The “fight or flight” response of the sympathetic nervous system is a direct result of the multisystem action of catecholamines. Secretion from the adrenal medulla proceeding the activation of the sympathetic nervous system functions to regulate blood pressure by contracting the smooth muscle in the vasculature (via alpha-1 receptors). The adrenergic receptors linked to blood vessels have an especially high affinity for norepinephrine relative to the other amines. Further musculoskeletal actions of catecholamines include enhanced contractility of cardiac muscle (via beta-1 receptors), contraction of the pupillary dilator (via alpha-1 receptors), piloerection (via alpha-1 receptors), and relaxation of smooth muscle in the gastrointestinal tract, urinary tract, and bronchioles (via beta-2 receptors). Both epinephrine and norepinephrine modulate metabolism to increase blood glucose levels by stimulating glycogenolysis in the liver (via beta-2 receptors), increased glucagon secretion (via beta-2 receptors) and decreased insulin secretion (via alpha-2 receptors) from the pancreas, and lipolysis in adipose tissue (via beta-3 receptors). Epinephrine also inhibits release of mediators from mast cells and basophils in type I hypersensitivity reactions.

After an external stimulus triggers the body’s stress response, the pituitary-adrenal axis and sympathetic division of the autonomic nervous system is activated. Glucocorticoids production increases in the adrenal cortex, and acetylcholine (Ach) is released from sympathetic splanchnic nerves. Ach binds to nicotinic receptors located on the membrane of chromaffin cells in the adrenal medulla. These receptors promote exocytosis of catecholamine-filled vesicles for transport in the bloodstream. In the blood, catecholamines target alpha and beta-adrenergic receptors, a family of g protein coupled receptors (GPCRs). These alpha and beta receptors can be further subdivided and subtyped with alphanumeric designation based on their cellular localization. The adrenergic receptors utilize either cyclic adenosine monophosphate (cAMP) or phosphoinositol second messenger systems to activate ion channels that ultimately mediate the body’s sympathetic response.

Laboratory studies to detect a pathological increase in circulating catecholamines due to adrenal neoplasm, pheochromocytoma, utilizes the normal excretion of metanephrines through the renal system. Increased levels of urinary or plasma metanephrines, the normal breakdown product of catecholamines, is a highly sensitive screening test for pheochromocytoma. Measuring VMA levels in a 24-hour urine collection is a highly specific test in the diagnosis of pheochromocytoma. CT, MRI, or PET imaging commonly follow a biochemical diagnosis of pheochromocytoma via urine studies to visualize the extent of the neoplastic process. Additional serum, imaging, and genetic investigations may be indicated proceeding the diagnosis of a pheochromocytoma due to its association with familial multiple endocrine neoplasia syndromes.

Impaired neurotransmission or excess circulating levels of catecholamines leads to pathophysiologic effects. Congenital catecholamine deficiency may occur as an exceedingly rare inborn error of adrenal medullary development. Functional deficiency due to impaired mechanisms of catecholamine release, reuptake, or receptor sensitivity has neurophysiologic effects involving dysregulation of mood and attention. Excess catecholamines and their pathophysiologic equivalents may arise from several etiologies including exogenous administration of frank catecholamines, derivative adrenergic agonists (e.g., isoproterenol, phenylephrine), or reuptake inhibitors (e.g., amphetamines, cocaine). Excess levels also may occur from endogenous catecholamine overproduction from a pheochromocytoma. The pathophysiologic response is increased in an exaggerated sympathetic response due to overactivation of adrenergic receptors.[10][11][12]

Catecholamines are implicated in the pharmacologic treatment of a multitude of diseases and disease processes. Epinephrine and norepinephrine are frequently used as vasopressive agents to treat acute hypotensive states, as well as in treatment algorithms for cardiac arrest. Their affinity to the alpha-1 receptor also is used to induce localized vasoconstriction to reduce bleeding during procedures such as wound closure. By the same mechanism, catecholamine-releasing agents in the form of sprays or ointments are used as nasal decongestants. The pharmacodynamic inhibition of catecholamine reuptake is commonly used in the psychiatric treatment of some depressive disorders, post-traumatic stress disorder, anxiety disorders, attention deficit disorder, and panic disorders. Catecholamine reuptake inhibitors also may be used to treat neuropathic and chronic musculoskeletal pain. Epinephrine is the universal treatment for anaphylaxis and is also used to treat other causes of laryngeal edema (e.g., croup) or bronchospasm. The blockage of adrenergic receptors otherwise activated by catecholamines is an integral part of the treatment of hypertension, congestive heart failure, and other cardiovascular diseases.

Of the several types of neoplasms arising from the adrenal gland, pheochromocytomas are tumors of the adrenal medulla responsible for unregulated secretion of catecholamines. Pheochromocytomas are particularly dangerous due to overactivation of adrenergic receptors which cause episodes of hypertensive urgency. Patients with pheochromocytomas also may experience episodes of other uncomfortable sympathomimetic symptoms including palpitations, sweating, headaches, or anxiety. Pheochromocytomas are often amenable to surgery with or without pharmacotherapy targeting adrenergic blockade.