RecruitingPhase 1NCT00004847

Diagnosis of Pheochromocytoma

Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Enrollment

3,000 participants

Start Date

Mar 22, 2000

Study Type

INTERVENTIONAL

Conditions

Pheochromocytoma Endocrine Disease Endocrine Diseases

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.

Eligibility

Min Age: 3 YearsMax Age: 120 Years

Inclusion Criteria16

Patients are eligible for inclusion in this study if they are adults or children of age 3 years old and up with known, sporadic or familial PHEO/PGL, on the basis of one or more of the following:
High levels of blood or urinary catecholamines, metanephrines, methoxytyramine or chromogranin A.
Highly suspected presence of PHEO/PGL based on imaging studies, even with normal biochemistry.
Personal or family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop PHEO/PGL.
Signed informed consent is required. The informed consent may be signed by the patient, parent/guardian in pediatric patients or legally authorized representative (LAR) in adults who lack-decision making capacity to consent to research participation.
Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.
Family Members of Patients Arm (Linkage Analysis)
Participants are eligible for inclusion in this study arm if they are:
Adult family members of patients enrolled in this study;
The index family member in this study has a suspected hereditary PHEO/PGL based on previous genetic testing and other suspicious hereditory patterns such as family history of multiple individuals with PHEO/PGL; early age of disease onset; multiplicity of primary tumors; recurrence, etc. and
Signed informed consent form is required
Children over 10 years old with very high suspicion of sporadic or familial PHEO/PGL based on at least one of the following:
The presence of new onset of symptoms typical of PHEO/PGL such as hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.
Family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop these tumors.
The presence of a tumor on conventional imaging including ultrasound, CT and/or MRI or \[123I\]-MIBG or PET imaging not limited to \[18F\]-FDG.
Children must give informed assent and be willing to return to the NIH for follow-up.

Exclusion Criteria14

Potential patients will be excluded on the basis of one or more of the following:
Pregnant or breastfeeding women
Severe cardiac dysfunction
Currently on dialysis
A pregnancy test is performed in women of childbearing age (up to age 55) as a screening after consenting. If a patient is found to have a positive pregnancy test, her participation in this protocol will be terminated. The patient can enroll or re-enroll in the protocol when she is no longer pregnant or breastfeeding.
In-person participating patients who are not willing to return to the NIH (e.g., after surgery or an initial evaluation) for more than 2 years may be removed from the protocol.
In adult patients (Excludes Linkage Analysis Arm)
Inability to lie still for the entire imaging time (e.g., cough, severe arthritis, etc.).
Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (e.g., severe claustrophobia, radiation phobia, etc.)
Any additional medical conditions, serious illness, or other extenuating circumstance that, in the opinion of the Principal Investigator, may significantly interfere with study compliance.
In pediatric patients:
Children of less than 10 years of age.
Children with impaired mental capacity that precludes informed assent.
Inability to lie still for the entire imaging time (e.g., cough, turbulent children, severe claustrophobia, etc.).

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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.