Pheochromocytoma: recommendations for clinical practice from the First International Symposium

Abstract

The First International Symposium on Pheochromocytoma, held in October 2005, included discussions about developments concerning these rare catecholamine-producing tumors. Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment. Measurement of plasma or urinary fractionated metanephrines, the most accurate screening approach, was recommended as the first-line test for diagnosis; reference intervals should favor sensitivity over specificity. Localization studies should only follow reasonable clinical evidence of a tumor. Preoperative pharmacologic blockade of circulatory responses to catecholamines is mandatory. Because approximately a quarter of tumors develop secondary to germ-line mutations in any one of five genes, mutation testing should be considered; however, it is not currently cost effective to test every gene in every patient. Consideration of tumor location, presence of multiple tumors, presence of metastases, and type of catecholamine produced is useful in deciding which genes to test. Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.

Key Points

  • A pheochromocytoma is an intra-adrenal paraganglioma; the current WHO nomenclature reserves the term 'pheochromocytoma' for paragangliomas of adrenal origin

  • Measurements of plasma or urinary fractionated metanephrines are the most accurate screening procedures

  • Localization studies should only follow reasonable clinical and/or biochemical evidence of a tumor

  • Although CT and MRI have excellent sensitivity for detecting most catecholamine-producing tumors, these anatomic imaging approaches lack the specificity required to unequivocally identify a mass as a pheochromocytoma or paraganglioma

  • Functional imaging offers an approach to overcome the limitations of anatomic imaging—the test of choice currently is 123I-labeled meta-iodobenzylguanide scintigraphy

  • Laparoscopic surgery is the treatment of choice. Preoperative pharmacologic blockade of adrenergic receptors is mandatory

  • Genetic testing is not currently cost-effective for every gene in every patient; consideration of tumor location, presence of multiple tumors or metastases, and type of catecholamine produced could be useful in deciding which genes to test

  • Malignancy cannot currently be diagnosed by assessment of the primary tumor tissue and is defined by the presence of metastases

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Figure 1: Scatterplots showing the distributions for plasma concentrations (A) or urinary outputs (B) of normetanephrine versus metanephrine in patients with confirmed pheochromocytoma or paraganglioma (gray squares) compared with patients in whom tumors were excluded (gray dots).
Figure 2: Algorithm for genetic testing for genes associated with pheochromocytoma.

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Correspondence to Arthur S Tischler.

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Pacak, K., Eisenhofer, G., Ahlman, H. et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. Nat Rev Endocrinol 3, 92–102 (2007). https://doi.org/10.1038/ncpendmet0396

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