T022

Metastatic paraganglioma with unknown genetics to screen or not to screen the family?

Falinska A; Vakilgilani, T; Woods D; Tanday R; Ling Y; Todd JF

Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust , Hammersmith Hospital, Du Cane  Road , London UK

Abstract:

We present a family of a 45 year old patient who presented to hospital acutely unwell with metastatic paragangliomas. Unfortunately due to rapidity of his presentation, no genetic testing was performed. He was found to have 5cm right carotid body tumour. His urine collections confirmed raised (seven times normal) 24 hour urine metanephrines 24.55umol (normal <3.47umol). Shortly after the initial diagnosis he was found to have extensive vertebral body metastases in cervical and thoracic spine, liver metastases and widespread lymphadenopathy. Lymph node biopsy confirmed metastatic paraganglioma. He originally came from India and there is no other family history of pheochromocytoma or paraganglioma other that in this individual. Both his parents died 20 years ago of unknown cause and he has 3 brothers and 3 sisters who live in London, India and USA. Two of his siblings are patients in our clinic. The younger brother is 43 years and clinically he is well. He has dominant thyroid nodule on the background of multinodular goitre with repeated FNAs confirming benign lesion. His older sister is 63 years old and suffers from chronic myeloid leukaemia.

Paragangliomas are rare and up to 30% are genetically determined. Multiple and metastatic paragangliomas are more common (17-85 %) in hereditary syndromes compared to only 1.2 % of sporadic cases. Malignancy rates are highest for paragangliomas that arise in the setting of an inherited mutation in the B subunit of the succinate dehydrogenase gene (SDHB).

Genetic testing is guided by the family history and clinical findings and is usually offered to all subjects undergoing surgery for head and neck paraganglioma and /or to the family of an individual with confirmed genetic mutation.

Our cases highlight important management issues. Should his siblings be tested for a susceptibility gene? If yes, genetic testing for which mutations? If genetic screen is negative, can the individuals be safely discharged or should they undergo long term biochemical screening? If not tested, should they be followed up as having presumed susceptibility gene or discharged form regular follow up?