Genetics and biology of pheochromocytoma

M. Mannelli, L. Simi, M. S. Gaglianò, G. Opocher, T. Ercolino, L. Becherini, G. Parenti

Research output: Contribution to journalArticlepeer-review


The familial forms of pheochromocytoma have recently been demonstrated to be more frequent than believed in the past. The genes currently known to be responsible for tumor formation are RET, VHL, NF1, SDHB, SDHC and SDHD. Germline mutations of these genes increase the risk of developing pheochromocytomas and/or paragangliomas which variably associate with other neoplasms and characterize diverse clinical syndromes such as MEN 2, von Hippel-Lindau (VHL), and neurofibromatosis type 1 (NF 1), or the PGL syndromes, respectively. Although the pathogenesis of pheochromocytoma/paraganglioma formation is still largely unknown, studies of the familial forms have started to uncover some pathways that favor tumor formation, such as activation of tyrosine-kinase, induction of hypoxia-inducible factors, activation of the oncogene Ras or reduced apoptosis. These studies have also demonstrated that various gene mutations can differently affect the biological characteristics of pheochromocytoma: for example, while the tumors are mostly adrenergic (epinephrine secreting) and episodically secreting in MEN 2, they are mostly noradrenergic (norepinephrine secreting) and continuously secreting in VHL. Biological variability can also be observed in the PGL syndromes where tumors develop in the head and neck and are parasympathetic in origin and non-secreting, or in the thorax and the abdomen, where they are sympathetic in origin and catecholamine secreting. Genetic testing in patients with pheochromocytomas or paragangliomas is, at present, strongly recommended and is mandatory in young patients or in cases of multiple or recurrent tumors. The clinical picture and the biological characteristics of the tumor may suggest the priority of the genes to be tested first.

Original languageEnglish
Pages (from-to)160-165
Number of pages6
JournalExperimental and Clinical Endocrinology and Diabetes
Issue number3
Publication statusPublished - Mar 2007


  • MEN 2
  • NF 1
  • Paraganglioma
  • Pheochromocytoma
  • RET
  • SDH
  • VHL

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism


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