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Prevention Medicine in Bilateral Phaeochromocytoma
Posted: 11 Dec 2018
There are 2 versions of this paper
Background: Adrenalectomy is standard of care for phaeochromocytomas, but for bilateral phaeochromocytoma, the recommendations are inconsistent. However, large studies systematically investigating long-term outcomes for total adrenalectomies compared to those for patients with adrenal-sparing operations are lacking. Methods A multi-center consortium-based registry was established to study clinical, genetic and surgical data in 623 patients with bilateral phaeochromocytomas.
Findings: Of 623 patients, median age at diagnosis was 30 (range 3-79) years and 48% were female. Synchronous bilateral phaeochromocytomas were diagnosed in 396 patients and metachronousphaeochromocytomas in 227 (36%); interval to second operations were up to 40 (median 6) years. In 96% of tested patients germline mutations were detected in the genes RET (56%), VHL (34%), and others (10%). Of 849 operations, 385 (45%) surgeries in 326 patients were planned as adrenal-sparing which was successful in 251. 372 patients became steroid-dependent. Follow-up was up to 53 (median 11) years. Adrenal crises developed in 67 patients (18%) during follow-up, and 49 (13%) had manifestations of iatrogenic Cushing syndrome. Of the steroid-independent patients, 34 (14%) had developed another phaeochromocytoma within the remnant adrenal after up to 27, median 8 years, all treated with removal of the new phaeochromocytoma. Overall survival was mainly influenced by non-phaeochromocytoma comorbidities, whereas only 1% died of metastatic phaeochromocytoma. Cortical-sparing operations did not affect survival.
Interpretation: Cortical-sparing operations avert lifelong steroid-dependency without affecting survival. Preoperative genetic testing is recommended even in unilateral phaeochromocytoma presentations to identify patients at heritable risk, to guide surgical approach, and inform for gene-specific extra-adrenal morbidities.
Funding Statement: Supported in part by the grant AZV 16-32665A to SarkaDvorakova and Petr Vlcek, and the Blank Foundation to Charis Eng.
Declaration of Interests: None of the authors have relevant conflicts of interest.
Ethics Approval Statement: The institutional review boards for human subjects’ protection or ethical committees of all participating centers approved this study. Patients provided written informed consent according to the protocols of respective institutional review boards. In The Netherlands data were collected anonymously, and no further Institutional Review Board approval is required.
Tsoy, Uliana and Amodru, Vincent and Walz, Martin K. and Bancos, Irina and Jeet, Ravinder Kaur and Qi, Xiaoping and Bandgar, Tushar and Jaiswal, Sanjeet Kumar and Petrov, Roman and Roslyakova, Anna and Yukina, Marina Y. and Horst-Schrivers, Anouk N. A. van der and Berends, Annika M.A. and Hoff, Ana O. and Castroneves, Luciana Audi and Ferrara, Alfonso Massimiliano and Rizzati, Silvia and Mian, Caterina and Dvorakova, Sarka and Hasse-Lazar, Kornelia and Kvachenyuk, Andrey and Peczkowska, Mariola and Loli, Paola and Erenler, Feyza and Zschiedrich, Stefan and Krauss, Tobias and Almeida, Madson Q. and Fragoso, Maria C. B. V. and Pereira, Maria A. A. and Liu, Longfei and Li, Minghao and Zhu, Feizhou and Recasens, Mònica and Costa, Josefina Biarnes and Wohllk, Nelson and Corssmit, Eleonora and Shafigullina, Zulfiya and Callissendorff, Jan and Juhlin, Carl Christofer and Grozinsky-Glasberg, Simona and Gross, David and Kunavisarut, Tada and Violante, Alice H. D. and Kocjan, Tomaz and Ngeow, Joanne and Yoel, Uri and Fraenkel, Merav and Simsir, Ilgin Yildirim and Ugurlu, Umit and Ziagaki, Athanasia and Schalin-Jäntti, Camilla and Díaz, Luis Robles and Kudlai, Inna Stepanovna and Gimm, Oliver and Scherbaum, Christina Rebecca and Barbon, Giovanni and Taschin, Elisa and Malinoc, Angelica and Khudiakova, Natalia Valeryevna and Ivanov, Nikita V. and Castinetti, Frederic and Vlček, Petr and Pfeifer, Marija and Beltsevich, Dmitry and Egorov, Viacheslav I. and Zovato, Stefania and Ploeckinger, Ursula and Makay, Özer and Grineva, Elena and Schiavi, Francesca and Jarzab, Barbara and Januszewicz, Andrzej and Opocher, Giuseppe and Shah, Nalini and Seufert, Jochen and Links, Thera P. and Larsson, Catharina and Lechan, Ronald M. and Bausch, Birke and Young, William F. and Eng, Charis and Neumann, Hartmut P. H., Prevention Medicine in Bilateral Phaeochromocytoma (April 12, 2018). Available at SSRN: https://ssrn.com/abstract=3296675