The adrenal glands are located on the upper poles of the kidneys and are composed of two parts: the outer part, called the cortex, and the inner part, called the medulla. The cortex comprises 80% of the gland and secretes several steroid hormones: the mineralocorticoids (aldosterone), androgens, and glucocorticoids (cortisol). The medulla makes up the remaining volume (20%) and secretes epinephrine, norepinephrine, and dopamine and is innervated by the parasympathetic and sympathetic nervous systems.

The hormones of the adrenal cortex are synthesized from cholesterol and acetate. Most corticosteroids (steroids) are produced in response to stimulation of the cortex by adrenocorticotropic hormone (ACTH) from the anterior pituitary, which in turn is stimulated by corticotropin-releasing hormone (CRH) in the hypothalamus. The secretion of ACTH is regulated by three factors: negative feedback, diurnal rhythms, and stress. Negative feedback due to high levels of cortisol or exogenous glucocorticoids suppresses CRH and ACTH. Secretion peaks 3 to 5 hours after sleep begins and declines throughout the day. This is referred to as diurnal rhythm. This pattern is reversed in those who work the night shift. ACTH secretion and cortisol levels are also increased in response to psychological or physical stress. In addition, the adrenals produce small amounts of androgens that are converted in peripheral tissues to estrogen and testosterone. Because of the cyclical pattern of glucocorticoids, it is important to obtain a morning cortisol level to accurately measure levels.

The glucocorticoids, such as cortisol, have metabolic, antiinflammatory, and growth-suppressing effects that include immune responses and antibody production. They increase blood glucose levels by promoting gluconeogenesis in the liver, decreasing cellular uptake of glucose, and stimulating protein catabolism in addition to inhibiting protein synthesis. They also promote lipogenesis and increase blood cholesterol. These hormones inhibit immune and inflammatory responses by suppressing the mediators of these responses and by depressing the action of T lymphocytes and macrophages. The glucocorticoids
produce a variety of additional effects because of the presence of receptors on extraadrenal tissues (Figure 22-1). In addition, they potentiate the effects of catecholamines, thyroid hormone, and growth hormone on adipose tissue. Cortisol is necessary for maintenance of life and protection from emotional and behavioral stress.