Addisonian crisis, or adrenal crisis, is a potentially life-threatening condition that results from an acute insufficiency of cortisol and requires immediate treatment. It is important to differentiate an Addisonian crisis from Addison Disease. Addison 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 cortisol. 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 and results in decreased cortisol only. 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. 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.
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. 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. Patients with primary adrenal insufficiency were slightly more likely than those with secondary adrenal insufficiency to have a crisis. The most frequent triggers were infectious causes. Studies of critically ill patients with septic shock (excluding patients with known adrenal insufficiency or patients on glucocorticoid therapy) have shown an incidence ranging from 19% to 54%. Secondary adrenal insufficiency has been demonstrated in 31% of patients admitted to a critical care unit.
Adrenal corticosteroids aid the body's ability to retain sodium, excrete potassium, and handle stress. 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.
Cortisol and aldosterone are glucocorticoid hormones synthesized from cholesterol by enzymes of the cytochrome P450 family in the zona fasciculate, the middle area of the adrenal cortex.
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. Additionally, excess cortisol may cause atrophy of the hippocampus, leading to memory loss. As a response to an environmental stressor, the hypothalamus releases corticotropin-releasing hormone (CRH). CRH stimulates the anterior pituitary to release corticotropin, which travels through the bloodstream to the adrenal cortex where corticotropin then upregulates cortisol production.
The primary actions of aldosterone cause the kidneys, gut, and salivary/sweat glands to affect electrolyte balance. Aldosterone stimulates reabsorption of sodium and secretion of potassium and hydrogen ions, which influences water retention or loss affecting blood volume and blood pressure. Renin is produced by the kidneys in response to renal sympathetic activity, decreased intrarenal blood pressure, or decreased sodium. Renin cleaves angiotensinogen into angiotensin I. Angiotensin I is converted to angiotensin II by the angiotensin-converting enzyme (ACE). Angiotensin II acts on the adrenal cortex, causing it to release aldosterone.
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 ascertain whether the patient has been compliant. Other useful elements of the history include any recent illnesses, surgeries, traumatic injuries, or other stressors.
Patients in acute adrenal crisis most often have prominent nausea, vomiting, and vascular collapse. They may be in shock and appear cyanotic and confused, delirious, or lethargic. Abdominal symptoms may take on features of an acute abdomen. 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.
It is important to keep an Addisonian crisis on the differential in cases of shock.
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. 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. More complex lab tests are sometimes used if the diagnosis remains unclear.
An EKG may show peaked T waves indicating hyperkalemia.
A chest radiograph should be ordered. 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.
This diagnosis requires quick identification and treatment. Fluids and glucocorticoid replacement are the mainstays of emergent therapy. One to 3 L of 0.9% saline or 5% dextrose in 0.9% saline should be infused in the first 12 to 24 hours. The dextrose-containing solution should be used in the setting of hypoglycemia. Volume status and urine output should be used to guide the resuscitation. In patients with known adrenal insufficiency presenting in crisis, hydrocortisone (100mg IV bolus), dexamethasone (4mg IV bolus), or any other glucocorticoid preparation can be used. In patients without known adrenal insufficiency, dexamethasone is preferred because the use of hydrocortisone in the acute setting can interfere with later diagnostic testing. If hydrocortisone is used, 50mg IV boluses should be administered every eight hours until vital signs have stabilized and the patient can take medication orally.
After initial stabilization of the patient using the above measures, the underlying cause of the crisis should be identified and treated.
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.