Pheochromocytoma Clinical Presentation

  • Author: Michael A Blake, MBBCh, MRCPI, FRCR; Chief Editor: George T Griffing, MD   more...
 
Updated: Dec 12, 2011
 

History

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.

Symptoms include the following:

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

Pheochromocytomas are known to occur in certain familial syndromes. These include multiple endocrine neoplasia (MEN) 2A and 2B, neurofibromatosis (von Recklinghausen disease), and von Hippel-Lindau (VHL) disease. The MEN 2A and 2B syndromes, which are autosomally inherited, have been traced to germline mutations in the ret proto-oncogene. The ret proto-oncogene, located on chromosome 10, encodes a tyrosine kinase receptor involved in the regulation of cell growth and differentiation. Pheochromocytomas occur bilaterally in the MEN syndromes in as many as 70% of cases.

MEN 2A (Sipple syndrome) is characterized by medullary thyroid carcinoma, hyperparathyroidism, pheochromocytomas, and Hirschsprung disease. Over 95% of cases of MEN 2A are associated with mutations in the ret proto-oncogene affecting 1 of 5 codons in exon 10 (codons 609, 611, 618, 620) or exon 11 (codon 634).

MEN 2B is characterized by medullary thyroid carcinoma, pheochromocytoma, mucosal neurofibromatosis, intestinal ganglioneuromatosis, Hirschsprung disease, and a marfanoid body habitus. A germline missense mutation in the tyrosine kinase domain of the ret proto-oncogene (exon 16, codon 918) has been reported to be present in 95% of patients with MEN 2B.

Novel mutations that cause hereditary pheochromocytoma have been identified in the MYC-associated factor X (MAX) gene. Loss of MAX function is correlated with metastatic potential.[8]

VHL disease is associated with pheochromocytoma, cerebellar hemangioblastoma, renal cell carcinoma, renal and pancreatic cysts, and epididymal cystadenomas. One study found that this syndrome was present in nearly 19% of patients with pheochromocytomas.[9] More than 75 germline mutations have been identified in a VHL suppressor gene located on chromosome 3.[10]

Neurofibromatosis, or von Recklinghausen disease, is characterized by congenital anomalies (often benign tumors) of the skin, nervous system, bones, and endocrine glands. Only 1% of patients with neurofibromatosis have been found to have pheochromocytomas, but as many as 5% of patients with pheochromocytomas have been found to have neurofibromatosis.

Other neuroectodermal disorders associated with pheochromocytomas include tuberous sclerosis (Bourneville disease, epiloia) and Sturge-Weber syndrome.

Pheochromocytomas may produce calcitonin, opioid peptides, somatostatin, corticotropin, and vasoactive intestinal peptide. Corticotropin hypersecretion has caused Cushing syndrome, and vasoactive intestinal peptide overproduction causes watery diarrhea.

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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
  • Neurofibromas
  • Tachyarrhythmias
  • Pulmonary edema
  • Cardiomyopathy
  • Ileus
  • Café au lait spots

The above-mentioned café au lait spots 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 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, MRCPI, FRCR is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Radiological Society of North America, Royal College of Physicians of Ireland, and Royal College of Surgeons in Ireland

Disclosure: Springer Royalty 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 and Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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

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.

Chief Editor

George T Griffing, MD  Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author James C Melby, MD, to the development and writing of the source article.

References

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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.
 
 
 
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