Pheochromocytomas are associated with all of the following familial disorders EXCEPT?
A. von Hippel-Lindau (VHL) syndromeCorrect Answer: C
Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors that originate from chromaffin cells of the adrenal medulla. While the majority are sporadic neoplasms, up to 40% have the disease as part of a familial disorder. These familial disorders all exhibit autosomal dominant inheritance and include MEN2 (mutations in RET proto-oncogene), VHL syndrome (mutations in the VHL tumor suppressor gene), and NF1 (mutation sin the NF1 gene). HNPCC is a genetic condition that demonstrates autosomal dominant inheritance; however, it is not associated with pheochromocytomas.
Approximately 50% of patients with MEN2, 20% of patients with VHL, and 1% of patients with NF1 will have a pheochromocytoma. When compared with each other, MEN2 patients are often more symptomatic with higher incidences of hypertension and higher plasma metanephrine (epinephrine metabolite) concentrations. VHL patients have higher plasma normetanephrine (norepinephrine) concentrations than MEN2 patients. When pheochromocytomas are diagnosed in the setting of no known familial disorder, clinicians should monitor closely for findings such as retinal angiomas in VHL syndrome, a thyroid mass in MEN2, café au lait spots, and neurofibromas in NF1. Any of these findings or a family history of pheochromocytoma should warrant genetic testing for early diagnosis and management.
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