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For further information, see CMDT Part 26-25: Pheochromocytoma & Paraganglioma

Key Features

Essentials of Diagnosis

  • 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

General Considerations

  • Pheochromocytomas

    • Arise from the adrenal medulla

    • Usually secrete both epinephrine and norepinephrine

  • Paragangliomas

    • 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 2A and 2B

    • von Recklinghausen neurofibromatosis type 1

    • Familial paraganglioma syndromes


  • 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

Clinical Findings

Symptoms and Signs

  • Some patients are normotensive and asymptomatic

  • Manifestations are variable, but typically include

    • Hypertension (81%) that may be paroxysmal or sustained

    • Headache (60%)

    • Palpitations (60%)

    • Diaphoresis (52%)

  • About 60% of patients have episodic nonspecific "spells"

  • Other symptoms include

    • Anxiety (often with a sense of impending doom)

    • Weakness/fatigue

    • Dyspnea

    • Nausea/vomiting

    • Tremor

    • Dizziness

    • Chest pain

    • Abdominal ...

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