Endocrine Abstracts

JOINT1223

Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with a heterogenous clinical behaviour. Among solid tumors, PPGLs have the most strong genetic predisposition with a specific geographical distribution pattern.

Aim: To compare the genotype and phenotype characteristics from two cohorts of patients with PPGLs from two different geographical and historical regions of Europe: Romania and Belgium.

Material and methods: For Romanian cohort retrospective clinical, imaging and genetic (germinal) data was collected from electronic medical records of 140 patients consecutively diagnosed with PPGLs at ‘C.I. Parhon’ National Institute of Endocrinology between 1987–2020. For newly diagnosed patients the same data was prospectively collected between 2020 and February 2024. For the Flemish cohort, we retrospectively retrieve data of 67 consecutively registered patients diagnosed with PPGLs in Endocrinology, Pathology and Surgery Departments from Ghent University Hospital (Belgium) registry, between 2002 and 2020.

Results: In the Romanian cohort were included 140 patients with PPGLs, with a mean age at diagnosis of 47.9±15.6 years. Ninety-seven (69.2%) were women, and 43 (30.7%) were men; 130 (92.8%) presented with PHEOs and 10 (7.2%) with PGLs. In the Flemish cohort were included 67 patients, with a mean age at diagnosis of 50±19 years, 38 (56.7%) women, 29 (43.3%) men, most of them presented with PHEO 42 (63%) and 25 (37%) with PGL. Patients from Flemish cohort had a better access to genetic test (90% in Flemish vs. 63% in Romanian cohort) resulting a higher percentage of hereditary cases (n=32, 40% vs. n=24, 36%). Romanian patients presented most frequently with RET – c.1902C>G (p.Cys634Trp) (n=22, 68.7%), while Flemish patients with SDHD – SDHD c.170-1 G>T (n=10, 41.7%) pathogenic variant. Based on this genetic background, Romanian patients presented more frequently with bilateral PHEOs, compared to Flemish cohort (19.3%; n=15; vs. 7% n=3; P=0.002), while Flemish patients presented more often with multiple PGLs (24% vs. 0%).

Conclusion: We can conclude that the different prevalence of pathogenic variants related to hereditary PPGLs in Romania [RET c.1902C>G (p.Cys634Trp)] versus Belgium [SDHx (SDHD c.170-1 G>T)], could be considered as a founder effect. While Flemish patients are more frequently incidentally diagnosed and develop more often multiple PGLs, Romanian patients had a higher PHEO/PGL ratio and had higher proportion of bilateral PHEOs compared to Flemish population.