Endocrine Abstracts

Pathogenic variants in the SDHx genes are responsible for ~20% of familial Phaeochromocytoma/Paraganglioma (PPGL) tumours. Metastatic disease is lower in SDHD in comparison to SDHA, B and C mutations. Although the genotype-phenotype relationship is not well established it is considered that truncating SDHD pathogenic variants have a higher risk of causing disease in comparison to missense variants. We present two cases of metastatic paraganglioma in patients with heterozygous c.242C>T (p.Pro81Leu) missense SDHD pathogenic variants. Patient 1 (aged 82) had multiple head and neck paragangliomas (left glomus jugulare and bilateral carotid body tumours) resected between 1969 and 1983. In 1988, metastatic deposits were identified in the liver which were treated with therapeutic MIBG. She had been under regular surveillance since (serial imaging and biochemistry). In 2020, in view of no recurrent disease and clinical stability with non-elevated plasma metanephrines, she was discharged from tertiary care. Patient 2 (aged 54): At the age of 18, a left vagal paraganglioma was resected. Subsequently he developed contralateral Jugular PGL. He was treated with stereotactic radiotherapy followed by gamma-knife radiosurgery in 2005. A small right sided carotid body PGL was also noted and remained stable in size over the years. Gallium-DOTATATE-avid left anterior pelvic bone metastasis were detected in 2017 and he received 4 cycles of Lutetium-177 PRRT (Peptide Receptor Radionuclide Therapy). He remains under regular surveillance for his stable disease. The above patients with the SDHD p.Pro81Leu missense pathogenic variant developed metastatic disease detected >15 years after their initial diagnosis of HNPGL. They represent 7% of our total cases (n= 27) with the same mutation (93% without metastases). We conclude that although there is lower reported risk of penetrance and metastatic disease in SDHD p.Pro81Leu pathogenic variant carriers compared to other SDHD variants, regular surveillance is required until 80 years of age.