Adrenal Insufficiency in Critically Ill Patients

Abstract

Two major types of adrenocortical hormones, the mineralocorticoids and the glucocorticoids, are secreted by the adrenal cortex. In addition to these, small amounts of sex hormones are secreted, especially androgenic hormones, which exhibit about the same effects in the body as the male sex hormone testosterone. The mineralocorticoids have gained this name because they especially affect the electrolytes of the extracellular fluids. The glucocorticoids have gained their name because they exhibit important effects that increase blood glucose concentration. They have additional effects on both protein and fat metabolism that are equally as important to body function as their effects on carbohydrate metabolism. At high levels, glucocorticoids are catabolic and result in loss of lean body mass. Their gluconeogenic effect increases blood glucose concentrations. Glucocorticoids modulate the immune response by increasing anti-inflammatory cytokine synthesis and decreasing proinflammatory cytokine synthesis. Their anti-inflammatory effects have been used for the treatment of chronic inflammatory diseases. In the central nervous system, they modulate perception and emotion and may produce marked changes in behavior. Severe illness and stress activate the hypothalamic- pituitary-adrenal (HPA) axis and stimulate the release of corticotropin [ACTH] from the pituitary, which in turn increases the release of cortisol from the adrenal cortex. This activation is an essential component of the general adaptation to illness and stress, and contributes to the maintenance of cellular and organ homeostasis . Even minor degrees of adrenal insufficiency increases the mortality of critically ill or injured patients. Acute adrenal insufficiency is a common and largely unrecognized disorder in critically ill patients. Acute adrenal insufficiency occurs in patients who are unable to increase their production of cortisol during acute stress. This includes patients with hypothalamic and pituitary disorders (secondary adrenal insufficiency) and patients with destructive diseases of the adrenal glands (primary adrenal insufficiency). Secondary adrenal insufficiency is common in patients who have been treated with exogenous corticosteroids. However, the most common cause of acute adrenal insufficiency is sepsis and the Systemic Inflammatory Response Syndrome (SIRS). Patients with chronic critical illness may acquire adrenal insufficiency while in the ICU. The adrenal insufficiency may have resulted from chronic secretion of systemic cytokines and other HPA axis-suppressive substances. These patients illustrate the importance of serial follow-up of adrenal function in long- term critically ill patients. In the majority of cases, it remains extremely difficult to recognize adrenal insufficiency in a patient in the intensive care unit. Important diagnostic clues are hemodynamic instability despite adequate fluid resuscitation and ongoing evidence of inflammation without an obvious source that does not respond to empirical treatment. There is now evidence to support the use of supplemental corticosteroids in patients with established septic shock who are in an ICU, especially in those with biochemical evidence of functional hypoadrenalism. Many randomized, controlled trials of hydrocortisone replacement in patients with septic shock have shown improvements in homodynamic and a reduction in the need for vasopressor therapy. In the largest randomized, placebo-controlled trial, treatment of 300 medical and surgical patients with 200 mg of hydrocortisone per day and 50 µg of fludrocortisone once daily for seven days significantly reduced mortality and the duration of vasopressor therapy. The benefits that were seen were restricted to patients who had a small increase in the cortisol level in response to the corticotropin test (an increase of less than 9 µg per deciliter from base line to the highest measurement at 30 or 60 minutes). Such patients should be treated with 50 mg of hydrocortisone intravenously every six hours or with similar amounts by continuous infusion. These treatments lead to moderately supraphysiologic cortisol levels, which may be important in overcoming an element of tissue- specific corticosteroid resistance.