Phaeochromocytoma (PH) and functional paraganglioma (FPGL) are neoplasm of chromaffin tissue that synthesise catecholamines and are mostly located in adrenal medulla (PH) or elsewhere (FPGL). Patients may also harbour non-secreting head and neck paragangliomas (PGL). Up to ¼ of PH/PGL are familial. A high degree of suspicion for PH and FPGL should be risen in case of spells, resistant hypertension, family history of PH/PGL, a genetic syndrome that predispose to PH (e.g. MEN2), a past history of resected PH and present history of recurrent hypertension and spells, and an incidentaloma with radiologic finding consistant with PH. The laboratory diagnosis of PH and FPGL relies on the identification of excessive secretion of catecholamines and/or their derivatives, which include norepinephrine (NE), epinephrine (E), and rarely dopamine (D) and their methoxylated metabolites metanephrines, such as normetanephrine (NM), metanephrine (M) and 3-methoxytyramine (3Met). These metabolites are produced continuosly and independently of catecholamine release, which may be modest, absent or paroxysmal, therefore should provide more accurate tests to diagnose PH. Consequently, current recommendations state that initial biochemical testing should include measurement of either plasma or urinary fractionated metanephrines or both. Metanephrines are further metabolised to sulphate conjugates resulting in concentrations up to 25 times the corresponding free compounds. Gastrointestinal tissues and renal function may influence the levels of conjugated metabolites. In urine, the common assay measures the sum of free and conjugated metanephines, while in the plasma they are determined separately. This might explain the diagnostic advantage of plasma compared to urinary measurement reported by some A. However, the small advantage of plasma free metanephrines assay in term of sensitivity does not likely account for its technical difficulty, and the reported differences between the performance of the 2 methods are small compared to the advantages of either test to tests for the parent plasma and urinary fractionated catecholamines. Sensitivity and specificity of these 4 assays will be further discussed, as well of VMA. In general, high sensitivity is associated with trade-off in specificity, with difficulties in distinguishing TP from FP. The extent of elevation should be considered. Any role for chromogranin A, NPY, NSE?
03 - 07 May 2008
European Society of Endocrinology