Treatment of pheochromocytoma in adults
- William F Young, Jr, MD, MSc
William F Young, Jr, MD, MSc
- Professor of Medicine
- Mayo Clinic College of Medicine
- Electron Kebebew, MD, FACS
Electron Kebebew, MD, FACS
- Senior Investigator
- Chief, Endocrine Oncology Branch
- National Cancer Institute
- Section Editors
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
- Sally E Carty, MD, FACS
Sally E Carty, MD, FACS
- Section Editor — Endocrine Surgery
- Professor, Chief, Division of Endocrine Surgery
- University of Pittsburgh School of Medicine
Pheochromocytoma is a rare neuroendocrine tumor, occurring in less than 0.2 percent of patients with hypertension [1,2]. In at least 25 percent of patients, the tumor is discovered incidentally during computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen for unrelated symptoms [3-6]. Studies have found that 19 of 33 patients (58 percent) and 40 of 57 patients (70 percent) with adrenal pheochromocytoma had their tumors discovered incidentally on imaging [5,6]. In other patients, the tumor is found only at autopsy . Among patients suspected to have a pheochromocytoma, the diagnosis is rarely confirmed. In one series, as an example, the diagnosis was established in only 1 of 300 patients evaluated for pheochromocytoma .
The treatment of pheochromocytoma will be reviewed here (algorithm 1). The clinical manifestations, diagnosis, and genetics of pheochromocytoma and management of metastatic pheochromocytoma are discussed separately. (See "Clinical presentation and diagnosis of pheochromocytoma" and "Pheochromocytoma in genetic disorders" and "Paraganglioma and pheochromocytoma: Management of malignant disease".)
MEDICAL PREPARATION FOR SURGERY
Once a pheochromocytoma is diagnosed, all patients should undergo a resection of the pheochromocytoma following appropriate medical preparation. Agents known to provoke a pheochromocytoma paroxysm (eg, glucagon, histamine, metoclopramide) should be avoided. Our approach is largely consistent with the Endocrine Society’s 2014 Clinical Practice Guidelines .
Resecting a pheochromocytoma is a high-risk surgical procedure and an experienced surgeon/anesthesiologist team is required. Cardiovascular and hemodynamic variables must be monitored closely. Continuous measurement of intra-arterial pressure and heart rhythm is required. In the setting of congestive heart failure or decreased cardiac reserve, monitoring of pulmonary capillary wedge pressure is indicated.
Preoperative medical therapy is aimed at:
- Young WF Jr. Adrenal causes of hypertension: pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord 2007; 8:309.
- Pacak K, Linehan WM, Eisenhofer G, et al. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001; 134:315.
- Kudva YC, Young WF Jr, Thompson GB, et al. Adrenal incidentaloma: An important component of the clinical presentation spectrum of benign sporadic adrenal pheochromocytoma. The Endocrinologist 1999; 9:77.
- Baguet JP, Hammer L, Mazzuco TL, et al. Circumstances of discovery of phaeochromocytoma: a retrospective study of 41 consecutive patients. Eur J Endocrinol 2004; 150:681.
- Motta-Ramirez GA, Remer EM, Herts BR, et al. Comparison of CT findings in symptomatic and incidentally discovered pheochromocytomas. AJR Am J Roentgenol 2005; 185:684.
- Oshmyansky AR, Mahammedi A, Dackiw A, et al. Serendipity in the diagnosis of pheochromocytoma. J Comput Assist Tomogr 2013; 37:820.
- Bravo EL. Pheochromocytoma: new concepts and future trends. Kidney Int 1991; 40:544.
- Fogarty J, Engel C, Russo J, et al. Hypertension and pheochromocytoma testing: The association with anxiety disorders. Arch Fam Med 1994; 3:55.
- Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99:1915.
- Lo CY, Lam KY, Wat MS, Lam KS. Adrenal pheochromocytoma remains a frequently overlooked diagnosis. Am J Surg 2000; 179:212.
- Tauzin-Fin P, Sesay M, Gosse P, Ballanger P. Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma. Br J Anaesth 2004; 92:512.
- Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC. Successful outcomes in pheochromocytoma surgery in the modern era. J Urol 1999; 161:764.
- Lebuffe G, Dosseh ED, Tek G, et al. The effect of calcium channel blockers on outcome following the surgical treatment of phaeochromocytomas and paragangliomas. Anaesthesia 2005; 60:439.
- Combemale F, Carnaille B, Tavernier B, et al. [Exclusive use of calcium channel blockers and cardioselective beta-blockers in the pre- and per-operative management of pheochromocytomas. 70 cases]. Ann Chir 1998; 52:341.
- Steinsapir J, Carr AA, Prisant LM, Bransome ED Jr. Metyrosine and pheochromocytoma. Arch Intern Med 1997; 157:901.
- McBride JF, Atwell TD, Charboneau WJ, et al. Minimally invasive treatment of metastatic pheochromocytoma and paraganglioma: efficacy and safety of radiofrequency ablation and cryoablation therapy. J Vasc Interv Radiol 2011; 22:1263.
- Young WF Jr. Endocrine hypertension. In: Williams textbook of endocrinology, 12th Ed, Melmed S, Polonsky KS, Larsen PR, Kronenberg HM (Eds), Saunders/Elsevier, Philadelphia 2011. p.545.
- Nehs MA, Ruan DT. Minimally invasive adrenal surgery: an update. Curr Opin Endocrinol Diabetes Obes 2011; 18:193.
- Rafat C, Zinzindohoue F, Hernigou A, et al. Peritoneal implantation of pheochromocytoma following tumor capsule rupture during surgery. J Clin Endocrinol Metab 2014; 99:E2681.
- Shen WT, Grogan R, Vriens M, et al. One hundred two patients with pheochromocytoma treated at a single institution since the introduction of laparoscopic adrenalectomy. Arch Surg 2010; 145:893.
- Walz MK, Alesina PF, Wenger FA, et al. Laparoscopic and retroperitoneoscopic treatment of pheochromocytomas and retroperitoneal paragangliomas: results of 161 tumors in 126 patients. World J Surg 2006; 30:899.
- Ellis RJ, Patel D, Prodanov T, et al. Response after surgical resection of metastatic pheochromocytoma and paraganglioma: can postoperative biochemical remission be predicted? J Am Coll Surg 2013; 217:489.
- Shen WT, Sturgeon C, Clark OH, et al. Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas. Surgery 2004; 136:1129.
- Power AH, Bower TC, Kasperbauer J, et al. Impact of preoperative embolization on outcomes of carotid body tumor resections. J Vasc Surg 2012; 56:979.
- Brown ML, Zayas GE, Abel MD, et al. Mediastinal paragangliomas: the mayo clinic experience. Ann Thorac Surg 2008; 86:946.
- Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. Hormones (Athens) 2009; 8:111.
- Diner EK, Franks ME, Behari A, et al. Partial adrenalectomy: the National Cancer Institute experience. Urology 2005; 66:19.
- Neumann HP, Reincke M, Bender BU, et al. Preserved adrenocortical function after laparoscopic bilateral adrenal sparing surgery for hereditary pheochromocytoma. J Clin Endocrinol Metab 1999; 84:2608.
- Baghai M, Thompson GB, Young WF Jr, et al. Pheochromocytomas and paragangliomas in von Hippel-Lindau disease: a role for laparoscopic and cortical-sparing surgery. Arch Surg 2002; 137:682.
- Lee JE, Curley SA, Gagel RF, et al. Cortical-sparing adrenalectomy for patients with bilateral pheochromocytoma. Surgery 1996; 120:1064.
- Walther MM, Herring J, Choyke PL, Linehan WM. Laparoscopic partial adrenalectomy in patients with hereditary forms of pheochromocytoma. J Urol 2000; 164:14.
- Yip L, Lee JE, Shapiro SE, et al. Surgical management of hereditary pheochromocytoma. J Am Coll Surg 2004; 198:525.
- Castinetti F, Qi XP, Walz MK, et al. Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study. Lancet Oncol 2014; 15:648.
- Grubbs EG, Rich TA, Ng C, et al. Long-term outcomes of surgical treatment for hereditary pheochromocytoma. J Am Coll Surg 2013; 216:280.
- Kaltsas GA, Papadogias D, Grossman AB. The clinical presentation (symptoms and signs) of sporadic and familial chromaffin cell tumours (phaeochromocytomas and paragangliomas). Front Horm Res 2004; 31:61.
- Frank-Raue K, Kratt T, Höppner W, et al. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2-relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996; 135:222.
- Brauckhoff M, Gimm O, Brauckhoff K, Dralle H. Repeat adrenocortical-sparing adrenalectomy for recurrent hereditary pheochromocytoma. Surg Today 2004; 34:251.
- Benhammou JN, Boris RS, Pacak K, et al. Functional and oncologic outcomes of partial adrenalectomy for pheochromocytoma in patients with von Hippel-Lindau syndrome after at least 5 years of followup. J Urol 2010; 184:1855.
- Nielsen SM, Rubinstein WS, Thull DL, et al. Genotype-phenotype correlations of pheochromocytoma in two large von Hippel-Lindau (VHL) type 2A kindreds with different missense mutations. Am J Med Genet A 2011; 155A:168.
- Okamoto T, Obara T, Ito Y, et al. Bilateral adrenalectomy with autotransplantation of adrenocortical tissue or unilateral adrenalectomy: treatment options for pheochromocytomas in multiple endocrine neoplasia type 2A. Endocr J 1996; 43:169.
- Col V, de Cannière L, Collard E, et al. Laparoscopic adrenalectomy for phaeochromocytoma: endocrinological and surgical aspects of a new therapeutic approach. Clin Endocrinol (Oxf) 1999; 50:121.
- Gill IS, Soble JJ, Sung GT, et al. Needlescopic adrenalectomy--the initial series: comparison with conventional laparoscopic adrenalectomy. Urology 1998; 52:180.
- Saunders BD, Doherty GM. Laparoscopic adrenalectomy for malignant disease. Lancet Oncol 2004; 5:718.
- Assalia A, Gagner M. Laparoscopic adrenalectomy. Br J Surg 2004; 91:1259.
- Cheah WK, Clark OH, Horn JK, et al. Laparoscopic adrenalectomy for pheochromocytoma. World J Surg 2002; 26:1048.
- Sprung J, O'Hara JF Jr, Gill IS, et al. Anesthetic aspects of laparoscopic and open adrenalectomy for pheochromocytoma. Urology 2000; 55:339.
- Ichikawa T, Mikami K, Suzuki H, et al. Laparoscopic adrenalectomy for pheochromocytoma. Biomed Pharmacother 2002; 56 Suppl 1:149s.
- Matsuda T, Murota T, Oguchi N, et al. Laparoscopic adrenalectomy for pheochromocytoma: a literature review. Biomed Pharmacother 2002; 56 Suppl 1:132s.
- Plouin PF, Duclos JM, Soppelsa F, et al. Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center. J Clin Endocrinol Metab 2001; 86:1480.
- Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000; 91:1118.
- Brunaud L, Nguyen-Thi PL, Mirallie E, et al. Predictive factors for postoperative morbidity after laparoscopic adrenalectomy for pheochromocytoma: a multicenter retrospective analysis in 225 patients. Surg Endosc 2016; 30:1051.
- Murphy MM, Witkowski ER, Ng SC, et al. Trends in adrenalectomy: a recent national review. Surg Endosc 2010; 24:2518.
- Bruynzeel H, Feelders RA, Groenland TH, et al. Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma. J Clin Endocrinol Metab 2010; 95:678.
- Akiba M, Kodama T, Ito Y, et al. Hypoglycemia induced by excessive rebound secretion of insulin after removal of pheochromocytoma. World J Surg 1990; 14:317.
- Amar L, Servais A, Gimenez-Roqueplo AP, et al. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab 2005; 90:2110.
- MEDICAL PREPARATION FOR SURGERY
- Combined alpha and beta-adrenergic blockade
- - Alpha-adrenergic blockade
- Blood pressure monitoring
- High sodium diet
- - Beta-adrenergic blockade
- Calcium channel blockers
- Familial pheochromocytoma
- Surgical outcome
- Acute hypertensive crises
- - Management
- Other complications
- Malignant pheochromocytoma
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Pre-operative preparation
- Familial pheochromocytoma
- Malignant disease