Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two primary enzymes responsible for the degradation of catecholamines. Norepinephrine, a neurotransmitter, undergoes degradation by MAO and COMT after being taken up into the presynaptic terminal. This degradation mechanism is also involved in breaking down circulating adrenal catecholamines. However, COMT plays a major role in methylating adrenal catecholamines in nonneuronal tissues like the liver and kidney. Clinical assessment of catecholamine production in patients often involves the measurement of urinary vanillylmandelic acid (VMA) and metanephrine. It is important to note that a significant portion of urinary VMA and metanephrine is derived from neuronal rather than adrenal catecholamines.

Pheochromocytomas are tumors of chromaffin tissue that overproduce catecholamines. While these tumors commonly occur in the adrenal medulla, they can also arise in other chromaffin cells of the autonomic nervous system. Pheochromocytomas are not frequently encountered, but they are the most common cause of adrenal medullary hyperfunction. Norepinephrine is the catecholamine most commonly elevated in pheochromocytoma cases. The symptoms associated with excessive catecholamine secretion are often sporadic rather than continuous, for reasons that remain unknown. These symptoms include hypertension, headaches (caused by hypertension), sweating, anxiety, palpitations, and chest pain. Interestingly, patients with this disorder may also exhibit orthostatic hypotension, despite the tendency for hypertension. This occurs due to the downregulation of receptors in response to hypersecretion of catecholamines, leading to a decreased postsynaptic response to norepinephrine. Consequently, the baroreceptor response to blood pressure shifts upon standing is blunted.

The zona fasciculata is responsible for producing cortisol, a glucocorticoid hormone. This zone consists of actively steroidogenic tissue composed of large cells arranged in straight cords. The cytoplasm of these cells appears "foamy" because it is filled with lipid droplets that represent stored cholesterol esters (CEs). While these cells can synthesize some cholesterol de novo, they also import a significant amount of cholesterol from the blood in the form of low-density lipoprotein (LDL). LDL particles bind to their receptor (LDLR) and are subsequently endocytosed. Within endolysosomes, a lysosomal lipase releases free cholesterol (FC) from CEs, and Niemann-Pick C (NPC) proteins transport the FC out of the endolysosome. After esterification by acyl CoA-cholesterol acyltransferase (ACAT), free cholesterol is stored in lipid droplets in the cytoplasm. This stored cholesterol undergoes continual conversion back into free cholesterol through the action of hormone-sensitive lipase (HSL), a process that is stimulated by adrenocorticotropic hormone (ACTH).

All steroid hormone synthesis begins in the mitochondria, where the first enzyme, CYP11A1, is anchored to the inner mitochondrial membrane. While several proteins are involved in transporting FC into the inner mitochondrial matrix, one crucial protein called steroidogenic acute regulatory protein (StAR protein) is essential for this process.
Two primary enzymes are involved in the degradation of catecholamines: monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). The neurotransmitter norepinephrine is degraded by MAO and COMT after uptake into the presynaptic terminal. This mechanism is also involved in the catabolism of circulating adrenal catecholamines. However, the predominant fate of adrenal catecholamines is methylation by COMT in nonneuronal tissues such as the liver and kidney. Urinary vanillylmandelic acid (VMA) and metanephrine are sometimes used clinically to assess the level of catecholamine production in a patient. Much of the urinary VMA and metanephrine is derived from neuronal rather than adrenal catecholamines.
Pheochromocytoma isatumorofchromaffintissuethatproducesexcessivequantitiesofcatecholamines.Thesearecommonlyadrenalmedullarytumors,buttheycanoccurinotherchromaffincellsoftheautonomicnervoussystem.Althoughpheochromocytomasarenotcommontumors,theyarethemostcommoncauseofhyperfunctioningoftheadrenalmedullary.Thecatecholaminemostfrequentlyelevatedinpheochromocytomaisnorepinephrine.Forunknownreasonsthesymptomsofexcessivecatecholaminesecretionareoftensporadicratherthancontinuous.Symptomsincludehypertension,headaches(fromhypertension),sweating,anxiety,palpitations,andchestpain.Inaddition,patientswiththisdisordermayshoworthostatichypotension(despitethetendencyforhypertension).Thisoccursbecausehypersecretionofcatecholaminescandecreasethepostsynapticresponsetonorepinephrineasaresultofdownregulationofthereceptors(see ).Consequentlythebaroreceptorresponsetobloodshiftsthatoccursonstandingisblunted.
The zona fasciculata produces the glucocorticoid hormone cortisol. This zone is an actively steroidogenic tissue composed of straight cords of large cells. These cells have a “foamy” cytoplasm because they are filled with lipid droplets that represent stored cholesterol esters (CEs). These cells make some cholesterol de novo but import a significant amount of cholesterol from the blood in the form of low-density lipoprotein (LDL). LDL particles bind to their receptor (LDLR) and are endocytosed. Within endolysosomes, free cholesterol (FC) is released from CEs by a lysosomal lipase, and the FC is transported out of the endolysosome by Niemann-Pick C (NPC) proteins. Free cholesterol is stored in lipid droplets in the cytoplasm after esterification by acyl CoA-cholesterol acyltransferase (ACAT) (
Fig. 43.7 ). The stored cholesterol is continually turned back into free cholesterol by hormone-sensitive lipase (HSL), a process that is increased in response to adrenocorticotropic hormone (ACTH; see
Regulation of
All steroid hormone synthesis begins in the mitochondria, where the first enzyme, CYP11A1, is attached to the inner mitochondrial membrane. Although several proteins appear to be involved in the transfer of FC into the inner mitochondrial matrix, one protein called steroidogenic acute regulatory protein (StAR protein) is indispensable in this process (see