Skip to main content
SpringerLink
Log in

Multiple Endocrine Neoplasia Type 1

  • Chapter
  • First Online:
Surgical Endocrinopathies

  • 870 Accesses

Abstract

Multiple endocrine neoplasia type 1 (MEN-1) is an inherited syndrome which typically presents with parathyroid hyperplasia, pituitary adenoma, and neuroendocrine tumors of the pancreas. It is uncommon with a prevalence of 2–3 cases per 100,000 of population and is equally distributed in males and females. MEN-1 has a high penetrance and an autosomal-dominant pattern of inheritance in which half of all children of an affected individual will inherit the trait, and the majority of gene carriers will ultimately develop the disease. MEN-1 is attributed to mutations in a tumor suppressor gene located on the long arm of chromosome 11. This gene encodes the unique menin protein, which is important in regulation of gene transcription and cellular division. Primary hyperparathyroidism (HPT) is the most common clinical manifestation and typically presents at 20–25 years of age. Treatment of MEN-1-associated HPT is best achieved by subtotal parathyroidectomy and cervical thymectomy; however, recurrence is common and revision surgery is often required. Pancreatic and duodenal neuroendocrine tumors (PNET) will occur in 50–70 % of cases and are the leading contributor to mortality in MEN-1. Gastrinomas are the most common symptomatic PNET accounting for 30–40 % of pancreatic lesions. Pancreatic resection is indicated in functional pancreatic insulinoma, glucagonoma, vasoactive intestinal peptide (VIP) tumors, as well as larger nonfunctioning lesions. Early surgical intervention for gastrinoma may help control symptoms and reduce the incidence of metastatic spread. However, treating the parathyroid disease first may significantly reduce the secretion of gastrin. Prolactinomas are the most common pituitary adenomas seen in MEN-1 and can mostly be managed with medication. Larger compressive macroadenomas or cases where medical therapy has failed can be treated with transsphenoidal surgery. Genetic testing should be considered in patients with HPT who present at a young age with prolactinoma or multiple pancreatic neuroendocrine tumors. Biochemical screening of family members in a known MEN-1 kindred should begin in adolescence.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 149.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Wilkinson S, Young M, Shepherd JJ. The prevalence of MEN-1 in Tasmania. Aust N Z J Surg. 1996;66(3):141–3.

    CAS  PubMed  Google Scholar 

  2. Erdheim J. Zur normalen und pathologischen Histologie der Glandula thyreoidea, parathyroidea und Hypophysis. Beit Z Path Anat Z Alllg Path. 1903;33:78.

    Google Scholar 

  3. Underdahl LO, Woolner LB, Black BM. Multiple endocrine adenomas; report of 8 cases in which the parathyroids, pituitary and pancreatic islets were involved. J Clin Endocrinol Metab. 1953;13(1):20–47.

    CAS  PubMed  Google Scholar 

  4. Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16(3):363–71.

    CAS  PubMed  Google Scholar 

  5. Steiner AL, Goodman AD, Powers SR. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine 1968;47(5):371–409.

    CAS  PubMed  Google Scholar 

  6. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Nat Acad Sci U S A. 2006;103(42):15558–63.

    CAS  Google Scholar 

  7. Georgitsi M, Raitila A, Karhu A, van der Luijt RB, Aalfs CM, Sane T, et al. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. 2007;92(8):3321–5.

    CAS  PubMed  Google Scholar 

  8. Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988;332(6159):85–7.

    CAS  PubMed  Google Scholar 

  9. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997;276(5311):404–7.

    CAS  PubMed  Google Scholar 

  10. Guru SC, Goldsmith PK, Burns AL, Marx SJ, Spiegel AM, Collins FS, et al. Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci U S A. 1998;95(4):1630–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. La P, Silva AC, Hou Z, Wang H, Schnepp RW, Yan N, et al. Direct binding of DNA by tumor suppressor menin. J Biol Chem. 2004;279(47):49045–54.

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Agarwal SK, Guru SC, Heppner C, Erdos MR, Collins RM, Park SY, et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 1999;96(1):143–52.

    CAS  PubMed  Google Scholar 

  13. Agarwal SK, Kennedy PA, Scacheri PC, Novotny EA, Hickman AB, Cerrato A, et al. Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res. 2005;37(6):369–74.

    CAS  PubMed  Google Scholar 

  14. Gobl AE, Berg M, Lopez-Egido JR, Oberg K, Skogseid B, Westin G. Menin represses JunD-activated transcription by a histone deacetylase-dependent mechanism. Biochim Biophys Acta. 1999;1447(1):51–6.

    CAS  PubMed  Google Scholar 

  15. Gallo A, Cuozzo C, Esposito I, Maggiolini M, Bonofiglio D, Vivacqua A, et al. Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation. Oncogene 2002;21(42):6434–45.

    CAS  PubMed  Google Scholar 

  16. Yumita W, Ikeo Y, Yamauchi K, Sakurai A, Hashizume K. Suppression of insulin-induced AP-1 transactivation by menin accompanies inhibition of c-Fos induction. Int J Cancer. 2003;103(6):738–44.

    CAS  PubMed  Google Scholar 

  17. Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci U S A. 2001;98(7):3837–42.

    PubMed Central  CAS  PubMed  Google Scholar 

  18. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971;68(4):820–3.

    PubMed Central  PubMed  Google Scholar 

  19. Agarwal SK, Debelenko LV, Kester MB, Guru SC, Manickam P, Olufemi SE, et al. Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. Hum Mutat. 1998;12(2):75–82.

    CAS  PubMed  Google Scholar 

  20. Schnepp RW, Mao H, Sykes SM, Zong WX, Silva A, La P, et al. Menin induces apoptosis in murine embryonic fibroblasts. J Biol Chem. 2004;279(11):10685–91.

    PubMed Central  CAS  PubMed  Google Scholar 

  21. Pannett AA, Thakker RV. Multiple endocrine neoplasia type 1. Endocr-Relat Cancer. 1999;6(4):449–73.

    CAS  PubMed  Google Scholar 

  22. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat. 2008;29(1):22–32.

    CAS  PubMed  Google Scholar 

  23. Bassett JH, Forbes SA, Pannett AA, Lloyd SE, Christie PT, Wooding C, et al. Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet. 1998;62(2):232–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Abe T, Yoshimoto K, Taniyama M, Hanakawa K, Izumiyama H, Itakura M, et al. An unusual kindred of the multiple endocrine neoplasia type 1 (MEN1) in Japanese. J Clin Endocr Metab. 2000;85(3):1327–30.

    CAS  PubMed  Google Scholar 

  25. Cavaco BM, Domingues R, Bacelar MC, Cardoso H, Barros L, Gomes L, et al. Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions. Clin Endocrinol. 2002;56(4):465–73.

    CAS  Google Scholar 

  26. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.

    CAS  PubMed  Google Scholar 

  27. Trump D, Farren B, Wooding C, Pang JT, Besser GM, Buchanan KD, et al. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 1996;89(9):653–69.

    CAS  PubMed  Google Scholar 

  28. Benson L, Ljunghall S, Akerstrom G, Oberg K. Hyperparathyroidism presenting as the first lesion in multiple endocrine neoplasia type 1. Am J Med. 1987;82(4):731–7.

    CAS  PubMed  Google Scholar 

  29. Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS, Liotta LA. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998;129(6):484–94.

    CAS  PubMed  Google Scholar 

  30. Marx SJ, Vinik AI, Santen RJ, Floyd JC, Jr., Mills JL, Green J, 3rd. Multiple endocrine neoplasia type I: assessment of laboratory tests to screen for the gene in a large kindred. Medicine 1986;65(4):226–41.

    CAS  PubMed  Google Scholar 

  31. Doherty GM. Multiple endocrine neoplasia type 1. J Surg Oncol. 2005;89(3):143–50.

    PubMed  Google Scholar 

  32. Machens A, Schaaf L, Karges W, Frank-Raue K, Bartsch DK, Rothmund M, et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol. 2007;67(4):613–22.

    Google Scholar 

  33. Lairmore TC, Piersall LD, DeBenedetti MK, Dilley WG, Mutch MG, Whelan AJ, et al. Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg. 2004;239(5):637–45; discussion 45–7.

    PubMed Central  PubMed  Google Scholar 

  34. Skogseid B, Eriksson B, Lundqvist G, Lorelius LE, Rastad J, Wide L, et al. Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. J Clin Endocrinol Metab. 1991;73(2):281–7.

    CAS  PubMed  Google Scholar 

  35. Doherty GM, Olson JA, Frisella MM, Lairmore TC, Wells SA, Jr., Norton JA. Lethality of multiple endocrine neoplasia type I. World J Surg. 1998;22(6):581–6 (discussion 6–7).

    CAS  PubMed  Google Scholar 

  36. Wilkinson S, Teh BT, Davey KR, McArdle JP, Young M, Shepherd JJ. Cause of death in multiple endocrine neoplasia type 1. Arch Surg. 1993;128(6):683–90.

    CAS  PubMed  Google Scholar 

  37. Dean PG, van Heerden JA, Farley DR, Thompson GB, Grant CS, Harmsen WS, et al. Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg. 2000;24(11):1437–41.

    CAS  PubMed  Google Scholar 

  38. Uchino S, Noguchi S, Sato M, Yamashita H, Yamashita H, Watanabe S, et al. Screening of the Men1 gene and discovery of germ-line and somatic mutations in apparently sporadic parathyroid tumors. Cancer Res. 2000;60(19):5553–7.

    CAS  PubMed  Google Scholar 

  39. Cope O. The study of hyperparathyroidism at the Massachusetts General Hospital. New Engl J Med. 1966;274(21):1174–82.

    CAS  PubMed  Google Scholar 

  40. Marx SJ, Menczel J, Campbell G, Aurbach GD, Spiegel AM, Norton JA. Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1. Clin Endocrinol. 1991;35(6):521–6.

    CAS  Google Scholar 

  41. Rizzoli R, Green J 3rd, Marx SJ. Primary hyperparathyroidism in familial multiple endocrine neoplasia type I. Long-term follow-up of serum calcium levels after parathyroidectomy. Am J Med. 1985;78(3):467–74.

    CAS  PubMed  Google Scholar 

  42. d’Alessandro AF, Montenegro FL, Brandao LG, Lourenco DM, Jr., Toledo Sde A, Cordeiro AC. Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1. Rev Assoc Med Bras (1992). 2012;58(3):323–7.

    Google Scholar 

  43. Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surgery 1984;95(1):14–21.

    CAS  PubMed  Google Scholar 

  44. Stalberg P, Carling T. Familial parathyroid tumors: diagnosis and management. World J Surg. 2009;33(11):2234–43.

    PubMed  Google Scholar 

  45. Versnick M, Popadich A, Sidhu S, Sywak M, Robinson B, Delbridge L. Minimally invasive parathyroidectomy provides a conservative surgical option for multiple endocrine neoplasia type 1-primary hyperparathyroidism. Surgery 2013;154(1):101–5.

    PubMed  Google Scholar 

  46. Friedman E, Sakaguchi K, Bale AE, Falchetti A, Streeten E, Zimering MB, et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. New Engl J Med. 1989;321(4):213–8.

    CAS  PubMed  Google Scholar 

  47. Brandi ML, Aurbach GD, Fitzpatrick LA, Quarto R, Spiegel AM, Bliziotes MM, et al. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1. New Engl J Med. 1986;314(20):1287–93.

    CAS  PubMed  Google Scholar 

  48. Agha A, Carpenter R, Bhattacharya S, Edmonson SJ, Carlsen E, Monson JP. Parathyroid carcinoma in multiple endocrine neoplasia type 1 (MEN1) syndrome: two case reports of an unrecognised entity. J Endocrinol Invest. 2007;30(2):145–9.

    CAS  PubMed  Google Scholar 

  49. Frank-Raue K, Leidig-Bruckner G, Lorenz A, Rondot S, Haag C, Schulze E, et al. [Hereditary variants of primary hyperparathyroidism–MEN1, MEN2, HPT-JT, FHH, FIHPT]. Dtsch Med Wochenschr (1946). 2011;136(38):1889–94.

    CAS  Google Scholar 

  50. Shih RY, Fackler S, Maturo S, True MW, Brennan J, Wells D. Parathyroid carcinoma in multiple endocrine neoplasia type 1 with a classic germline mutation. Endocr Pract. 2009;15(6):567–72.

    PubMed  Google Scholar 

  51. Dionisi S, Minisola S, Pepe J, De Geronimo S, Paglia F, Memeo L, et al. Concurrent parathyroid adenomas and carcinoma in the setting of multiple endocrine neoplasia type 1: presentation as hypercalcemic crisis. Mayo Clin Proc. 2002;77(8):866–9.

    PubMed  Google Scholar 

  52. del Pozo C, Garcia-Pascual L, Balsells M, Barahona MJ, Veloso E, Gonzalez C, et al. Parathyroid carcinoma in multiple endocrine neoplasia type 1. Case report and review of the literature. Hormones (Athens, Greece). 2011;10(4):326–31.

    Google Scholar 

  53. Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.

    CAS  PubMed  Google Scholar 

  54. Nilubol N, Weinstein L, Simonds WF, Jensen RT, Phan GQ, Hughes MS, et al. Preoperative localizing studies for initial parathyroidectomy in MEN1 syndrome: is there any benefit? World J Surg. 2012;36(6):1368–74.

    PubMed  Google Scholar 

  55. Bilezikian JP, Khan AA, Potts JT, Jr. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J Clin Endocrinol Metab. 2009;94(2):335–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  56. Jensen RT. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med. 1998;243(6):477–88.

    CAS  PubMed  Google Scholar 

  57. Norton JA, Venzon DJ, Berna MJ, Alexander HR, Fraker DL, Libutti SK, et al. Prospective study of surgery for primary hyperparathyroidism (HPT) in multiple endocrine neoplasia-type 1 and Zollinger-Ellison syndrome: long-term outcome of a more virulent form of HPT. Ann Surg. 2008;247(3):501–10.

    PubMed Central  PubMed  Google Scholar 

  58. Burgess JR, David R, Greenaway TM, Parameswaran V, Shepherd JJ. Osteoporosis in multiple endocrine neoplasia type 1: severity, clinical significance, relationship to primary hyperparathyroidism, and response to parathyroidectomy. Arch Surg. 1999;134(10):1119–23.

    CAS  PubMed  Google Scholar 

  59. Coutinho FL, Lourenco DM, Jr., Toledo RA, Montenegro FL, Correia-Deur JE, Toledo SP. Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy. Clin Endocrinol. 2010;72(4):462–8.

    Google Scholar 

  60. Lourenco DM, Jr., Coutinho FL, Toledo RA, Goncalves TD, Montenegro FL, Toledo SP. Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1. Clinics (Sao Paulo, Brazil). 2012;67(Suppl 1):99–108.

    Google Scholar 

  61. Lourenco DM, Jr., Toledo RA, Mackowiak, II, Coutinho FL, Cavalcanti MG, Correia-Deur JE, et al. Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile. Eur J Endocrinol. 2008;159(3):259–74.

    CAS  PubMed  Google Scholar 

  62. Kann PH, Bartsch D, Langer P, Waldmann J, Hadji P, Pfutzner A, et al. Peripheral bone mineral density in correlation to disease-related predisposing conditions in patients with multiple endocrine neoplasia type 1. J Endocrinol Invest. 2012;35(6):573–9.

    CAS  PubMed  Google Scholar 

  63. Elaraj DM, Skarulis MC, Libutti SK, Norton JA, Bartlett DL, Pingpank JF, et al. Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery 2003;134(6):858–64; discussion 64–5.

    PubMed  Google Scholar 

  64. Feldman AL, Sharaf RN, Skarulis MC, Bartlett DL, Libutti SK, Weinstein LS, et al. Results of heterotopic parathyroid autotransplantation: a 13-year experience. Surgery 1999;126(6):1042–8.

    CAS  PubMed  Google Scholar 

  65. Shepet K, Alhefdhi A, Usedom R, Sippel R, Chen H. Parathyroid cryopreservation after parathyroidectomy: a worthwhile practice? Ann Surg Oncol. 2013;20(7):2256–60.

    PubMed Central  PubMed  Google Scholar 

  66. Borot S, Lapierre V, Carnaille B, Goudet P, Penfornis A. Results of cryopreserved parathyroid autografts: a retrospective multicenter study. Surgery 2010;147(4):529–35.

    PubMed  Google Scholar 

  67. Caccitolo JA, Farley DR, van Heerden JA, Grant CS, Thompson GB, Sterioff S. The current role of parathyroid cryopreservation and autotransplantation in parathyroid surgery: an institutional experience. Surgery 1997;122(6):1062–7.

    CAS  PubMed  Google Scholar 

  68. Wells SA, Jr., Burdick JF, Hattler BG, Christiansen C, Pettigrew HM, Abe M, et al. The allografted parathyroid gland: evaluation of function in the immunosuppressed host. Ann Surg. 1974;180(6):805–13.

    PubMed Central  PubMed  Google Scholar 

  69. Wells SA, Jr., Christiansen C. The transplanted parathyroid gland: evaluation of cryopreservation and other environmental factors which affect its function. Surgery 1974;75(1):49–55.

    CAS  PubMed  Google Scholar 

  70. Ferolla P, Falchetti A, Filosso P, Tomassetti P, Tamburrano G, Avenia N, et al. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J Clin Endocrinol Metab. 2005;90(5):2603–9.

    CAS  PubMed  Google Scholar 

  71. Teh BT, Zedenius J, Kytola S, Skogseid B, Trotter J, Choplin H, et al. Thymic carcinoids in multiple endocrine neoplasia type 1. Ann Surg. 1998;228(1):99–105.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Hellman P, Skogseid B, Oberg K, Juhlin C, Akerstrom G, Rastad J. Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 1. Surgery 1998;124(6):993–9.

    CAS  PubMed  Google Scholar 

  73. Goudet P, Murat A, Cardot-Bauters C, Emy P, Baudin E, du Boullay Choplin H, et al. Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). World J Surg. 2009;33(6):1197–207.

    PubMed  Google Scholar 

  74. Recuero Diaz JL, Embun Flor R, Menal Munoz P, Hernandez Ferrandez J, Arraras Martinez MJ, Rivas de Andres JJ. Thymic carcinoid associated with multiple endocrine neoplasia syndrome type I. Arch Bronconeumol. 2013;49(3):122–5.

    PubMed  Google Scholar 

  75. Gibril F, Chen YJ, Schrump DS, Vortmeyer A, Zhuang Z, Lubensky IA, et al. Prospective study of thymic carcinoids in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metabol. 2003;88(3):1066–81.

    CAS  Google Scholar 

  76. Burgess JR, Giles N, Shepherd JJ. Malignant thymic carcinoid is not prevented by transcervical thymectomy in multiple endocrine neoplasia type 1. Clin Endocrinol. 2001;55(5):689–93.

    CAS  Google Scholar 

  77. Hellman P, Skogseid B, Juhlin C, Akerstrom G, Rastad J. Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1. World J Surg. 1992;16(4):718–22 (discussion 22–3).

    CAS  PubMed  Google Scholar 

  78. Prinz RA, Gamvros OI, Sellu D, Lynn JA. Subtotal parathyroidectomy for primary chief cell hyperplasia of the multiple endocrine neoplasia type I syndrome. Ann Surg. 1981;193(1):26–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  79. van Heerden JA, Kent RB, 3rd, Sizemore GW, Grant CS, ReMine WH. Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience. Arch Surg. 1983;118(5):533–6.

    PubMed  Google Scholar 

  80. Lambert LA, Shapiro SE, Lee JE, Perrier ND, Truong M, Wallace MJ, et al. Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Arch Surg. 2005;140(4):374–82.

    PubMed  Google Scholar 

  81. Waldmann J, Lopez CL, Langer P, Rothmund M, Bartsch DK. Surgery for multiple endocrine neoplasia type 1-associated primary hyperparathyroidism. Br J Surg. 2010;97(10):1528–34.

    CAS  PubMed  Google Scholar 

  82. Schreinemakers JM, Pieterman CR, Scholten A, Vriens MR, Valk GD, Rinkes IH. The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg. 2011;35(9):1993–2005.

    PubMed  Google Scholar 

  83. Tonelli F, Marcucci T, Giudici F, Falchetti A, Brandi ML. Surgical approach in hereditary hyperparathyroidism. Endocr J. 2009;56(7):827–41.

    PubMed  Google Scholar 

  84. Rudberg C, Akerstrom G, Palmer M, Ljunghall S, Adami HO, Johansson H, et al. Late results of operation for primary hyperparathyroidism in 441 patients. Surgery 1986;99(6):643–51.

    CAS  PubMed  Google Scholar 

  85. Salmeron MD, Gonzalez JM, Sancho Insenser J, Goday A, Perez NM, Zambudio AR, et al. Causes and treatment of recurrent hyperparathyroidism after subtotal parathyroidectomy in the presence of multiple endocrine neoplasia 1. World J Surg. 2010;34(6):1325–31.

    PubMed  Google Scholar 

  86. Shepherd JJ, Burgess JR, Greenaway TM, Ware R. Preoperative sestamibi scanning and surgical findings at bilateral, unilateral, or minimal reoperation for recurrent hyperparathyroidism after subtotal parathyroidectomy in patients with multiple endocrine neoplasia type 1. Arch Surg. 2000;135(7):844–8.

    CAS  PubMed  Google Scholar 

  87. Levin KE, Gooding GA, Okerlund M, Higgins CB, Norman D, Newton TH, et al. Localizing studies in patients with persistent or recurrent hyperparathyroidism. Surgery 1987;102(6):917–25.

    CAS  PubMed  Google Scholar 

  88. Kelly HR, Hamberg LM, Hunter GJ. 4D-CT for preoperative localization of abnormal parathyroid glands in patients with hyperparathyroidism: accuracy and ability to stratify patients by unilateral versus bilateral disease in surgery-naive and re-exploration patients. AJNR Am J Neuroradiol. 2014;35(1):176–81.

    CAS  PubMed  Google Scholar 

  89. Carty SE, Norton JA. Management of patients with persistent or recurrent primary hyperparathyroidism. World J Surg. 1991;15(6):716–23.

    CAS  PubMed  Google Scholar 

  90. Cheung K, Wang TS, Farrokhyar F, Roman SA, Sosa JA. A meta-analysis of preoperative localization techniques for patients with primary hyperparathyroidism. Ann Surg Oncol. 2012;19(2):577–83.

    PubMed  Google Scholar 

  91. Witteveen JE, Kievit J, van Erkel AR, Morreau H, Romijn JA, Hamdy NA. The role of selective venous sampling in the management of persistent hyperparathyroidism revisited. Eur J Endocrinol. 2010;163(6):945–52.

    CAS  PubMed  Google Scholar 

  92. Ogilvie CM, Brown PL, Matson M, Dacie J, Reznek RH, Britton K, et al. Selective parathyroid venous sampling in patients with complicated hyperparathyroidism. Eur J Endocrinol. 2006;155(6):813–21.

    CAS  PubMed  Google Scholar 

  93. Reidel MA, Schilling T, Graf S, Hinz U, Nawroth P, Buchler MW, et al. Localization of hyperfunctioning parathyroid glands by selective venous sampling in reoperation for primary or secondary hyperparathyroidism. Surgery 2006;140(6):907–13 (discussion 13).

    PubMed  Google Scholar 

  94. Chaffanjon PC, Voirin D, Vasdev A, Chabre O, Kenyon NM, Brichon PY. Selective venous sampling in recurrent and persistent hyperparathyroidism: indication, technique, and results. World J Surg. 2004;28(10):958–61.

    PubMed  Google Scholar 

  95. Kivlen MH, Bartlett DL, Libutti SK, Skarulis MC, Marx SJ, Simonds WF, et al. Reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1. Surgery 2001;130(6):991–8.

    CAS  PubMed  Google Scholar 

  96. Shepherd JJ. The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg. 1991;126(8):935–52.

    CAS  PubMed  Google Scholar 

  97. Majewski JT, Wilson SD. The MEA-I syndrome: an all or none phenomenon? Surgery 1979;86(3):475–84.

    CAS  PubMed  Google Scholar 

  98. Kloppel G, Willemer S, Stamm B, Hacki WH, Heitz PU. Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients. Cancer. 1986;57(9):1824–32.

    CAS  PubMed  Google Scholar 

  99. Le Bodic MF, Heymann MF, Lecomte M, Berger N, Berger F, Louvel A, et al. Immunohistochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia, type I. Am J Surg Pathol. 1996;20(11):1378–84.

    CAS  PubMed  Google Scholar 

  100. Anlauf M, Schlenger R, Perren A, Bauersfeld J, Koch CA, Dralle H, et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome. Am J Surg Pathol. 2006;30(5):560–74.

    PubMed  Google Scholar 

  101. Thompson NW, Lloyd RV, Nishiyama RH, Vinik AI, Strodel WE, Allo MD, et al. MEN I pancreas: a histological and immunohistochemical study. World J Surg. 1984;8(4):561–74.

    CAS  PubMed  Google Scholar 

  102. Pipeleers-Marichal M, Somers G, Willems G, Foulis A, Imrie C, Bishop AE, et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome. New Engl J Med. 1990;322(11):723–7.

    CAS  PubMed  Google Scholar 

  103. Lips CJ, Koppeschaar HP, Berends MJ, Jansen-Schillhorn van Veen JM, Struyvenberg A, Van Vroonhoven TJ. The importance of screening for the MEN 1 syndrome: diagnostic results and clinical management. Henry Ford Hosp Med J. 1992;40(3–4):171–2.

    CAS  PubMed  Google Scholar 

  104. Skogseid B, Oberg K, Eriksson B, Juhlin C, Granberg D, Akerstrom G, et al. Surgery for asymptomatic pancreatic lesion in multiple endocrine neoplasia type I. World J Surg. 1996;20(7):872–6 (discussion 7).

    CAS  PubMed  Google Scholar 

  105. Lowney JK, Frisella MM, Lairmore TC, Doherty GM. Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size. Surgery 1998;124(6):1043–8 (discussion 8–9).

    CAS  PubMed  Google Scholar 

  106. Norton JA, Jensen RT. Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome. Ann Surg. 2004;240(5):757–73.

    PubMed Central  PubMed  Google Scholar 

  107. Tomassetti P, Campana D, Piscitelli L, Casadei R, Santini D, Nori F, et al. Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol. 2005;16(11):1806–10.

    CAS  PubMed  Google Scholar 

  108. Triponez F, Dosseh D, Goudet P, Cougard P, Bauters C, Murat A, et al. Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg. 2006;243(2):265–72.

    PubMed Central  PubMed  Google Scholar 

  109. Triponez F, Goudet P, Dosseh D, Cougard P, Bauters C, Murat A, et al. Is surgery beneficial for MEN1 patients with small (< or = 2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg. 2006;30(5):654–62 (discussion 63–4).

    PubMed  Google Scholar 

  110. Goudet P, Murat A, Binquet C, Cardot-Bauters C, Costa A, Ruszniewski P, et al. Risk factors and causes of death in MEN1 disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) cohort study among 758 patients. World J Surg. 2010;34(2):249–55.

    PubMed  Google Scholar 

  111. Lopez CL, Waldmann J, Fendrich V, Langer P, Kann PH, Bartsch DK. Long-term results of surgery for pancreatic neuroendocrine neoplasms in patients with MEN1. Langenbeck’s Arch Surg. 2011;396(8):1187–96.

    Google Scholar 

  112. Ekeblad S, Skogseid B, Dunder K, Oberg K, Eriksson B. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res. 2008;14(23):7798–803.

    CAS  PubMed  Google Scholar 

  113. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg. 1955;142(4):709–23 (discussion 24–8).

    PubMed Central  CAS  PubMed  Google Scholar 

  114. Gregory RA, Grossman MI, Tracy HJ, Bentley PH. Nature of the gastric secretagogue in Zollinger-Ellison tumours. Lancet 1967;2(7515):543–4.

    CAS  PubMed  Google Scholar 

  115. Gregory RA, Tracy HJ, French JM, Sircus W. Extraction of a gastrin-like substance from a pancreatic tumour in a case of Zollinger-Ellison syndrome. Lancet 1960;1(7133):1045–8.

    CAS  PubMed  Google Scholar 

  116. Farley DR, van Heerden JA, Grant CS, Miller LJ, Ilstrup DM. The Zollinger-Ellison syndrome. A collective surgical experience. Ann Surg. 1992;215(6):561–9 (discussion 9–70).

    PubMed Central  CAS  PubMed  Google Scholar 

  117. Roy PK, Venzon DJ, Shojamanesh H, Abou-Saif A, Peghini P, Doppman JL, et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine. 2000;79(6):379–411.

    CAS  PubMed  Google Scholar 

  118. Norton JA, Fraker DL, Alexander HR, Venzon DJ, Doppman JL, Serrano J, et al. Surgery to cure the Zollinger-Ellison syndrome. New Engl J Med. 1999;341(9):635–44.

    CAS  PubMed  Google Scholar 

  119. Akerstrom G, Stalberg P, Hellman P. Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 1. Clinics (Sao Paulo, Brazil). 2012;67 Suppl 1:173–8.

    Google Scholar 

  120. Yu F, Venzon DJ, Serrano J, Goebel SU, Doppman JL, Gibril F, et al. Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome. J Clin Oncol. 1999;17(2):615–30.

    CAS  PubMed  Google Scholar 

  121. Thompson NW. Management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1. Surg Oncol Clin North Am. 1998;7(4):881–91.

    CAS  Google Scholar 

  122. Thompson NW. Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both. J Intern Med. 1998;243(6):495–500.

    CAS  PubMed  Google Scholar 

  123. Wamsteker EJ, Gauger PG, Thompson NW, Scheiman JM. EUS detection of pancreatic endocrine tumors in asymptomatic patients with type 1 multiple endocrine neoplasia. Gastrointest Endosc. 2003;58(4):531–5.

    PubMed  Google Scholar 

  124. Naswa N, Sharma P, Soundararajan R, Karunanithi S, Nazar AH, Kumar R, et al. Diagnostic performance of somatostatin receptor PET/CT using 68 Ga-DOTANOC in gastrinoma patients with negative or equivocal CT findings. Abdom Imaging. 2013;38(3):552–60.

    PubMed  Google Scholar 

  125. Gomez M, Ferrando R, Vilar J, Hitateguy R, Lopez B, Moreira E, et al. [99mTc-OCTREOTIDE in patients with neuroendocrine tumors from the GI tract]. Acta Gastroenterol Latinoam. 2010;40(4):332–8.

    PubMed  Google Scholar 

  126. Bhate K, Mok WY, Tran K, Khan S, Al-Nahhas A. Functional assessment in the multimodality imaging of pancreatic neuro-endocrine tumours. Minerva Endocrinol. 2010;35(1):17–25.

    CAS  PubMed  Google Scholar 

  127. Li ML, Norton JA. Gastrinoma. Curr Treat Options Oncol. 2001;2(4):337–46.

    CAS  PubMed  Google Scholar 

  128. Norton JA, Fraker DL, Alexander HR, Gibril F, Liewehr DJ, Venzon DJ, et al. Surgery increases survival in patients with gastrinoma. Ann Surg. 2006;244(3):410–9.

    PubMed Central  PubMed  Google Scholar 

  129. Doherty GM. Multiple endocrine neoplasia type 1: duodenopancreatic tumors. Surg Oncol. 2003;12(2):135–43.

    PubMed  Google Scholar 

  130. Doherty GM, Thompson NW. Multiple endocrine neoplasia type 1: duodenopancreatic tumours. J Intern Med. 2003;253(6):590–8.

    CAS  PubMed  Google Scholar 

  131. Bartsch DK, Fendrich V, Langer P, Celik I, Kann PH, Rothmund M. Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann Surg. 2005;242(6):757–64 (discussion 64–6).

    PubMed Central  PubMed  Google Scholar 

  132. Hausman MS, Jr., Thompson NW, Gauger PG, Doherty GM. The surgical management of MEN-1 pancreatoduodenal neuroendocrine disease. Surgery 2004;136(6):1205–11.

    PubMed  Google Scholar 

  133. Norton JA, Alexander HR, Fraker DL, Venzon DJ, Gibril F, Jensen RT. Comparison of surgical results in patients with advanced and limited disease with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome. Ann Surg. 2001;234(4):495–505 (discussion -6).

    PubMed Central  CAS  PubMed  Google Scholar 

  134. Tonelli F, Fratini G, Falchetti A, Nesi G, Brandi ML. Surgery for gastroenteropancreatic tumours in multiple endocrine neoplasia type 1: review and personal experience. J Intern Med. 2005;257(1):38–49.

    CAS  PubMed  Google Scholar 

  135. Jaskowiak NT, Fraker DL, Alexander HR, Norton JA, Doppman JL, Jensen RT. Is reoperation for gastrinoma excision indicated in Zollinger-Ellison syndrome? Surgery 1996;120(6):1055–62 (discussion 62–3).

    CAS  PubMed  Google Scholar 

  136. Ito T, Igarashi H, Uehara H, Jensen RT. Pharmacotherapy of Zollinger-Ellison syndrome. Expert Opin Pharmacother. 2013;14(3):307–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  137. Demeure MJ, Klonoff DC, Karam JH, Duh QY, Clark OH. Insulinomas associated with multiple endocrine neoplasia type I: the need for a different surgical approach. Surgery 1991;110(6):998–1004 (discussion -5).

    CAS  PubMed  Google Scholar 

  138. Mehrabi A, Fischer L, Hafezi M, Dirlewanger A, Grenacher L, Diener MK, et al. A systematic review of localization, surgical treatment options, and outcome of insulinoma. Pancreas 2014;43(5):675–86.

    PubMed  Google Scholar 

  139. Giudici F, Nesi G, Brandi ML, Tonelli F. Surgical management of insulinomas in multiple endocrine neoplasia type 1. Pancreas 2012;41(4):547–53.

    CAS  PubMed  Google Scholar 

  140. Crippa S, Zerbi A, Boninsegna L, Capitanio V, Partelli S, Balzano G, et al. Surgical management of insulinomas: short- and long-term outcomes after enucleations and pancreatic resections. Arch Surg. 2012;147(3):261–6.

    PubMed  Google Scholar 

  141. Levy-Bohbot N, Merle C, Goudet P, Delemer B, Calender A, Jolly D, et al. Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol. 2004;28(11):1075–81.

    PubMed  Google Scholar 

  142. Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87(2):457–65.

    CAS  PubMed  Google Scholar 

  143. Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, et al. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. 2008;32(4):534–43.

    PubMed  Google Scholar 

  144. Sachithanandan N, Harle RA, Burgess JR. Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1. Cancer 2005;103(3):509–15.

    PubMed  Google Scholar 

  145. Harpole DH, Jr., Feldman JM, Buchanan S, Young WG, Wolfe WG. Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg. 1992;54(1):50–4 (discussion 4–5).

    PubMed  Google Scholar 

  146. Teh BT. Thymic carcinoids in multiple endocrine neoplasia type 1. J Intern Med. 1998;243(6):501–4.

    CAS  PubMed  Google Scholar 

  147. Vidal A, Iglesias MJ, Fernandez B, Fonseca E, Cordido F. Cutaneous lesions associated to multiple endocrine neoplasia syndrome type 1. J Eur Acad Dermatol Venereol. 2008;22(7):835–8.

    CAS  PubMed  Google Scholar 

  148. Asgharian B, Turner ML, Gibril F, Entsuah LK, Serrano J, Jensen RT. Cutaneous tumors in patients with multiple endocrine neoplasm type 1 (MEN1) and gastrinomas: prospective study of frequency and development of criteria with high sensitivity and specificity for MEN1. J Clin Endocrinol Metab. 2004;89(11):5328–36.

    CAS  PubMed  Google Scholar 

  149. Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol. 1997;133(7):853–7.

    CAS  PubMed  Google Scholar 

  150. Skogseid B, Rastad J, Gobl A, Larsson C, Backlin K, Juhlin C, et al. Adrenal lesion in multiple endocrine neoplasia type 1. Surgery 1995;118(6):1077–82.

    Google Scholar 

  151. Asgharian B, Chen YJ, Patronas NJ, Peghini PL, Reynolds JC, Vortmeyer A, et al. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004;10(3):869–80.

    CAS  PubMed  Google Scholar 

  152. Funayama T, Sakane M, Yoshizawa T, Takeuchi Y, Ochiai N. Tanycytic ependymoma of the filum terminale associated with multiple endocrine neoplasia type 1: first reported case. Spine J. 2013;13(8):e49–54.

    PubMed  Google Scholar 

  153. Al-Salameh A, Francois P, Giraud S, Calender A, Bergemer-Fouquet AM, de Calan L, et al. Intracranial ependymoma associated with multiple endocrine neoplasia type 1. J Endocrinol Invest. 2010;33(5):353–6.

    CAS  PubMed  Google Scholar 

  154. Kato H, Uchimura I, Morohoshi M, Fujisawa K, Kobayashi Y, Numano F, et al. Multiple endocrine neoplasia type 1 associated with spinal ependymoma. Intern Med. 1996;35(4):285–9.

    CAS  PubMed  Google Scholar 

  155. Gatta-Cherifi B, Chabre O, Murat A, Niccoli P, Cardot-Bauters C, Rohmer V, et al. Adrenal involvement in MEN1. Analysis of 715 cases from the Groupe d’etude des Tumeurs Endocrines database. Eur J Endocrinol. 2012;166(2):269–79.

    CAS  PubMed  Google Scholar 

  156. Kharb S, Pandit A, Gundgurthi A, Garg MK, Brar KS, Kannan N, et al. Hidden diagnosis of multiple endocrine neoplasia-1 unraveled during workup of virilization caused by adrenocortical carcinoma. Indian J Endocrinol Metab. 2013;17(3):514–8.

    PubMed Central  PubMed  Google Scholar 

  157. Griniatsos JE, Dimitriou N, Zilos A, Sakellariou S, Evangelou K, Kamakari S, et al. Bilateral adrenocortical carcinoma in a patient with multiple endocrine neoplasia type 1 (MEN1) and a novel mutation in the MEN1 gene. World J Surg Oncol. 2011;9:6.

    PubMed Central  PubMed  Google Scholar 

  158. Haase M, Anlauf M, Schott M, Schinner S, Kaminsky E, Scherbaum WA, et al. A new mutation in the menin gene causes the multiple endocrine neoplasia type 1 syndrome with adrenocortical carcinoma. Endocrine 2011;39(2):153–9.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Endocrine Surgical Unit, University of Sydney, AMA House, Suite 202, 69 Christie St, St. Leonards, NSW, Australia

    Kuan-Chi Wang MBBS & Prof Mark Sywak MBBS, MMedSci (Clin Epi), FRACS

Authors
  1. Kuan-Chi Wang MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prof Mark Sywak MBBS, MMedSci (Clin Epi), FRACS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Sywak MBBS, MMedSci (Clin Epi), FRACS .

Editor information

Editors and Affiliations

  1. Divisions of General Surgery and Surgical Oncology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

    Janice L. Pasieka

  2. Department of Surgery, Columbia University Medical Center, New York, New York, USA

    James A. Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Wang, KC., Sywak, M. (2015). Multiple Endocrine Neoplasia Type 1. In: Pasieka, J., Lee, J. (eds) Surgical Endocrinopathies. Springer, Cham. https://doi.org/10.1007/978-3-319-13662-2_58

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-13662-2_58

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-13661-5

  • Online ISBN: 978-3-319-13662-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation