Introduction
Background
In 1912, a pathologist named Pick coined the term pheochromocytoma — after the Greek words phaios, meaning dark or dusky, and chroma, meaning color — to describe the chromaffin reaction seen in adrenomedullary tumors. The tumors arise from the chromaffin cells of the adrenal medulla and are associated with increased catecholamine production. Although chromaffin tissue is also present elsewhere in the body, such as in the mediastinum, along the aorta, and in the pelvis, the term pheochromocytoma is reserved for tumors that arise from the adrenal medulla. Chromaffin cell tumors at other locations are more appropriately called paragangliomas or chemodectomas, although the term extra-adrenal pheochromocytoma is still applied.
Detecting the tumors is important for a number of reasons. First, hypertension is usually cured with the removal of the tumor, whereas untreated patients are at risk for a lethal hypertensive paroxysm and long-term sequelae of the disease. Second, the discovery of a pheochromocytoma may indicate the presence of a familial disorder. Third, approximately 10% of pheochromocytomas are malignant. Incidentally, pheochromocytomas are called the 10% tumor because they are associated with a 10% risk of malignancy, because 10% of the tumors are bilateral, and because 10% of the tumors are extra-adrenal. Early detection may reduce the risk of metastasis.
Pathophysiology
Pheochromocytomas most commonly arise sporadically, but they can also appear as part of a syndrome, such as multiple endocrine neoplasia (MEN) syndrome type 2A or 2B, von Hippel-Lindau syndrome, tuberous sclerosis, neurofibromatosis, Carney complex, and Sturge-Weber syndrome, among others. In 10% of patients, pheochromocytomas are inherited. These familial cases tend to occur in younger patients.
The location and tendency to involve multiple sites vary depending on whether the tumor is part of a syndrome. Thus, bilateral adrenal pheochromocytomas are seen more commonly in the MEN syndromes, although they may be seen in approximately 10% of sporadic cases. Furthermore, the presence of adrenomedullary hyperplasia preceding the occurrence of pheochromocytomas is highly suggestive of an underlying MEN syndrome. Establishing the diagnosis is important for the patient and family because the risk of other tumors involves the entire family, and early detection of the other components of the syndrome is important for successful management.
Usually, tumors are larger than 3 cm when seen. They are highly vascular, and larger tumors are prone to hemorrhage and necrosis, even when they are benign.
Approximately 10% of pheochromocytomas are malignant. Some authors believe that the size of the tumor is poorly correlated with malignancy. The diagnosis of a benign or a malignant pheochromocytoma cannot be accurately determined by the histologic appearance; it depends on the presence or absence of metastasis. Metastases have been reported in lymphatic tissue, as well as in the lungs, liver, bones, and brain. Vascular invasion, local or distant metastasis, and a deoxyribonucleic acid (DNA) ploidy pattern (DNA diploidy is more benign than other patterns) affect the prognosis. The risk of malignancy is lower in patients with familial tumors than in patients with sporadic tumors.
Frequency
United States
The true incidence is unknown.
International
The true incidence is unknown. Tumors are believed to increase blood pressure in approximately 0.1-0.5% of patients with newly diagnosed hypertension. Some authors report a higher incidence of right-sided adrenal pheochromocytomas, whereas others report the same incidence of pheochromocytomas in both glands.
Mortality/Morbidity
Although rare, pheochromocytomas can, if unrecognized, result in serious morbidity or in mortality.
- The most severe complication is pheochromocytoma crisis, which includes any manifestation of obtundation, as well as shock, disseminated intravascular coagulopathy, seizures, rhabdomyolysis, acute renal failure, and death.
- Other complications include the reactivation of Graves disease or transient thyrotoxicosis, as well as hypercalcemia as a result of tumor secretion of a parathyroid hormone – related protein, noncardiogenic pulmonary edema, acute abdomen, and renal infarction, among others.
- The high risk of provoking a hypertensive crisis during the manipulation of an adrenal gland is well known.
Race
No racial predilection is reported in patients with tumors that arise sporadically.
Sex
The male-to-female ratio is almost 1:1.
Age
Pheochromocytomas most commonly occur in adults aged 20-40 years. In children, the disease is almost always inherited.
Anatomy
The adrenal glands are paired, solid organs that lie within the perirenal fascia near the kidneys. Each adrenal gland is anatomically, functionally, and embryologically divided into the peripheral cortex, which forms most of the bulk of the gland, and the medulla. The medulla is composed of chromaffin cells derived from the neural crest; thus, it is related to the sympathetic nervous system.
The adrenal gland on the right side is located directly posterior to the inferior vena cava (IVC), between the right crus of the diaphragm and the liver. The left adrenal gland is located more caudally and may be seen on the same imaging section that shows the kidney. On computed tomography (CT) scans and axial magnetic resonance images, each gland is seen as a linear or inverted Y- or V-shaped organ located superior, medial, and anterior to each kidney. Note that neither CT scanning nor magnetic resonance imaging (MRI) can be used to distinguish between the adrenal cortex and the medulla.
Many extra-adrenal pheochromocytomas are at the pelvic brim in the organ of Zuckerkandl.
Presentation
Increased catecholamine production by a pheochromocytoma results in hypertension, which may be episodic, as classically described, or sustained. Not uncommonly, patients are entirely normotensive between episodes. A triad of headaches, palpitations, and diaphoresis is described in pheochromocytoma and is seen in most patients. Patients with familial syndromes may be asymptomatic.
Patients with pheochromocytomas in the bladder wall may present with postvoiding loss of consciousness as a result of catecholamine release.
Patients who may be referred for imaging of the adrenal glands include those with new or worsening diabetes mellitus (owing to impaired glucose regulation) and those with hypertensive crisis after anesthesia, surgery, or treatment with medications. Imaging may also be performed in patients with a known history of multiple endocrine problems.
Laboratory tests include the estimation of serum or urinary catecholamine levels, of urinary vanillylmandelic acid and metanephrine levels, and of other metabolite levels. Pheochromocytoma is diagnosed when a combination of clinical signs and symptoms and elevated catecholamine levels are present.
Preferred Examination
CT scanning and MRI have higher sensitivity in detecting pheochromocytomas than do nuclear medicine scanning with iodine-131 metaiodobenzylguanidine (131 I-MIBG), although131 I-MIBG uptake is more specific. Some authors prefer to use metaiodobenzylguanidine (MIBG) uptake scanning as the initial screening modality because it enables whole-body imaging, making it useful for the detection of extra-adrenal tumors and metastatic deposits.
Once an adrenal or extra-adrenal tumor is detected, CT scanning or MRI of the region may be performed for anatomic localization prior to surgical removal. If131 I-MIBG uptake is negative but the clinical findings suggest pheochromocytoma, CT scanning or MRI of the chest or abdomen may be performed, because the false-negative rate of MIBG scintigraphy is 10%.
Limitations of Techniques
Unfortunately, the cost and lack of availability of MIBG studies restrict its use. In addition, imaging with131 I-MIBG can be time-consuming, and the technique has limited ability to provide sufficiently accurate information for surgery. Therefore, some authors recommend the use of at least 2 of the following modalities: CT scanning, MRI, and MIBG uptake studies. Although123 I-MIBG scanning requires a shorter imaging time than does131 I-MIBG scanning, it is less available, and the Food and Drug Administration has not yet approved it for use in adrenal imaging.
CT scanning is quick and relatively inexpensive, and it offers good spatial localization. CT scan findings are not specific enough to distinguish masses caused by pheochromocytoma from other adrenal masses. Additionally, some authors report a risk of hypertensive crisis after the injection of contrast material.
MRI is more specific for pheochromocytomas than is CT scanning, but some patients cannot tolerate MRI.
Differential Diagnoses
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References
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Further Reading
Keywords
adrenal medullary tumor, paragangliomas, chemodectomas
