Abstract
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 demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.
Highlights
Pheochromocytomas are tumors that store and release catecholamines in excess, leading to episodes of hypertension, profuse sweating, headaches, panic attacks, arrhythmia, stroke, and death.1 According to the World Health Organization classification, the term pheochromocytoma is reserved for adrenal location, whereas similar tumors outside the adrenals are named paragangliomas.2 Bilateral pheochromocytomas may present either synchronously or metachronously
Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%)
Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma
Summary
Pheochromocytomas are tumors that store and release catecholamines in excess, leading to episodes of hypertension, profuse sweating, headaches, panic attacks, arrhythmia, stroke, and death. According to the World Health Organization classification, the term pheochromocytoma is reserved for adrenal location, whereas similar tumors outside the adrenals are named paragangliomas. Bilateral pheochromocytomas may present either synchronously or metachronously. According to the World Health Organization classification, the term pheochromocytoma is reserved for adrenal location, whereas similar tumors outside the adrenals are named paragangliomas.. Bilateral pheochromocytomas may present either synchronously or metachronously. Bilateral pheochromocytomas are often heritable and have been shown to occur mainly in patients with multiple endocrine neoplasia type 2 (MEN 2) caused by germline mutations of the RET (rearranged during transfection) proto-oncogene, von Hippel-Lindau disease (VHL; VHL gene) and the paragangliomas syndromes types 1 and 4 caused by mutations in the succinate dehydrogenase (SDH) subunit D (SDHD) and B (SDHB) genes, respectively.. In bilateral pheochromocytomas, the removal of the tumor only vs the entire adrenal gland remains an open question. The 2014 Endocrine Society management guidelines recommend cortical-sparing adrenalectomy for bilateral and hereditary pheochromocytoma based on low grade of evidence. Following guidelines in specialized centers demonstrated favorable short-term outcomes, uncertainty remains because of the greater than 10% risk of metastatic pheochromocytomas and the potential of developing new ipsilateral pheochromocytomas.
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