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Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

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Trial Information

Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

Pheochromocytomas/paragangliomas are rare but clinically important chromaffin cell tumors
that typically arise from the adrenal gland 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 and radio-iodinated
metaiodobenzylguanidine (MIBG) scanning can yield false-negative results in patients
harboring the tumor. Computed tomographic (CT) and magnetic resonance imaging (MRI) lack
sufficient specificity. The molecular mechanisms by which genotypic changes predispose to
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, and responses to standard screening tests such as glucagon stimulation and
clonidine suppression tests. This protocol focuses on molecular and genetic studies that may
elucidate the bases for predisposition to develop pheochromocytomas/paragangliomas and for
expression of different neurochemical phenotypes and malignant potentials, new imaging
approaches, based on [(18)F]-6F-dopamine ([(18)F]-6F-DA), and
[(18)F]-L-3,4-dihydroxyphenylalanine ((18)F]-DOPA) positron emission tomographic (PET)
scanning, [99m]Tc-methoxyisobutylisonitrile SPECT scintigraphy (99m Tc-MIBI), and new
biochemical diagnostic criteria, based on measurement of plasma metanephrines. We also want
to evaluate the benefits romidepsin pretreatment for uptake enhancement of [(123/131)I]-MIBG
in pheochromocytoma/paraganglioma tumors.

Inclusion Criteria


Patients are adults or children with known or suspected sporadic or familial
pheochromocytoma/paraganglioma, on the basis of one or more of the following:

- new onset of hypertension or hypertensive episodes and symptoms suggestive of
pheochromocytoma/paraganglioma (sweating, headache, pallor, palpitations);

- high levels of blood or urinary catecholamines or metanephrines.

- family history of pheochromocytoma/paraganglioma or genetic mutations known to
predispose individuals to develop pheochromocytoma/paraganglioma.

- patients performing DEXA scan are adults above 25 and below 45 years of age.

Patients must be willing to return to NIH for follow-up evaluation.

Patients with pheochromocytoma/paraganglioma will be accepted based on referral from


Children of age less than 18 years are excluded from F-FLT PET scanning

Imaging studies are not done in pregnant or lactating women. A pregnancy test is performed
in women of child-bearing age (up to age 55). In those with positive results, no PET
scanning, MIBG scanning, contrast CT, or vena cava sampling is performed.

Glucagon and clonidine testing are not performed in pregnant women.

Pregnant women who are greater than 26 weeks pregnant are excluded from admission to the
Clinical Center but may be studied as outpatients.

Patients with impaired mental capacity that precludes informed consent.

Type of Study:


Study Design:


Outcome Measure:

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.

Principal Investigator

Karel Pacak, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

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


United States: Federal Government

Study ID:




Start Date:

February 2000

Completion Date:

Related Keywords:

  • Pheochromocytoma
  • Neurofibromatosis
  • Multiple Endocrine Neoplasia (MEN)
  • von Hippel-Lindau Disease
  • Norepinephrine
  • Epinephrine
  • Metanephrines
  • PET
  • Paraganglioma
  • Pheochromocytoma
  • Paraganglioma
  • Pheochromocytoma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892
Johns Hopkins University Baltimore, Maryland  21205