Endocrine Abstracts (2008) 15 OC1

Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B gene mutation carriers

Umasuthan Srirangalingam1, Lisa Walker2, Bernard Khoo1, Fiona MacDonald3, Daphne Gardner4, Terence J Wilkin4, Robert H Skelly5, Emad George6, David Spooner7, John P Monson1, Ashley B Grossman1, Scott A Akker1, Patrick J Pollard8, Nick Plowman1, Norbert Avril1, Dan M Berney1, Jacky M Burrin1, Rodney Reznek1, VK Ajith Kumar9, Eamonn R Maher3 & Shern L Chew1

1St Bartholomew’s Hospital, London, UK; 2Churchill Hospital, Oxford, UK; 3University of Birmingham School of Medicine, Birmingham, UK; 4Derriford Hospital, Plymouth, UK; 5Colchester General Hospital, Colchester, UK; 6Queen Elizabeth Hospital, King’s Lynn, UK; 7Queen Elizabeth Medical Centre, Birmingham, UK; 8University of Oxford, Oxford, UK; 9Great Ormond Street Hospital, London, UK.

Background: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations.

Objective: To describe the clinical manifestations of subjects with SDH-B gene mutations.

Design: Retrospective case series.

Patients: Thirty-two subjects with SDH-B gene mutations followed-up between 1975 and 2007. Mean follow-up of 5.8 years (S.D. 7.4, range 0–31).

Measurements: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management.

Results: Sixteen of Thirty-two subjects (50%) were affected by disease. Ten different mutations in the SDH-B gene were seen with 2 previously undescribed. A family history of disease was noted in 18% of index subjects. Mean age at diagnosis was 34 years (S.D. 15.4, range 10–62), with a 50% penetrance by the age of 26 years in affected subjects. 41% (13/32) of all subjects were hypertensive and 39% (12/31) had elevated secretions of catecholamines/metabolites. 19% (6/32) of subjects had adrenal disease and 38% (12/32) had extra-adrenal disease. 25% (8/32) of subjects had abdominal paragangliomas, 9% (3/32) pelvic, 6% (2/32) thoracic and 3% (1/32) had a head and neck paraganglioma. 9% (3/32) had multifocal disease. Metastatic paragangliomas developed in 16% (5/32) of subjects. One subject also had a metastatic type II papillary renal cell carcinoma. The overall malignancy rate was 19% (6/32). A carotid artery dissection, patent foramen ovale and an aortic aneurysm were noted in subjects without hypertension.

Conclusion: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.

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