Pheochromocytoma

The most common catecholamine-secreting tumor of the adrenal medulla is the pheochromocytoma.

Incidence of pheochromocytoma and paraganglioma is about 0.6 cases per hundred thousand person-years.

Functional lesions can synthesize and secrete catecholamines leading to headache, sweating and tachycardia.

Catecholamine-secreting pheochromocytomas and paragangliomas are important endocrine  tumors with up to 19% having a life-threatening manifestations as their presentation.

A broad spectrum of presenting symptoms which include the classic triad of headaches, palpitations, and profuse sweating.

Pheochromocytomas and paragangliomas may present with hypertensive emergency, myocardial infarction, heart failure, stroke, hypertension, arrhythmia, aortic dissection, acute psychiatric crisis or even multisystem organ failure.

Commonly anxiety and panic attacks are present.

Patients can experience palpitations, chest pain, dyspnea, nausea and vomiting, weakness, weight loss, polyuria, polydipsia, visual disturbances, arrhythmias, and psychiatric disorders.

Unexplained orthostatic hypotension with paroxysmal or refractory hypertension is an important diagnostic finding.

Approximately 10% are malignant, and the malignant variant is histologically and biochemically the same as benign tumors.

Lesions that contain succinate dehydrogenase B are more likely to develop malignant disease, and patients with this mutation have a shorter survival.

Hallmark of catecholamine excess is myocyte necrosis,inflammation and hemorrhage.

Repeated ventricular stunning by catecholamine excess may lead to ventricular dysfunction.

Surges in circulating catecholamine release may occur spontaneously or be precipitated by induction of anesthesia, by the use of sympathomimetic medications, or manipulation of the tumor at surgery.

Hypertensive emergencies, acute pulmonary edema, acute myocardial ischemia or infarction, arrhythmias, congestive heart failure, and hemodynamic collapse or complications.

Emergent complications of pheochromocytoma associated with a high risk of death, unless rapid implementation of therapy.

Asymptomatic cases of pheochromocytoma and paraganglioma are being discovered on the basis of family and germline mutation testing.

In pregnancy maternal and fetal outcomes or poor, with maternal mortality in excess of 40% and fetal mortality exceeding 50% in the absence of appropriate treatment (Shenker JG).

Hypertensive crises during pregnancy may be related to pressure from the gravid uterus, uterine contractions, tumor hemorrhage, anesthesia, labor and vaginal delivery.

It may be difficult to distinguish pheochromocytoma from preeclampsia during pregnancy.

Common sites of metastases include lymph nodes, bone, liver and lung.

Incidence peaks in the fourth decade.

Lesion is relatively rare in patients younger than 20 years of age.

The diagnosis is confirmed by measurement of urinary and fractionated plasma catecholamines and metanephrines.

Diagnosis of pheochromocytoma or paraganglioma requires both proof of excessive release of catecholamines and documentation of the presence of a tumor.

Increase in plasma fractionated metanephrines has a mean sensitivity of 97% and a specificity of 93% for diagnosis.

Measurement of fractionated catecholamines epinephrine, norepinephrine and dopamine is less sensitive for diagnosis, but elevated values of greater than two times normal are also diagnostic.

Mild increase in the fractionated metanephrines and catecholamines in plasma and urine are common in patients who do not have pheochromocytoma.

The specificity of urine metanephrines is very poor until the results are more than three –five fold elevated and even then, positive predictive value remains less than 20%. 

Tricyclic antidepressants, anti-psychotic drugs, serum reuptake or norepinephrine reuptake inhibitors and levodopa dopa can cause increase in endogenous catecholamines, and can lead to false positive tests.

Venlafaxine, selective serotonin-reuptake inhibitors, tricyclic antidepressants should be avoided during diagnostic evaluation as they could elevate normetanephrine levels.

Caffeine intake, smoking, and other sympathomimetic factors may increase adrenergic receptors and should be discontinued for at least 24 hours before blood sampling.

Alpha adrenergic receptor blockers and Beta adrenergic receptor blockers may reduce catecholamine related symptoms and signs and mask the diagnosis.

Monoamine oxidase inhibitors block the conversion of norepinephrine to dihydroxyphenylglycol, with a greater release of norepinephrine

Acetaminophen may interfere with liquid chromatography assays and should be avoided before blood sampling.

Plasma chromogranin A., a protein that is released along with catecholamines has been used for the diagnosis of this lesion.

Plasma chromogranin A. levels correlate well with plasma metanephrines and tumor burden.

Neuron-specific enolase is a screening marker that may be elevated in patients with malignant disease.

A wide variety of imaging techniques can be used in the valuation of this lesion and include CT scans, MRI and ultrasound.

I131, I123 MIBG, are imaging techniques that can be used as these materials are taken up by adrenal tissues.

MIBG scanning is used for diagnosis and staging of the disease, as well as PET scans.

Primary treatment for malignant diseases, surgical.

Perioperative mortality is 1 to 3%, with adequate pretreatment, but on an emergency basis surgery may be associated with poor outcome.

Preoperative management includes the use of alpha-adrenergic-receptor blockade with phenoxybanzamine , which is utilized over a period of 10 to 14 days. Along with a high salt diet until blood pressure is controlled.

Beta-adrenergic-receptor blockers can be introduced following several days alpha-adrenergic blockade.

Radio-pharmaceuticals such as I 131, or I 123 MIBG have been used for metastatic disease.

A review of 116 patients who received a 131 MIB an objective tumor response was seen in 30%, stable disease and 57% and progressive disease in 13%.

The benefits of chemotherapy have been limited, but agents such as cyclophosphamide, vincristine, DTIC, cisplatin, Etoposide, and an anthracycline have been associated with some success.

The tyrosine kinase inhibitor sunitinib, (Sutent), has been effected in early trials.