- Published on
Emergency And Acute Medicine – Pheochromocytoma
Pheochromocytoma is a catecholamine-producing tumor arising from chromaffin tissue of the sympathetic nervous system. Most tumors originate in the adrenal medulla, with approximately 80% being solitary adrenal tumors (more commonly right-sided), 10% bilateral (often inherited), and 10% extra-adrenal (paragangliomas) located in the abdomen, thorax, neck, or bladder. About 10% are malignant. The condition is rare, occurring in approximately 2–8 per million people per year, and accounts for 0.2–0.4% of hypertensive patients, although it is more common in those with severe or refractory hypertension. It typically presents between the third and fifth decades of life, affects males and females equally, and is diagnosed postmortem in nearly half of cases. Approximately 10% are asymptomatic and discovered incidentally on imaging.
Up to 25% of cases are inherited in an autosomal dominant pattern and are associated with syndromes such as Multiple Endocrine Neoplasia type 2A, Multiple Endocrine Neoplasia type 2B, and von Hippel–Lindau disease. MEN 2A includes medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN 2B includes medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and skeletal abnormalities. Von Hippel–Lindau disease is associated with retinal and CNS hemangioblastomas, renal and pancreatic cysts, and pheochromocytoma. Other associations include neurofibromatosis, tuberous sclerosis, and paragangliomas.
The tumor synthesizes and stores catecholamines similarly to the normal adrenal medulla, predominantly secreting norepinephrine and, less commonly, epinephrine. Some epinephrine-predominant tumors may cause hypotensive episodes. Catecholamine release may occur spontaneously due to tumor necrosis or changes in blood flow, or may be triggered by trauma, exercise, surgery, anesthesia, glucagon, metoclopramide, steroids, tyramine-containing foods, iodinated contrast, tricyclic antidepressants, β-blockers, or sympathomimetics.
Hypertension is the most common manifestation and may be paroxysmal, sustained, or sustained with superimposed paroxysms. Classic paroxysms consist of abrupt episodes of severe hypertension, throbbing bilateral headache, tachycardia or palpitations, diaphoresis, pallor, anxiety, and tremulousness. Episodes typically last minutes to hours and increase in frequency and severity over time. Some patients are normotensive, particularly those with small tumors or familial disease. Chronic symptoms may include orthostatic hypotension due to reduced plasma volume, constipation or ileus from decreased peristalsis, weight loss, glucose intolerance, anxiety, and fatigue.
Acute crisis may present with prolonged severe hypertension or shock, hyperpyrexia, lactic acidosis, multiorgan failure, pulmonary edema from stress cardiomyopathy (including Takotsubo), stroke, myocardial infarction, aortic dissection, or acute abdomen due to tumor necrosis or mesenteric infarction. Physical findings often include severe hypertension with orthostatic changes, tachycardia, diaphoresis, pallor, tremor, mydriasis, and signs of hypertensive retinopathy. Café-au-lait spots or thyroid nodules may suggest associated syndromes. Tumors are usually not palpable.
Initial evaluation includes accurate blood pressure measurement with orthostatic readings and ECG to assess for ischemia or dysrhythmia. Laboratory findings may show elevated hemoglobin from hemoconcentration, leukocytosis from demargination, hyperglycemia, lactic acidosis, renal dysfunction, or hypercalcemia (in MEN 2A). The best screening test is plasma-free fractionated metanephrines, which are highly sensitive but may yield false positives. A normal result effectively excludes the diagnosis. Confirmation is typically performed with 24-hour urine collection for catecholamines and metanephrines, including creatinine to confirm adequate sampling. Numerous medications and substances can interfere with results.
Imaging with CT or MRI is used to localize tumors once biochemical confirmation is obtained. MRI is particularly useful for extra-adrenal lesions. Metaiodobenzylguanidine (MIBG) scanning has high specificity but limited sensitivity. Fine-needle aspiration is contraindicated due to risk of catecholamine surge.
Management of hypertensive crisis requires prompt α-adrenergic blockade. Phentolamine is traditionally used as an IV bolus followed by infusion, with aggressive fluid resuscitation to counteract vasodilation-induced hypotension. Alternatively, nicardipine or nitroprusside infusions may be used. β-blockers may be added only after adequate α-blockade to control reflex tachycardia. β-blockade must never be initiated before α-blockade, as unopposed α-stimulation can precipitate severe hypertension. Ventricular arrhythmias may require lidocaine or esmolol.
For preoperative or chronic management, phenoxybenzamine is initiated at least 7 days prior to surgery and titrated gradually. Selective α1-blockers such as doxazosin or terazosin are alternatives. β-blockers are added after adequate α-blockade if tachycardia persists. Calcium-channel blockers may also be used. Metyrosine can inhibit catecholamine synthesis in refractory cases.
Patients with suspected pheochromocytoma and labile blood pressure, hypertensive crisis, arrhythmias, or end-organ damage require admission. Stable patients with mild hypertension may be discharged with close follow-up and initiation of appropriate antihypertensive therapy. Plasma-free metanephrines should ideally be drawn during a hypertensive episode for maximal sensitivity.
Clinically, the combination of paroxysmal severe hypertension, headache, palpitations, and intense diaphoresis is highly suggestive of pheochromocytoma. Pallor rather than flushing is typical. Orthostatic hypotension is common and may worsen after α-blockade if volume repletion is inadequate. The diagnosis should be considered in unexplained shock, cardiomyopathy, recurrent hypertensive crises, or new-onset glucose intolerance with weight loss. Under no circumstances should β-blockers be administered before adequate α-blockade in suspected pheochromocytoma.
0 Comments
