Diagnosis of Pheochromocytoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00004847
Recruitment Status : Recruiting
First Posted : March 3, 2000
Last Update Posted : November 6, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Brief 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.

Condition or disease

Detailed Description:
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.

Study Type : Observational
Estimated Enrollment : 2400 participants
Official Title: Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma
Study Start Date : March 1, 2000

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
  • Patients are adults or children of any age with known, sporadic or familial PHEO/PGL, on the basis of one or more of the following:

    1. High levels of blood or urinary catecholamines, metanephrines, methoxytyramine or chromogranin A.
    2. Highly suspected presence of PHEO/PGL based on imaging studies, even with normal biochemistry.
    3. Personal or family history of PHEO/PGL or genetic mutations known to predispose individuals to develop PHEO/PGL.
  • Normal volunteers over the age of 18 years, including those with normal or high blood pressure, are to be used for reference values regarding biochemical and imaging diagnosis of PHEO/PGL. Normal volunteers with high blood pressure can be on blood pressure medication.
  • Patients and normal volunteers can be studied to provide blood/urine samples for biochemical, proteomic, and/or genetic and epigenetic analysis.
  • Signed informed consent is required.
  • Patients must be willing to return to NIH for follow-up evaluation.
  • Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.
  • Patients with PHEO/PGL will be accepted through clinician or self- referrals.


Potential patients will be excluded on the basis of one or more of the following:

  1. Pregnant (based on a pregnancy test done either outside the NIH or at the NIH) or breastfeeding women
  2. Severe cardiac dysfunction
  3. Currently on dialysis

    -A pregnancy test is performed in women of childbearing age (up to age 55). If after enrollment to this protocol, a patient is found to have a positive pregnancy test, her participation in this protocol will be terminated..

    • Research scans are contraindicated in patients with proven myelodysplastic syndrome.
    • 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.
    • Pregnant and lactating women will not be included in the protocol because their participation as a demographic is not essential to this study. The information we are seeking can be acquired from a cohort of non-pregnant patients. The exclusion of pregnant women does not preclude these patients from receiving appropriate care and management from an outside facility.


    -In adult patients:

    --Imaging studies are not done in patients that have the following exclusion criteria:

    ---Pregnant and lactating women,

    ---Patients with a body weight of (Bullet)400 pounds due to weight limitations of PET/CT/MRI scanners or patients who are not able to enter the bore of PET/CT/MRI scanners due to BMI,

    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 (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.

    ---Additionally, DCE-MRI is not done in patients with acute or chronic renal insufficiency since gadolinium chelate injection is contraindicated in those patients. In patients where DCE-MRI is considered, a creatinine clearance measurement is performed as a clinically indicated test by the Department of Laboratory Medicine at the NIH Clinical Center. Patients with impaired kidney function will not undergo DCE-MRI. DCE-MRI is also not done in patients with severe claustrophobia or who have iron or metal in the MRI scan site, in patients with pacemakers or defibrillators, or in patients with an allergy to gadolinium. Very rarely, gadolinium at the site of injection or the dosed limb can cause skin and soft tissue necrosis, thrombosis, fasciitis, and compartment syndrome requiring surgical intervention.

    -In pediatric patients:

    --Inclusion criteria for research PET imaging in children

    ---Children over 10 years old with very high suspicion of sporadic or familial pheochromocytoma/paraganglioma (e.g. the presence of new onset of hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.) family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop these tumors, or the presence of a tumor on conventional imaging /ultrasounds, CT, MRI.

    • Children must give written informed assent and be willing to return to the NIH for follow-up.
    • Female patients of childbearing age must have a negative pregnancy test on the day of the enrollment into this protocol and within 24 hours of any treatment or test involving radioactivity or radiation exposure. They should be abstinent or use appropriate contraception while taking part in the study, which involves radiation.

      --Exclusion criteria for research PET imaging in children

    • Children of less than 10 years of age,
    • Children with impaired mental capacity that precludes informed assent,
    • Pregnant or lactating female adolescents,
    • Inability to lie still for the entire imaging time (e.g. cough, turbulent children, severe claustrophobia, etc.).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00004847

Contact: Marianne M Knue, C.R.N.P. (301) 827-3355
Contact: Karel Pacak, M.D. (301) 402-4594

United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Karel Pacak, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Identifier: NCT00004847     History of Changes
Other Study ID Numbers: 000093
First Posted: March 3, 2000    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: September 27, 2018

Studies a U.S. FDA-regulated Drug Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Multiple Endocrine Neoplasia (MEN)
Von Hippel-Lindau Disease

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue