Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours.
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.
Srirangalingam
Umasuthan
U
Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. u.sriangalingam@qmul.ac.uk
Khoo
Bernard
B
Walker
Lisa
L
MacDonald
Fiona
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Skelly
Robert H
RH
George
Emad
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Spooner
David
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Johnston
Linda B
LB
Monson
John P
JP
Grossman
Ashley B
AB
Drake
W M
WM
Akker
Scott A
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Pollard
Patrick J
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Plowman
Nick
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Avril
Norbert
N
Berney
Daniel M
DM
Burrin
Jacky M
JM
Reznek
Rodney H
RH
Kumar
V K Ajith
VK
Maher
Eamonn R
ER
Chew
Shern L
SL
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
D002395:Catecholamines; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human