The goal of this study is to develop better methods of diagnosis 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. Diagnostic tests may include the following:

1. Blood tests - Two blood tests-glucagon stimulation and clonidine suppression-are done that require insertion of intravenous (i.v.) catheters (thin flexible tubes) into arm veins. While the patient rests lying down, a drug (glucagon or clonidine) is given through the i.v. line. Blood pressure and heart rate are monitored frequently, and blood is collected from the i.v. line to measure levels of catecholamines and their breakdown products, metanephrines.
2. Regional venous sampling - Selective vena caval sampling may be required for some patients. A catheter is placed into a large blood vessel called the inferior vena cava, through which blood circulating in the body returns to the heart. Blood samples are collected for measurement of catecholamines and metanephrines.
3. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 131I-MIBG scanning. These scans may be done before and after surgical removal of pheochromocytoma.
4. PET imaging - Positron emission tomography (PET) scanning is done using an injection of a radioactive catecholamine called fluorodopamine. The fluorodopamine enters pheochromocytoma cells, making the tumor radioactive and visible on the PET scan. The scan takes up to about 2 hours.
5. Urine - A 24-hour urine collection is collected for analysis.
6. Genetic testing - A small blood sample is collected for DNA analysis.

PLEASE NOTE: Until further notice, we are not offering MIBG131 at this time.

Pheochromocytomas 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 result from release of catecholamines (e.g., norepinephrine and epinephrine) by the tumor. If a pheochromocytoma 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 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 and magnetic resonance imaging lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to development of pheochromocytoma remain unknown, even in patients with identified mutations. Moreover, pheochromocytomas 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 elucidate the bases for predisposition to develop pheochromocytomas 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-dihyroxyphenylalanine ([(18)F-DOPA) positron emission tomographic (PET) scanning, [99m]Tc-methoxyisobutylisonitrile SPECT scintigraphy ((99m)Tc-MIBI), and new bicochemical diagnostic criteria, based on measurement of plasma metanephrines.

• Linnoila RI, Keiser HR, Steinberg SM, Lack EE. Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol. 1990 Nov;21(11):1168-80.
• Raue F, Frank-Raue K, Grauer A. Multiple endocrine neoplasia type 2. Clinical features and screening. Endocrinol Metab Clin North Am. 1994 Mar;23(1):137-56. Review.
• Easton DF, Ponder MA, Cummings T, Gagel RF, Hansen HH, Reichlin S, Tashjian AH Jr, Telenius-Berg M, Ponder BA. The clinical and screening age-at-onset distribution for the MEN-2 syndrome. Am J Hum Genet. 1989 Feb;44(2):208-15.

• 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:

1. new onset of hypertension or hypertensive episodes and symptoms suggestive of pheochromocytoma (sweating, headache, pallor, palpitations);
2. high levels of blood or urinary catecholamines or metanephrines.
3. family history of pheochromocytoma or genetic mutations known to predispose individuals to develop pheochromocytoma.
4. 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 clinicians.

EXCLUSION CRITERIA:

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.