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 with normal serum thyroxine (T₄) and thyroid-stimulating hormone (TSH)

• About 50% discovered as an incidental mass on imaging

• 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 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 6 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 ...