Endocrine Abstracts

A 50-year-old female with complex chronic hypoxic congenital heart disease was incidentally identified with a 2 cm extra-vesicular nodule of the bladder during a surveillance ultrasound scan. Suspicious of a bladder carcinoma she uneventfully underwent open partial cystectomy. Histology confirmed a bladder paraganglioma with local lymph node invasion. Post-operative biochemical work-up disclosed raised plasma metanephrine”s: normetadrenaline 7073 pmol/l (120-1180 pmol/l), metadrenaline 485 pmol/l (80-510 pmol/l), 3-methoxythyramine <120 pmol/l and normal range chromogranin A and B. She was also polycythaemic and had an extensive background of multiple cardiac surgeries. Her symptoms were minimal with infrequent sweating and mood changes. Our Patient was started on doxazosin. Previously she was on bisoprolol and her blood pressure remained systolic <130 mmHg. Further whole body MRI imaging detected multiple nodes in the neck and mediastinum. Eleven-gene panel did not identify genetic mutations. There was no family history of paragangliomas. A 68Ga-DOTATATE PET CT was arranged which showed avidity to multiple mediastinal nodules; largest 3 cm and bilateral sub-centimetre carotid paragangliomas. Additionally somatic testing was arranged. In view of her complex cardiac anatomy and previous sternotomies a conservative management plan was adopted. We started our patient on somatostatin analogue Lanreotide to medically treat her multiple paraganglioma”s. Repeat 68Ga-DOTATATE PET CT scan on Lanreotide showed nil changes. Plan is to continue surveillance scans and yearly plasma metanephrine”s. Hypoxia results in tumorigenesis and has been linked to paragangliomas/phaechromocytomas through activation of hypoxia-inducible-factor (HIF) proteins. Congenital heart disease and paragangliomas/phaechromocytomas can cause polycythaemia. There is an increased occurrence of head and neck paragangliomas in chronic hypoxia. Germline mutations are present in 40% of paragangliomas/phaechromocytomas cases; amongst these SDHx and VHL gene mutations are associated with pseudohypoxia-related-cluster-1 driven paragangliomas. Other HIF’s have been linked to development of paragangliomas/phaechromocytomas such as EGLN1 and EPAS1. Although we have not been able to identify an inherited cause of paragangliomas it is possible that there could be a change in later samples. Somatic testing is new to UK and allows us to further develop knowledge and management strategies. Storing sample is advocated. This case highlights a unique complex case of multiple paragangliomas in a chronic hypoxic individual. We believe a chronic hypoxic state has contributed to her disease burden and her management is dependent on her baseline functionality. Pharmacological treatments are limited, understanding of hypoxia pathways may help in future developments of HIF inhibitors.