Diagnosis and Treatment of Adrenal Insufficiency in the Critically Ill Patient

Kwame Asare, Pharm.D.


Pharmacotherapy. 2007;27(11):1512-1528. 

In This Article

Abstract and Introduction

The reported incidence of adrenal insufficiency varies greatly depending on the population of critically ill patients studied, the test and cutoff levels used, and the severity of illness. Several studies have shown increased mortality in patients with very low or very high baseline cortisol levels. Manifestations of adrenal insufficiency in the critically ill patient are numerous and nonspecific, so clinicians are urged to have a high index of suspicion and be alert to important diagnostic clues, such as hyponatremia, hyperkalemia, and hypotension, that are refractory to fluids and vasopressors without any clear causation. Multiple tests have been developed to diagnose adrenal insufficiency, but the most commonly used test in the intensive care unit is the adrenocorticotropic hormone (ACTH) stimulation test. The low-dose ACTH stimulation test has been shown to be more sensitive and specific than the high-dose test; however, the high-dose test is preferred since the low-dose test has not been validated. Although diagnosing adrenal insufficiency continues to be difficult in the critically ill patient, administration of highdose corticosteroids, defined as methylprednisolone 30 mg/kg/day or more (or its equivalent), over a short period of time provides no overall benefit and may even be harmful; however, administration of low-dose corticosteroids for a longer duration decreases both the amount of the time that vasopressors are required and mortality at 28 days. Hydrocortisone 200-300 mg/day, administered in divided doses or as a continuous infusion, is the preferred corticosteroid in patients with septic shock and should be started as early as possible. For patients in whom the ACTH stimulation test cannot be given immediately, clinicians are urged to consider using dexamethasone until such time that the test can be administered, since, unlike hydrocortisone, it does not interfere with the cortisol test.

Chronic primary adrenal insufficiency was first recognized by Addison in 1844 and described in 1855 in one of the classic articles in medicine.[1] Subnormal cortisol production is the hallmark of the condition. The deficiency of cortisol secretion by the adrenal cortex has been shown to increase morbidity and mortality in patients with septic shock.[2] Septic shock has been associated with a greater than 50% mortality rate,[3,4] and very little progress has been made.[4,5] Administration of corticosteroids to adrenalectomized animals improved survival,[6] whereas the continued suppression of adrenocortical function increased the mortality rate in critically ill patients.[7] The frequency and diagnosis of adrenal insufficiency in critically ill patients remain controversial despite studies demonstrating beneficial outcomes from treatment. Adrenal insufficiency is estimated to occur at a rate of 0-30% in the critically ill population[8,9] and may be as high as 25-40% in patients with septic shock,[10,11] depending on the specific tests and threshold used to diagnose adrenal insufficiency, underlying disease, and severity of illness.


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