In June 2014, the Endocrine Society published its first clinical practice guideline for pheochromocytoma and paraganglioma, rare but sometimes dangerous tumors.
Pheochromocytoma is a rare tumor arising from chromaffin cells of the adrenal gland. Paraganglioma is a tumor derived from extra-adrenal chromaffin cells, usually in the thorax, abdomen or pelvis.1
Pheochromocytomas and paragangliomas (PPGL) are usually benign but have malignant potential. These tumors commonly produce one or more catecholamines. Untreated PPGL leads to significant cardiovascular morbidity and mortality.1
“These are the first practice guidelines put out by the Endocrine Society for this very rare disorder. Only a few people in the world have experience dealing with PPGL, so these guidelines can help fill in the knowledge gaps,” said William F. Young Jr., MD, professor and chair of endocrinology, diabetes, metabolism and nutrition at the Mayo Clinic in Rochester, Minn. Dr. Young is also an author of the guidelines.
Why the Guidelines Are Important
The guidelines were created for several reasons. PPGL is a rare disorder, with an incidence of less than 0.6%. However, autopsy studies suggest that these tumors may be missed.
In children with high blood pressure (BP), PPGL may be responsible for close to 2% of cases, and at least one-third of patients are now found to have inherited mutations for PPGL. Therefore, genetic testing for family members may now result in earlier diagnosis.1
“A missed diagnosis or poor management can be tragic. A missed PPGL may become malignant and metastatic. At the end of the guidelines, we stress the importance of getting these patients to a treatment center experienced in managing [PPGL],” Dr. Young said.
“There is not all that much that is new in the guidelines. It is generally what we have been doing,” said Stuart Alan Weinerman, MD, chief at Long Island Jewish Medical Center, and assistant professor of endocrinology at Hofstra North Shore-LIJ School of Medicine in Long Island, N.Y.
“The value of these evidence-based guidelines is that they get everybody on the same page. That means improved quality of care.”
Most doctors know the symptoms of PPGL, which include episodes of high BP, pounding heartbeat, extreme sweating, headache and pallor. The disease usually develops in people aged 20 to 50 years.2The guidelines recommend initial testing for PPGL with plasma free or urinary fractionated metanephrines.1
“This is not new. We have known these are the best tests for screening for about 14 years,” said Dr. Young.
The guidelines also recommend imaging studies if biochemical evidence is confirmed. They suggest CT scan as the best first choice over MRI.
“This is one of the few new wrinkles,” Dr. Weinerman said. “In the past many doctors would do an MRI first.
The guidelines do, however, recommend MRI as an imaging study in patients with metastatic disease.1
“These testing recommendations are important because 40% to 50% of all these tumors are now linked to inherited genes. In 1990 we had identified just one gene. We now have 15,” said Dr. Young.
The guidelines recommend engaging all patients in decisions regarding genetic testing. Both pre-test and post-test counseling should be made available.1
For all patients with PPGL, a clinical feature-driven algorithm for specific genetic testing is recommended in the guidelines. Patients with paraganglioma should be tested for succinate dehydrogenase (SDH) mutations.1
“The expansion of genetic testing is new. I would use the guidelines as a reference for which genetic tests to order,” Dr. Weinerman said.
According to the guidelines, minimally invasive, laparoscopic adrenalectomy is the treatment of choice for most pheochromocytomas. Open resection is suggested for large or invasive pheochromocytomas and for most paragangliomas.
Perioperative management should include preoperative blockade using an alpha-adrenergic receptor blocker. Plasma and urine metanephrines should be monitored postoperatively for recurrent or metastatic disease, according to the guidelines.1
“It should not be assumed that a surgeon who does lots of laparoscopic gall bladder procedures is experienced enough to operate on a pheochromocytoma. These tumors are fragile. A fracture of the tumor during removal can result in an inside spoil that could lead to incurable malignancy,” warned Dr. Young.
Due to the rarity and complexity of PPGLs, the guidelines recommend a personalized approach for testing, imaging, treatment and follow-up care. They also recommend having these evaluations and treatments conducted at a medical center by a multidisciplinary team with appropriate expertise.1
“One of the weaknesses of the guidelines is an absence of good options for treating and managing malignant PPGL. There is no cure and nothing new here. We are still using the same chemotherapy regimens we were using in the 1980s. That is an area where we would like to see some future research and progress,” Dr. Young said.
“The recommendation for specialized care is important and could be used to convince insurance companies to pay for transfer from a community hospital to a major medical center where appropriate care would be available. Overall, these guidelines make a lot of sense and serve as a good standard reference for all clinical endocrinologists,” said Dr. Weinerman.
- Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942.
- National Cancer Institute. Pheochromocytoma and paraganglioma treatment (PDQ®). http://www.cancer.gov/cancertopics/pdq/treatment/pheochromocytoma/HealthProfessional. Accessed August 2014.