Introduction to Pheochromocytoma and Paraganglioma

Pheochromocytomas are uncommon tumors that arise from cells of the sympathetic nervous system and may secrete catecholamines (adrenalin). Such tumors are usually found within one or both adrenal glands (90%), but may arise in other areas of sympathetic nerve cells, and are then called paragangliomas. About 10% are found to be malignant at the time or immediately after the primary tumor is discovered. Another 5% of individuals with pheochromocytomas are later found to have malignant or recurrent disease. Interestingly, about 10% of such patients do not have hypertension at all or may have hypertension only during surgical procedures or very intermittently at which time a hypertensive crisis can occur.

Pheochromocytomas are a rare cause of hypertension, being the underlying cause of only about .01% of cases of high blood pressure. The manifestations of pheochromocytoma are varied and often not particularly specific and it is easy to understand why such a rare tumor may not be diagnosed immediately by even the most astute physician. Headache, perspiration or palpitation are symptoms found in 90% of such patients. Anxiety, tremor, high blood sugar, nausea, thoracic or abdominal pains, weakness, weight loss, shortness of breath, visual disturbances and heat intolerance are other occasional symptoms. Patients can also sometimes present with confusion or psychosis, constipation, tingling sensations, seizures, or high blood counts as well as Raynaud’s phenomenon. Ironically, patients can also have a slow heart beat (bradycardia) or hypotension, particularly when standing up suddenly.

Treatment of pheochromocytomas involves blocking the effect of catecholamines with an alpha adrenergic blocker such as doxazosin or phenoxybenzamine.  We also use calcium channel blockers, such as nifedipine.   After adequate block, it then becomes safe to surgically remove the pheochromocytoma or paraganglioma. Even relatively large pheochromocytomas have been successfully removed at UCSF Medical Center, usually via laparoscopy. Patients with metastatic or recurrent pheochromocytoma or paraganglioma present a difficult problem. Chemotherapy has not been particularly successful. Radiation therapy can be given to bone metastasis.  An alternative is I-131 MIBG therapy.  For many years, I was the principal investigator for a UCSF phase II clinical trial (later a compassionate use protocol) for I-131 MIBG therapy.  This involves treating patients with metastatic or recurrent pheochromocytoma (and similar tumors) which take up MIBG (metaiodobenzylguanadine). I-131 MIBG can be given to such patients in high doses. The tumor takes up the isotope and delivers a dose of beta radiation to itself.

AZEDRA (iodobenguane I-131) is an FDA-approved form of I-131 MIBG therapy, produced by Progenics Pharmaceuticals / Lantheus called Azedra .

Our UCSF Azedra protocol for malignant pheochromocytomas and paragangliomas involves extensive pre and post-treatment evaluations. Treatment require radiation isolation in a lead-shielded room. The therapy and adjuvant medication does cause nausea, so we pre-treat patients with ondansetron. The treatment course takes several days.

Azedra treatment is currently considered helpful but is unlikely to be curative, although several cases of complete remissions have occurred. Symptomatic or objective responses to treatment occur in over 70% of patients.

LUTATHERA  (lutetium Lu 177 dotatate) is also called PPRT (peptide receptor radionuclied therapy) is a newer form of radioisotope therapy for patients with metastatic pheochromocytoma and paraganglioma.  Lutathera is FDA-approved for treating patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are positive for somatostatin receptors on diagnostic dotatate PET scanning.  Treatment typically requires four therapies of about 200 mCi each, given every two months.  Pre-treatment with intravenous peptides is required for renal protection.  This treatment delivers mostly beta radiation to the tumors with negligible gamma radiation, so patients typically do not require hospitalization for radiation isolation.


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