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Titolo:
PLASMA METANEPHRINES ARE MARKERS OF PHEOCHROMOCYTOMA PRODUCED BY CATECHOL-O-METHYLTRANSFERASE WITHIN TUMORS
Autore:
EISENHOFER G; KEISER H; FRIBERG P; MEZEY E; HUYNH TT; HIREMAGALUR B; ELLINGSON T; DUDDEMPUDI S; EIJSBOUTS A; LENDERS JWM;
Indirizzi:
NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 10,ROOM 4D20,10 CTR DR BETHESDA MD 20892 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH BETHESDA MD 20892 UNIV GOTHENBURG,DEPT CLIN PHYSIOL GOTHENBURG SWEDEN UNIV NIJMEGEN ST RADBOUD HOSP,DEPT RHEUMATOL NL-6500 HB NIJMEGEN NETHERLANDS UNIV NIJMEGEN ST RADBOUD HOSP,DEPT INTERNAL MED NL-6500 HB NIJMEGEN NETHERLANDS
Titolo Testata:
The Journal of clinical endocrinology and metabolism
fascicolo: 6, volume: 83, anno: 1998,
pagine: 2175 - 2185
SICI:
0021-972X(1998)83:6<2175:PMAMOP>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
VESICULAR MONOAMINE TRANSPORTER; EXTRANEURONAL METABOLISM; DIAGNOSIS; 3,4-DIHYDROXYPHENYLGLYCOL; NOREPINEPHRINE; LOCALIZATION; CELLS; RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
G. Eisenhofer et al., "PLASMA METANEPHRINES ARE MARKERS OF PHEOCHROMOCYTOMA PRODUCED BY CATECHOL-O-METHYLTRANSFERASE WITHIN TUMORS", The Journal of clinical endocrinology and metabolism, 83(6), 1998, pp. 2175-2185

Abstract

This study examined whether the high sensitivity of plasma free metanephrines for diagnosis of pheochromocytoma may result from production of free metanephrines within tumors. Presence in pheochromocytomas of catechol-O-methyltransferase (COMT), the enzyme responsible for conversion of catecholamines to metanephrines, was confirmed by Western blotanalysis, enzyme assay, and immunohistochemistry. Western blot analysis and enzyme assay indicated that membrane-bound and not soluble COMTwas the predominant form of the enzyme in pheochromocytoma. Immunohistochemistry revealed colocalization of COMT in the same chromaffin cells where catecholamines are translocated into storage vesicles by the vesicular monoamine transporter. Levels of free metanephrines in pheochromocytoma over 10,000 times higher than plasma concentrations in thesame patients before removal of tumors indicated production of metanephrines within tumors. Comparisons of the production of metanephrines in patients with pheochromocytoma with production from catecholamines released or infused into the circulation indicated that more than 93% of the consistently elevated levels of circulating free metanephrines in patients with pheochromocytoma are derived from metabolism before and not after release of catecholamines into the circulation. The data indicate that the elevated plasma levels of free metanephrines in patients with pheochromocytoma are derived from catecholamines produced and metabolized within tumors. Some tumors do not secrete catecholamines, but all appear to metabolize catecholamines to free metanephrines, thus explaining the better sensitivity of plasma free metanephrines over other tests for diagnosis of pheochromocytoma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 07:13:07