Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy
Authors: Hartmut P. H. Neumann, Uliana Tsoy, Irina Bancos, Vincent Amodru, Martin K. Walz, Amit Tirosh, Ravinder Jeet Kaur, Travis McKenzie, Xiaoping Qi, Tushar Bandgar, Roman Petrov, Marina Y. Yukina, Anna Roslyakova, Anouk N. A. van der Horst-Schrivers, Annika M. A. Berends, Ana O. Hoff, Luciana Audi Castroneves, Alfonso Massimiliano Ferrara, Silvia Rizzati, Caterina Mian, Sarka Dvorakova, Kornelia Hasse-Lazar, Andrey Kvachenyuk, Mariola Peczkowska, Paola Loli, Feyza Erenler, Tobias Krauss, Madson Q. Almeida, Longfei Liu, Feizhou Zhu, Mònica Recasens, Nelson Wohllk, Eleonora P. M. Corssmit, Zulfiya Shafigullina, Jan Calissendorff, Simona Grozinsky-Glasberg, Tada Kunavisarut, Camilla Schalin-Jäntti, Frederic Castinetti, Petr Vlcek, Dmitry Beltsevich, Viacheslav I. Egorov, Francesca Schiavi, Thera P. Links, Ronald M. Lechan, Birke Bausch, William F. Young, Charis Eng
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. <h3>Objective</h3> To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. <h3>Design, Setting, and Participants</h3> This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. <h3>Exposures</h3> Total or cortical-sparing adrenalectomy. <h3>Main Outcomes and Measures</h3> Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. <h3>Results</h3> Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes<i>RET</i>(282 patients [54%]),<i>VHL</i>(184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. <h3>Conclusions and Relevance</h3> Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.