14 - The Adrenal Cortex and Its Disorders

Abstract

The adrenal cortex produces dozens of steroids having varying degrees of glucocorticoid, mineralocorticoid, and androgenic activity. Cortisol, the principal glucocorticoid, and aldosterone, the principal mineralocorticoid, are essential for normal physiology. Steroidogenesis entails more than 25 enzymes and cofactors arrayed in complex pathways that differ among the various types of steroidogenic cells; some important pathways are newly described. Evaluation of adrenal function entails steroid measurements in basal, stimulated, and inhibited states. Many technologies are used for steroid measurements, yielding different results; the endocrinologist must be familiar with the assay technologies used and normal values by age and sex. Adrenal insufficiency (Addison disease) may be attributable to autoimmune, infectious, or genetic causes. Glucocorticoid excess (Cushing syndrome) may be caused by adrenocorticotropic hormone (ACTH) of pituitary or tumor origin, or caused by adrenal genetic disorders or tumors. Mineralocorticoid excess (hyperaldosteronism) may be caused by adrenal tumors (Conn syndrome) associated with genetic disorders of potassium channels. Steroid hormones act via nuclear receptors; genetic disorders affecting these may mimic steroidal excess or deficiency states. In all, over 100 genes relevant to steroid hormone production, metabolism, or action may be seen as adrenal disorders. Deficiency states are known for most of these, yielding complex clinical phenotypes attributable to deficient hormonal products and accumulated hormonal precursors. Many apparently unrelated medical conditions and commonly used drugs may increase or decrease steroid metabolism. Steroids are widely used as therapeutic agents; the relative activities of different agents as glucocorticoids, mineralocorticoids, and growth suppressants are discordant. Withdrawal from long-term glucocorticoid treatment may be difficult and require substantial time.