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Comparative Study
. 2019 Aug 2;2(8):e198898.
doi: 10.1001/jamanetworkopen.2019.8898.

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

Hartmut P H Neumann  1 , Uliana Tsoy  2 , Irina Bancos  3 , Vincent Amodru  4 , Martin K Walz  5 , Amit Tirosh  6 , Ravinder Jeet Kaur  3 , Travis McKenzie  7 , Xiaoping Qi  8 , Tushar Bandgar  9 , Roman Petrov  10 , Marina Y Yukina  11 , Anna Roslyakova  11 , Anouk N A van der Horst-Schrivers  12 , Annika M A Berends  12 , Ana O Hoff  13 , Luciana Audi Castroneves  13 , Alfonso Massimiliano Ferrara  14 , Silvia Rizzati  14 , Caterina Mian  15 , Sarka Dvorakova  16 , Kornelia Hasse-Lazar  17 , Andrey Kvachenyuk  18 , Mariola Peczkowska  19 , Paola Loli  20 , Feyza Erenler  21 , Tobias Krauss  22 , Madson Q Almeida  13 , Longfei Liu  23 , Feizhou Zhu  24 , Mònica Recasens  25 , Nelson Wohllk  26 , Eleonora P M Corssmit  27 , Zulfiya Shafigullina  28 , Jan Calissendorff  29 , Simona Grozinsky-Glasberg  30 , Tada Kunavisarut  31 , Camilla Schalin-Jäntti  32 , Frederic Castinetti  4 , Petr Vlcek  33 , Dmitry Beltsevich  11 , Viacheslav I Egorov  10 , Francesca Schiavi  14 , Thera P Links  12 , Ronald M Lechan  21 , Birke Bausch  34 , William F Young Jr  8 , Charis Eng  35 ; International Bilateral-Pheochromocytoma-Registry Group
Collaborators, Affiliations
Comparative Study

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

Hartmut P H Neumann et al. JAMA Netw Open. .

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: Total or cortical-sparing adrenalectomy.

Main outcomes and measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality.

Results: 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.

Conclusions and relevance: 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Neumann reported grants and personal fees from 70-3313-Ne1 by the Deutsche Krebshilfe (German Cancer Foundation), grants and personal fees from NE571/5-3 by the Deutsche Forschungsgemeinschaft (German Research Foundation), and grants and personal fees from LSHC-CT2005 518200 by the European Union during the conduct of the study. Dr Bancos reported membership on the advisory board of HRA PHARMA outside the submitted work. Dr Qi reported grants from the National Natural Science Foundation of China (81871136) and grants from the Key Project of Zhejiang Province Science and Technology Plan, China (2014C03048-1) during the conduct of the study. No other disclosures were reported.

Figures

Figure.
Figure.. Schema for Bilateral Pheochromocytoma Registrants, Their Operations, and Steroid-Dependent vs Steroid-Independent Outcomes
MEN 2 indicates patients with medullary thyroid carcinoma plus pheochromocytoma and/or patients with a RET mutation; VHL, pheochromocytoma with hemangioblastoma of eyes or central nervous system and/or patients with a VHL mutation; other, patients with a mutation in one of the genes SDHD, SDHB, MAX, or TMEM127 or signs of neurofibromatosis type 1 or clinically familial pheochromocytomas.
See this image and copyright information in PMC

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