Metanephrines are consistently secreted in pheochromocytomas and paragangliomas (PPGL), whereas catecholamine production is intermittent. The risk of false-negative results is therefore high when plasma catecholamines are used as a first-line screening test (sensitivity 85% and specificity 81%). Current guidelines recommend metanephrines (plasma or urinary) as the preferred initial screening test for PPGL.
Plasma metanephrine testing however has limitations including posture related variability, as patients should ideally be supine for at least 20 mins before sampling via a pre-installed intravenous catheter. Additionally, the samples must be transported on ice because metanephrines are unstable in whole blood if they cannot be processed promptly by the laboratory. This instability is not an issue in urine as collection occurs in acidified containers. These preanalytical challenges make urinary metanephrines a more practical alternative for outpatients as failure to meet these conditions increases the risk of false positives for plasma metanephrines. Both plasma and urinary metanephrines have high sensitivity for screening (99% and 97% respectively) and combining these tests do not improve diagnostic performance.
Joint recommendation with the Canadian Association of Medical Biochemist
Sources:
Eisenhofer G, et al. Biochemical Assessment of Pheochromocytoma and Paraganglioma. Endocr Rev. 2023 Sep 15;44(5):862-909. PMID: 36996131.
Pommer G, et al. Preanalytical Considerations and Outpatient Versus Inpatient Tests of Plasma Metanephrines to Diagnose Pheochromocytoma. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3689- e3698. PMID: 35767279.
Sbardella E, et al. Pheochromocytoma: An approach to diagnosis. Best Pract Res Clin Endocrinol Metab. 2020 Mar;34(2):101346. Epub 2019 Oct 22. PMID: 31708376.
Shen Y, et al. Biochemical diagnosis of pheochromocytoma and paraganglioma. In: Mariani-Costantini R, ed. Paraganglioma: A Multidisciplinary Approach. Codon Publications. [Internet]. 2019. [cited April 22, 2024].