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:
- 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.
- 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.
- 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.
- Genetic testing - A small blood sample is collected for DNA analysis and other analyses.
Primary Outcome Measures:
- To investigate the use of radiopharmaceutical tracer, F(18)-FLT for PET/CT scan in evaluating cellular proliferative behavior of various genetically inherited and sporadic pheochromocytomas and paragagliomas in adult patients.
| Estimated Enrollment:
| Study Start Date:
||March 1, 2000
Pheochromocytomas and paragangliomas are rare but clinically important chromaffin cell tumors that typically arise from the adrenal gland or from extra-adrenal paraganglia, respectively and constitute a surgically correctable cause of chronic hypertension. The clinical features and consequences of pheochromocytoma/paraganglioma result from the release of catecholamines (e.g., norepinephrine and epinephrine) by the tumor. If a pheochromocytoma/paraganglioma is undetected, stimuli that normally would not pose a hazard, such as surgery, childbirth, or general anesthesia, can evoke catecholamine secretion by the tumor, with clinically significant and even catastrophic outcomes. The diagnosis of pheochromocytoma/paraganglioma and its localization can be challenging, because measurements of plasma levels or urinary excretion of catecholamines and their metabolites as well as radio-iodinated metaiodobenzylguanidine (MIBG) scanning can yield false-positive/negative results in patients harboring the tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to the development of pheochromocytoma/paraganglioma remain unknown, even in patients with identified mutations. Moreover, pheochromocytomas/paragangliomas in patients with hereditary predispositions differ in terms of their growth, malignant potential, catecholamine phenotype, responses to standard screening tests, such as the clonidine suppression test, various imaging modalities, and different therapeutic options. This protocol focuses on developmental, molecular, genetic, epigenetic, proteomic, metabolomics, and other types of studies to elucidate the bases for predisposition to develop pheochromocytomas/paragangliomas and for expression of different neurochemical phenotypes and malignant potentials including therapeutic responses. Furthermore, this protocol will also use new imaging approaches, for example [(18)F]-6F-dopamine ([(18)F]-6F-DA), [(18)F]-L-3,4-dihydroxyphenylalanine ([(18F)]-DOPA), and [(68)Ga]-DOTA-Tyr-octreotate ([(68)Ga]-DOTATATE) positron emission tomography (PET)/CT, as well as PET/MRI scanning, and dynamic contrast-enhanced MRI. Additionally, new biochemical diagnostic criteria exist for the measurement of plasma metanephrines and methoxytyramine for the clinical diagnosis and localization of these tumors. This protocol will also evaluate the benefits of histone deacetylase inhibitors (e.g. romidepsin) pretreatment for uptake enhancement of [(123/131)I]-MIBG in pheochromocytoma/paraganglioma tumors.