Pheochromocytoma

Pheochromocytoma

 

Pheochromocytoma is a catecholamine producing tumor (epinephrine, norepinephrine).

Epidemiology

  • Incidence – 2-8/1,000,000 in the U.S.
  • Age – peak 30-60 years
  • Sex – nearly equal male/female distribution
  • Occurrence – most are sporadic (90%)

Risk Factors

  • Multiple Endocrine Neoplasia 2 (MEN2)
    • RET gene
    • Types
      • 2a – medullary thyroid carcinoma (MTC), pheochromocytoma (multicentric, bilateral), parathyroid adenoma
      • 2b – MTC, pheochromocytoma (multicentric, bilateral) intestinal ganglioneuromatosis
      • Familial medullary thyroid cancer (FMTC) – MTC only
  • Von Hippel-Landau (VHL)
    • VHL gene
    • Type 2
      • A – retinal and CNS hemangioblastomas, epididymal cystadenomas, pheochromocytomas (multicentric, adrenal, bilateral) and endolymphatic sac tumors
      • B – renal cell cysts and carcinomas, retinal and CNS pheochromocytomas, epididymal cystadenomas (multicentric, adrenal, bilateral) and endolymphatic sac tumors
      • C – pheochromocytoma only
  • Familial paraganglioma syndrome (PGL syndromes)
    • SDHB (PGL4) and SDHD (PGL10) genes
    • Head and neck tumors, pheochromocytoma (adrenal and extra-adrenal), abdominal and thoracic paragangliomas
  • Neurofibromatosis type 1 (von Recklinghausen disease)
    • NF-1 gene
    • Multiple fibromas on skin and mucosa, café au lait spots and pheochromocytoma
  • Other rare syndromes
    • Ataxia-telangiectasia
    • Sturge-Weber
    • Tuberous sclerosis

Pathophysiology

  • Located in adrenal medulla 90% of the time
  • May occur where chromaffin cells are present

Clinical Presentation

  • Hypertension (HTN)
    • Sustained HTN in >50% of patients
    • May be severe
  • Paroxysmal attacks
    • Sudden onset
    • Duration – several minutes to hours
    • Headache, diaphoresis, chest pain, pallor, tachycardia, nausea
  • May be induced by certain drugs (opiates, anesthetics, glucagon, MAO inhibitors)
  • Cardiac signs
    • Tachycardia, arrhythmia, bradycardia
    • Heart failure
    • Hypertensive encephalopathy
    • Myocardial infarction
    • Sudden death
  • Metastatic disease
    • Most common sites of metastases – lung, lymph nodes, bones, liver

Diagnosis

  • Laboratory testing
    • Plasma metanephrine and normetanephrine
      • Metabolic products of catecholamines
      • False-positives do occur
    • Urine metanephrine and normetanephrine
      • 24-hour specimen
      • May be a better test in patients at low risk for tumor (fewer false positives)
    • Urine catecholamines
      • Epinephrine and norepinephrine
    • Plasma catecholamines
      • Epinephrine and norepinephrine
    • Clonidine stimulation test is rarely needed
  • Imaging localization
  • Following biochemical confirmation – MRI/CT and metaiodobenzylguanidine (MIBG) scan

Differential Diagnosis  

  • Essential hypertension
  • Anxiety attack
  • Subarachnoid hemorrhage
  • Diencephalic seizures

Disease Monitoring

  • Laboratory testing
    • Chromogranin A  
    • Neuroendocrine marker
      • Nonspecific for pheochromocytoma
      • May be used to monitor response to treatment or relapse since levels have been noted to correlate well with plasma metanephrines and tumor mass

Disease Screening

  • Consider genetic testing in family members

See Also