Diagnose, Locate, Treat: Disarming Rare Tumors, One Step at a Time
Day to day,
Dr. Karel Pacak is steeped in the technical details and complex scientific language of his cancer specialty: rare tumors known as
pheochromocytoma and paraganglioma. But when asked about his goals, he uses a simpler word: hope.
Dr. Pacak (pronounced
POT-sak), who leads the
Section on Medical Neuroendocrinology in the NICHD’s
Division of Intramural Research, treats patients with these two rare types of tumors. In combining research and care, he said, his ultimate goal is to give his patients hope for a better life.
Listen to Dr. Pacak explain why pheochromocytoma and paraganglioma so often go undiagnosed.
A text alternative is available at
http://www.nichd.nih.gov/news/profiles/researchers/pacak/Pages/transcript1.aspx
Follow the links below to read more about pheochromocytoma and paraganglioma, Dr. Pacak’s career, and the research advances that are leading to new ways to detect and treat these conditions.
Difficult to Diagnose
From the Czech Republic to NIH
Taking the “Rare” Out of “Rare Disease”
Diagnostic Advances
Finding the Tumor
Diagnose, Locate, and Treat
More Information
Difficult to Diagnose
Only about 1,000 people in the United States are diagnosed with pheochromocytoma or paraganglioma each year, according to Dr. Pacak. These tumors send excess stress hormones into the bloodstream, producing symptoms such as high blood pressure, heart palpitations, sweating, anxiety, and severe headaches. However, because these symptoms are often attributed to other causes, typically only half of those who develop pheochromocytoma and/or paraganglioma are diagnosed, he said.
The two types of tumors are similar, but they are found in different places in the body. Pheochromocytomas form on the
adrenal glands, atop the kidneys. Paragangliomas are usually found in the head and neck, but they can also be found on the heart, bladder, spine, chest, abdomen, or pelvis.
Only a small percentage of the tumors are malignant. Even when benign, however, they can be dangerous because of the excess hormones they release. These hormones, called catecholamines, are produced by the adrenal glands and include adrenalin, norepinephrine, and metanephrine. If a tumor remains undetected it will continue to release excess hormones, which can lead to stroke, heart attack, or even death.
From the Czech Republic to NIH
Dr. Pacak grew up in the Czech Republic and attended medical school at Charles University in Prague.
He came to the National Institutes of Health (NIH) in 1990 as a visiting fellow at the National Institute of Neurological Disorders and Stroke (NINDS). After doing his residency at the Washington Hospital Center, he returned to the NIH in 1997 for a fellowship in endocrinology—the study of hormones—at NICHD, where he has remained.
“When I started a fellowship in endocrinology here at the NICHD, I was thinking, ‘How can I use my knowledge about the catecholamines and, of course, my interest in endocrinology and oncology?’ ” Dr. Pacak said. “So, when I put everything together, pheochromocytoma and paraganglioma won. And, of course, I wanted to put together a program that would focus on these patients. I wanted to have better diagnostic tools and better treatments.”
Taking the “Rare” Out of “Rare Disease”
Considering that he has treated at least 300 people with pheochromocytoma or paraganglioma over the years, these tumors are no longer rare to Dr. Pacak. He believes that familiarity with the diseases has contributed to his treatment and research success.
“I have to say that we have excellent doctors outside the NIH and they do a great job,” Dr. Pacak said. “But, of course, the experience for many doctors is limited because it’s a very rare disease.”
Most of Dr. Pacak’s patients have already been diagnosed when they come to the NIH. Some patients are referred by other doctors, and others find him through the Internet or social media.
WATCH: Dr. Pacak comments on advantages NIH offers patients
Diagnostic Advances
Research in the Pacak lab feeds directly into improvements in diagnosing and treating patients with these specific tumors. For example, Dr. Pacak and his collaborators developed a blood test to more accurately determine whether a pheochromocytoma or paraganglioma tumor is present. The test, which detects metanephrine byproducts in the blood, is now considered the diagnostic standard.
“This biochemical test is very sensitive and able to detect the presence of tumors less than one centimeter in size,” Dr. Pacak said. “And, of course, when we detect these tumors, imaging follows to locate the tumors. The patients are operated on, and the outcome for these patients is extremely good....and because this test is very sensitive and specific, we can get these tumors early enough and help patients before they have large tumors and develop metastatic disease.”
In addition to offering patients an earlier diagnosis, the test can reduce costs by forestalling the need for additional tests.
Dr. Pacak’s research team also recently found that when blood contains elevated levels of byproducts of dopamine, another catecholamine, pheochromocytoma or paraganglioma tumors are more likely to spread. Combined with information about the patient’s genetics and the tumor’s characteristics, this “signal” will allow practitioners to assess the likelihood of malignancy and manage patients in a more timely manner.
Finding the Tumor
Once the tumor’s presence has been detected, the trick is to find out exactly where it is. Accurate localization is important to the surgeon who removes the tumor.
Dr. Pacak uses fluorodopamine positron emission tomography, developed at NIH, that makes tumors visible on special scanners. The technology helps doctors find the tumors for treatment and monitor the progress of treatment. This imaging method has proved especially useful for monitoring cases in which tumors metastasize aggressively. Improving ways to find tumors is an active area of research for his lab.
WATCH: Dr. Pacak explains advances in pinpointing tumors
Another part of the Pacak lab’s work is to find new treatments for malignant pheochromocytoma and paraganglioma. This research includes screening drugs, working with animal models, and handling experimental cell lines to help develop new drugs.
“We have some very promising drugs that we think could be used for the treatment of our patients,” Dr. Pacak said. “They are still experimental drugs, but we feel that incorporating these drugs into the current drug regimen or coming up with a new regimen will be possible. We are planning mini-clinical trials to test those drugs.”
WATCH: Dr. Pacak begins clinical trials
Diagnose, Locate, and Treat
As a result of Dr. Pacak’s research, patients can receive a quicker and more accurate diagnosis. Once patients are diagnosed, the location of the tumor can be determined much more precisely, before surgery even begins. There is also a way to better identify which tumors are likely to spread.
“Based on the very good new discoveries in genomics and proteomics, I feel hopeful that there will be some new treatments for patients with this disease, especially those that have a metastatic pheochromocytoma or paraganglioma,” Dr. Pacak said.
Ultimately, he aims to make life better for his patients: “I would say our goal would be to return our patients to their homes, to their moms and their dads, or to their children. And this is why we are now focusing mainly—after 14 years in this field—on therapeutic options.”
More Information
For more information on pheochromocytoma and paraganglioma, use the following links:
-
Division of Intramural Research
-
Program in Reproductive and Adult Endocrinology
- A to Z Health Topics
- NICHD Connection
- News
- National Cancer Institute
- National Library of Medicine
- Sources
- Zhang, Z., Yang, C., Lorenzo, F., Merino, M., Fojo, T., Kebebew, E., … & Pacak, K. (2012). Somatic HIF2A gain-of-function mutations in paraganglioma with polycythemia.
The New England Journal of Medicine, 367, 922–930.
PMID: 22931260
- Jochmanova, I., Yang, C., Zhuang, Z., & Pacak, P. (2013). Hypoxia-inducible factor signaling in pheochromocytoma: Turning the rudder in the right direction.
Journal of the National Cancer Institute,
105,1270–1283.
PMID: 23940289
- Eisenhofer, G., Lenders, J. W., Siegert, G., Bornstein, S. R., Friberg, P., ... & Pacak, K. (2011). Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status.
European Journal of Cancer,48, 1739–1749.
PMID: 22036874
- Timmers, H. J., Kozupa, A., Chen, C. C., Carrasquillo, J. A., Ling, A., Eisenhofer, G., … & Pacak, K. (2007). Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma.
Journal of Clinical Oncology,25, 2262–2269.
PMID: 17538171
- Pacak, K., Jochmanova, I., Prodanov, T., Yang, C., Meriono, M. J., Fojo, T., … & Zhuang Z. (2013). New syndrome of paraganglioma and somatostatinoma associated with polycythemia.
Journal of Clinical Oncology, 31, 1690–1698.
PMID: 23509317