Although the presence of signs and symptoms of catecholamine excess remains the principal reason for initial suspicion of pheochromocytoma, this does not imply that all pheochromocytomas exhibit such manifestations. Increasing proportions of these tumors are now being discovered incidentally during imaging procedures for unrelated conditions or during routine periodic screening in patients with identified mutations that predispose to the tumor. In such patients the clinical presentation may differ considerably from those in whom the tumor is suspected based on signs and symptoms.

The varied signs and symptoms of pheochromocytoma (Table 1) mainly reflect the hemodynamic and metabolic actions of the catecholamines produced and secreted by the tumors .

Hypertension is the most common sign and may be sustained or paroxysmal, with the latter more usual presentation occuring on a background of normotension or sustained hypertension. Pheochromocytoma may also present with hypotension, particularly postural hypotension or alternating episodes of high and low blood pressure .

As illustrated in Table 1, symptoms of pheochromocytoma are wide ranging and, in isolation, not uncommon in the general population. Headache occurs in up to 90% of patients with pheochromocytoma . In some patients catecholamine-induced headache may be similar to tension headache. Excessive, most commonly truncal, sweating occurs in approximately 60-70% patients. A typical sign of catecholamine excess is also pallor seen in approximately 27% of patients whereas flushing is much less common. The presence of triad including headache, palpitations and sweating in patients with hypertension arouse immediate suspicion for a pheochromocytoma. Other common complaints are palpitations and dyspnea, weight loss despite normal appetite (caused by catecholamine-induced glycogenolysis and lipolysis), visual problems during an attack and profound tiredness and polyuria most commonly experienced after an attack. Most patients also present with severe episodes of anxiety, nervousness, or panic attacks. Less frequent clinical manifestations include fever of unknown origin (hypermetabolic state) and constipation . Except for clinical signs and symptoms as described above, patients with malignant pheochromocytoma present with pain (most commonly in bones) due to metastatic lesions.

Attacks (spells) of signs and symptoms may occur weekly, several times daily, or as infrequently as once every few months; Most last less than an hour, but rarely more than several days. Attacks may be precipitated by palpitation of the tumor, postural changes, exertion, anxiety, trauma, pain, ingestion of foods or beverages containing tyramine (certain cheeses, beers, and wines), use of certain drugs (histamine, glucagon, tyramine, phenothiazine, metoclopramide, adrenocorticotropic hormone), intubation, induction of anesthesia, chemotherapy, endoscopy, catheterization, and micturition or bladder distention (with bladder tumors).

Highly variable symptomatology in patients with pheochromocytoma, may reflect variations in nature and types of catecholamines secreted, as well as co-secretion of neuropeptides: vasoactive intestinal peptide, corticotrophin, neuropeptide Y, atrial natriuretic factor, growth hormone-releasing factor; somatostatin, parathyroid hormone-related peptide, calcitonin, and adrenomedulin. The classic example is the pheochromocytoma with ectopic secretion of corticotrophin or corticotrophin-releasing factor, resulting in the presentation of Cushing’s syndrome. Pheochromocytomas have also been described that secrete excessive amounts of vasoactive intestinal peptide, this resulting in presentation of watery diarrhea and hypokalaemia.