Multiple Endocrine Neoplasia Syndromes

  • Harold Chen
Living reference work entry


The multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant conditions predisposing affected individuals to benign and malignant tumors of the pituitary, thyroid, parathyroid, adrenal, endocrine, pancreas, paraganglion, or nonendocrine organs. The classic MEN syndromes include MEN type 1 (MEN1) and MEN type 2 (MEN2). The prevalence of MEN1 is estimated to be 1 in 20,000–40,000 individuals and that of MEN2 is estimated to be 1 in 35,000 individuals (DeLellis et al. 2004).


Primary Hyperparathyroidism Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia Type Parathyroid Carcinoma Thymic Carcinoid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. American Thyroid Association Guidelines Task Force, Kloos, R. T., Eng, C., Evans, D. B., et al. (2009). Medullary thyroid cancer: Management guidelines of the American Thyroid Association. Thyroid, 19, 565–612.CrossRefGoogle Scholar
  2. Brandi, M. L., Gagel, R. F., Angeli, A., et al. (2001). Guidelines for diagnosis and therapy of MEN type 1 and type 2. Journal of Clinical Endocrinology and Metabolism, 86, 5658–5671.CrossRefPubMedGoogle Scholar
  3. Brenner, M. E., & Jacene, H. A. (2008). Recurrent or residual hyperparathyroidism and thyroid cancer effectively evaluated with scintigraphy. Otolaryngologic Clinics of North America, 41, 1117–1133.CrossRefPubMedGoogle Scholar
  4. Callender, G. G., Rich, T. A., & Perrier, N. D. (2008). Multiple endocrine neoplasia syndromes [Review]. Surgical Clinics of North America, 88, 863–895.CrossRefPubMedGoogle Scholar
  5. Da Silva, A. M., Maciel, R. M., Da Silva, M. R., et al. (2003). A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism, 88, 5438–5443.CrossRefPubMedGoogle Scholar
  6. Dean, P. G., van Heerden, J. A., Farley, D. R., et al. (2000). Are patients with multiple endocrine neoplasia type 1 prone to premature death? World Journal of Surgery, 24, 1437–1441.CrossRefPubMedGoogle Scholar
  7. DeLellis, R. A., Lloyd, R. V., Heitz, P. U., et al. (2004). Pathology and genetics: Tumours of the endocrine organs. In P. Kleihues & L. H. Sobin (Eds.), World Health Organization classification of tumours (Vol. 10, p. 257). Lyon: IARC Press.Google Scholar
  8. Diaz-Thomas, A. (2014). Pediatric multiple endocrine neoplasia. Medscape Reference. Updated 22 Aug 2014. Available at:
  9. Doherty, G. M. (2005). Multiple endocrine neoplasia type 1. Journal of Surgical Oncology, 89(2005), 143–150.CrossRefPubMedGoogle Scholar
  10. Doherty, G. M., Olson, J. A., Frisella, M. M., et al. (1998). Lethality of multiple endocrine neoplasia type I. World Journal of Surgery, 22, 581–586.CrossRefPubMedGoogle Scholar
  11. Dvorakova, S., Vaclavikova, E., Duskova, J., et al. (2005). Exon 5 of the RET proto-oncogene: A newly detected risk exon for familial medullary thyroid carcinoma, a novel germ-line mutation Gly321Arg. Journal of Endocrinological Investigation, 28, 905–909.CrossRefPubMedGoogle Scholar
  12. Eng, C., Clayton, D., Schuffenecker, I., et al. (1996). The relationship between specific ret proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: International RET mutation consortium analysis. Journal of the American Medical Association, 276, 1575–1579.CrossRefPubMedGoogle Scholar
  13. Falchetti, A., Marini, F., Luzi, E., et al. (2008). Multiple endocrine neoplasms [Review]. Best Practice & Research. Clinical Rheumatology, 22, 149–163.CrossRefGoogle Scholar
  14. Gagel, R. F., & Marx, S. J. (2007). Multiple endocrine neoplasia. In P. R. Larsen, H. Kronenburg, S. Melmed, & K. Polonsky (Eds.), Williams textbook of endocrinology (11th ed.). Orlando: W. B. Saunders & Company, November (Section X, Chapter 40).Google Scholar
  15. Gimm, O., Marsh, D. J., Andrew, S. D., et al. (1997). Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation. Journal of Clinical Endocrinology and Metabolism, 82, 3902–3904.CrossRefPubMedGoogle Scholar
  16. Giusti, f., Marini, F., & Brandi, M. L. (2015). Multiple endocrine neoplasia type 1. Updated 12 Feb 2015. Available at:
  17. Grajo, J. R., Paspulati, R. M., Sahani, D. V., et al. (2016). Multiple endocrine neoplasia syndromes. A comprehensive imaging review. Radiologic Clinics of North America, 54, 441–451.CrossRefPubMedGoogle Scholar
  18. Hoff, A. O., Cote, G. J., & Gagel, R. F. (2000). Multiple endocrine neoplasias. Annual Review of Physiology, 62, 377–411.CrossRefPubMedGoogle Scholar
  19. Krampitz, G. W., & Norton, J. A. (2014). RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. Cancer, 120, 1920–1931.CrossRefPubMedGoogle Scholar
  20. Lee, M., & Pellegata, N. S. (2013a). Multiple endocrine neoplasia syndromes associated with mutation of p27. Journal of Endocrinological Investigation, 36, 781–787.PubMedGoogle Scholar
  21. Lee, M., & Pellegata, N. S. (2013b). Multiple endocrine neoplasia type 4. Frontiers of Hormone Research, 41, 63–78.CrossRefPubMedGoogle Scholar
  22. Lewis, C. E., & Yeh, M. W. (2008). Inherited endocrinopathies: An update [Minireview]. Molecular Genetics and Metabolism, 94, 271–282.CrossRefPubMedGoogle Scholar
  23. Lips, C. J., Landsvater, R. M., Hoppener, J. W., et al. (1994). Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type2A. The New England Journal of Medicine, 331, 828–835.CrossRefPubMedGoogle Scholar
  24. Machens, A., Niccoli-Sire, P., Hoegel, J., et al. (2003). Early malignant progression of hereditary medullary thyroid cancer. The New England Journal of Medicine, 349, 1517–1525.CrossRefPubMedGoogle Scholar
  25. Marini, F., Falehetti, A., Del Monte, F., et al. (2006a). Multiple endocrine neoplasia type I. Orphanet Journal of Rare Diseases, 1, 38–46.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Marini, F., Falchetti, A., Del Monte, F., et al. (2006b). Multiple endocrine neoplasia type 2 [Review]. Orphanet Journal of Rare Diseases, 1, 45–50.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Marinoni, I., & Pellegata, N. S. (2011). p27kip1: A new multiple endocrine neoplasia gene? Neuroendocrinology, 93, 19–28.CrossRefPubMedGoogle Scholar
  28. Marquard, M. S., & Eng, C. (2015). Multiple endocrine neoplasia type 2. GeneReviews. Updated 25 June 2015. Available at:
  29. Molatore, S., & Pellegata, N. S. (2010). The MENX syndrome and p27: Relationships with multiple endocrine neoplasia. Progress in Brain Research, 182, 295–320.CrossRefPubMedGoogle Scholar
  30. Moline, J., & Eng, C. (2010). Multiple endocrine neoplasia type 2. GeneReviews. Updated 4 May 2010. Available at:
  31. Mulligan, L. M., Eng, C., Healey, C. S., et al. (1994). Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nature Genetics, 6, 70–74.CrossRefPubMedGoogle Scholar
  32. Mulligan, L. M., Marsh, D. J., Robinson, B. G., et al. (1995). Genotype-phenotype correlation in multiple endocrine neoplasia type 2: Report of the International RET Mutation Consortium. Journal of Internal Medicine, 238, 343–346.CrossRefPubMedGoogle Scholar
  33. O’Riordain, D. S., O’Brien, T., Weaver, A. L., et al. (1994). Medullary thyroid carcinoma in multiple endocrine neoplasia types 2A and 2B. Surgery, 116, 1017–1023.PubMedGoogle Scholar
  34. Pack, S., Turner, M. L., Zhuang, Z., et al. (1998). Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene. The Journal of Investigative Dermatology, 110, 438–440.CrossRefPubMedGoogle Scholar
  35. Pellegata, N. S. (2012). MENX and MEN4. Clinics, 67, 13–18.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Pellegata, N. S., Quintanilla-Martinez, L., Siggelkow, H., et al. (2006). Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proceedings of National Academy of Sciences of United States of America, 103, 15558–15563.CrossRefGoogle Scholar
  37. Raue, F., & Frank-Raue, K. (2012). Genotype-phenotype correlation in multiple endocrine neoplasia type 2. Clinics, 67(S1), 69–75.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Richards, M. L. (2015). Multiple endocrine neoplasia, type 2. Medscape Reference. Updated 11 Dec 2015. Available at:
  39. Romei, C., Pardi, E., Cetani, F., et al. (2012). Genetic and clinical features of multiple endocrine neoplasia types 1 and 2. Journal of Oncology, 2012, 1915.CrossRefGoogle Scholar
  40. Santoro, M., Carlomagno, F., Melillo, R. M., et al. (2004). Dysfunction of the RET receptor in human cancer. Cellular and Molecular Life Sciences, 61, 2954–2964.CrossRefPubMedGoogle Scholar
  41. Schimke, R. N., Hartmann, W. H., Prout, T. E., et al. (1968). Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas. A possible regulatory defect in the differentiation of chromaffin tissue. The New England Journal of Medicine, 279, 1–7.CrossRefPubMedGoogle Scholar
  42. Schuffenecker, I., Billaud, M., Calender, A., et al. (1994). RET proto-oncogene mutations in French MEN 2A and FMTC families. Human Molecular Genetics, 3, 1939–1943.CrossRefPubMedGoogle Scholar
  43. Schussheim, D. H., Skarulis, M. C., Agarwal, S. K., et al. (2001). Multiple endocrine neoplasia type 1: New clinical and basic findings. Trends in Endocrinology and Metabolism, 12, 173–178.CrossRefPubMedGoogle Scholar
  44. Thakker, R. V. (2001). Multiple endocrine neoplasia. Hormone Research, 56, 67–72.CrossRefPubMedGoogle Scholar
  45. Thakker, R. V., Newey, P. J., Walls, G. V., et al. (2012). Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). Journal of Clinical Endocrinology and Metabolism, 97, 2990–3011.CrossRefPubMedGoogle Scholar
  46. Vortmeyer, A. O., Böni, R., Pack, S. D., et al. (1999). Perivascular cells harboring multiple endocrine neoplasia type 1 alterations are neoplastic cells in angiofibromas. Cancer Research, 59, 274–278.PubMedGoogle Scholar
  47. Wilkinson, S., Teh, B. T., Davey, K. R., et al. (1993). Cause of death in multiple endocrine neoplasia type 1. Archives of Surgery, 128, 683–690.CrossRefPubMedGoogle Scholar
  48. Wray, C. J., Rich, T. A., Waguespack, S. G., et al. (2008). Failure to recognize multiple endocrine neoplasia 2B: More common than we think? Annals of Surgical Oncology, 15, 293–301.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Perinatal and Clinical Genetics, Department of PediatricsLSU Health Sciences CenterShreveportUSA
  2. 2.Medical GeneticsShriners Hospitals for Children, Shreveport, LAShreveportUSA

Personalised recommendations