Description

• A pheochromocytoma is a rare neuroendocrine tumor arising from the adrenal or extra-adrenal chromaffin tissue and, less commonly, the sympathetic ganglia.
• These tumors are catecholamine-producing: Norepinephrine (NE) > epinephrine (EPI) >>> dopamine (DA).
• System(s) affected: Endocrine; Nervous; Cardiovascular
• Synonym(s): Chromaffin tumors; Paragangliomas

Epidemiology

• 500–1,000 cases/yr diagnosed in the US
• <0.2% of people with severe hypertension (HTN)

• 1:6,500–1:2,500 in Western countries
• Affects all genders and ages; usually diagnosed in 4th–5th decade of life, familial cases diagnosed 1 decade earlier

Risk Factors

• Familial pheochromocytoma
• Familial paraganglioma
• Multiple endocrine neoplasia type 2 (MEN-2)
• von Hippel-Lindau disease (VHL)
• von Recklinghausen neurofibromatosis type 1 (NF-1)

• Rearranged during transfection (RET) proto-oncogene
• von Hippel-Lindau disease tumor suppressor gene (VHL)
• Neurofibromatosis type 1 tumor suppressor gene (NH 1)
• Genes encoding 4 succinate dehydrogenase complex (SDH) subunits
• Gene encoding the enzyme responsible for flavination of the SDHA subunit
• Tumor suppressor TMEM127 gene

Pathophysiology

Pheochromocytoma is a tumor that releases catecholamines into the circulation. Catecholamines interact with adrenergic receptors to produce various effects that could induce severe lethal cardiovascular and cerebrovascular complications:

• Stimulation of α₁ receptors (NE > EPI) causes smooth muscle constriction resulting in high BP (arteriolar vasoconstriction).
• Stimulation of α₂ receptors (EPI > NE) causes smooth muscle contraction, cardiac muscle relaxation, and inhibition of hormones, such as insulin, resulting in elevated blood glucose levels.
• Stimulation of β₁ receptors (EPI = NE) causes heart muscle contraction resulting in increased heart rate.
• Stimulation of β₂ receptors (EPI >> NE) causes smooth muscle relaxation.

Etiology

• In 80% of cases, it is a sporadic disease of unknown etiology.
• In 20% of cases, it has familial origin and is a component of 1 of the following 4 autosomaldominant diseases:
  • MEN-2
  • VHL
  • Hereditary paraganglioma syndrome (PGL)
  • NF-1
• Tumor location:
  • 80% are solitary and unilateral.
  • 20% are divided between bilateral lesions and extra-adrenal masses (organ of Zuckerkandl, neck, mediastinum, abdomen, pelvis)

Commonly Associated Conditions

• Multiple endocrine neoplasia type IIA (medullary thyroid carcinoma and primary hyperparathyroidism)
• Multiple endocrine neoplasia type IIB (medullary thyroid carcinoma and mucosal neuromas)
• von-Hippel-Lindau disease (retinal angiomas, cerebellar hemangioblastomas, renal cysts, carcinomas, pancreatic cysts, epididymal cystadenomas)
• Neurofibromatosis type 1
• Sturge-Weber syndrome
• Tuberous sclerosis
• Carney syndrome (gastric epithelioid leiomyosarcoma, pulmonary chondroma, extra-adrenal paraganglioma)
• Familial paraganglioma
• Ataxia-telangiectasia
• Renal artery stenosis