Pheochromocytoma in von Hippel-Lindau Disease: Clinical Features and Comparison With Sporadic Pheochromocytoma

Objectives: Pheochromocytomas and paragangliomas (PPGLs) are manifestations of von Hippel-Lindau (VHL) disease. This study aims to describe the clinical features of PPGLs in VHL patients and the distinctions between VHL disease-related PPGLs and sporadic PPGLs.

Design, patients and measurements: The study included all patients with VHL disease and PPGLs treated in a single centre from 2007 to 2023. A total of 145 patients were included in the sporadic PPGLs group. Their clinical data were retrospectively reviewed. Genetic testing for VHL mutation was conducted using Sanger sequencing. Statistical analysis was performed using SPSS 22.

Results: Fifty-nine (65.6%) of the 90 VHL disease patients had PPGLs (male: female, 38:21; age at diagnosis, 25.0 ± 13.3 years). 42 (71.2%) patients had lesions only in the adrenal gland, and 16 (27.1%) patients had lesions both in and out of the adrenal gland. 45 (76.3%) patients had multiple lesions. Eighteen (45.0%) patients developed recurrence after surgery. Fifty-eight patients with PPGLs underwent genetic testing and had pathogenic or likely pathogenic mutations in the VHL gene. Fifty-three (91.4%) patients had missense mutations, 34 of which were located in the Elongin-C binding domain. The hotspot mutation sites were codon 161 and codon 167. Five novel mutations were identified. The clinical characteristics showed no significant differences between groups with different mutation sites. Compared to sporadic PPGLs, VHL disease-related PPGLs were more frequently located in the adrenal gland (71.2% vs. 49.0%, p < 0.001), had a higher prevalence of multiple lesions (76.3% vs. 11.0%, p < 0.001), and secreted noradrenaline (80.4% vs. 43.2%, p < 0.001). They were also more likely to relapse after surgery (45.0% vs. 15.3%, p < 0.001).

Conclusion: VHL disease-related PPGLs were often multifocal and noradrenergic, and more likely to relapse compared with sporadic PPGLs. No relationships were identified between the mutation sites and the clinical characteristics of PPGLs.