Familial pheochromocytoma is associated with multiple endocrine neoplasias, VHL and neurofibromatosis1 and should be screened by plasma fractionated metanephrines levels. The next step is to obtain 24-hour urinary fractionated metanephrine levels. Imaging should be considered if the initial tests are positive. Genetic testing also should be performed in high-risk patients.

• According to the Endocrine Society, biochemical screening for pheochromocytoma in recommended among patients with:
  • VHL syndrome– started at 5 years of age with biochemical surveillance every year for the rest of life.
  • Signs or symptoms suggesting catecholamine excess, especially if the symptoms are paroxysmal.
  • Unexpected blood pressure changes to drugs, surgery, or anesthesia
  • Unexplained blood pressure variability
  • Incidentaloma, even if the patient is normotensive
  • Blood pressure that is difficult to control
  • History of previous treatment for pheochromocytoma or paraganglioma
  • Hereditary risk of pheochromocytoma or paraganglioma in family members
  • Syndromic features relating to a pheochromocytoma-related hereditary syndromes ^[1]
• Plasma fractionated metanephrine level is the best test. If elevated, 24-hour urinary fractionated metanephrines should be done.

Anatomic imaging should be used when norepinephrine levels are elevated more than two times upper normal limits.^[2]

• For high-risk children, screening for pheochromocytoma should begin by 11 years of age.
• For moderate risk patients, screening should be started by 16 years of age.
• If positive, adrenal imaging (CT) or (MRI) should be performed.

• Genetic testing should be performed in:^[1]
  • Patients with a family history of pheochromocytoma
  • Tumors or malignant or extra-adrenal pheochromocytoma
  • Families whose infants or young children have Hirschsprung disease
  • First-degree relatives of a patient with proven germline RET mutation
  • Patients with cutaneous lichen amyloidosis
  • Patients with known RET mutations.
  • Parents whose young children have MEN 2A/2B