Pheochromocytoma: pitfalls in the biochemical evaluation

Abstract

The current work-up of a patient suspected to have a pheochromocytoma starts with the measurement of plasma or urine metanephrines. Notably, up to a quarter of these patients will have a false positive result. When the plasma or urine metanephrines are less than the 4-fold upper limit of normal, clinicians struggle between the fear of missing a potentially fatal condition and ordering costly follow up tests. In many cases, ordering unnecessary imaging studies may only increase the level of patient anxiety. This article will review various physiologic factors, pathologic conditions and medications that may influence the levels of catecholamines and their metabolites yielding false positive or false negative results. Acquiring familiarity with these conditions as well as interfering medications will equip clinicians with better interpretation skills of the biochemical tests.

Keywords::

• catecholamines
• dopamine
• false negative
• false positive
• metanephrines
• pheochromocytoma

Acknowledgements

We are indebted to C Faiman for reviewing the manuscript and for his thoughtful suggestions.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Up to a quarter of patients evaluated for pheochromocytoma will have at least one false-positive biochemical test.

• We recommend plasma fractionated metanephrines (metanephrines) for screening purposes.

• metanephrines are continuously made out of catecholamines stored in the pheochromocytoma vesicular stores; therefore, biochemical evaluation of patients suspected to have pheochromocytoma may be done at any time irrespective of the presence or absence of symptoms.

• Plasma metanephrines >fourfold the upper limit of normal range (ULN) usually establishes the diagnosis.

• The majority of false-positive results are related to the plasma or urine normetanephrine (NMN) fraction; any degree of elevation in the plasma or urine MN should be carefully evaluated and not ignored as false positive.

• Most patients with plasma or urine NMN <twofold the ULN do not have pheochromocytoma; such patients should have their levels repeated in intervals.

• Patients with plasma NMN level between two- to fourfold the ULN need close monitoring and further evaluation to rule out an underlying pheochromocytoma.

• Review the medication list for possible interference and if a drug interaction is suspected, then consider stopping it and repeating the levels afterward; familiarity with the assay used and its potential drug interference profile is critical.

• Drugs most frequently associated with false-positive results are tricyclic antidepressants and phenoxybenzamine.

• Evaluation for underlying medical conditions including renal impairment and repeating the blood draws in the supine position after 30 min of rest may help to eliminate some of the false-positive results.

• Rare false-negative results in pheochromocytoma may be seen in patients with tumors <2 cm in size, dopamine-secreting tumors, early stage familial pheochromocytoma syndromes, early recurrence, small residual tumor tissue after surgical resection and in patients with metastatic pheochromocytoma after resection of the primary tumor.

Notes