eMedicine Specialties > Endocrinology > Adrenal Gland

Pheochromocytoma

Author: Ann T Sweeney, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Tufts University School of Medicine
Coauthor(s): Michael A Blake, MRCPI, FRCR, Assistant Professor, Department of Radiology, Harvard Medical School; Staff Radiologist, Division of Abdominal Imaging, Massachusetts General Hospital
Contributor Information and Disclosures

Updated: Jul 31, 2009

Introduction

Background

Pheochromocytoma is a rare catecholamine-secreting tumor derived from chromaffin cells. Tumors that arise outside the adrenal gland are termed extra-adrenal pheochromocytomas or paragangliomas. Because of excessive catecholamine secretion, pheochromocytomas may precipitate life-threatening hypertension or cardiac arrhythmias. If the diagnosis of a pheochromocytoma is overlooked, the consequences could be disastrous, even fatal; however, if a pheochromocytoma is found, it is potentially curable. (See images below and Images 1-2.)

Axial, T2-weighted magnetic resonance imaging (MR...

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.

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Axial, T2-weighted magnetic resonance imaging (MR...

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 demonstra...

Abdominal computed tomography (CT) scan demonstrating left suprarenal mass of soft tissue attenuation representing a paraganglioma.

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Abdominal computed tomography (CT) scan demonstra...

Abdominal computed tomography (CT) scan demonstrating left suprarenal mass of soft tissue attenuation representing a paraganglioma.


The term pheochromocytoma (in Greek, phios means dusky, chroma means color, and cytoma means tumor) refers to the color the tumor cells acquire when stained with chromium salts. Roux performed the first surgical resection of a pheochromocytoma in Lausanne, Switzerland in 1926. Later the same year, Charles Mayo performed the first surgical resection in the United States.1

Pathophysiology

The clinical manifestations of a pheochromocytoma result from excessive catecholamine secretion by the tumor. Catecholamines typically secreted, either intermittently or continuously, include norepinephrine and epinephrine; rarely, dopamine is secreted. The biological effects of catecholamines are well known. Stimulation of alpha-adrenergic receptors results in elevated blood pressure, increased cardiac contractility, glycogenolysis, gluconeogenesis, and intestinal relaxation. Stimulation of beta-adrenergic receptors results in an increase in heart rate and contractility.

Catecholamine secretion in pheochromocytomas is not regulated in the same manner as in healthy adrenal tissue. Unlike the healthy adrenal medulla, pheochromocytomas are not innervated, and catecholamine release is not precipitated by neural stimulation. The trigger for catecholamine release is unclear, but multiple mechanisms have been postulated, including direct pressure, medications, and changes in tumor blood flow.

Relative catecholamine levels also differ in pheochromocytomas. Most pheochromocytomas secrete norepinephrine predominantly, whereas secretions from the normal adrenal medulla are composed of roughly 85% epinephrine. Familial pheochromocytomas are an exception because they secrete large amounts of epinephrine. Thus, the clinical manifestations of a familial pheochromocytoma differ from those of a sporadic pheochromocytoma.

Frequency

United States

Pheochromocytomas are rare, reportedly occurring in 0.05-0.2% of hypertensive individuals. Patients may be completely asymptomatic. A retrospective study from the Mayo Clinic revealed that in 50% of cases, the diagnosis was made at autopsy.2 Approximately 10% of pheochromocytomas are discovered incidentally. Pheochromocytomas may occur in certain familial syndromes, including multiple endocrine neoplasia (MEN) 2A and 2B, neurofibromatosis, and von Hippel-Lindau (VHL) disease.

Mortality/Morbidity

Although pheochromocytomas are rare, making the diagnosis is critical because the malignancy rate is 10%, they may be associated with a familial syndrome, they may precipitate life-threatening hypertension, and the patient may be cured completely with their removal.

  • Cardiovascular morbidity: Many cardiac manifestations are associated with pheochromocytomas. Hypertension is the most common complication. Cardiac arrhythmias, such as atrial and ventricular fibrillation, may occur because of excessive plasma catecholamine levels. Other complications include myocarditis, signs and symptoms of myocardial infarction,3 dilated cardiomyopathy, and pulmonary edema, either of cardiac or noncardiac origin.
  • Neurologic complications: A pheochromocytoma-induced hypertensive crisis may precipitate hypertensive encephalopathy, which is characterized by altered mental status, focal neurologic signs and symptoms, or seizures. Other neurologic complications include stroke due to cerebral infarction or an embolic event secondary to a mural thrombus from a dilated cardiomyopathy. Intracerebral hemorrhage also may occur because of uncontrolled hypertension.

Race

Pheochromocytomas occur in people of all races, although they are diagnosed less frequently in blacks.

Sex

Pheochromocytomas occur with equal frequency in males and females.

Age

Pheochromocytomas may occur in persons of any age. The peak incidence, however, is between the third and the fifth decades of life. Approximately 10% occur in children. In children, 50% of pheochromocytomas are solitary intra-adrenal, 25% are present bilaterally, and 25% are extra-adrenal.

Clinical

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 MEN 2A and 2B, neurofibromatosis (von Recklinghausen disease), and 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.
    • 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.4 More than 75 germline mutations have been identified in a VHL suppressor gene located on chromosome 3.5
    • 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.

Physical

The clinical signs associated with pheochromocytomas include hypertension, postural hypotension, retinopathy, fever, pallor, tremor, café au lait spots, and neurofibromas.

  • Clinical signs
    • Hypertension (paroxysmal in 50% of cases)
    • Postural hypotension (from volume contraction)
    • Hypertensive retinopathy
    • Weight loss
    • Pallor
    • Fever
    • Tremor
    • Neurofibromas
    • Café au lait spots: These are patches of cutaneous pigmentation that vary from 1-10 mm and 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.
    • Tachyarrhythmias
    • Pulmonary edema
    • Cardiomyopathy
    • Ileus
  • Laboratory features
    • Hyperglycemia
    • Hypercalcemia
    • Erythrocytosis

Causes

  • Precipitants of a hypertensive crisis
    • Anesthesia induction
    • Opiates
    • Dopamine antagonists
    • Cold medications
    • Radiographic contrast media
    • Drugs that inhibit catecholamine reuptake, such as tricyclic antidepressants and cocaine
    • Childbirth

More on Pheochromocytoma

Overview: Pheochromocytoma
Differential Diagnoses & Workup: Pheochromocytoma
Treatment & Medication: Pheochromocytoma
Follow-up: Pheochromocytoma
Multimedia: Pheochromocytoma
References
Further Reading
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References

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Keywords

pheochromocytoma, adrenal gland, adrenal glands, catecholamine, catecholamines, paraganglioma, multiple endocrine neoplasia, catecholamine-secreting tumor, extra-adrenal pheochromocytomas, familial pheochromocytoma, sporadic pheochromocytoma, multiple endocrine neoplasia 2A, multiple endocrine neoplasia 2B, MEN 2A, MEN 2B, neurofibromatosis, von Hippel-Lindau disease, VHL disease, pheochromocytoma-induced hypertensive crises, hypertensive encephalopathy, Von Recklinghausen disease, Sipple syndrome, tuberous sclerosis, Bourneville disease, Epiloia, Sturge-Weber syndrome, Cushing syndrome, postural hypotension, hypertensive retinopathy, cafe au lait spots

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Contributor Information and Disclosures

Author

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.

Coauthor(s)

Michael A Blake, MRCPI, FRCR, Assistant Professor, Department of Radiology, Harvard Medical School; Staff Radiologist, Division of Abdominal Imaging, Massachusetts General Hospital
Michael A Blake, 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: Nothing to disclose.

Medical Editor

Daniel Einhorn, MD, FACP, FACE, Medical Director, Scripps/Whittier Diabetes Institute, Department of Medicine, Associate Clinical Professor of Medicine, University of California at San Diego School of Medicine
Daniel Einhorn, MD, FACP, FACE is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, Phi Beta Kappa, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Professor, Department of Internal Medicine, Southern Illinois University School of Medicine
Romesh Khardori, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
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.

 
 
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