[The diagnosis of atypical pheochromocytoma: a challenge for the biologist as well]

Biological diagnosis of pheochromocytoma is relatively easy in those cases releasing great amounts of catecholamines with strong clinical features; instead, diagnosis could be more problematic in atypical or asymptomatic familial pheochromocytoma with small tumors secreting low catecholamine amounts. Several plasma and urine adrenergic markers must be used to confirm the clinical suspicion. We have discussed the biological data of three totally asymptomatic pheochromocytomas (cases no 2, 3, 4) and one case with a very discrete clinical manifestation (no 1). Three patients had very small tumors (4, 7 and 25 g) secreting preeminently adrenaline, one patient had a 45 g adrenal incidentaloma without clinical expression. Our study shows that, in these special cases, except for an inconstant increase of adrenaline, plasma and urine catecholamines and urine VMA can be normal. The most useful markers are plasma and urine methoxyamines. However, plasma methoxyamines are the most sensitive because their increase over reference values is by far greater than in urines. Several factors may explain these findings: a low tumoral secretion, the nature of the released amine, the short half-life of catecholamines in plasma and, in some cases, the involvement of intratumoral catecholamine metabolism. Analysis of the ratio NMN/MN in plasma provides an additional diagnosis tool to reveal adrenaline secretion abnormalities.