Endocrine Abstracts

Case: A 69 year old gentleman with a past medical history of essential hypertension presented to medical services with symptoms of weight loss, muscle weakness and fatigue. Following blood tests, a CT scan, liver biopsy and biochemical screening, a metastatic phaeochromocytoma was diagnosed. He was commenced on alpha and beta blockade. Further imaging, including a MIBG scan, showed non-resectable disease therefore he underwent therapeutic MIBG treatment. Following a good response, he underwent a debulking laparoscopic left adrenalectomy and tissue was sent to the 100 000 Genome Project. Further therapeutic MIBG was planned but unfortunately his disease progressed significantly and he succumbed to his illness. His family history revealed members with breast and ovarian cancer. As part of his routine clinical care, he was referred for genetic testing. Standard testing for inherited causes of phaeochromocytoma were negative however the genetic analysis from the 100 000 Genome Project revealed a variant in the BRIP1 gene c.2392C>T p.(Arg798Ter).

Discussion: The BRCA-1 interacting protein 1 gene (BRIP-1, also known as BRCA-1 associated c-terminal helicase 1, OMIM:605882) is located on chromosome 17q23.2 and encodes the BRIP-1 protein which is part of the DEAH helicase family and is involved in the DNA repair of the BRCA-1 gene. BRIP-1 mutations are known to be associated with the development of breast and ovarian cancer, as well as Fanconi anaemia, however we believe this is the first reported case of a BRIP-1 mutation being associated with metastatic phaeochromocytoma. Following the discovery of this mutation, members of his family have been invited to undergo genetic screening to further define their risk. This case highlights the importance of referring patients with phaeochromocytoma and paraganglioma for genetic testing to help identify new genetic aberrations that may be associated with these conditions and could be the target of new precision medicines.