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Phaeochromocytomas in VHL disease
  1. A S KASHYAP
  1. Department of Medicine
  2. Department of Hospital Administration
  3. Armed Forces Medical College, Pune 411040, India
    1. SUREKHA KASHYAP
    1. Department of Medicine
    2. Department of Hospital Administration
    3. Armed Forces Medical College, Pune 411040, India

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      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.3Eisenhofer et al 3 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

      The large amount of catechol-O-methyltransferase in chromaffin cells is the reason for the high sensitivity of plasma normetanephrine and metanephrine assay in detecting phaeochromocytomas. The membrane-bound enzyme has much higher affinity for catecholamines than does the soluble enzyme present in other tissues; thus, the adrenal gland constitutes the single largest source of normetanephrine and metanephrine in plasma.5

      Inadequate sensitivity of plasma and urinary catecholamines or their metabolites is a problem in periodic screening for phaeochromocytomas, particularly in patients with VHL disease. In these patients, small suspicious masses may be identified by imaging studies, but phaeochromocytomas may not secrete catecholamines in sufficient amounts to cause an abnormal result on a biochemical test. This should be overcome by the superior sensitivity of plasma normetanephrine measurement.

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