What is the appropriate workup and management of pheochromocytoma?

From the Guidelines

The appropriate workup for pheochromocytoma begins with biochemical testing, specifically measuring plasma free metanephrines or 24-hour urinary fractionated metanephrines and catecholamines, as recommended by the most recent guidelines 1. The diagnosis of pheochromocytoma is crucial due to its high morbidity and mortality if left untreated, and the fact that one-third of cases are inherited 1.

Key Steps in Workup and Management

• Biochemical testing should be the initial step, considering the high sensitivity and specificity of plasma free metanephrines (96%−100% sensitivity, 89%−98% specificity) and urinary fractionated metanephrines (86%−97% sensitivity, 86%−95% specificity) 1.
• Imaging studies, including CT or MRI of the abdomen and pelvis, should be performed after biochemical confirmation to localize the tumor 1.
• Functional studies like 123I-MIBG scintigraphy or 18F-FDG PET/CT may be necessary if the tumor is not identified on conventional imaging.
• Management involves surgical resection as the definitive treatment, with careful preoperative preparation to prevent hypertensive crisis during surgery, including alpha-adrenergic blockade and volume expansion 1.
• Alpha-adrenergic blockade should be initiated 7-14 days before surgery, and beta-blockers should only be added after adequate alpha blockade to prevent unopposed alpha-adrenergic stimulation 1.
• Intraoperative management requires preparation for blood pressure fluctuations, and postoperative monitoring for hypotension and hypoglycemia is essential.
• Long-term follow-up with periodic biochemical testing is crucial to detect recurrence, particularly in patients with genetic syndromes or large tumors 1.

From the FDA Drug Label

INDICATION AND USAGE Phenoxybenzamine hydrochloride capsules are indicated in the treatment of pheochromocytoma, to control episodes of hypertension and sweating. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. The appropriate workup and management of pheochromocytoma includes:

• Controlling episodes of hypertension and sweating using phenoxybenzamine hydrochloride capsules 2
• Using a beta-blocking agent concomitantly if tachycardia is excessive 2 Key points to consider in the management of pheochromocytoma:
• Dosage adjustment: The dosage of phenoxybenzamine should be adjusted to fit the needs of each patient, with small initial doses slowly increased until the desired effect is obtained or side effects become troublesome 2
• Monitoring: Patients should be observed on each dosage level before instituting another increase 2

From the Research

Biochemical Diagnosis

• The diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor 3.
• Plasma free metanephrines and urinary fractionated metanephrines are the most sensitive tests for diagnosing pheochromocytoma, with sensitivities of 99% and 97%, respectively 3.
• The measurement of plasma or fractionated urine metanephrines is the hormonal determination of choice for the biochemical diagnosis 4.
• Total urinary normetanephrine and platelet norepinephrine are also sensitive tests, with sensitivities of 96.9% and 93.8%, respectively 5.

Localization and Imaging

• Once the biochemical diagnosis is confirmed, the next step is the localization study 4.
• Cross-sectional imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) are usually used to localize the tumor 6.
• Metaiodobenzylguanidine (MIBG) scintigraphy can be used to image pheochromocytomas, but it is not necessary for tumor localization and should be used selectively 6.
• MIBG scintigraphy can be useful in combination with diagnostic tests in urine, blood, or platelets to improve the sensitivity of diagnosis 5.

Preoperative Management

• Preoperative treatment with alpha blockers should be instituted at least 7-14 days before adrenalectomy 4.
• Phenoxybenzamine, prazosin, and doxazosin are effective alpha blockers for preoperative preparation, with no significant difference in operative and postoperative blood pressure and plasma volume control among the three groups 7.
• In low-risk patients, the omission of presurgical treatment could be considered if the surgery is performed in centers with experience and a strict monitoring of the patient is carried out during the perioperative period 4.

Genetic Study

• A genetic study is recommended in all patients with pheochromocytomas, as 40% of cases are hereditary 4.