Relative Adrenal Failure in the ICU: An Identifiable Problem Requiring Treatment
Section snippets
Physiology
The adrenal gland is made of two functional units: the medulla, which produces sympathetic system hormones (epinephrine and norepinephrine) and the cortex consisting of three zones: (1) the zona glomerulosa, superficially located and producing mineralocorticoids (aldosterone and to a lesser extent corticosterone), (2) the zona reticularis, deeper seated and producing weak androgens, and (3) the zona fasciculata, producing glucocorticoids (cortisol and cortisone). Cortisol, the main
The hypothalamic-pituitary-adrenal axis
Cortisol production and secretion is stimulated mainly by the adrenocorticotropin hormone (ACTH) produced in the anterior pituitary. ACTH also stimulates the production of adrenal androgens and, to a lesser extent, of mineralocorticoids [4]. The main stimulators of ACTH production are the corticotrophin hormone (CRH) and arginine vasopressin (AVP), which are secreted by the hypothalamus. Catecholamines, angiotensin II, serotonin, and vasoactive intestinal peptide (VIP) are also known
Metabolic effects
Glucocorticoids play a major role in glucose metabolism, stimulating neoglucogenesis and glycogenolysis, inducing peripheral insulin resistance, and leading to an increase in blood glucose concentration [11]. They also stimulate lipolysis and inhibit glucose uptake by the adipocytes. They inhibit protein synthesis and activate proteinolysis in muscles, liberating amino acids that serve as substrate for neoglucogenesis. They activate osteoclasts, inhibit osteoblasts, inhibit intestinal calcium
Activation of the hypothalamic-pituitary-adrenal axis during stress
Whatever its cause, whether physical (severe infection, trauma, burns, illness, or surgery) or psychological, stress activates the hypothalamic-pituitary-adrenal (HPA) axis with increasing ACTH secretion and cortisol blood levels. Stress also results in a decrease in CBG, leading to an increase in free cortisol blood levels [21], [22]. Cytokines also might increase receptor affinity for glucocorticoids [23]. With stress, the circadian rhythm of diurnal cortisol secretion is lost and there is an
Relative adrenal failure in ICU: birth and death
Secretory failure of the adrenal glands was first implicated as a factor in the pathogenesis of circulatory shock associated with infection after the original report of Waterhouse and Friderichsen [25], [26]. More recent evidence of the critical role of intact adrenal activity in the immediate response to stress came from the observation that the use of etomidate, which blocks the synthesis of cortisol by reversible inhibition of 11-β-hydroxylase, was associated with an increase in ICU
Adrenal-hypothalamic-pituitary axis dysfunction mechanisms in severe sepsis
Glucocorticoid insufficiency may be related to a decrease in glucocorticoid synthesis (ie, AI) or to a reduced delivery of glucocorticoid to target tissues and cells [5].
Clinical diagnosis
Clinical features of AI include abdominal pain, various mental changes, gastrointestinal alterations, hypoglycemia, hyponatremia, hyperglycemia, hyperkalemia, neutropenia, eosinophilia, and fever. The hemodynamic profile often shows a high cardiac output and a low systemic vascular resistance. Many of these signs are not specific to AI. They can be related to various critical illnesses. The biochemical disturbances often are masked by fluid regimens. It is therefore difficult to recognize AI.
Summary
AI is a common and often under diagnosed disorder in critically ill patients. Increased glucocorticoid action is an essential component of the stress response, and even minor degrees of AI can be fatal. It is thus of paramount importance that ICU physicians be aware of this critical illness complication. The diagnosis relies on clinical suspicion and ACTH test results. Hydrocortisone is the mainstay of treatment. It should be started as soon as the ACTH test is performed in patients who have
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