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

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 MianSarka 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 Vlček, Dmitry Beltsevich, Viacheslav I. Egorov, Francesca Schiavi, Thera P. Links, Ronald M. Lechan, Birke Bausch, William F. Young, Charis Eng

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJAMA Network Open
DOIs
StateAccepted/In press - Jan 1 2019

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Adrenalectomy
Pheochromocytoma
Morbidity
Mortality
Addison Disease
Cushing Syndrome
Survival
Adrenal Insufficiency
Germ-Line Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy. / 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; Vlček, Petr; Beltsevich, Dmitry; Egorov, Viacheslav I.; Schiavi, Francesca; Links, Thera P.; Lechan, Ronald M.; Bausch, Birke; Young, William F.; Eng, Charis.

In: JAMA Network Open, 01.01.2019.

Research output: Contribution to journalArticle

Neumann, HPH, Tsoy, U, Bancos, I, Amodru, V, Walz, MK, Tirosh, A, Kaur, RJ, McKenzie, T, Qi, X, Bandgar, T, Petrov, R, Yukina, MY, Roslyakova, A, Van Der Horst-Schrivers, ANA, Berends, AMA, Hoff, AO, Castroneves, LA, Ferrara, AM, Rizzati, S, Mian, C, Dvorakova, S, Hasse-Lazar, K, Kvachenyuk, A, Peczkowska, M, Loli, P, Erenler, F, Krauss, T, Almeida, MQ, Liu, L, Zhu, F, Recasens, M, Wohllk, N, Corssmit, EPM, Shafigullina, Z, Calissendorff, J, Grozinsky-Glasberg, S, Kunavisarut, T, Schalin-Jäntti, C, Castinetti, F, Vlček, P, Beltsevich, D, Egorov, VI, Schiavi, F, Links, TP, Lechan, RM, Bausch, B, Young, WF & Eng, C 2019, 'Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy', JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2019.8898
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 ; Vlček, Petr ; Beltsevich, Dmitry ; Egorov, Viacheslav I. ; Schiavi, Francesca ; Links, Thera P. ; Lechan, Ronald M. ; Bausch, Birke ; Young, William F. ; Eng, Charis. / Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy. In: JAMA Network Open. 2019.
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title = "Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy",
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.",
author = "Neumann, {Hartmut P.H.} and Uliana Tsoy and Irina Bancos and Vincent Amodru and Walz, {Martin K.} and Amit Tirosh and Kaur, {Ravinder Jeet} and Travis McKenzie and Xiaoping Qi and Tushar Bandgar and Roman Petrov and Yukina, {Marina Y.} and Anna Roslyakova and {Van Der Horst-Schrivers}, {Anouk N.A.} and Berends, {Annika M.A.} and Hoff, {Ana O.} and Castroneves, {Luciana Audi} and Ferrara, {Alfonso Massimiliano} and Silvia Rizzati and Caterina Mian and Sarka Dvorakova and Kornelia Hasse-Lazar and Andrey Kvachenyuk and Mariola Peczkowska and Paola Loli and Feyza Erenler and Tobias Krauss and Almeida, {Madson Q.} and Longfei Liu and Feizhou Zhu and M{\`o}nica Recasens and Nelson Wohllk and Corssmit, {Eleonora P.M.} and Zulfiya Shafigullina and Jan Calissendorff and Simona Grozinsky-Glasberg and Tada Kunavisarut and Camilla Schalin-J{\"a}ntti and Frederic Castinetti and Petr Vlček and Dmitry Beltsevich and Egorov, {Viacheslav I.} and Francesca Schiavi and Links, {Thera P.} and Lechan, {Ronald M.} and Birke Bausch and Young, {William F.} and Charis Eng",
year = "2019",
month = "1",
day = "1",
doi = "10.1001/jamanetworkopen.2019.8898",
language = "English (US)",
journal = "JAMA network open",
issn = "2574-3805",
publisher = "American Medical Association",

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TY - JOUR

T1 - Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

AU - Neumann, Hartmut P.H.

AU - Tsoy, Uliana

AU - Bancos, Irina

AU - Amodru, Vincent

AU - Walz, Martin K.

AU - Tirosh, Amit

AU - Kaur, Ravinder Jeet

AU - McKenzie, Travis

AU - Qi, Xiaoping

AU - Bandgar, Tushar

AU - Petrov, Roman

AU - Yukina, Marina Y.

AU - Roslyakova, Anna

AU - Van Der Horst-Schrivers, Anouk N.A.

AU - Berends, Annika M.A.

AU - Hoff, Ana O.

AU - Castroneves, Luciana Audi

AU - Ferrara, Alfonso Massimiliano

AU - Rizzati, Silvia

AU - Mian, Caterina

AU - Dvorakova, Sarka

AU - Hasse-Lazar, Kornelia

AU - Kvachenyuk, Andrey

AU - Peczkowska, Mariola

AU - Loli, Paola

AU - Erenler, Feyza

AU - Krauss, Tobias

AU - Almeida, Madson Q.

AU - Liu, Longfei

AU - Zhu, Feizhou

AU - Recasens, Mònica

AU - Wohllk, Nelson

AU - Corssmit, Eleonora P.M.

AU - Shafigullina, Zulfiya

AU - Calissendorff, Jan

AU - Grozinsky-Glasberg, Simona

AU - Kunavisarut, Tada

AU - Schalin-Jäntti, Camilla

AU - Castinetti, Frederic

AU - Vlček, Petr

AU - Beltsevich, Dmitry

AU - Egorov, Viacheslav I.

AU - Schiavi, Francesca

AU - Links, Thera P.

AU - Lechan, Ronald M.

AU - Bausch, Birke

AU - Young, William F.

AU - Eng, Charis

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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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