Tumors that secrete chatecholamines are rare (incidence 0.8/100.000) and may be responsible for up to 0.2 percent of hypertension cases. The majority occurs in a sporadic fashion, although 30% may be a part of a genetic or familial disorder, such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau syndrome and neurofibromatosis type 1. Approximately 85-90% of the tumors are located on the adrenals, and 10-15% are extra-adrenal (paragangliomas).
The clinical presentation, diagnosis and treatment of pheochromocytoma (and paragangliomas) is discussed below.
SIGNS & SYMPTOMS:
Symptoms occur in ~50% of patients and are often episodic and paroxysmal in nature.
The classic triad consists of headache, hypertension and sweating. Other clinical features that may be present include palpitations, diaphoresis, tremors, weakness, anxiety and cardiomyopathy.
If a diagnosis of pheochromocytoma is suspected, evidence of catecholamine hypersecretion should be obtained. This evidence may be obtained through the measurement of metanephrines and catecholamines on 24h urine or plasma fractionated metanephrines (drawn supine from indwelling cannula after 30 minutes). These tests should be performed only after the discontinuation of some medications that may interfere with the results (e.g. tricyclic antidepressants, levodopa, decongestionants, amphetamines, buspirone, ethanol).
The plasma fractionated metanephrines have very good negative predictive value, but poor specificity, so a negative test may exclude the disease, but a positive test does not confirm it.
After biochemical confirmation (e.g. urine normetanephrine >900mcg/24h, norepinephrine >170mcg/24h, epinephrine >35mcg/24h or dopamine >700mcg/24h OR plasma metanephrine >0.3nmol/L and normetanephrine >0.66 nmol/L), an imaging method should be used to locate the tumor (CT/MRI of the abdomen and pelvis).
If the imaging is positive (or negative but suspicion remains high) functional imaging such as iodine-123 metaiodobenzylguanidine scintigraphy (123I MIBG) or fludeoxyglucose-positron emission tomography (FDG-PET) should be obtained.
Every patient with a established diagnosis of pheochromocytoma should be treated with resection of the tumor.
Before surgery it is important to prepare the patient, since the risk of hypertensive crisis during the resection and hypotension after the resection is very high.
Alpha-blockers should be given 10-14 days before surgery (e.g. phenoxybenzamine 10mg BID, with dose increments of 10mg every 2 days up to max of 100mg/day). High-sodium diet (>5g/day) is recommended after the third day of the alpha-blocker in order to improve the intravascular contraction that is common in patients with pheochromocytoma.
After the alpha-blockage is performed, beta-blockers should be given 2-3 days before surgery. It should be started with short-acting beta-blockers (e.g. propranolol 10mg q6hr). If the patient is able to tolerate well, it can be changed for a long acting beta-blocker. The target heart-rate is 60-80 bpm.
In patients that cannot tolerate the alpha and beta adrenergic blockage or in those who cannot reach proper blood pressure control despite optimum adrenergic blockage, calcium channel blockers can be used (e.g. nicardipine 30mg PO BID preoperatively and IV infusion intraoperatively).
The adrenalectomy should be performed by an experienced surgeon, preferentially through laparoscopic approach. For tumors larger than 6cm an open resection is a better option. Patients with familial disease (e.g. MEN2) and evidence of bilateral disease should receive bilateral adrenalectomy.
During surgery, hypertension can be treated with IV nitroprusside, phentolamine or nicardipine, and arrhytmias may be treated with lidocaine or beta-blockers (e.g. esmolol). After resection, hypotension should be treated with fluids and vasopressors if needed.
Postoperative concerns include hypotension (may be managed with fluids), hypoglicemia (may be managed with glucose) and adrenal insufficiency in patients with bilateral resection (may be managed with hydrocortisone 100mg IV q8h for 24h then tapering over three days to 25mg IV or PO BID OR prednisone 10mg PO qDay).
Malignant pheochromocytomas or paragangliomas (metastatic disease) may benefit from resections for symptomatic control and chemotherapy (cyclophosphamide, vincristine, and dacarbazine )
SOURCES & FURTHER READING:
- Lenders JWM et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab (2014) 99 (6): 1915-1942.
- Bravo EL, Tagle R. Pheochromocytoma: State-of-the-Art and Future Prospects. Endocr Rev (2003) 24 (4): 539-553. Endocr Rev 2003; 24 (4): 539-553.
- Pacak K et al. Recent Advances in Genetics, Diagnosis, Localization, and Treatment of Pheochromocytoma. Ann Intern Med. 2001;134(4):315-329.
- Lenders JWM et al. Biochemical Diagnosis of PheochromocytomaWhich Test Is Best? JAMA. 2002;287(11):1427-1434.
- Amar L et al. Genetic Testing in Pheochromocytoma or Functional Paraganglioma. Journal of Clinical Oncology 23, no. 34 (December 2005) 8812-8818.
- Benn DE et al. Clinical Presentation and Penetrance of Pheochromocytoma/Paraganglioma Syndromes. J Clin Endocrinol Metab (2006) 91 (3): 827-836.