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

Pheochromocytoma in genetic disorders

William F Young, Jr, MD, MSc
Section Editors
André Lacroix, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Kathryn A Martin, MD


Pheochromocytoma is a rare neoplasm, probably occurring in less than 0.2 percent of patients with hypertension [1,2]. Pheochromocytoma in genetic disorders will be reviewed here. The diagnosis and treatment of pheochromocytoma are discussed separately. (See "Clinical presentation and diagnosis of pheochromocytoma" and "Treatment of pheochromocytoma in adults".)


Most catecholamine-secreting tumors are sporadic. However, approximately 30 percent of patients have the disease as part of a familial disorder; in these patients, the catecholamine-secreting tumors are more likely to be bilateral adrenal pheochromocytomas or paragangliomas.

Hereditary catecholamine-secreting tumors typically present at a younger age than sporadic neoplasms [3]. Sporadic pheochromocytoma is usually diagnosed on the basis of symptoms or an incidental discovery on computed imaging, whereas syndromic pheochromocytoma is frequently diagnosed earlier in the course of disease because of biochemical surveillance or genetic testing [4].

Familial pheochromocytoma — There are several familial disorders associated with adrenal pheochromocytoma, all of which have autosomal dominant inheritance: von Hippel-Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN2) and, less commonly, neurofibromatosis type 1 (NF1).

The approximate frequency of pheochromocytoma in these disorders is 10 to 20 percent in VHL syndrome, 50 percent in MEN2, and 0.1 to 5.7 percent with neurofibromatosis type 1 [5,6]. (See "Clinical features, diagnosis, and management of von Hippel-Lindau disease" and "Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2" and "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis".)

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: Feb 24, 2016.
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. 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.
  2. Pacak K, Linehan WM, Eisenhofer G, et al. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001; 134:315.
  3. Neumann HP, Bausch B, McWhinney SR, et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 2002; 346:1459.
  4. Pawlu C, Bausch B, Reisch N, Neumann HP. Genetic testing for pheochromocytoma-associated syndromes. Ann Endocrinol (Paris) 2005; 66:178.
  5. Walther MM, Herring J, Enquist E, et al. von Recklinghausen's disease and pheochromocytomas. J Urol 1999; 162:1582.
  6. Dluhy RG. Pheochromocytoma--death of an axiom. N Engl J Med 2002; 346:1486.
  7. Plouin PF, Chatellier G, Fofol I, Corvol P. Tumor recurrence and hypertension persistence after successful pheochromocytoma operation. Hypertension 1997; 29:1133.
  8. Neumann HP, Berger DP, Sigmund G, et al. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N Engl J Med 1993; 329:1531.
  9. Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel-Lindau disease. Q J Med 1990; 77:1151.
  10. Neumann HP, Vortmeyer A, Schmidt D, et al. Evidence of MEN-2 in the original description of classic pheochromocytoma. N Engl J Med 2007; 357:1311.
  11. Eisenhofer G, Walther MM, Huynh TT, et al. Pheochromocytomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes. J Clin Endocrinol Metab 2001; 86:1999.
  12. Kirmani S, Young WF. Hereditary Paraganglioma-Pheochromocytoma Syndromes. In: Gene Reviews [Internet], Pagon RA, Adam MP, Bird TD, et al (Eds), University of Washington, Seattle, WA 2012.
  13. Yao L, Schiavi F, Cascon A, et al. Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas. JAMA 2010; 304:2611.
  14. Comino-Méndez I, Gracia-Aznárez FJ, Schiavi F, et al. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 2011; 43:663.
  15. Castro-Vega LJ, Buffet A, De Cubas AA, et al. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet 2014; 23:2440.
  16. Mannelli M, Rapizzi E, Fucci R, et al. 15 YEARS OF PARAGANGLIOMA: Metabolism and pheochromocytoma/paraganglioma. Endocr Relat Cancer 2015; 22:T83.
  17. Erickson D, Kudva YC, Ebersold MJ, et al. Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 2001; 86:5210.
  18. Niemann S, Müller U. Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet 2000; 26:268.
  19. Astuti D, Latif F, Dallol A, et al. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 2001; 69:49.
  20. Lee SC, Chionh SB, Chong SM, Taschner PE. Hereditary paraganglioma due to the SDHD M1I mutation in a second Chinese family: a founder effect? Laryngoscope 2003; 113:1055.
  21. Baysal BE, Ferrell RE, Willett-Brozick JE, et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000; 287:848.
  22. Astuti D, Douglas F, Lennard TW, et al. Germline SDHD mutation in familial phaeochromocytoma. Lancet 2001; 357:1181.
  23. Benn DE, Gimenez-Roqueplo AP, Reilly JR, et al. Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 2006; 91:827.
  24. Young WF Jr, Abboud AL. Editorial: paraganglioma--all in the family. J Clin Endocrinol Metab 2006; 91:790.
  25. Neumann HP, Pawlu C, Peczkowska M, et al. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 2004; 292:943.
  26. Schiavi F, Boedeker CC, Bausch B, et al. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA 2005; 294:2057.
  27. Burnichon N, Rohmer V, Amar L, et al. The succinate dehydrogenase genetic testing in a large prospective series of patients with paragangliomas. J Clin Endocrinol Metab 2009; 94:2817.
  28. Buffet A, Venisse A, Nau V, et al. A decade (2001-2010) of genetic testing for pheochromocytoma and paraganglioma. Horm Metab Res 2012; 44:359.
  29. Jafri M, Whitworth J, Rattenberry E, et al. Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma. Clin Endocrinol (Oxf) 2013; 78:898.
  30. Jiménez C, Cote G, Arnold A, Gagel RF. Review: Should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes? J Clin Endocrinol Metab 2006; 91:2851.
  31. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99:1915.
  32. 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.
  33. Welander J, Söderkvist P, Gimm O. Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. Endocr Relat Cancer 2011; 18:R253.
  34. Erlic Z, Rybicki L, Peczkowska M, et al. Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients. Clin Cancer Res 2009; 15:6378.