What causes pheochromocytoma?
The cause of most pheochromocytomas is not known. A small minority (about 10-20%) of pheochromocytomas arise because a person has an inherited susceptibility to them. Inherited pheochromocytomas are associated with four separate syndromes: Multiple Endocrine Neoplasia, type 2A (MEN2A), Multiple Endocrine Neoplasia, type 2B (MEN2B), von Hippel-Lindau disease (VHL) and Neurofibromatosis type 1 (NF1). Individuals with pheochromocytomas as part of any of these four
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syndromes usually have other medical conditions as well. People with MEN2A often have cancer (usually thyroid cancer) and other hormonal problems. Individuals with MEN2B can also have cancer and hormonal problems, but also have other abnormal physical features. Both MEN2A and MEN2B are due to genetic alterations or mutations in a gene called RET, found at chromosome 10q11.2. Individuals with VHL often have other benign tumors of the central nervous system and pancreas, and can sometimes have renal cell cancer. This syndrome is caused by a mutation in the VHL gene, found at chromosome 3p25-26. Individuals with NF1 often have neurofibromas (benign tumors of the peripheral nervous system). NF1 is caused by mutations in the NF1 gene, found at chromosome 17q11.
All of these disorders are inherited in an autosomal dominant inheritance pattern. With autosomal dominant inheritance, men and women are equally likely to inherit the syndrome. In addition, children of individuals with the disease are at 50% risk of inheriting it. Genetic testing is available for these four syndromes (MEN2A, MEN2B, VHL and NF1) but, due to the complexity, genetic counseling should be considered before testing.
Paragangliomas are masses that occur in sympathetic neural tissues. The masses consist of chromaffin cells and generally result in elevated serum levels of catecholamines (e.g., adrenaline, epinephrine, dopamine). This can lead to episodic or systemic hypertension, tachycardia, diaphoresis, and/or headache. Initial tests for these masses include the measurement of catecholamine metabolites (VMA and metanephrines) in urine. The majority of paragangliomas (90%) occur in the adrenal medulla, and are called pheochromocytomas. In fact, in common usage, the term 'paraganglioma' is applied only to extra-adrenal masses; pheochromocytoma is the more common term. Extra-adrenal masses can occur in any sympathetic neural tissue, but arise most often in the organs of Zuckerkandl (confluence of sympathetic tissue just below the aortic bifurcation), the sympathetic trunk, and the bladder. |
