Describe the clinical presentation of and diagnostic criteria for pheochromocytoma

Describe the clinical presentation of and diagnostic criteria for pheochromocytoma.

The classic presentation of pheochromocytoma is a triad of symptoms including headache, diaphoresis, and palpitations. This triad plus the presence of hypertension are almost pathognomonic. However, fewer than 20% of patients present with these symptoms. The remainder pre-sent with only one or two signs or symptoms and require vigilance to diagnose.

Hypertension, either sustained or paroxysmal, is the most common presenting sign (90%) with pheochromocy-toma, although the tumor accounts for only 0.1–0.5% of all cases of hypertension. The most common symptom is headache, secondary to hypertension. Other symptoms attributable to severe hypertension are nausea, vomiting, and slow palpitations. Hypertension may be precipitated by abdominal palpation, postural alterations, exercise, drugs, surgery, or micturition in the case of bladder tumors. Tumors producing predominantly epinephrine or dopamine are more likely to cause palpitations, diaphoresis, and, rarely, panic attacks.

Chronic exposure to elevated levels of catecholamines predisposes to cardiomyopathy. Chronic norepinephrine stimulation leads to hypertrophic changes, and chronic epinephrine and dopamine stimulation leads to high-output failure. Rarely, the tumor will present with con-gestive heart failure, myocardial infarction, or cerebral hemorrhage.

Diagnostic confirmation requires laboratory studies. Norepinephrine, epinephrine, and dopamine can be mea-sured directly in serum or urine. Measurement of these catecholamines is sensitive in patients with sustained hypertension, but may give false-negative results in patients with paroxysmal symptoms. Norepinephrine and epinephrine are metabolized by catechol-O-methyltrans-ferase to normetanephrine and metanephrine, respectively. In turn, these are both metabolized to vanillylmandelic acid (VMA), which is excreted in the urine. Dopamine, which can also be measured directly, is metabolized to homovanillic acid (HVA), which is often confused with VMA. Urinary screening of these metabolites is very sensitive but not very specific because numerous stress-related conditions may lead to their elevation. Metabolism of catecholamines to free metanephrines occurs within the tumor cells, and is independent of catecholamine release. Thus, measurement of free serum metanephrines is reliable in almost all patients. Methyldopa or monoamine oxidase inhibitors interfere with urinary VMA determinations.

CT and magnetic resonance imaging (MRI) can detect even very small lesions (0.5 cm or less in diameter) and are particularly useful in locating adrenal lesions. Tumors are extra-adrenal in 10–15% of cases, and many of these are missed on CT or MRI. Additional tests to determine the presence and location of these small tumors include metaiodobenzylguanidine (mIBG) scintigraphy, and positron emission tomography (PET) using ¹¹C-hydroxyephedrine. These will highlight active neuroendocrine tissue. In complex diagnostic cases, differential venous sampling for catecholamines may also give clues to the tumor location.

Most pharmacologic tests for diagnosing pheochromocy-toma are outmoded. Administration of histamine, tyramine, or glucagon risks hypertensive crises from stimulation of the tumor. One useful and safe pharmacologic challenge is the clonidine suppression test. Clonidine administration will produce a lowering of plasma catecholamine levels in hypertensive patients without a pheochromocytoma, but have no effect in patients with the tumor.