title: Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours.
abstract: Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. u.sriangalingam@qmul.ac.uk
authors.forename: Umasuthan
authors.initials: U
authors.lastname: Srirangalingam
authors.forename: Bernard
authors.initials: B
authors.lastname: Khoo
authors.forename: Lisa
authors.initials: L
authors.lastname: Walker
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
authors.forename: Robert H
authors.initials: RH
authors.lastname: Skelly
authors.forename: Emad
authors.initials: E
authors.lastname: George
authors.forename: David
authors.initials: D
authors.lastname: Spooner
authors.forename: Linda B
authors.initials: LB
authors.lastname: Johnston
authors.forename: John P
authors.initials: JP
authors.lastname: Monson
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Grossman
authors.forename: W M
authors.initials: WM
authors.lastname: Drake
authors.forename: Scott A
authors.initials: SA
authors.lastname: Akker
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pollard
authors.forename: Nick
authors.initials: N
authors.lastname: Plowman
authors.forename: Norbert
authors.initials: N
authors.lastname: Avril
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Berney
authors.forename: Jacky M
authors.initials: JM
authors.lastname: Burrin
authors.forename: Rodney H
authors.initials: RH
authors.lastname: Reznek
authors.forename: V K Ajith
authors.initials: VK
authors.lastname: Kumar
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Shern L
authors.initials: SL
authors.lastname: Chew
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D002395:Catecholamines; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human