Pheochromocytomas are neural crest-derived tumors that produce catecholamines, such as epinephrine and norepinephrine, and arise mainly from the adrenal gland. Closely affiliated tumors of extra-adrenal paraganglia are also known as extra-adrenal pheochromocytomas. All these functional chromaffin tumors can result in substantial morbidity and mortality due to catecholamine over-secretion.
Pheochromocytoma can have exceptionally variable clinical presentation – from rare and escalating hypercatecholaminergic incidents, through rather stable hypertension, to dire and clinically malignant illness that can be complicated by hypertensive crisis, acute myocardial infarction, stroke, and a myriad of other emergent conditions.
Causes of Pheochromocytoma
A majority of pheochromocytomas are sporadic; nevertheless, in about 30 percent of patients this condition arises as part of a familial disorder. In such cases, the catecholamine-secreting tumors are usually presented as bilateral adrenal pheochromocytomas (or paragangliomas).
When compared to sporadic neoplasms, hereditary pheochromocytomas typically present in younger individuals. Sporadic pheochromocytoma is thus usually diagnosed according to the symptoms or, sometimes, as an incidental finding on computed imaging, while syndromic pheochromocytoma is regularly diagnosed earlier in the course of disease by employing biochemical and/or genetic surveillance.
The catecholamines – epinephrine and norepinephrine – exert their action on α- and β-adrenoceptors that are found throughout the human body with various organ-specific distributions. Both catecholamines show overlapping but also distinctive activity on the different groups of those adrenoreceptors. Specifically, epinephrine has stronger activity on β2-adrenoceptors than norepinephrine, whereas norepinephrine is considered a more potent agonist of β1-adrenoceptors.
Still, the propinquity of sites of epinephrine and norepinephrine release to aforementioned adrenoceptors and the ensuing concentrations at the effector sites are two key determinants of adrenoceptor-mediated clinical responses to these two aromatic amines (i.e. catecholamines).
Signs and symptoms of pheochromocytoma can be highly varied, reflecting the hemodynamic and metabolic activities of the catecholamines that are produced and secreted by the tumors. Attacks (or spells) may occur several times a day, weekly, or very infrequently (e.g., once every few months), while the episodes may last from just a few seconds to one or more hours or even longer in patients with chronically elevated catecholamines.
High blood pressure or hypertension is the most common sign and a cardinal feature of pheochromocytoma, which may be sustained or paroxysmal. Hypertensive crisis, stroke, or shock sometimes also occur in patients with inadequately controlled disease. Pheochromocytoma may also present with low blood pressure, most often as orthostatic hypotension or as fluctuating episodes of high and low blood pressure.
Headache is seen in up to 90% of patients with pheochromocytoma, which can be similar to tension headache in presentation. The excessive and most commonly truncal sweating affects approximately 60-70% patients, while pallor is seen in about 27% of patients. Flushing is much less commonly observed.
The occurrence of the triad that includes headache, palpitations, and excessive generalized sweating in patients with hypertension should immediately arouse suspicion that pheochromocytoma is the underlying cause. A tachycardia during a blood pressure surge should also point towards this diagnosis.
Other common symptoms are severe anxiety, fatigue, weakness, tremulousness, nausea, dyspnea, weight loss despite normal appetite (which is a result of catecholamine-induced breakdown of sugar and fat storages), visual issues during an attack and overwhelming tiredness following an attack.
The attacks can be triggered by palpitation of the tumor, exertion, postural changes, trauma, anxiety, pain, foods or drinks containing tyramine such as certain cheeses and beers, the use of certain drugs tyramine, histamine, metoclopramide, phenothiazine, chemotherapy, induction of anesthesia, endoscopy, catheterization, as well as micturition or bladder distention.
Such kaleidoscopic symptomatology in patients with pheochromocytoma reflects variations in nature and types of secreted catecholamines, but also co-secretion of neuropeptides (corticothropin, vasoactive intestinal peptide, neuropeptide Y, growth hormone-releasing factor, parathyroid hormone-related peptide, somatostatin, and adrenomedulin).
Reviewed by Susha Cheriyedath, MSc