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Pheochromocytoma Clinical Presentation

  • Author: Michael A Blake, MBBCh; Chief Editor: George T Griffing, MD  more...
 
Updated: Jun 30, 2016
 

History

Symptoms and signs of pheochromocytoma include the following:

  • Headache
  • Diaphoresis
  • Palpitations
  • Tremor
  • Nausea
  • Weakness
  • Pallor
  • Anxiety, sense of doom
  • Epigastric pain
  • Flank pain
  • Constipation
  • Weight loss

The classic history of a patient with a pheochromocytoma includes spells characterized by headaches, palpitations, and diaphoresis in association with severe hypertension. These 4 characteristics together are strongly suggestive of a pheochromocytoma. In the absence of these 3 symptoms and hypertension, the diagnosis may be excluded.

The spells may vary in occurrence from monthly to several times per day, and the duration may vary from seconds to hours. Typically, they worsen with time, occurring more frequently and becoming more severe as the tumor grows.

Pheochromocytomas occur in certain familial syndromes. These include multiple endocrine neoplasia (MEN) types 2A and 2B, neurofibromatosis (von Recklinghausen disease), and von Hippel-Lindau (VHL) disease, as well as others (see Etiology). In general, these hereditary cancer syndromes are inherited in an autosomal dominant manner.

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Physical Examination

Clinical signs associated with pheochromocytomas include the following:

  • Hypertension: Paroxysmal in 50% of cases
  • Postural hypotension (from volume contraction)
  • Hypertensive retinopathy
  • Weight loss
  • Pallor
  • Fever
  • Tremor
  • Tachyarrhythmias [6]
  • Pulmonary edema
  • Cardiomyopathy
  • Diabetes mellitus [25]
  • Ileus

Sinus tachycardia (presenting as palpitations) is the most common cardiac rhythm abnormality in patients with pheochromocytoma, but more serious ventricular arrhythmias or conduction disturbances may also occur. Other cardiac manifestations include reversible dilated or hypertrophic cardiomyopathy; Takotsubo cardiomyopathy has gained increasing recognition.[6]

When pheochromocytoma occurs as part of a hereditary syndrome, other manifestations of the syndrome may be noted. In patients with neurofibromatosis, these include neurofibromas and café au lait spots. The latter are patches of cutaneous pigmentation that vary from 1-10 mm and can occur any place on the body; characteristic locations include the axillae and intertriginous areas (groin). The name café au lait refers to the color of the lesions, which varies from light to dark brown.

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Contributor Information and Disclosures
Author

Michael A Blake, MBBCh MRCPI, FRCR, Assistant Professor, Department of Radiology, Harvard Medical School; Staff Radiologist, Division of Abdominal Imaging, Massachusetts General Hospital

Michael A Blake, MBBCh is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Radiological Society of North America, Royal College of Surgeons in Ireland, Royal College of Physicians of Ireland

Disclosure: Received royalty from Springer for book editor.

Coauthor(s)

Ann T Sweeney, MD Associate Professor, Department of Medicine, Division of Endocrinology, Tufts University School of Medicine

Ann T Sweeney, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, et al. A current review of the etiology, diagnosis, and treatment of pediatric pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010 May. 95(5):2023-37. [Medline].

  2. Sheps SG, Jiang NS, Klee GG, van Heerden JA. Recent developments in the diagnosis and treatment of pheochromocytoma. Mayo Clin Proc. 1990 Jan. 65(1):88-95. [Medline].

  3. Yeterian EH, Pandya DN. Corticothalamic connections of the superior temporal sulcus in rhesus monkeys. Exp Brain Res. 1991. 83(2):268-84. [Medline].

  4. Elenkova A, Matrozova J, Zacharieva S, Kirilov G, Kalinov K. Adiponectin - A possible factor in the pathogenesis of carbohydrate metabolism disturbances in patients with pheochromocytoma. Cytokine. 2010 Jun. 50(3):306-10. [Medline].

  5. Därr R, Lenders JWM, Hofbauer LC, Naumann B, Bornstein SR, Eisenhofer G. Pheochromocytoma: Update on Disease Management. Ther Adv in Endo and Metab. 2012;3(1):11-26. [Full Text].

  6. Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A. Cardiovascular manifestations of phaeochromocytoma. J Hypertens. 2011 Nov. 29(11):2049-60. [Medline].

  7. Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol. 2002 May. 26(5):551-66. [Medline].

  8. Eisenhofer G, Pacak K, Huynh TT, Qin N, Bratslavsky G, Linehan WM, et al. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. Endocr Relat Cancer. 2011 Feb. 18(1):97-111. [Medline].

  9. Ferreira VM, Marcelino M, Piechnik SK, et al. Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction. J Am Coll Cardiol. 2016 May 24. 67 (20):2364-74. [Medline]. [Full Text].

  10. Eisenhofer G, Lenders JW, Timmers H, Mannelli M, Grebe SK, Hofbauer LC, et al. Measurements of plasma methoxytyramine, normetanephrine, and metanephrine as discriminators of different hereditary forms of pheochromocytoma. Clin Chem. 2011 Mar. 57(3):411-20. [Medline]. [Full Text].

  11. Eisenhofer G, Rivers G, Rosas AL, Quezado Z, Manger WM, Pacak K. Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management. Drug Saf. 2007. 30(11):1031-62. [Medline].

  12. Eng C. Seminars in medicine of the Beth Israel Hospital, Boston. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's disease. N Engl J Med. 1996 Sep 26. 335(13):943-51. [Medline].

  13. Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F, Landa I, et al. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet. 2011 Jun 19. 43(7):663-7. [Medline].

  14. Burnichon N, Cascon A, Schiavi F, Morales NP, Comino-Mendez I, et al. MAX mutations cause hereditary and sporadic pheochromocytoma and paraganglioma. Clin Cancer Res. 2012 May 15. 18(10):2828-37. [Medline].

  15. Neumann HP, Berger DP, Sigmund G, Blum U, Schmidt D, Parmer RJ, et al. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N Engl J Med. 1993 Nov 18. 329(21):1531-8. [Medline].

  16. Gergics P, Patocs A, Toth M, Igaz P, Szucs N, Liko I, et al. Germline VHL gene mutations in Hungarian families with von Hippel-Lindau disease and patients with apparently sporadic unilateral pheochromocytomas. Eur J Endocrinol. 2009 Sep. 161(3):495-502. [Medline].

  17. Niemann S, Becker-Follmann J, Nurnberg G, Ruschendorf F, Sieweke N, et al. Assignment of PGL3 to chromosome 1 (q21-q23) in a family with autosomal dominant non-chromaffin paraganglioma. Am J Med Genet. 2001 Jan 1. 98(1):32-6. [Medline].

  18. Burnichon N, Briere JJ, Libe R, Vescovo L, Riviere J, et al. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1. 19(15):3011-20. [Medline]. [Full Text].

  19. Kunst HP, Rutten MH, de Mönnink JP, Hoefsloot LH, Timmers HJ, Marres HA, et al. SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin Cancer Res. 2011 Jan 15. 17(2):247-54. [Medline].

  20. van den Akker EL, de Krijger RR, de Herder WW, Drop SL. Congenital hemihypertrophy and pheochromocytoma, not a coincidental combination?. Eur J Pediatr. 2002 Mar. 161(3):157-60. [Medline].

  21. Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc. 1983 Dec. 58(12):802-4. [Medline].

  22. Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007 Feb 8. 356(6):601-10. [Medline].

  23. Boulkina LS, Newton CA, Drake AJ 3rd, Tanenberg RJ. Acute myocardial infarction attributable to adrenergic crises in a patient with pheochromocytoma and neurofibromatosis 1. Endocr Pract. 2007 May-Jun. 13(3):269-73. [Medline].

  24. Lenders JW. Pheochromocytoma and pregnancy: a deceptive connection.Eur J Endocrinol. 2012 Feb;166(2):143-50. Epub 2011 Sep 2.

  25. La Batide-Alanore A, Chatellier G, Plouin PF. Diabetes as a marker of pheochromocytoma in hypertensive patients. J Hypertens. 2003 Sep. 21(9):1703-7. [Medline].

  26. Tucker ME. Endocrine Society first to address rare adrenal-tumor care. Medscape Medical News. June 5, 2014. [Full Text].

  27. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Jun. 99(6):1915-42. [Medline].

  28. [Guideline] Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010 Aug. 39(6):775-83. [Medline]. [Full Text].

  29. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, et al. Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA. 2002 Mar 20. 287(11):1427-34. [Medline].

  30. de Jong WH, Eisenhofer G, Post WJ, Muskiet FA, de Vries EG, Kema IP. Dietary influences on plasma and urinary metanephrines: implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab. 2009 Aug. 94(8):2841-9. [Medline].

  31. Jimenez 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 Aug. 91(8):2851-8. [Medline].

  32. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR, et al. Biochemical diagnosis of pheochromocytoma: how to distinguish true- from false-positive test results. J Clin Endocrinol Metab. 2003 Jun. 88(6):2656-66. [Medline].

  33. Lenders JW, Pacak K, Huynh TT, Sharabi Y, Mannelli M, Bratslavsky G, et al. Low sensitivity of glucagon provocative testing for diagnosis of pheochromocytoma. J Clin Endocrinol Metab. 2010 Jan. 95(1):238-45. [Medline]. [Full Text].

  34. Szolar DH, Korobkin M, Reittner P, Berghold A, et al. Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT. Radiology. 2005 Feb. 234(2):479-85. [Medline].

  35. Park BK, Kim CK, Kwon GY, Kim JH. Re-evaluation of pheochromocytomas on delayed contrast-enhanced CT: washout enhancement and other imaging features. Eur Radiol. 2007 Nov. 17(11):2804-9. [Medline].

  36. Baid SK, Lai EW, Wesley RA, Ling A, Timmers HJ, Adams KT, et al. Brief communication: radiographic contrast infusion and catecholamine release in patients with pheochromocytoma. Ann Intern Med. 2009 Jan 6. 150(1):27-32. [Medline]. [Full Text].

  37. Bessell-Browne R, O'Malley ME. CT of pheochromocytoma and paraganglioma: risk of adverse events with i.v. administration of nonionic contrast material. AJR Am J Roentgenol. 2007 Apr. 188(4):970-4. [Medline].

  38. Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR, et al. Pheochromocytoma: an imaging chameleon. Radiographics. 2004 Oct. 24 Suppl 1:S87-99. [Medline].

  39. Faria JF, Goldman SM, Szejnfeld J, Melo H, Kater C, Kenney P, et al. Adrenal masses: characterization with in vivo proton MR spectroscopy--initial experience. Radiology. 2007 Dec. 245(3):788-97. [Medline].

  40. Kim S, Salibi N, Hardie AD, Xu J, Lim RP, Lee VS, et al. Characterization of adrenal pheochromocytoma using respiratory-triggered proton MR spectroscopy: initial experience. AJR Am J Roentgenol. 2009 Feb. 192(2):450-4. [Medline].

  41. Wiseman GA, Pacak K, O'Dorisio MS, Neumann DR, Waxman AD, Mankoff DA, et al. Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma: results from a prospective multicenter trial. J Nucl Med. 2009 Sep. 50(9):1448-54. [Medline].

  42. Fottner C, Helisch A, Anlauf M, Rossmann H, Musholt TJ, Kreft A, et al. 6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of extraadrenal and hereditary pheochromocytomas and paragangliomas: correlation with vesicular monoamine transporter expression. J Clin Endocrinol Metab. 2010 Jun. 95(6):2800-10. [Medline].

  43. Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin Endocrinol Metab. 2010 Jun. 95(6):2596-606. [Medline].

  44. Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, et al. Superiority of fluorodeoxyglucose positron emission tomography to other functional imaging techniques in the evaluation of metastatic SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol. 2007 Jun 1. 25(16):2262-9. [Medline].

  45. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma. Eur J Nucl Med Mol Imaging. 2010 Mar. 37(3):484-93. [Medline].

  46. Yamamoto S, Hellman P, Wassberg C, Sundin A. 11C-hydroxyephedrine positron emission tomography imaging of pheochromocytoma: a single center experience over 11 years. J Clin Endocrinol Metab. 2012 Jul. 97(7):2423-32. [Medline].

  47. Wong C, Yu R. Preoperative preparation for pheochromocytoma resection: physician survey and clinical practice. Exp Clin Endocrinol Diabetes. 2010 Jul. 118(7):400-4. [Medline].

  48. Kwon SY, Lee KS, Lee JN, et al. Risk factors for hypertensive attack during pheochromocytoma resection. Investig Clin Urol. 2016 May. 57 (3):184-90. [Medline]. [Full Text].

  49. Pravenec M, Kren V, Klír P, Simonet L, Kurtz T. Identification of genes determining spontaneous hypertension. Review article. Sb Lek. 1991 Jun. 93(5-6):136-41. [Medline]. [Full Text].

  50. Scholten A, Vriens MR, Cromheecke GJ, Borel Rinkes IH, Valk GD. Hemodynamic instability during resection of pheochromocytoma in MEN versus non-MEN patients. Eur J Endocrinol. 2011 Jul. 165(1):91-6. [Medline].

  51. Nau P, Demyttenaere S, Muscarella P, Narula V, Hazey JW, Ellison EC, et al. Pheochromocytoma does not increase risk in laparoscopic adrenalectomy. Surg Endosc. 2010 Nov. 24(11):2760-4. [Medline].

  52. Li QY, Li F. Laparoscopic adrenalectomy in pheochromocytoma: retroperitoneal approach versus transperitoneal approach. J Endourol. 2010 Sep. 24(9):1441-5. [Medline].

  53. Scholten A, Valk GD, Ulfman D, Borel Rinkes IH, Vriens MR. Unilateral subtotal adrenalectomy for pheochromocytoma in multiple endocrine neoplasia type 2 patients: a feasible surgical strategy. Ann Surg. 2011 Dec. 254(6):1022-7. [Medline].

  54. Barone JE. Pheochromocytoma Crisis Is Not a Surgical Emergency. Medscape Medical News. January 18, 2013. Available at http://www.medscape.com/viewarticle/777889. Accessed: January 29, 2013.

  55. Scholten A, Cisco RM, Vriens MR, Cohen JK, Mitmaker EJ, Liu C, et al. Pheochromocytoma crisis is not a surgical emergency. J Clin Endocrinol Metab. 2013 Feb. 98(2):581-91. [Medline].

 
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Axial, T2-weighted magnetic resonance imaging (MRI) scan showing large left suprarenal mass of high signal intensity on a T2-weighted image. The mass is a pheochromocytoma.
Abdominal computed tomography (CT) scan demonstrating left suprarenal mass of soft-tissue attenuation representing a paraganglioma.
Adrenalectomy specimen containing pheochromocytoma. Non-neoplastic adrenal cortex (yellow) surrounds a small tan-red tumor in the medullary region, representing a pheochromocytoma.
H and E, high power, showing classic "balls of cells" feature of a pheochromocytoma. Endocrine tumors such as a pheochromocytoma typically show some degree of nuclear pleomorphism ("endocrine atypia") which does not indicate malignancy.
 
 
 
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