Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Pheochromocytoma and paraganglioma in children

William F Young, Jr, MD, MSc
Section Editors
Alberto S Pappo, MD
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD


Pheochromocytomas and paragangliomas are rare tumors in children. Tumors that arise from the adrenal medulla are termed pheochromocytomas, and secrete catecholamines. Tumors with extra-adrenal origins are called paragangliomas, and either secrete catecholamines or are nonfunctional.

This topic review will discuss the clinical presentation, diagnosis, and management of pheochromocytomas and catecholamine-secreting paragangliomas in children. Given the limited experience with pheochromocytomas in children and the similarity in clinical presentation, diagnosis, and treatment among children and adults, the following discussion includes some data derived from the adult literature. Detailed reviews of these tumors in adults are presented separately. (See "Clinical presentation and diagnosis of pheochromocytoma" and "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology".)


Pheochromocytoma – Pheochromocytomas are catecholamine-secreting tumors that arise from the chromaffin cells of the adrenal medulla.

Paraganglioma – Paragangliomas arise from the paraganglia of the autonomic nervous system outside of the adrenal medulla. Those that involve the sympathetic nervous system usually secrete catecholamines and typically are located in the lower mediastinum, abdomen, and pelvis. Those that involve the parasympathetic nervous system are usually nonfunctional and often located in the skull base, neck, and upper mediastinum. This topic review will focus only on catecholamine-secreting tumors, and not nonfunctional paragangliomas. (See "Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology".)

Because pheochromocytomas and catecholamine-secreting paragangliomas have similar clinical presentations and are treated with similar approaches, many clinicians use the term "pheochromocytoma" to refer to both types of tumors. However, the distinction between pheochromocytoma and paraganglioma is an important one because of the implications for associated neoplasms, risk for malignancy, and implications for genetic testing.  

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Nov 08, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Januszewicz P, Wieteska-Klimczak A, Wyszyńska T. Pheochromocytoma in children: difficulties in diagnosis and localization. Clin Exp Hypertens A 1990; 12:571.
  2. Wyszyńska T, Cichocka E, Wieteska-Klimczak A, et al. A single pediatric center experience with 1025 children with hypertension. Acta Paediatr 1992; 81:244.
  3. Fonkalsrud EW. Pheochromocytoma in childhood. Prog Pediatr Surg 1991; 26:103.
  4. Lenders JW, Eisenhofer G, Mannelli M, Pacak K. Phaeochromocytoma. Lancet 2005; 366:665.
  5. Beltsevich DG, Kuznetsov NS, Kazaryan AM, Lysenko MA. Pheochromocytoma surgery: epidemiologic peculiarities in children. World J Surg 2004; 28:592.
  6. Ciftci AO, Tanyel FC, Senocak ME, Büyükpamukçu N. Pheochromocytoma in children. J Pediatr Surg 2001; 36:447.
  7. Pham TH, Moir C, Thompson GB, et al. Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center. Pediatrics 2006; 118:1109.
  8. Pamporaki C, Hamplova B, Peitzsch M, et al. Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab 2017; 102:1122.
  9. Chen H, Sippel RS, O'Dorisio MS, et al. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas 2010; 39:775.
  10. Kaufman BH, Telander RL, van Heerden JA, et al. Pheochromocytoma in the pediatric age group: current status. J Pediatr Surg 1983; 18:879.
  11. Perel Y, Schlumberger M, Marguerite G, et al. Pheochromocytoma and paraganglioma in children: a report of 24 cases of the French Society of Pediatric Oncology. Pediatr Hematol Oncol 1997; 14:413.
  12. Neumann HP, Bausch B, McWhinney SR, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002; 346:1459.
  13. Dluhy RG. Pheochromocytoma--death of an axiom. N Engl J Med 2002; 346:1486.
  14. Siqueira DR, Ceolin L, Ferreira CV, et al. Role of RET genetic variants in MEN2-associated pheochromocytoma. Eur J Endocrinol 2014; 170:821.
  15. Thosani S, Ayala-Ramirez M, Palmer L, et al. The characterization of pheochromocytoma and its impact on overall survival in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 2013; 98:E1813.
  16. Walther MM, Herring J, Enquist E, et al. von Recklinghausen's disease and pheochromocytomas. J Urol 1999; 162:1582.
  17. Gruber LM, Erickson D, Babovic-Vuksanovic D, et al. Pheochromocytoma and paraganglioma in patients with neurofibromatosis type 1. Clin Endocrinol (Oxf) 2017; 86:141.
  18. Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma. J Urol 1992; 147:1.
  19. Bender BU, Altehöfer C, Januszewicz A, et al. Functioning thoracic paraganglioma: association with Von Hippel-Lindau syndrome. J Clin Endocrinol Metab 1997; 82:3356.
  20. Freier DT, Tank ES, Harrison TS. Pediatric and adult pheochromocytomas. A biochemical and clinical comparison. Arch Surg 1973; 107:252.
  21. Caty MG, Coran AG, Geagen M, Thompson NW. Current diagnosis and treatment of pheochromocytoma in children. Experience with 22 consecutive tumors in 14 patients. Arch Surg 1990; 125:978.
  22. Albanese CT, Wiener ES. Routine total bilateral adrenalectomy is not warranted in childhood familial pheochromocytoma. J Pediatr Surg 1993; 28:1248.
  23. Ein SH, Shandling B, Wesson D, Filler Rm. Recurrent pheochromocytomas in children. J Pediatr Surg 1990; 25:1063.
  24. Webb TA, Sheps SG, Carney JA. Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2. Am J Surg Pathol 1980; 4:121.
  25. Young WF Jr, Abboud AL. Editorial: paraganglioma--all in the family. J Clin Endocrinol Metab 2006; 91:790.
  26. Goldstein RE, O'Neill JA Jr, Holcomb GW 3rd, et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999; 229:755.
  27. Pattarino F, Bouloux PM. The diagnosis of malignancy in phaeochromocytoma. Clin Endocrinol (Oxf) 1996; 44:239.
  28. Hamidi O, Young WF Jr, Iñiguez-Ariza NM, et al. Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years. J Clin Endocrinol Metab 2017; 102:3296.
  29. Bravo EL. Pheochromocytoma: new concepts and future trends. Kidney Int 1991; 40:544.
  30. 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.
  31. Ludwig AD, Feig DI, Brandt ML, et al. Recent advances in the diagnosis and treatment of pheochromocytoma in children. Am J Surg 2007; 194:792.
  32. Bholah R, Bunchman TE. Review of Pediatric Pheochromocytoma and Paraganglioma. Front Pediatr 2017; 5:155.
  33. Barontini M, Levin G, Sanso G. Characteristics of pheochromocytoma in a 4- to 20-year-old population. Ann N Y Acad Sci 2006; 1073:30.
  34. Kohane DS, Ingelfinger JR, Nimkin K, Wu CL. Case records of the Massachusetts General Hospital. Case 16-2005. A nine-year-old girl with headaches and hypertension. N Engl J Med 2005; 352:2223.
  35. Ein SH, Pullerits J, Creighton R, Balfe JW. Pediatric pheochromocytoma. A 36-year review. Pediatr Surg Int 1997; 12:595.
  36. Pomares FJ, Cañas R, Rodriguez JM, et al. Differences between sporadic and multiple endocrine neoplasia type 2A phaeochromocytoma. Clin Endocrinol (Oxf) 1998; 48:195.
  37. Walther MM, Reiter R, Keiser HR, et al. Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma. J Urol 1999; 162:659.
  38. Park JH, Kim KS, Sul JY, et al. Prevalence and patterns of left ventricular dysfunction in patients with pheochromocytoma. J Cardiovasc Ultrasound 2011; 19:76.
  39. Shub C, Cueto-Garcia L, Sheps SG, et al. Echocardiographic findings in pheochromocytoma. Am J Cardiol 1986; 57:971.
  40. Stein PP, Black HR. A simplified diagnostic approach to pheochromocytoma. A review of the literature and report of one institution's experience. Medicine (Baltimore) 1991; 70:46.
  41. Lake CR, Zaloga G, Bray J, et al. Transient hypertension after two phenylpropanolamine diet aids and the effects of caffeine: a placebo-controlled follow-up study. Am J Med 1989; 86:427.
  42. Keiser HR. Surreptitious self-administration of epinephrine resulting in 'pheochromocytoma'. JAMA 1991; 266:1553.
  43. Lefebvre H, Richard R, Noblet C, et al. Life-threatening pseudophaeochromocytoma after toloxatone, terbutaline, and phenylephrine. Lancet 1993; 341:555.
  44. Torres AD, Rai AN, Hardiek ML. Mercury intoxication and arterial hypertension: report of two patients and review of the literature. Pediatrics 2000; 105:E34.
  45. Louie AK, Louie EK, Lannon RA. Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder. Am J Cardiol 1992; 70:1306.
  46. Moreau D, Weissman MM. Panic disorder in children and adolescents: a review. Am J Psychiatry 1992; 149:1306.
  47. Biederman J, Faraone SV, Marrs A, et al. Panic disorder and agoraphobia in consecutively referred children and adolescents. J Am Acad Child Adolesc Psychiatry 1997; 36:214.
  48. Fogarty J, Engel C, Russo J, et al. Hypertension and pheochromocytoma testing: The association with anxiety disorders. Arch Fam Med 1994; 3:55.
  49. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99:1915.
  50. Gardet V, Gatta B, Simonnet G, et al. Lessons from an unpleasant surprise: a biochemical strategy for the diagnosis of pheochromocytoma. J Hypertens 2001; 19:1029.
  51. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001; 86:5658.
  52. Bravo EL. Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 1994; 15:356.
  53. Langrehr JM, Bahra M, Kristiansen G, et al. Neuroendocrine tumor of the pancreas and bilateral adrenal pheochromocytomas. A rare manifestation of von Hippel-Lindau disease in childhood. J Pediatr Surg 2007; 42:1291.
  54. Mannelli M, Ercolino T, Giachè V, et al. Genetic screening for pheochromocytoma: should SDHC gene analysis be included? J Med Genet 2007; 44:586.
  55. Sawka AM, Jaeschke R, Singh RJ, Young WF Jr. A comparison of biochemical tests for pheochromocytoma: measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab 2003; 88:553.
  56. Brain KL, Kay J, Shine B. Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population. Clin Chem 2006; 52:2060.
  57. Perry CG, Sawka AM, Singh R, et al. The diagnostic efficacy of urinary fractionated metanephrines measured by tandem mass spectrometry in detection of pheochromocytoma. Clin Endocrinol (Oxf) 2007; 66:703.
  58. Peaston RT, Lennard TW, Lai LC. Overnight excretion of urinary catecholamines and metabolites in the detection of pheochromocytoma. J Clin Endocrinol Metab 1996; 81:1378.
  59. Héron E, Chatellier G, Billaud E, et al. The urinary metanephrine-to-creatinine ratio for the diagnosis of pheochromocytoma. Ann Intern Med 1996; 125:300.
  60. Sawka AM, Singh RJ, Young WF Jr. Fractionated plasma metanephrines are highly sensitive but less specific than urinary total metanephrines and catecholamines in detection of pheochromocytoma. Program and Abstracts of The Endocrine Society's 83rd Annual Meeting, Denver June 20-23, 2001. Abstract #P1-642, p 285.
  61. Freel EM, Stanson AW, Thompson GB, et al. Adrenal venous sampling for catecholamines: a normal value study. J Clin Endocrinol Metab 2010; 95:1328.
  62. Bouloux PG, Fakeeh M. Investigation of phaeochromocytoma. Clin Endocrinol (Oxf) 1995; 43:657.
  63. Turner MC, DeQuattro V, Falk R, et al. Childhood familial pheochromocytoma. Conflicting results of localization techniques. Hypertension 1986; 8:851.
  64. Miskulin J, Shulkin BL, Doherty GM, et al. Is preoperative iodine 123 meta-iodobenzylguanidine scintigraphy routinely necessary before initial adrenalectomy for pheochromocytoma? Surgery 2003; 134:918.
  65. Taïeb D, Sebag F, Hubbard JG, et al. Does iodine-131 meta-iodobenzylguanidine (MIBG) scintigraphy have an impact on the management of sporadic and familial phaeochromocytoma? Clin Endocrinol (Oxf) 2004; 61:102.
  66. Hemmelgarn BR, McAlister FA, Grover S, et al. The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I--Blood pressure measurement, diagnosis and assessment of risk. Can J Cardiol 2006; 22:573.
  67. Turner MC, Lieberman E, DeQuattro V. The perioperative management of pheochromocytoma in children. Clin Pediatr (Phila) 1992; 31:583.
  68. Weingarten TN, Welch TL, Moore TL, et al. Preoperative Levels of Catecholamines and Metanephrines and Intraoperative Hemodynamics of Patients Undergoing Pheochromocytoma and Paraganglioma Resection. Urology 2017; 100:131.
  69. Butz JJ, Yan Q, McKenzie TJ, et al. Perioperative outcomes of syndromic paraganglioma and pheochromocytoma resection in patients with von Hippel-Lindau disease, multiple endocrine neoplasia type 2, or neurofibromatosis type 1. Surgery 2017; 162:1259.
  70. Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC. Successful outcomes in pheochromocytoma surgery in the modern era. J Urol 1999; 161:764.
  71. 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.
  72. Butz JJ, Weingarten TN, Cavalcante AN, et al. Perioperative hemodynamics and outcomes of patients on metyrosine undergoing resection of pheochromocytoma or paraganglioma. Int J Surg 2017; 46:1.
  73. 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.
  74. Pretorius M, Rasmussen GE, Holcomb GW. Hemodynamic and catecholamine responses to a laparoscopic adrenalectomy for pheochromocytoma in a pediatric patient. Anesth Analg 1998; 87:1268.
  75. Clements RH, Goldstein RE, Holcomb GW 3rd. Laparoscopic left adrenalectomy for pheochromocytoma in a child. J Pediatr Surg 1999; 34:1408.
  76. Miller KA, Albanese C, Harrison M, et al. Experience with laparoscopic adrenalectomy in pediatric patients. J Pediatr Surg 2002; 37:979.
  77. Walther MM, Keiser HR, Choyke PL, et al. Management of hereditary pheochromocytoma in von Hippel-Lindau kindreds with partial adrenalectomy. J Urol 1999; 161:395.
  78. Lee JE, Curley SA, Gagel RF, et al. Cortical-sparing adrenalectomy for patients with bilateral pheochromocytoma. Surgery 1996; 120:1064.
  79. Neumann HP, Bender BU, Reincke M, et al. Adrenal-sparing surgery for phaeochromocytoma. Br J Surg 1999; 86:94.
  80. 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.
  81. Diner EK, Franks ME, Behari A, et al. Partial adrenalectomy: the National Cancer Institute experience. Urology 2005; 66:19.
  82. Evans DB, Lee JE, Merrell RC, Hickey RC. Adrenal medullary disease in multiple endocrine neoplasia type 2. Appropriate management. Endocrinol Metab Clin North Am 1994; 23:167.
  83. Ein SH, Weitzman S, Thorner P, et al. Pediatric malignant pheochromocytoma. J Pediatr Surg 1994; 29:1197.
  84. Strajina V, Dy BM, Farley DR, et al. Surgical Treatment of Malignant Pheochromocytoma and Paraganglioma: Retrospective Case Series. Ann Surg Oncol 2017; 24:1546.
  85. Averbuch SD, Steakley CS, Young RC, et al. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med 1988; 109:267.
  86. Shapiro B, Sisson JC, Wieland DM, et al. Radiopharmaceutical therapy of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med 1991; 35:269.
  87. Goncalves E, Ninane J, Wese FX, et al. Familial phaeochromocytoma: successful treatment with 131I-MIBG. Med Pediatr Oncol 1990; 18:126.
  88. Pacak K, Fojo T, Goldstein DS, et al. Radiofrequency ablation: a novel approach for treatment of metastatic pheochromocytoma. J Natl Cancer Inst 2001; 93:648.
  89. 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.
  90. Plouin PF, Chatellier G, Fofol I, Corvol P. Tumor recurrence and hypertension persistence after successful pheochromocytoma operation. Hypertension 1997; 29:1133.
  91. www.survivorshipguidelines.org (Accessed on October 21, 2017).
  92. Rednam SP, Erez A, Druker H, et al. Von Hippel-Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res 2017; 23:e68.