Pheochromocytomas and Paragangliomas in Von Hippel-Lindau Disease: Not a Needle in a Haystack

Overview

Journal Endocr Connect

Specialty Endocrinology

Date 2021 Oct 1

PMID 34596579

Citations 9

Authors

Joao Castro-Teles

Bernardo Sousa-Pinto

Sandra Rebelo

Duarte Pignatelli

Affiliations

Soon will be listed here.

Abstract

Objective: Pheochromocytomas are a hallmark feature of von Hippel-Lindau disease (vHL). To our knowledge, this is the first systematic review with meta-analysis evaluating the frequency of pheochromocytomas and/or paragangliomas (PPGLs) in patients with vHL, as well as among patients with different vHL subtypes.

Design: Systematic review with meta-analysis.

Methods: We searched on MEDLINE, Scopus, and Web of Science. We included primary studies assessing participants with vHL and reporting on the frequency of PPGL. We performed random-effects meta-analysis to quantitatively assess the frequency of PPGL, followed by meta-regression and subgroup analysis. Risk of bias analysis was performed to assess primary studies' methodological quality.

Results: We included 80 primary studies. In 4263 patients with vHL, the pooled frequency of PPGL was 19.4% (95% CI = 15.9-23.6%, I2 = 86.1%). The frequency increased to 60.0% in patients with vHL type 2 (95% CI = 53.4-66.3%, I2 = 54.6%) and was determined to be of 58.2% in patients with vHL type 2A (95% CI = 49.7-66.3%, I2 = 36.2%), compared to 49.8% in vHL type 2B (95% CI = 39.9-59.7%, I2 = 42.7%), and 84.1% in vHL type 2C (95% CI = 75.1-93.1%, I2 = 0%). In meta-regression analysis, more recent studies were associated with a higher frequency of PPGL. All studies had at least one internal validity item classified as 'high risk of bias,' with 13% studies having low risk of bias in all external validity items.

Conclusions: PPGLs are a common manifestation of vHL. Despite methodological limitations and differences across primary studies, our results point to the importance of PPGL screening in patients with vHL.

Citing Articles

New Developments in VHL-Associated Neuroendocrine Neoplasms.

Tsoli M, Panagaki M, Tasouli E, Kolomodi D, Kaltsas G Curr Oncol Rep. 2025; 27(1):59-67.

PMID: 39757325 DOI: 10.1007/s11912-024-01631-5.

Novel Gene Variants in a Nationwide Cohort of Patients with Pheochromocytoma and Paraganglioma.

Martinez de Lapiscina I, Diego E, Baquero C, Fernandez E, Menendez E, Moure M Int J Mol Sci. 2024; 25(22).

PMID: 39596125 PMC: 11593415. DOI: 10.3390/ijms252212056.

Surveillance in Children and Adolescents with von Hippel-Lindau (VHL)-Related Pheochromocytomas and Paragangliomas: A Survey of MET and Freiburg-VHL Registries in Germany.

Kotsis F, Kunstreich M, Redlich A, Rhein K, Ganner A, Walz G J Kidney Cancer VHL. 2024; 11(4):15-27.

PMID: 39588063 PMC: 11586502. DOI: 10.15586/jkcvhl.v11i4.362.

Genetics, Pathophysiology, and Current Challenges in Von Hippel-Lindau Disease Therapeutics.

Gomez-Virgilio L, Velazquez-Paniagua M, Cuazozon-Ferrer L, Silva-Lucero M, Gutierrez-Malacara A, Padilla-Mendoza J Diagnostics (Basel). 2024; 14(17).

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Current prospects of hereditary adrenal tumors: towards better clinical management.

Ohmoto A, Hayashi N, Takahashi S, Ueki A Hered Cancer Clin Pract. 2024; 22(1):4.

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