Pheochromocytoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [2] Mohammed Abdelwahed M.D[3]
Overview
Pheochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands and extra-adrenal chromaffin tissue, which fail to involute after birth, they secrete excessive amounts of catecholamines, usually epinephrine and norepinephrine. Extra-adrenal paragangliomas (often described as extra-adrenal pheochromocytomas) are closely related, though less common. Pheochromocytoma originates from the chromaffin cells of the sympathetic nervous system ganglia and is named based upon the primary anatomical site of origin. The incidence of pheochromocytoma ranges from a low of 0.2 per 100,000 persons to a high of 0.8 per 100,000 persons. The average age at diagnosis is 24.9 years in hereditary cases and 43.9 years in sporadic cases with men and women are equally affected. MRI and CT scan are used for the diagnosis of pheochromocytoma. Surgery is the mainstay of the treatment.
Historical Perspective
In 1886, Fränkel made the first description of a patient with pheochromocytoma. In 1912, Ludwig Pick formulated the term pheochromocytoma.1912. In 1926, the first surgical removal of pheochromocytoma in the Military Medical Academy in Yugoslavia was performed by Professor Isidor Papo.
Pathophysiology
Pheochromocytoma arises from chromaffin cells of the adrenal medulla.On gross pathology, pheochromocytoma has a multinodular and a multicentric pattern of growth. On microscopic histopathological analysis, nesting (Zellballen) pattern composed of well-defined clusters of tumor cells separated by fibrovascular stroma is a characteristic finding. It may be benign or malignant, familial origin(multiple endocrine neoplasia type 2) or sporadic one. Both of them have genetic origin depends on a large number of genes: VHL, SDH, NF1, RET.
Classification
Pheochromocytoma may be classified based on nature of the tumor into benign and malignant. It can also be classified based on spread into local, regional, and metastatic.Another classification based on origin divides pheochromocytoma into familial, non-familial and sporadic forms.
Causes
Pheochromocytoma develops in called chromaffin cells, found in adrenal medulla which secretes adrenaline, noradrenaline, and dopamine. The genetic base of pheochromocytoma depends on 2 clusters: cluster 1 tumors are noradrenergic. Cluster 2 tumors are adrenergic. Familial pheochromocytoma may be caused by a mutation of either SDHD, VHL, SDHB, RET, NF1 genes.
Differentiating Pheochromocytoma from other Diseases
Pheochromocytoma must be differentiated from other causes of paroxysmal hypertension including severe paroxysmal hypertension (Pseudopheochromocytoma), panic disorder, Factitious hypertension, carcinoid syndrome, Migraine headache, Hyperthyroidism, Renovascular hypertension, Hypoglycemia, Labile hypertension (White coat hypertension), Stroke and compression of the lateral medulla, Seizures, Baroreflex failure, and drugs.
Epidemiology and Demographics
The incidence of pheochromocytoma ranges from a low of 0.2 per 100,000 persons to a high of 0.8 per 100,000 persons. The average age at diagnosis is 24.9 years in hereditary cases and 43.9 years in sporadic cases with men and women equally affected.
Risk Factors
Pheochromocytoma is more common in third decade of life, people with family history of multiple endocrine neoplasias, Von Hippel-Lindau disease, neurofibromatosis type 1, hereditary paraganglioma syndromes.
Screening
Familial pheochromocytoma is associated with multiple endocrine neoplasias, VHL and neurofibromatosis1 and should be screened by plasma fractionated metanephrines levels. The next step is to obtain 24-hour urinaryfractionated metanephrine levels. Imaging should be considered if the initial tests are positive. Genetic testing also should be performed in high-risk patients
Natural History, Complications and Prognosis
Pheochromocytoma is an adrenaline-secreting tumor, usually develop in the fifth decade of life. Symptoms start with tachycardia, hypertension, headache, and sweating. A massive release of catecholamines can cause hyperglycemia, malignant hypertension, and metastasis. The prognosis of pheochromocytoma is generally good but metastatic pheochromocytoma has a 5-year survival rate of approximately 50%.
Diagnosis
History and Symptoms
Symptoms of pheochromocytoma include palpitations, anxiety, and headaches.
Physical Examination
Common physical exam findings of pheochromocytoma include tachycardia, hypertension, and orthostatic hypotension.
Laboratory Findings
Laboratory findings consistent with the diagnosis of pheochromocytoma include elevated catecholamines and metanephrine levels.
Electrocardiogram
On EKG, pheochromocytoma is characterized by the presence of sinus tachycardia and supraventricular tachycardia.
X-ray
There are no x-ray findings associated with pheochromocytoma.
CT
Head, neck, chest, and abdominal CT scans may be helpful in the diagnosis of pheochromocytoma.
MRI
Head, neck, chest, and abdominal MRI may be helpful in the diagnosis of pheochromocytoma.
Other Imaging Findings
123I-metaiodobenzylguanidine (MIBG) scintigraphy coupled with CT scan imaging can be used for diagnosis of pheochromocytoma.
Other Diagnostic Studies
Clonidine suppression test may be used in the diagnosis of pheochromocytoma.
Treatment
Medical Therapy
Treatment with alpha-blockers (example: phenoxybenzamine) followed by beta-blockers (example: atenolol) is required before surgery. Other drugs can be used such as calcium channel blockers and metyrosine. Adjunctive chemotherapy and radiation are used in metastatic disease. Hypertensive crisis can be managed by using sodium nitroprusside, phentolamine, and nicardipine.
Surgery
Surgery is the mainstay of treatment for pheochromocytoma. Adrenalectomy; Laparoscopic transabdominal and retroperitoneal approaches have been used successfully for nonmetastatic abdominal pheochromocytomas. The patient should receive glucocorticoid stress coverage in bilateral adrenalectomy.
Primary Prevention
Biochemical screening for family members of MEN2 patients is mandatory. Genetic testing should be performed in first-degree relatives of a patient with proven germline RET mutation.
Secondary Prevention
Preoperative treatment of pheochromocytoma is the best way to reduce complications and postoperative follow up is the best way to reduce recurrence.