Pheochromocytoma

Tumor of chromaffin tissue (neuroectodermal origin), most commonly affecting the adrenal medulla (90% of patients), but may occur in any tissue derived embryologically from the neuroectoderm, including any sympathetic ganglia, the GI tract, bladder, and thorax. Catecholamine-secreting tumor.

Chromaffin Tumors.

Total incidence: 2 to 8 cases per 1 million people of which 10% occur in children. It is the cause of 1 to 2% of systemic hypertension cases in the pediatric population. Compared to adults, children are more likely to present tumors that are bilateral, multiple, or extraadrenal in origin. Familial cases are also more common in children and adolescents. It is more frequent in boys than in girls.

Autosomal dominant. Mutation of RET protooncogene that is located on chromosome 10. Pheochromocytoma can be associated with Neurofibromatosis type I, von Hippel-Lindau Disease, Multiple Endocrine Neoplasia type IIa (Sipple syndrome), Tuberous Sclerosis (Bourneville disease), Sturge-Weber Disease, or Carney triad (gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal pheochromocytoma).

Ninety percent of tumors are benign; multiple sites occur in approximately 35% of children and in 8% of adults. Epinephrine can only arise from the adrenal medulla, norepinephrine can arise from any sympathetic tissue. Elevated catecholamines cause an increase supraventricular rhythm, hypertension, increased cardiac contractility, and rate. Hyperglycemia may result from alpha-2 antagonism of insulin secretion. The catecholamines are metabolized by monoamine oxidase and catechol-O-methyltransferase, 5% of norepinephrine being excreted unchanged; urinary levels reflect plasma levels.

History and examination, especially finding of paroxysmal or sustained hypertension at a young age. Demonstration of elevated urine catecholamine levels.

Symptoms include sweating, palpitations, headache, pallor, vomiting, weight loss, polyuria, polydipsia, and chest pain, which may be cardiac in origin. Examination reveals hypertension, which may be sustained or paroxysmal tachycardia, hypertensive retinopathy, and possibly signs of ventricular failure caused by dilated cardiomyopathy. The ECG may reveal dysrhythmia. In childhood, other catecholamine-secreting tumors, such as neuroblastoma, ganglioneuroblastoma, and ganglioneuroma, should be considered in the differential diagnosis. The tumor may be defined by ultrasonography, CT scan, or MRI scan. Laboratory investigations may reveal a raised hematocrit. Urinary vanillylmandelic acid (VMA) and metanephrines are elevated, as are plasma catecholamine levels. Extraadrenal sites of tumor should be excluded by 131metaiodobenzylguanidine (MIBG) uptake scan. In children, norepinephrine is usually the predominant catecholamine. In case of metastatic malignant tumor, therapeutic doses of 131I-MIBG are administered.

History: Inquire for symptoms of dysrhythmia or ventricular dysfunction. Catecholamine-induced cardiomyopathy is present in approximately 58% of patients. Cardiovascular assessment: ECG, echocardiography. Start alpha blockade. Competitive alpha-antagonists (e.g., phentolamine, prazosin) have been used but do not give the same stability as noncompetitive blockade (phenoxybenzamine). Beta blockade may be started after alpha blockade to control dysrhythmias. The minimum duration for alpha blockade is 36 hours, although the optimal period is not defined. End points used for adequate blockade have included a 5% drop in hematocrit or the maximum dose of phenoxybenzamine at which the side effects are tolerated by the individuals. Respiratory assessment: Chest radiograph to exclude pulmonary congestion. Renal function: Check renal function; hypertensive nephropathy may be present and nephrectomy is occasionally necessary to achieve tumor excision. Metabolic factors: Check blood glucose (insulin rarely needed); exclude hypercalcemia.

Premedication may be desirable. Invasive monitoring, central venous pressure, arterial blood pressure are essential. Swan-Ganz catheter can be useful. Induction of anesthesia and tracheal intubation can be a period of major cardiovascular instability. Surgery is performed by laparotomy or laparoscopy. There may be a place for pulmonary artery catheter use in select patients. Careful attention to patient positioning. Prepare a vasodilator such as sodium nitroprusside to control surges in blood pressure during tumor manipulation. According to the local team experience, other vasodilators may be used (e.g., phentolamine and calcium antagonists such as nicardipine, magnesium sulfate). Esmolol is probably the beta blockade of choice to control dysrhythmias. Hypotension following tumor excision or clamping of its venous drainage should initially be treated with volume loading but a transient infusion of the catecholamine secreted by the removed tumor is sometimes necessary. Communication with the surgeon is mandatory to enable stopping the vasodilator infusion just before tumor excision or venous clamping. Epidural supplementation of general anesthesia is reported but is probably only of use for postoperative analgesia because its intraoperative use may complicate the anesthetic. Postoperatively monitor for hypotension, hypertension, and hypoglycemia in a critical care setting.

Haloperidol, pancuronium, and desflurane are contraindicated. Atropine should be used with caution. The use of magnesium sulfate is recommended to control symptoms and signs of sudden release of catecholamines.

Paraganglioma: This is an extraadrenal pheochromocytoma-like tumor. It is thoracic (posterior mediastinum) in 15% of cases and rarely can secrete catecholamines. It is also located within the bladder.