Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes

Graeme Eisenhofer, McClellan M. Walther, Thanh Truc Huynh, Sheng Ting Li, Stefan R. Bornstein, Alexander Vortmeyer, Massimo Mannelli, David S. Goldstein, W. Marston Linehan, Jacques W.M. Lenders, Karel Pacak

Research output: Contribution to journalArticle

234 Scopus citations

Abstract

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.

Original languageEnglish (US)
Pages (from-to)1999-2008
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number5
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Eisenhofer, G., Walther, M. M., Huynh, T. T., Li, S. T., Bornstein, S. R., Vortmeyer, A., Mannelli, M., Goldstein, D. S., Linehan, W. M., Lenders, J. W. M., & Pacak, K. (2001). Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes. Journal of Clinical Endocrinology and Metabolism, 86(5), 1999-2008. https://doi.org/10.1210/jcem.86.5.7496