Pheochromocytomas in Multiple Endocrine Neoplasia Type 2

Recent Results Cancer Res. 2015:204:157-78. doi: 10.1007/978-3-319-22542-5_7.


Pheochromocytoma (PC) is a neuroendocrine tumor that originates from chromaffin cells of the adrenal medulla. The production of catecholamines, including epinephrine, norepinephrine and dopamine, may lead to haemodynamic instability. Over 30% of PCs are associated with germline mutations, including re-arranged in transfection (RET) mutations seen in multiple endocrine neoplasia type 2 (MEN2) syndromes. Around 40% of individuals with MEN2 develop PC, though it is rarely the presenting feature. Compared to sporadic PC, MEN2-associated PC is more likely to be epinephine secreting and demonstrate bilateral adrenal involvement, and is less likely to be malignant. The diagnosis of PC requires clinical suspicion and biochemical testing, followed by imaging studies. Novel nuclear medicine modalities, including FDG positron emission tomography (PET) and 68Ga DOTATATE PET have added to the conventional techniques of 123I-metaiodobenzylguanindine (MIBG) scintigraphy, computer tomography and magnetic resonance imaging. Treatment of PC is surgical and requires peri-operative alpha and, frequently, beta blockade. Novel surgical techniques, such as adrenal sparing surgery and a laparoscopic approach, have decreased peri-operative morbidity. Surveillance for PC is life long, due to the risk of metastatic disease.

Keywords: MEN2; Paraganglioma; Pheochromocytoma; Treatment.

Publication types

  • Review

MeSH terms

  • Adrenal Gland Neoplasms* / genetics
  • Adrenal Gland Neoplasms* / pathology
  • Adrenal Gland Neoplasms* / therapy
  • Adrenalectomy
  • Adrenergic Antagonists / therapeutic use
  • Diagnostic Imaging
  • Genetic Predisposition to Disease
  • Humans
  • Multiple Endocrine Neoplasia Type 2a* / genetics
  • Multiple Endocrine Neoplasia Type 2a* / pathology
  • Multiple Endocrine Neoplasia Type 2a* / therapy
  • Multiple Endocrine Neoplasia Type 2b* / genetics
  • Multiple Endocrine Neoplasia Type 2b* / pathology
  • Multiple Endocrine Neoplasia Type 2b* / therapy
  • Mutation
  • Phenotype
  • Pheochromocytoma* / genetics
  • Pheochromocytoma* / pathology
  • Pheochromocytoma* / therapy
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-ret / genetics
  • Treatment Outcome


  • Adrenergic Antagonists
  • Proto-Oncogene Proteins c-ret
  • RET protein, human