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Essentials of Diagnosis
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Attacks of headache, perspiration, palpitations, anxiety; multisystem crisis
Hypertension: sustained but often paroxysmal, especially during surgery or delivery; may be orthostatic
Elevated plasma free fractionated metanephrines
About 50% are discovered incidentally on imaging studies
Frequent germline mutations
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General Considerations
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Pheochromocytomas
Paragangliomas (“extra-adrenal” pheochromocytomas”)
Arise from sympathetic paraganglia and frequently metastasize
About 50% secrete norepinephrine; the rest are nonfunctional or secrete only dopamine, normetanephrine, or serum chromogranin A (CgA)
Pheochromocytomas or paragangliomas may be located in either or both adrenals or anywhere along the sympathetic nervous chain, and sometimes in the mediastinum, heart, or bladder
~95% of pheochromocytomas and sympathetic paragangliomas arise in the abdomen or pelvis; of these, ~ 90% are pheochromocytomas located in one or both adrenals
Extra-adrenal paragangliomas can be located anywhere sympathetic ganglia are present, particularly in the periaortic and perinephric region (75%), bladder and pelvis (15%), and thorax (10%)
Attacks can be spontaneous; however, they can also be triggered by
Exercise
Bending
Lifting
Emotional stress
Surgery or minor procedures
Certain drugs (eg, fluoxetine, monoamine oxidase inhibitors, caffeine, nicotine, decongestants, amphetamines, cocaine, ionic intravenous contrast, and epinephrine)
Non-chromaffin paragangliomas arise in the head or neck, particularly in the carotid body, jugular-tympanic region, or vagal body; only about 4% secrete catecholamines
About 40% of patients with pheochromocytomas or paragangliomas harbor a germline mutation in 1 of at least 16 known susceptibility genes that predispose to the tumor, usually in an autosomal dominant manner with incomplete penetrance
Germline mutations causing some hereditary forms of pheochromocytoma and paraganglioma identified in genes encoding mitochondrial succinate dehydrogenase subunit B (SDHB), D (SDHD), and rarely C (SDHC)
Genetic disorders that predispose to pheochromocytomas and paragangliomas include
von Hippel–Lindau disease type 2; associated with a 30% lifetime incidence of pheochromocytoma that can present as early as age 5 years or later in adulthood
Multiple endocrine neoplasia type 2 and 3 (2A and 2B)
von Recklinghausen neurofibromatosis type 1
Familial paraganglioma syndromes
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Pheochromocytomas and paragangliomas are rare: < 0.4% of hypertension cases
Incidence is higher with moderate to severe hypertension
Yearly incidence is 2–6 new cases per million; however, many cases are undiagnosed during life, since the prevalence in autopsy series is 1 in 2000
These tumors are dangerous and deceptive, causing death in one-third of patients prior to diagnosis
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Some patients are normotensive and asymptomatic
Manifestations are variable, but typically include
About 60% of patients have episodic nonspecific "spells"
Other symptoms include