Research on pheochromocytoma and paraganglioma is conducted through the NICHD’s Division of Intramural Research (DIR), in the Pacak Lab , within the Program in Reproductive and Adult Endocrinology (PRAE) and the Loh Lab , in the Program on Developmental Neuroscience :
- Gene Mutations That Are Associated with Early Malignant Pheochromocytoma
Researchers examine the genetics of pheochromocytoma to help characterize the disease. In current studies on the genetics of pheochromocytoma, researchers are attempting to identify genes that are associated with malignancy, which is known to substantially shorten patient survival.
In one DIR study, researchers examined the age of initial diagnosis (when the patient’s first tumor was found) of patients who had metastatic disease (the presence of tumors in tissues such as the bone, lungs, liver, or lymph nodes). Researchers looked at all individuals evaluated who had metastatic disease and determined when they were first diagnosed (either in childhood/adolescence or in adulthood) and then determined whether or not they had a genetic predisposition to disease. It was discovered that the majority of those patients whose first tumor developed in childhood or adolescence and later developed metastatic disease had a mutation in the SDHB gene.
While it is well-established that SDHB mutations lead to aggressive tumors, this study helped further describe the clinical presentation of SDHB-related pheochromocytoma/paraganglioma. This study may also help direct genetic testing (testing for SDHB mutations in patients with early tumor development and metastatic disease) and proper follow up (tumor screening for metastatic disease in patients with SDHB mutations and early tumor development). PMID: 21969497)
- A Novel Marker for Metastatic Pheochromocytomas
Measurement of higher than normal catecholamine levels is used in the diagnosis of pheochromocytoma. Catecholamines are transformed in the body into several products called metabolites, which can also be measured to diagnose pheochromocytoma. Benign pheochromocytoma can often be cured by tumor removal, but malignant pheochromocytoma, which spreads to other parts of the body, cannot be cured. The discovery of methods to identify patients who have early malignant pheochromocytoma is important to address shorter survival in these patients.1
This study examined whether catecholamine-related metabolites could be used to diagnose malignant pheochromocytoma. The researchers found that patients with higher than normal levels of one metabolite, methoxytyramine, had malignant pheochromocytoma. Methoxytyramine could be used to identify patients with malignant pheochromocytoma and tailor treatment for malignancy. (PMID: 22036874)
- Proteins in Blood Can Indicate Pheochromocytoma Type
Approximately one-third of pheochromocytoma cases are associated with familial inheritance of a mutated gene.2 Pheochromocytoma cases are often distinguished by the presence of different mutations. These hereditary mutations are passed from parents to their children. Catecholamines and their related metabolites are measured to diagnose pheochromocytoma. Recently, there has been an interest in diagnosing a patient's mutations through measurement of higher than normal catecholamines and related metabolites. Knowledge of specific disease predisposing mutations can help care providers personalize the required treatment and follow up. The most common mutations found in patients with pheochromocytoma include VHL, SDHB, SDHD, MEN2, and NF1.
This study examined whether various metabolites of catecholamines could help distinguish various hereditary forms of the tumor. The researchers examined pheochromocytoma patients who had mutations in the VHL, SDHB, SDHD, MEN2, or NF1 genes. The researchers were able to group patients according to their gene mutations based on the amount of the different metabolites measured in their blood. These findings show that the distinct patterns of blood levels of different metabolites can be a cost-effective method (versus full genetic testing) to determine a patient's mutations. PMID: 21262951)
- A Gene Mutation is Associated with Tumor Growth
NICHD researchers analyzed tumors from two patients who had paragangliomas. Analysis of the tumor tissue revealed that it contained an alteration in one of the family of genes called hypoxia-inducible factors (HIFs). HIFs have been implicated in the development of tumors and the progression of cancers. The researchers found that the altered HIF2A gene generated proteins that were broken down more slowly than the typical form of the gene. In the presence of these proteins, the researchers also documented increased levels of a hormone that stimulates the production of red blood cells.
HIF genes are most active in conditions of low oxygen, such as in tumor tissue. The researchers concluded that the mutation may have altered gene activity in a way that led to more tumors growing in the bodies of the patients they examined. The discovery may help clarify how some tumors generate a new blood supply to sustain their growth. The finding could lead to information on how to hinder the growth of tumors and treat cancers associated with excessive production of red blood cells. (PMID: 22931260)
- The International Patient Symposium on Pheochromocytoma: Working Together Today For a Better Tomorrow, held June 28–29, 2012, in Washington, DC, brought together leading clinicians from around the world to educate patients and primary care physicians about pheochromocytoma. Researchers presented the latest information on the diagnosis, genetics, and treatments of pheochromocytoma, and patients had the opportunity to ask questions and interact with experts in this disease.
- The 3rd International Symposium on Pheochromocytoma, held September 14–17, 2011, in Paris, France, brought together investigators and health care professionals from around the world who have a common interest in pheochromocytoma.
- Blake, M. A. (2011). Pheochromocytoma. Retrieved April 5, 2012, from http://emedicine.medscape.com/article/124059-overview
- Karasek, D., Shah, U., Frysak, Z., Stratakis, C., Pacak, K. (In press). An update on the genetics of pheochromocytoma. Journal of Human Hypertension, doi:10.1038/jhh.2012.20.