[Biological diagnosis of pheochromocytoma: impact of technological improvement]

Laboratory diagnosis of pheochromocytoma must give evidence of increased catecholamine production. This requires measurement of catecholamines and their metabolites (normetanephrine NMN, metanephrine MN and/or VMA) in urine or in plasma. The various assays can be also performed during dynamic test that stimulate or inhibit catecholamine release. The recent introduction in biochemistry of high performance liquid chromatography coupled to electrochemical detection (HPLC-ED) has greatly reduced drug-induced interference and has therefore narrowed the reference value range. The two groups of compounds that have most benefited from such analytical improvements are urinary metanephrines and VMA. The technical progress has greatly simplified the laboratory diagnosis of pheochromocytoma both by improving the reliability of already available compounds and by favouring the development of news markers. However, the diagnostic sensitivity of the various urinary and plasmatic markers remains very unequal and the diagnosis of pheochromocytoma requires a carefully planned sequence of studies including appropriate biochemical tests able to affirm or to exclude the diagnosis with a high degree of security while reducing the duration and cost of the investigation. Among urinary markers, metanephrines remain the most direct indices of catecholamine hypersecretion and provide the most reliable biochemical indicators of the existence of pheochromocytoma. The diagnostic sensitivity of urinary metanephrines (about 98%) greatly exceeds that of catecholamines and VMA (60-70%). These differences are related to the diversity and specificity of physiological mechanisms involved in the synthesis, the release and inactivation of markers (catecholamines, metanephrines, VMA) and to the variety of clinical presentations and secretory patterns of pheochromocytomas. Considering the practical necessity of simplifying the collection of laboratory samples, use of plasma assays for the diagnosis of pheochromocytoma has become increasingly routine. However, plasma catecholamines--even when assayed during the clonidine suppression test--have not fully lived up to expectations. The diagnostic sensitivity is far better (about 98%) with the recently developed assays of plasma methoxyamines which, owing to their long half-life, provide long-lasting indicators of the catecholamine discharge and are elevated even in tumors without clinical expression. Laboratory diagnosis is relatively easy when the patient bears a large tumor releasing considerable amounts of catecholamines and metabolites; it becomes more challenging in the case of small tumors or of pretumoral hyperplasia in which only the most reliable biochemical markers are able to confirm the diagnosis of pheochromocytoma.