The following is a partial list of differential diagnosis of hypertension:

Pheochromocytomas are catecholamine-secreting tumors of chromaffin tissue. The precise etiology of these tumors is unknown. They are usually located in the adrenal medulla or sympathetic paraganglia but may be found anywhere chromaffin tissue exists. These locations extend from the base of the skull to the anus. Traditionally, it was thought that 90% of pheochromocytomas were found in the adrenal medulla and 10% occurred elsewhere. Prevalence of extra-adrenal tumors is now thought to be as high as 20%. These are commonly called paragangliomas.

Pheochromocytomas account for only 0.1% of all cases of arterial hypertension. They are prevalent in 0.005% to 0.01% of the population. When unsuspected or improperly managed during surgery, the hemodynamic effects of the released catecholamines can be profound.

The adrenal glands are paired, mustard-colored structures positioned superior and slightly medial to the kidneys in the retroperitoneal space. Each gland is supplied by three arteries: the superior adrenal arteries derived from the inferior phrenic artery, the middle adrenal arteries derived from the aorta, and the inferior adrenal arteries derived from the renal artery. In contrast to the arterial supply, each adrenal gland usually is drained by a single, major adrenal vein. The right adrenal vein is usually short and drains into the inferior vena cava (IVC), whereas the left adrenal vein is longer and empties into the left renal vein. Accessory veins occur in 5% to 10% of patients and are an important consideration during pheochromocytoma resection.

In most respects, the cortex and medulla of the adrenal gland can be considered as two completely distinct organs that happen to colocalize during development. They are of separate
embryologic origin; the medullary portion is derived from the chromaffin ectodermal cells of the neural crest and develops in parallel with the sympathetic system during development, and the cortex originates around the fifth week of gestation from mesodermal tissue near the gonads on the adrenogenital ridge.

The chromaffin cells become enclosed within the cortex to form the medulla. The organs of Zuckerkandl are paraganglia around the aorta at the level of the kidney anterior to the inferior aorta. Accessory areas for the occurrence of pheochromocytoma are in the mediastinum, in the bladder, occasionally in the neck, in the sacrococcygeal region, or in the anal or vaginal areas.

The adrenal medulla primarily secretes three substances, all of which are catecholamines: epinephrine, norepinephrine, and dopamine. These three compounds are found in all the chromaffin cells of the sympathetic nervous system, which includes the adrenal medulla, aberrant tissue along the sympathetic chain, and paraganglia. Both norepinephrine and dopamine are found at the endings of the postganglionic fibers of the sympathetic nervous system and in the central nervous system.

These catecholamines exert their effects by acting on β-adrenergic and α-adrenergic receptors. β-Receptor stimulation results in G protein-mediated activation of adenylate (adenylyl) cyclase, which increases cyclic adenosine monophosphate (cAMP) levels.

Stimulation of the α₁ subtype of the α-receptor results in G protein-mediated hydrolysis of phospholipid membranes, which cause an increase in cytoplasmic Ca²⁺ levels and subsequent smooth muscle contraction. The stimulation of α₂ receptors, conversely, inhibits the action of adenylate cyclase and decreases cAMP (Fig. 22.1).

The pharmacologic response is dependent on the location of the catecholamine receptors throughout the body. The distribution and density of the receptors will determine the predominant response to each catecholamine.

The synthesis of endogenous catecholamines begins with the active transport of the amino acid tyrosine from the circulation into postganglionic sympathetic nerve endings. The hydroxylation of tyrosine is regarded as the rate-limiting step of the pathway (Fig. 22.2). The termination of the action of catecholamines occurs primarily through reuptake at nerve terminals. Diffusion and metabolism, by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), also play a role in termination of action.

The adrenal cortex secretes more than 30 different corticosteroids. These can be divided into three major classes: mineralocorticoids, glucocorticoids, and sex steroids (the androgens and estrogen).

The precursor of all corticosteroids is cholesterol. Aldosterone is the most important mineralocorticoid secreted by the adrenal cortex, whereas cortisol is the most important glucocorticoid secreted. The adrenal cortex is also responsible for secreting sex steroids.

Each of these substances is secreted by different zones. The mineralocorticoids are secreted by the zona glomerulosa, glucocorticoids are secreted by the zona fasciculata, and sex steroids are secreted by the zona reticularis.

The glucocorticoids have their predominant mechanism of action on intermediary metabolism. These effects include increased gluconeogenesis, fatty acid mobilization, protein
catabolism, and anti-inflammatory effects. Cortisol may improve cardiac function by improving responsiveness of β-adrenergic receptors. Approximately 95% of the glucocorticoid activity is from the secretion of cortisol.

The mineralocorticoids predominantly act on the body minerals, such as sodium and potassium. By conserving sodium ions, they sustain extracellular fluid volume. They also help maintain normal potassium plasma concentrations.