Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

Summary

The goal of this study is to develop better methods of diagnosis, localization, and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth. Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Main diagnostic and research tests may include the following: 1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out. 2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma. 3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours. 4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses.

Description

Eligibility

Age range

3–120 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  ([18F]-DOPA)

  is L 3, 4 dihydroxyphenylalanine (L-DOPA) labeled with the radioactive isotope 18F. In general, PPGLs belong to the group of neuroendocrine tumors. This heterogeneous group of tumors takes up amino acids, transforms them into biogenic amines (dopamine and serotonin) by decarboxylation and stores the amines in vesicles. L DOPA is a precursor of catecholamines (dopamine, norepinephrine and epinephrine). Epinephrine conversion to dopamine is catalyzed by the aromatic amino acid decarboxylase. According to previous and current studies, \[18F\]-DOPA PET is highly sensitive and specific for detection of PHEO/PGL67-69. However, there are only a few reports in the literature using \[18F\]-DOPA as a PET agent and particularly for patients with metastatic PPGLs. PET imaging will be done together with either a CT, an MRI or both modalities.

• Drug
  ([18F]-6F-DA)

  is an imaging agent developed at the NIH, that may improve specificity and sensitivity in the localization of PPGLs. \[18F\]-6F-DA enters cells via the membrane norepinephrine transporter. Once inside cells, \[18F\]-6F-DA is translocated via the vesicular monoamine transporter into storage vesicles, where the radioactivity is concentrated. After injection of \[18F\]-6F-DA, the much faster disappearance of \[18F\]-6F-DA-derived radioactivity from the bloodstream and non-neuronal cells than from chromaffin cells should enable rapid visualization of PPGLs by PET scanning.

Location