David D Hamilton, Bryan A Cotton

Adrenocortical insufficiency occurs when there is inadequate release of cortisol from the adrenal cortex. Disturbances of the hypothalamic-pituitary-adrenal axis are common following trauma, surgical stress, and critical illness. While this is often a protective mechanism, these responses may become "uncoupled" or maladaptive resulting in an exacerbation of organ failure and higher mortality rates. In these clinical settings, the patient presents with a persistent systemic inflammation state, a hyperdynamic cardiovascular response, and vasopressor dependent shock. As such, the occurrence of adrenal insufficiency in the setting of critical illness is most appropriately termed critical illness-related corticosteroid insufficiency. In these settings, recent data suggests that these patients may benefit from a short course of low-dose steroid replacement therapy. Cosyntropin, a synthetic derivative of adrenocorticotropic hormone, is being used with increased frequency in the evaluation and diagnosis of adrenocortical insufficiency in this patient population. A random cortisol level is checked before a 250-μg injection of cosyntropin and then 30-60 minutes later. The cortisol levels and response to cosyntropin may be interpreted to identify an insufficient adrenal response. Of note, the setting of critical illness can greatly affect the cosyntropin test sensitivity on identifying adrenal insufficiency. Changes in the stress response during critical illness combined with the resuscitation and management of these patients greatly disturbs serum protein levels, especially those of albumin and transcortin. Common intensive care unit (ICU) diagnoses such as sepsis and malnutrition can increase baseline levels and blunt the cortisol response to cosyntropin stimulation, respectively. As well, numerous pharmacological agents routinely used in the ICU have been shown to interfere with cortisol levels and cosyntropin responsiveness. While steroids have a place in the ICU, specific dosing and length of administration remain inconsistent.