title: Age at diagnosis of pheochromocytoma differs according to catecholamine phenotype and tumor location.
abstract: BACKGROUND
  Pheochromocytomas and paragangliomas (PPGLs) are diagnosed earlier in patients with hereditary than sporadic disease. Whether other factors influence age at diagnosis is unclear.
  
  
  OBJECTIVE
  We examined ages at which PPGLs were diagnosed according to different catecholamine phenotypes and locations of tumors.
  
  
  METHODS
  Retrospective multicenter study.
  
  
  METHODS
  Patients with PPGLs included 172 with and 183 without identified germline mutations or hereditary syndromes. BIOCHEMICAL MEASUREMENTS: Differences in plasma concentrations of metanephrine, a metabolite of epinephrine, were used to distinguish epinephrine-producing tumors from those lacking epinephrine production.
  
  
  RESULTS
  Patients with epinephrine-producing tumors were diagnosed 11 yr later (P < 0.001) than those with tumors lacking appreciable epinephrine production. Among patients without evidence of a hereditary condition, those with and without epinephrine-producing tumors had respective mean ± se ages of 50 ± 2 and 42 ± 2 yr (P < 0.001) at diagnosis. Patients with multiple endocrine neoplasia type 2 and neurofibromatosis type 1, all with epinephrine-producing tumors, were similarly diagnosed with disease at a later age than patients with tumors that lacked appreciable epinephrine production secondary to mutations of von Hippel-Lindau and succinate dehydrogenase genes (40 ± 2 vs. 31 ± 1 yr, P < 0.001). Among the latter patients, those with multifocal tumors were diagnosed earlier than those with solitary tumors (19 ± 3 vs. 34 ± 2 yr, P < 0.001).
  
  
  CONCLUSIONS
  The variations in ages at diagnosis associated with different tumor catecholamine phenotypes and locations suggest origins of PPGLs from different chromaffin progenitor cells with variable susceptibility to disease causing mutations. Different optimal age cut-offs for mutation testing are indicated for patients with and without epinephrine-producing tumors (44-49 vs. 30-35 yr, respectively).
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Department of Medicine III, University of Dresden, 01307 Dresden, Germany. Graeme.Eisenhofer@uniklinikum-dresden.de
authors.forename: Graeme
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Timmers
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Oliver
authors.initials: O
authors.lastname: Tiebel
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: King
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Vocke
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Gennady
authors.initials: G
authors.lastname: Bratslavsky
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D000311:Adrenal Glands / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D002648:Child; D016208:Databases, Factual; D004837:Epinephrine / Q000097:blood; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000502:physiology; D016518:Neurofibromatosis 2 / Q000235:genetics; D010641:Phenotype; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics; D055815:Young Adult; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D002395:Catecholamines; D008676:Metanephrine; D013385:Succinate Dehydrogenase; D004837:Epinephrine