- Clinical science
A pheochromocytoma is a catecholamine-secreting tumor that typically develops in the adrenal medulla. Pheochromocytomas are usually benign (∼ 90% of cases) but may also be malignant. Classic clinical features are due to excess sympathetic nervous system stimulation and involve episodic blood pressure crises with paroxysmal headaches, diaphoresis, heart palpitations, and pallor. However, pheochromocytomas may also be asymptomatic or manifest with persistent hypertension. Elevated catecholamine metabolites in the plasma or urine confirm the diagnosis, while imaging studies in patients with positive biochemistry are used to determine the location of the tumor. Surgical resection is the treatment of choice but is only carried out once alpha-adrenergic blockade with phenoxybenzamine has become effective.
- The majority of pheochromocytomas are benign, unilateral, catecholamine-producing tumors, that rarely produce other hormones such as EPO.
- Tumors arise from chromaffin cells, which are derived from the neural crest.
- Localization 
- 25% of pheochromocytomas are hereditary (germline mutations):
MAry P. sang “superCALi-fragilistic-EXpiali-DOcious” to the children 10 times: 10% of pheochromocytomas are MAlignant; 10% show CALcifications; 10% are EXtrarenal; 10% are DUal sided, i.e., bilateral; and 10% affect children.
Clinical presentation is related to fluctuating levels of excess epinephrine, norepinephrine, and dopamine secretion, therefore, symptoms are relapsing and remitting (episodic hyperadrenergic syndrome).
- Episodic hypertension (or persistent hypertension in some cases) 
- Paroxysmal 
- Weight loss due to increased basal metabolism
- Signs of EPO is secreted, if
- Other features consistent with associated familial disorders:
- MEN 2A: medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia
- MEN 2B: medullary thyroid cancer, pheochromocytoma, oral/intestinal neuromas, and marfanoid habitus
- NF1: cutaneous neurofibromas, cafe-au-lait spots, and Lisch nodules
- VHL: renal cell carcinoma, hemangioblastoma, angiomatosis, and pheochromocytoma
5 most important Problems (5 P’s) of Pheochromocytoma: increased blood Pressure, head Pain (headache), Perspiration, Palpitations, and Pallor
Laboratory tests 
Whenever possible, all medications should be put on hold one week prior to testing.
- Best initial test: plasma free metanephrines test 
- Confirmatory test: metanephrines and catecholamines in 24-hour urine (high specificity) 
Clonidine suppression test (rarely used)
- Principle of the test: In healthy patients, clonidine normally significantly decreases plasma catecholamine levels by at least 30%.
- Evaluation of results: If pheochromocytoma is present, catecholamine levels will fail to decrease upon clonidine administration, as the tumor will continue to produce catecholamines.
- Genetic testing: if MEN2A, MEN2B, NF1, or VHL is suspected
- Immunohistochemical staining: positive for chromogranin, synaptophysin, and NSE
Other diagnostic tests 
- 24-hour ambulatory blood pressure monitoring
- Adrenal/abdominal CT or MRI (after positive biochemistry tests to localize tumor)
- Scintigraphy (MIBG)
- Other imagistic tests: to search for potential additional tumors in patients with pheochromocytoma and MEN2A, MEN2B, NF1, or VHL
Pheochromocytoma is often referred to as “the great mimic” because signs and symptoms are similar to those produced by many other clinical conditions. 
The differential diagnoses listed here are not exhaustive.
Management consists of preoperative blood pressure management and then surgery.
- Preoperative blood pressure management: combined alpha-adrenergic and beta-adrenergic blockade
Laparoscopic tumor resection (adrenalectomy): treatment of choice
- No-touch technique
- Open surgical resection is reserved for large or invasive tumors.
Prognosis and follow-up 
- Most patients with benign pheochromocytoma become normotensive after tumor resection. 
- Long-term annual biochemical monitoring for recurrence is indicated in all patients.
- Benign pheochromocytoma recurs in ∼ 15% of patients, usually 5–15 years after surgery.
- Benign pheochromocytoma: primary therapy with phenoxybenzamine
- Metaiodobenzylguanidine (MIBG) therapy: Because MIBG is similar in structure to norepinephrine, it is taken up by sympathetic nerve cells, including neuroblastoma or pheochromocytoma tumor cells, throughout the body. When MIBG is combined with radioactive iodine, it can be used as a treatment that delivers radiation directly to cancer cells.
- Otherwise, palliative treatment (chemotherapy, tumor embolization)
Starting beta-blockers before alpha-blockers is contraindicated. Beta-blockers cancel out the vasodilatory effect of peripheral beta-2 adrenoceptors, potentially leading to unopposed alpha-adrenoceptor stimulation, causing vasoconstriction and ultimately hypertensive crisis.