Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

• Published in: JAMA network open 2019-08, Vol.2 (8), p.e198898-e198898
• Main Authors: Neumann, Hartmut P H, Tsoy, Uliana, Bancos, Irina, Amodru, Vincent, Walz, Martin K, Tirosh, Amit, Kaur, Ravinder Jeet, McKenzie, Travis, Qi, Xiaoping, Bandgar, Tushar, Petrov, Roman, Yukina, Marina Y, Roslyakova, Anna, van der Horst-Schrivers, Anouk N A, Berends, Annika M A, Hoff, Ana O, Castroneves, Luciana Audi, Ferrara, Alfonso Massimiliano, Rizzati, Silvia, Mian, Caterina, Dvorakova, Sarka, Hasse-Lazar, Kornelia, Kvachenyuk, Andrey, Peczkowska, Mariola, Loli, Paola, Erenler, Feyza, Krauss, Tobias, Almeida, Madson Q, Liu, Longfei, Zhu, Feizhou, Recasens, Mònica, Wohllk, Nelson, Corssmit, Eleonora P M, Shafigullina, Zulfiya, Calissendorff, Jan, Grozinsky-Glasberg, Simona, Kunavisarut, Tada, Schalin-Jäntti, Camilla, Castinetti, Frederic, Vlcek, Petr, Beltsevich, Dmitry, Egorov, Viacheslav I, Schiavi, Francesca, Links, Thera P, Lechan, Ronald M, Bausch, Birke, Young, Jr, William F, Eng, Charis
• Format: Article
• Language: English
• Subjects: Cushing syndrome; Diabetes and Endocrinology; Mortality; Online Only; Original Investigation
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2019.8898

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. 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. 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. Total or cortical-sparing adrenalectomy. Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. 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 RET (282 patients [54%]), VHL (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. Patients undergoing cortical-sparing adrenalectomy did not