Supplemental Table S8. Pheochromocytoma: Screening and diagnosis
Screening
  1. To screen for pheochromocytoma
    1. 24-hr urinary total metanephrines and catecholamines (sensitivity of about 95%) or 24-hr urine fractionated metanephrines (sensitivity of about 100%) should be measured. Concomitant measurement of 24-hr urine creatinine should also be performed to confirm accurate collection.
    2. Plasma free metanephrines and free normetanephrines, where available, may also be considered (sensitivity up to 99%).
    3. Urinary VMA measurements should not be used for screening.
  2. Keep in mind that potential false positives should be considered in the setting of:
    1. Interfering drugs
    2. Incorrect patient preparation and positioning (for plasma metanephrine measures)
    3. Mild elevation of screening values (i.e., less than two-fold upper limit of normal)
    4. Normal values on repeat testing
    5. Only 1 abnormal biochemical test in the panel of assays
    6. Atypical imaging results for pheochromocytoma
    7. A low pre-test probability of pheochromocytoma
    8. Acute illness/hospitalization
  3. In the presence of borderline biochemical test results or potentially false positive results, repeat testing may be performed and/or the clonidine suppression test may be used. This should be done before imaging is requested to avoid identifying potential incidentalomas
  4. Imaging (e.g., CT, MRI, +/- MIBG) should generally be performed only done after biochemical confirmation of disease.
Treatment
  1. Definitive treatment is with surgical resection. Preoperative planning is recommended for blood pressure control and volume expansion:
    1. Alpha blockade should be started 10-14 days preoperatively. Typical options include phenoxybenzamine (a long-acting, non-selective irreversible α-blocker), prazosin, or doxazosin.
    2. Other anti-hypertensives may be added as necessary but diuretics should be avoided if possible. Oral beta-blockers may be considered after achieving adequate alpha blockade to control tachycardia and prevent arrhythmias during surgery.
    3. Volume replacement and liberal sodium intake should be encouraged as volume contraction is common in this condition. Intravenous volume expansion in the perioperative period is recommended to prevent postoperative shock.
  2. Postoperatively, long-term follow-up is recommended with urinary or plasma metanephrines to screen for recurrence, especially in those with a genetic predisposition.
  3. Genetic testing should be considered for individuals <50 years of age, multiple lesions, malignant lesions, bilateral pheochromocytomas or paragangliomas, or those with a family history of pheochromocytoma or paraganglioma.