Endocrine Tumours in Neurofibromatosis Type 1, Tuberous Sclerosis and Related Syndromes

Best Pract Res Clin Endocrinol Metab. 2010 Jun;24(3):439-49. doi: 10.1016/j.beem.2010.02.002.


Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Endocrine Gland Neoplasms / drug therapy
  • Endocrine Gland Neoplasms / genetics*
  • Endocrine Gland Neoplasms / metabolism
  • Endocrine Gland Neoplasms / pathology
  • Humans
  • Neurofibromatosis 1 / drug therapy
  • Neurofibromatosis 1 / genetics*
  • Neurofibromatosis 1 / metabolism
  • Neurofibromatosis 1 / pathology
  • Neurofibromin 1 / genetics*
  • Neurofibromin 1 / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis / drug therapy
  • Tuberous Sclerosis / genetics*
  • Tuberous Sclerosis / pathology


  • Neurofibromin 1
  • MTOR protein, human
  • TOR Serine-Threonine Kinases