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For further information, see CMDT Part 26-22: 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 metanephrines with normal serum thyroxine (T4) and thyroid-stimulating hormone (TSH)

  • Frequent germline mutations

General Considerations

  • Pheochromocytomas

    • Arise from the adrenal medulla

    • Usually secrete both epinephrine and norepinephrine

  • Paragangliomas

    • Arise from sympathetic paraganglia and often metastasize

    • About 50% secrete norepinephrine; the rest are nonfunctional or secrete only dopamine, normetanephrine, or serum chromogranin A (CgA)

    • Tumoral secretion of norepinephrine or neuropeptide Y causes hypertension

    • Excessive epinephrine causes tachyarrhythmias

  • 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

  • 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)

  • 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)

  • 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

Demographics

  • Pheochromocytomas are rare: < 0.4% of hypertension cases

  • Incidence is higher with moderate to severe hypertension

  • Yearly incidence is 2–4 new cases per million; however, many cases are undiagnosed during life, since the prevalence in autopsy series is 1 in 2000

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 58% 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 pain

    • Paresthesias

    • Constipation

  • Vasospasm changes during attack

    • Raynaud syndrome

    • Mottled cyanosis and facial pallor

    • Facial flushing and drenching sweats may occur as attack subsides

  • Epinephrine secretion may cause

    • Episodic tachyarrhythmias

    • Orthostatic hypotension

    • Syncope

  • Cardiac manifestations include acute coronary syndrome, cardiomyopathy, heart failure, and potentially fatal dysrhythmias

  • Abdominal pain, nausea, vomiting, constipation, and even ischemic bowel can occur

  • Large or hemorrhagic abdominal tumors can also cause abdominal pain

  • Patients may experience nervousness and irritability, increased appetite, and loss of weight

  • During pregnancy, pheochromocytomas can produce hypertension and proteinuria, mimicking eclampsia; vaginal delivery can produce hypertensive crisis followed by postpartum shock

  • Catecholamine-induced cardiomyopathy can present with shock

  • Confusion, psychosis, paresthesias, seizures, transient ischemic attacks, or stroke may occur with cerebrovascular vasoconstriction or hemorrhagic stroke

  • Aortic aneurysms may dissect and rupture

  • Multisystem crisis

    • Can occur spontaneously or it may be provoked by surgery, vaginal delivery, or treatment of metastatic disease

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