Phaeochromocytomas in VHL disease

Sir,Varghese et al,1 reported an interesting case of von Hippel-Lindau (VHL) disease in a patient who also had left adrenal tumour. This is likely to be a phaeochromocytoma.2 The authors had excluded phaeochromocytoma, as urinary normetadrenaline secretion was normal. However, plasma normetanephrine and metanephrine estimation has been found to be a more sensitive and specific test for detection of phaeochromocytomas in VHL disease and multiple endocrine neoplasia type 2 (MEN-2), compared to plasma concentrations of catecholamines (norepinephrine and epinephrine), urinary excretion of norepinephrine, epinephrine, metanephrines (normetanephrine and metanephrine combined), and vanillylmandelic acid.3Eisenhoferet al3 found that in 35 patients with histologically confirmed phaeochromocytomas (26 patients with VHL and nine patients with MEN-2), sensitivity of measurements of plasma normetanephrine and metanephrine for the diagnosis of phaeochromocytoma was 97%, a sensitivity significantly higher than that of 65% for urinary metanephrines (p<0.001). This high sensitivity was accompanied by high specificity (96%), while urinary metanephrines had a specificity of 95%. In all patients with VHL disease or MEN-2 who also had phaeochromocytomas, the plasma concentrations of normetanephrine were increased by an average of 348% above the upper reference limit, compared to 55% for urinary metanephrines (p<0.001). This high sensitivity for plasma normetanephrine and metanephrine has also been reported for sporadic phaeochromocytomas.4