The adrenal cortex synthesizes and secretes several hormones. Among them are the glucocorticoid cortisol, the mineralocorticoid aldosterone, and a small amount of the sex steroid androgen. Aldosterone, under the influence of the renin-angiotensin system and other metabolic pathways, regulates sodium, potassium, and water retention in the body. Cortisol has a powerful antiinflammatory effect, modifies the body’s immune response, and influences metabolic processes. The production of cortisol is controlled by a negative feedback loop involving the hypothalamus-anterior pituitary-adrenal cortex (HPA) axis (Figure 51-1). A low level of plasma cortisol stimulates the anterior pituitary to increase production of ACTH, which, in turn, stimulates the adrenal cortex to increase cortisol secretion. Similarly, a high level of circulating cortisol prompts downregulation of ACTH production and a resultant decrease in adrenal cortex production of cortisol.

Cortisol is naturally secreted in an uneven pattern over 24 hours, totaling 10 mg/day in normal adults. Secretion is highest during the early morning hours—2:00 to 7:00 am—and lowest in the evening—6:00 pm to midnight.

Mechanism of Action

Glucocorticoids affect the metabolism of carbohydrates, proteins, and fats. They have direct and indirect effects on immune response, modulate inflammatory response, and play a role in the body’s response to stressful stimuli (i.e., fasting states). All drugs in this class are remarkably similar and may be discussed as a group; the most important differences between these drugs consist of duration of action and degree of inherent mineralocorticoid activity, which causes sodium and fluid retention (Table 51-2). Mineralocorticoid activity is needed in adrenal insufficiency but not in severe inflammation. Both cortisone and hydrocortisone have glucocorticoid and mineralocorticoid properties. Their synthetic analogs prednisone, prednisolone, and methylprednisolone have both effects as well, although glucocorticoid effects predominate. By contrast, triamcinolone, dexamethasone, and betamethasone have exclusively glucocorticoid antiinflammatory activity.