2020 9:34:05 AM
PubMed Link:
Addisonian Crisis


Addisonian crisis, or adrenal crisis, is a potentially life-threatening condition that results from an acute insufficiency of adrenal hormones (glucocorticoid or mineralocorticoid) and requires immediate treatment[1]. It is important to differentiate an Addisonian crisis from Addison Disease which has a more gradual course. An illness or acute stress can precipitate adrenal crisis in the setting of Addison's disease[2]. Addison's Disease is a condition in which the adrenal glands do not produce enough steroid hormones and occurs over several months.


An Addisonian crisis results from an acute lack of glucocorticoids or mineralocorticoids. This condition most often occurs in a patient with known adrenal insufficiency, either primary or secondary. Primary adrenal insufficiency (Addison Disease) results in decreased cortisol as well as aldosterone. Some causes of primary adrenal insufficiency include autoimmune causes, adrenal hemorrhage, medications, infection, congenital adrenal hyperplasia. Secondary adrenal insufficiency is caused by decreased ACTH by the pituitary gland. Causes of secondary adrenal insufficiency include cessation of steroid therapy, pituitary disease, head trauma, postpartum pituitary necrosis, and infiltrative disorders of the pituitary or hypothalamus. An Addisonian crisis may develop when adrenal insufficiency goes untreated or the patient experiences stress such as from infection, surgery, trauma, myocardial infarction, dehydration, exposure to cold, burns, or overexertion[3]. An Addisonian crisis can occur in patients with previously normal adrenal functions in situations that result in adrenal or pituitary injury or when suddenly stopping long-term steroid treatment without tapering.

Drugs associated with Addisonian crisis include:

  • Ketoconazole
  • Rapid withdrawal of corticosteroids
  • Rifampin
  • Phenytoin
  • Mitotane


An Addisonian crisis frequently occurs in patients with known adrenal insufficiency. Studies in patients on chronic replacement therapy for adrenal insufficiency have revealed an incidence of 5 to 10 adrenal crises/100 patient years and suggested a mortality rate from an adrenal crisis of 0.5/100 patient-years[1][2][4]. Of 444 patients in one study, 42% reported at least one crisis; the frequency of crises was calculated to be 6.3/100 patient years[2][5]. Patients with primary adrenal insufficiency were slightly more likely than those with secondary adrenal insufficiency to have a crisis[6]. The most frequent triggers of adrenal crisis are infectious causes[2][4]. Studies of critically ill patients with septic shock (excluding patients with known adrenal insufficiency or patients on glucocorticoid therapy) have shown an incidence of adrenal insufficiency of up to 57%[7][8].


Adrenal corticosteroids aid the body's ability to retain sodium, excrete potassium and handle stress[9]. Deficient levels cause increased renal sodium loss and potassium reabsorption, resulting in decreased intravascular volume, vascular tone, cardiac output, and renal perfusion. This, in turn, lowers arterial blood pressure, which may lead to postural hypotension, compensatory tachycardia, and eventual vascular collapse. Reduced renal perfusion causes water retention, which dilutes the extracellular fluid and causes the cells to leak potassium. Circulatory collapse impairs urinary excretion of waste products, causing elevated levels of blood urea nitrogen and creatinine.

As a response to an environmental stressor, the hypothalamus releases corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary to release adrenocorticotropin hormone (ACTH), which travels through the bloodstream to the adrenal cortex and upregulates cortisol production. Cortisol is a glucocorticoid hormone synthesized from cholesterol by enzymes of the cytochrome P450 family in the zona fasciculate, the middle area of the adrenal cortex[9]. Cortisol is the primary hormone involved in the human stress response and has multiple effects throughout the body. It helps regulate the supply of glucose in the body by triggering gluconeogenesis or stimulating glycogen synthesis in the liver. It affects pH by regulating sodium and potassium levels. It weakens the immune response by preventing T-cell proliferation and preventing T-cells from recognizing interleukin signals[10]. Additionally, excess cortisol may cause atrophy of the hippocampus, leading to memory loss.

History and Physical

It is important to determine if the patient has a history of adrenal insufficiency. If the patient is on chronic steroids, it is important to know whether the patient has been compliant or not. Other useful elements of the history include any recent illnesses, surgeries, traumatic injuries or other stressors. The one illness that should be sought is meningococcemia which can cause Addisonian crisis.

The salient feature of patients in acute adrenal crisis is circulatory collapse[6]. They might have symptoms like nausea, vomiting, fever and lower chest/ abdominal pain along with the low blood pressure[1][2][6]. They may appear cyanotic due to shock. Sometimes the patients are confused, delirious, or lethargic. Abdominal symptoms may take on features of an acute abdomen[11]. Patients may have hyperpyrexia, with temperatures reaching 105 F or higher, and may be comatose. In acute adrenal hemorrhage, the patient can deteriorate with sudden collapse, abdominal or flank pain, and nausea with or without hyperpyrexia[12]


It is important to keep an Addisonian crisis on the differential in cases of shock, especially since adrenal crisis can be the patient's first presentation of adrenal insufficiency.

Initial laboratory testing should include serum chemistry (particularly sodium, potassium, glucose, and calcium), blood count, cortisol level, adrenocorticotropic hormone (ACTH), aldosterone, renin, and thyroid function[11]. The serum chemistry is used to guide initial therapy. Patients often have hypoglycemia, hyponatremia, hyperkalemia, and hypercalcemia. Although a reliable diagnosis of underlying adrenal insufficiency is not possible during the adrenal crisis, measurement of blood ACTH and cortisol during the crisis (before treatment with corticosteroids is given) is often enough to make a preliminary diagnosis. Once the crisis is controlled, an ACTH stimulation test can be performed to help make a specific diagnosis[11]. More complex lab tests are sometimes used if the diagnosis remains unclear.

An EKG may show peaked T waves from hyperkalemia or short QT interval from hypercalcemia[13]. A chest radiograph, urine studies, and blood cultures should be ordered to evaluate any infection. A CT scan of the abdomen may show hemorrhage in the adrenals, calcification of the adrenals (seen with tuberculosis) or metastasis. In cases of secondary adrenal insufficiency, a head CT scan may show the destruction of the pituitary (i.e., empty sella syndrome) or a pituitary mass lesion.

Treatment / Management

This diagnosis requires quick identification and treatment. Fluids and glucocorticoid replacement are the mainstays of emergent therapy. Two to three liters of normal saline or 5% dextrose in normal saline should be infused in the first 12 to 24 hours[14]. The dextrose-containing solution should be used in the setting of hypoglycemia. Volume status and urine output should be used to guide the resuscitation. Dexamethasone (4 mg IV bolus) or hydrocortisone (100 mg IV bolus) can be used In patients with known adrenal insufficiency presenting in crisis[9][11]. In patients without known adrenal insufficiency, dexamethasone is preferred because it does not interfere with the diagnostic testing, unlike hydrocortisone. Maintenance steroid replacement is required - dexamethasone 4 mg IV every 12 hours or hydrocortisone 50 mg IV every 6 hours until vital signs have stabilized and the patient can take medication orally[9]. If the patient does not have known adrenal insufficiency, an ACTH stimulation test should be performed. It can then be followed by testing to determine the cause of the adrenal insufficiency. After initial stabilization of the patient using the above measures, the underlying cause of the crisis should be identified and treated[11].

Some patients may require pressor support to over come the hypotension.

Differential Diagnosis

  1. Septic shock
  2. Distributive shock due to inflammation (acute pancreatitis, burns, etc)
  3. Cardiogenic shock
  4. Hypovolemic shock (hemorrhagic versus nonhemorrhagic)
  5. Obstructive shock (pulmonary embolus, cardiac tamponade, etc)


The outlook for patients with Addisonian crisis depends on the time of treatment. Delays in treatment usually have poor outcomes. Patients with bilateral adrenal hemorrhage (prior to the era of CT scans) had 100% mortality. Today, with improved imaging, most of these patients survive. Patients who present with impaired mental status and loss of consciousness usually do not survive.


Current Guidelines for Addisonian crisis

  1. In acutely ill patients with signs and symptoms suggestive of acute adrenal insufficiency, one should rule of Addisonian crisis
  2. Assess blood pressure and perform orthostasis
  3. Determine the history of steroid use
  4. Perform appropriate tests like sodium, potassium, creatinine, urea, TSH, cortisol and plasma ACTH levels
  5. In stable patients, consider performing a short Synacthen test.
  6. Never delay treatment because of testing
  7. If in doubt and suspicion is high, administer IV hydrocortisone and hydrate patient.

Enhancing Healthcare Team Outcomes

The diagnosis and management of Addisonian crises require an interprofessional team because the disorder is difficult to diagnose, has non-specific clinical features and is associated with nearly 100% mortality if treatment is delayed. Most patients present to the emergency department and the triage nurse should be familiar with the signs and symptoms of this life-threatening disorder. Prompt admission and communication should be made to the emergency department physician. While the endocrine consult is made, laboratory workup and imaging tests should be ordered. At the same time, nurses should have two large bore IVs with fluids running and have the patient hooked up to a monitor. The pharmacist should determine if the patient has been on prior corticosteroids.

The radiologist should be informed about an urgent CT scan to determine if there is adrenal hemorrhage. However, good clinical acumen is needed before sending an unstable patient to an unmonitored radiology suite. If the patient is unstable, a mobile team should monitor the patient while being transported to the radiology department.

The endocrinologist, internist intensivist, infectious disease expert, and nephrologist should play an active role in the management. After initial stabilization of the patient using the above measures, the underlying cause of the crisis should be identified and treated[11]. Once the patient has been managed as an inpatient, he or she can be followed by the primary care provider or nurse practitioner.  The pharmacist has to educate the patient on medication compliance to prevent a recurrence. Untreated cases have mortality in excess of 90%.[15]

Finally, the interprofessional team should urge the patient to wear an ID bracelet detailing the Addisonian crisis.


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