1. Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy
- Author
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Neumann, H.P.H., Tsoy, U., Bancos, I., Amodru, V., Walz, M.K., Tirosh, A., Kaur, R.J., McKenzie, T., Qi, X.P., Bandgar, T., Petrov, R., Yukina, M.Y., Roslyakova, A., Horst-Schrivers, A.N.A. van der, Berends, A.M.A., Hoff, A.O., Castroneves, L.A., Ferrara, A.M., Rizzati, S., Mian, C., Dvorakova, S., Hasse-Lazar, K., Kvachenyuk, A., Peczkowska, M., Loli, P., Erenler, F., Krauss, T., Almeida, M.Q., Liu, L.F., Zhu, F.Z., Recasens, M., Wohllk, N., Corssmit, E.P.M., Shafigullina, Z., Calissendorff, J., Grozinsky-Glasberg, S., Kunavisarut, T., Schalin-Jantti, C., Castinetti, F., Vlcek, P., Beltsevich, D., Egorov, V.I., Schiavi, F., Links, T.P., Lechan, R.M., Bausch, B., Young, W.F., Eng, C., Jaiswal, S.K., Zschiedrich, S., Fragoso, M.C.B.V., Pereira, M.A.A., Li, M.H., Costa, J.B., Juhlin, C.C., Gross, D., Violante, A.H.D., Kocjan, T., Ngeow, J., Yoel, U., Fraenkel, M., Simsir, I.Y., Ugurlu, M.U., Ziagaki, A., Diaz, L.R., Kudlai, I.S., Gimm, O., Scherbaum, C.R., Abebe-Campino, G., Barbon, G., Taschin, E., Malinoc, A., Khudiakova, N.V., Ivanov, N.V., Pfeifer, M., Zovato, S., Ploeckinger, U., Makay, O., Grineva, E., Jarzab, B., Januszewicz, A., Shah, N., Seufert, J., Opocher, G., Larsson, C., Int Bilateral-Pheochromocytoma-Reg, Ege Üniversitesi, HUS Abdominal Center, Endokrinologian yksikkö, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), 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, Monica, Wohllk, Nelson, Corssmit, Eleonora P. M., Shafigullina, Zulfiya, Calissendorff, Jan, Grozinsky-Glasberg, Simona, Kunavisarut, Tada, Schalin-Jantti, Camilla, Castinetti, Frederic, Vlcek, Petr, Beltsevich, Dmitry, Egorov, Viacheslav, I, Schiavi, Francesca, Links, Thera P., Lechan, Ronald M., Bausch, Birke, Young, William F., Jr., Eng, Charis, Jaiswal, Sanjeet Kumar, Zschiedrich, Stefan, Fragoso, Maria C. B., V, Pereira, Maria A. A., Li, Minghao, Biarnes Costa, Josefina, Juhlin, Carl Christofer, Gross, David, Violante, Alice H. D., Kocjan, Tomaz, Ngeow, Joanne, Yoel, Uri, Fraenkel, Merav, Simsir, Ilgin Yildirim, Ugurlu, M. Umit, Ziagaki, Athanasia, Robles Diaz, Luis, Kudlai, Inna Stepanovna, Gimm, Oliver, Scherbaum, Christina Rebecca, Abebe-Campino, Gadi, Barbon, Giovanni, Taschin, Elisa, Malinoc, Angelica, Khudiakova, Natalia Valeryevna, Ivanov, Nikita, V, Pfeifer, Marija, Zovato, Stefania, Ploeckinger, Ursula, Makay, Ozer, Grineva, Elena, Jarzab, Barbara, Januszewicz, Andrzej, Shah, Nalini, Seufert, Jochen, Opocher, Giuseppe, Larsson, Catharina, and Lee Kong Chian School of Medicine (LKCMedicine)
- Subjects
Male ,endocrine system diseases ,SURGERY ,medicine.medical_treatment ,Adrenal Gland Neoplasms ,030230 surgery ,Primary Adrenal Insufficiency ,0302 clinical medicine ,Interquartile range ,Paraganglioma ,Registries ,Original Investigation ,OUTCOMES ,integumentary system ,Adrenal crisis ,Adrenalectomy ,General Medicine ,GERMLINE MUTATIONS ,3. Good health ,Online Only ,Diabetes and Endocrinology ,PARAGANGLIOMA ,CONFER ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,Adult ,medicine.medical_specialty ,endocrine system ,GENETICS ,Urology ,Pheochromocytoma ,Bilateral Pheochromocytomas ,03 medical and health sciences ,Young Adult ,medicine ,Adrenal insufficiency ,MANAGEMENT ,Humans ,Medicine [Science] ,RECURRENCE ,Retrospective Studies ,business.industry ,Research ,Retrospective cohort study ,medicine.disease ,PREDISPOSITION ,3121 General medicine, internal medicine and other clinical medicine ,Morbidity ,Neoplasm Recurrence, Local ,business ,Organ Sparing Treatments - Abstract
Key Points Question Is cortical-sparing adrenalectomy associated with increased pheochromocytoma-specific morbidity and mortality for patients with bilateral pheochromocytomas compared with total adrenalectomy? Findings In this cohort study of 625 patients with bilateral pheochromocytomas, most had hereditary syndromes, but 36% initially presented with unilateral pheochromocytoma. Bilateral total adrenalectomy resulted in a high rate of adverse effects from glucocorticoid replacement therapy, whereas cortical-sparing surgery was not associated with a worse outcome. Meaning These findings suggest that cortical-sparing surgery may be the preferred approach for patients at risk for, or diagnosed with, bilateral pheochromocytomas, especially those harboring a germline mutation in one of the known predisposition genes., This cohort study compares outcomes associated with cortical-sparing adrenalectomy vs total adrenalectomy for patients with bilateral pheochromocytomas., 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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- 2019