This study examined whether different forms of hereditary pheochromocytoma are characterized by different catecholamine phenotypes and whether this is reflected by differences in plasma concentrations of normetanephrine, metanephrine and methoxytyramine the respective O-methylated metabolites of norepinephrine, epinephrine and dopamine. Subjects included 154 patients with hereditary pheochromocytoma, 72 with tumors associated with von HippelLindau (VHL) syndrome, 39 with multiple endocrine neoplasia type 2 (MEN 2), 4 with neurofibromatosis type 1 (NF1), 34 with mutations of the succinate dehydrogenase type B (SDHB) gene and 5 of the succinate dehydrogenase type D (SDHD) gene. Plasma and urinary catecholamines and metabolites, and tumor tissue catecholamines in a subset of patients, were measured by HPLC. Relative proportions of norepinephrine, epinephrine and dopamine in tumor tissue were closely matched by relative increases of plasma O-methylated metabolites, but not by those of the parent catecholamines. Patients with tumors due to MEN 2 or NF1 had increases in both plasma metanephrine and normetanephrine, whereas those with mutations of VHL, SDHD and SDHB genes showed increases mainly in plasma normetanephrine. Plasma levels of methoxytyramine were increased in 65% of patients with tumors due to mutations of the SDHB gene, but were otherwise generally normal. The study establishes that differences in tumor catecholamine phenotypes can be accurately assessed using measurements of plasma O-methylated metabolites and that these phenotypes differ markedly among patients with different hereditary forms of pheochromocytoma. This information may be useful in determining relative likelihoods of different disease-causing mutations in patients who otherwise have no clinical stigmata or family history consistent with a hereditary syndrome.
03 - 07 May 2008
European Society of Endocrinology