Skip to main content
SpringerLink
Log in

Risk Factors and Causes of Death in MEN1 Disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) Cohort Study Among 758 Patients

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

The natural history of multiple endocrine neoplasia type 1 (MEN1) is known through single-institution or single-family studies. We aimed to analyze the risk factors and causes of death in a large cohort of MEN1 patients.

Methods

Overall, 758 symptomatic MEN1 patients were identified through the GTE network (Groupe d’étude des Tumeurs Endocrines), which involves French and Belgian genetics laboratories responsible for MEN1 diagnosis and 80 clinical reference centers. The causes of death were analyzed. A frailty model, including time-dependent variables, was used to assess the impact of each clinical lesion, except for hyperparathyroidism, on survival.

Results

The median follow-up was 6.3 years. Female gender, family history of MEN1, and recent diagnosis were associated with a lower risk of death. Compared with nonaffected patients, those with thymic tumors (hazard ratio [HR] = 4.64, 95% CI = 1.73-12.41), glucagonomas–vipomas–somatostatinomas (HR = 4.29, 95% CI = 1.54-11.93), nonfunctioning pancreatic tumors (HR = 3.43, 95% CI = 1.71-6.88), and gastrinoma (HR = 1.89, 95% CI = 1.09-3.25) had a higher risk of death after adjustment for age, gender, and diagnosis period. The increased risk of death among patients with adrenal tumors was not significant, but three patients died from aggressive adrenal tumors. Pituitary tumors, insulinomas, and bronchial tumors did not increase the risk of death. The proportion of MEN1-related deaths decreased from 76.8 to 71.4% after 1990.

Conclusions

The prognosis of MEN1 disease has improved since 1980. Thymic tumors and duodenopancreatic tumors, including nonsecreting pancreatic tumors, increased the risk of death. Rare but aggressive adrenal tumors may also cause death. Most deaths were related to MEN1. New recommendations on abdominal and thoracic imaging are required.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wermer P (1954) Genetic aspects of adenomatosis of endocrine glands. Am J Med 16:363–371

    Article  CAS  PubMed  Google Scholar 

  2. Majewski JT, Wilson SD (1979) The MEA-I syndrome: an all or none phenomenon? Surgery 86:475–484

    CAS  PubMed  Google Scholar 

  3. Shepherd JJ (1991) The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg 126:935–952

    CAS  PubMed  Google Scholar 

  4. Trump D, Farren B, Wooding C et al (1996) Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 89:653–669

    CAS  PubMed  Google Scholar 

  5. Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671

    Article  CAS  PubMed  Google Scholar 

  6. Marini F, Falchetti A, Monte FD et al (2006) Multiple endocrine neoplasia type 1. Orphanet J Rare Dis 1:38

    Article  PubMed  Google Scholar 

  7. Agarwal SK, Kester MB, Debelenko LV et al (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6:1169–1175

    Article  CAS  PubMed  Google Scholar 

  8. Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407

    Article  CAS  PubMed  Google Scholar 

  9. Lemmens I, Van de Ven WJ, Kas K et al (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet 6:1177–1183

    Article  CAS  PubMed  Google Scholar 

  10. Wilkinson S, Teh BT, Davey KR et al (1993) Cause of death in multiple endocrine neoplasia type 1. Arch Surg 128:683–690

    CAS  PubMed  Google Scholar 

  11. Doherty GM, Olson JA, Frisella MM et al (1998) Lethality of multiple endocrine neoplasia type I. World J Surg 22:581–586; discussion 586-587

    Article  CAS  PubMed  Google Scholar 

  12. Dean PG, van Heerden JA, Farley DR et al (2000) Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg 24:1437–1441

    Article  CAS  PubMed  Google Scholar 

  13. Cougard P, Goudet P, Peix JL et al (2000) Insulinomas in multiple endocrine neoplasia type 1. Report of a series of 44 cases by the multiple endocrine neoplasia study group. Ann Chir 125:118–123

    Article  CAS  PubMed  Google Scholar 

  14. Verges B, Boureille F, Goudet P et al (2002) Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab 87:457–465

    Article  CAS  PubMed  Google Scholar 

  15. Goudet P, Peschaud F, Mignon M et al (2004) Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from the endocrine tumor group (ETG). Ann Chir 129:149–155

    Article  CAS  PubMed  Google Scholar 

  16. Levy-Bohbot N, Merle C, Goudet P et al (2004) Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol 28:1075–1081

    Article  PubMed  Google Scholar 

  17. Triponez F, Dosseh D, Goudet P et al (2006) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243:265–272

    Article  PubMed  Google Scholar 

  18. Triponez F, Goudet P, Dosseh D et al (2006) Is surgery beneficial for MEN1 patients with small (<=2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 30:1–9

    Article  Google Scholar 

  19. Goudet P, Murat A, Cardot-Bauters C et al (2009) 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 33:1197–1207

    Article  PubMed  Google Scholar 

  20. Giraud S, Zhang CX, Serova-Sinilnikova O et al (1998) Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 63:455–467

    Article  CAS  PubMed  Google Scholar 

  21. Albert I, Jais JP (2000) The use of frailty models in genetic studies: application to the relationship between end-stage renal failure and mutation type in Alport syndrome. European Community Alport Syndrome Concerted Action Group (ECASCA). J Epidemiol Biostat 5:169–175

    CAS  PubMed  Google Scholar 

  22. Dancourt V, Quantin C, Abrahamowicz M et al (2004) Modeling recurrence in colorectal cancer. J Clin Epidemiol 57:243–251

    Article  CAS  PubMed  Google Scholar 

  23. Lips CJ, Vasen HF, Lamers CB (1984) Multiple endocrine neoplasia syndromes. Crit Rev Oncol Hematol 2:117–184

    Article  CAS  PubMed  Google Scholar 

  24. Ekeblad S, Skogseid B, Dunder K et al (2008) Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res 14:7798–7803

    Article  CAS  PubMed  Google Scholar 

  25. Skogseid B, Rastad J, Gobl A et al (1995) Adrenal lesion in multiple endocrine neoplasia type 1. Surgery 118:1077–1082

    Article  CAS  PubMed  Google Scholar 

  26. Langer P, Cupisti K, Bartsch DK et al (2002) Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg 26:891–896

    Article  PubMed  Google Scholar 

  27. Wermers RA, Khosla S, Atkinson EJ et al (1998) Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 104:115–122

    Article  CAS  PubMed  Google Scholar 

  28. Nilsson IL, Wadsten C, Brandt L et al (2004) Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease. Surgery 136:981–987

    Article  PubMed  Google Scholar 

  29. Ogard CG, Engholm G, Almdal TP et al (2004) Increased mortality in patients hospitalized with primary hyperparathyroidism during the period 1977–1993 in Denmark. World J Surg 28:108–111

    Article  PubMed  Google Scholar 

  30. Michels KB, Xue F, Brandt L et al (2004) Hyperparathyroidism and subsequent incidence of breast cancer. Int J Cancer 110:449–451

    Article  CAS  PubMed  Google Scholar 

  31. Remontet L, Esteve J, Bouvier AM et al (2003) Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique 51:3–30

    CAS  PubMed  Google Scholar 

  32. Mayo JR, Aldrich J, Muller NL (2003) Radiation exposure at chest CT: a statement of the Fleischner Society. Radiology 228:15–21

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Mr. Philip Bastable for help with translation of the manuscript into English. We also acknowledge the coauthors: C. Ajzenberg, J.J. Altman, F. Archambeaud, J.R. Attali, C. Badet, J. Barbier, M. Barthet, E. Baudin, B. Bauduceau, P. Bernades, X. Bertagna, J. Bertherat, P. Boissel, P. Bouchard, J.M. Boyaval, L. Bresler, J.F. Bretagne, J. Bringer, L. Brunaud, J. Burger, P. Carenco, P. Caron, B. Cathebras, M. Celerier, O. Chabre, G. Chabrier, D. Chadenas, P. Chanson, D. Charitanski, J.A. Chayvialle, C. Colmar Montiel, J.M. Comas, B. Conte Devolx, A. Cortot, E. Cosson, P. Cougard, P. Cubertafond, P. D’Anella, P. Darsy, T. Defechereux, F. Delecourt, J. Denis, C. Derrien, D. Dewailly, H. du Boullay-Choplin, A.S. Dramais, C. Droumaguet, C. Dubost, F. Duron, B. Emperauger-Beauvais, P. Emy, S. Gauthier, A.P. Gimenez Roqueplo, B. Goichot, D. Goldfain, M. Gosselin, I. Guilhem, P.J. Guillausseau, P. Hamon, J.F. Henry, P.J. Jaquet, V. Kerlan, J.M. Khun, B. Knebelmann, J.L. Kraimps, A. Krivtzky, J.D. Lalau, P. Lecomte, J.J. Legros, D. Levoir, B. Maizeray-Cailliau, D. Malet, M. Malinski, G. Mantion, C. Mathe, M. Mathonnet, D. Melliere, E.H. Metman, M. Meurisse, R. Modigliani, M. Monsaigeon, C. Naouri, C. Oliver, F. Olivier, J. Orgiazzi, M. Parneix, C. Partenski, J.L. Peix, A. Penfornis, A. Pradignac, C. Pouget, M. Pugeat, M.L. Raffin-Sanson, M. Rodier, P. Roger, V. Rohmer, P. Rougier, H. Rousset, J. Roy, J.L. Sadoul, E. Sarfati, J.L. Schlienger, M. Schlumberger, P. Seve, D. Simon, O. Soubrane, J.C. Soule, P. Thieblot, C. Thivolet, P. Thomopoulos, G. Turpin, P. Valensi, M.C. Vantighem, M.F. Verger, B. Verges, O. Verier-Mine, E. Verlet, B. Vialettes, R. Viard, S. Walter, A. Warnet, B. Wechsler, J.L. Wemeau, G. Weryha, B. Woehl-Kremer.

Author information

Authors and Affiliations

  1. Service de Chirurgie Endocrinienne, Centre Hospitalier Universitaire, Dijon, France

    Pierre Goudet

  2. Faculté de médecine de Dijon, Centre d’Epidemiologie des Populations, Université de Bourgogne, EA4184, Dijon, France

    Pierre Goudet

  3. Clinique d’Endocrinologie, Centre Hospitalier Universitaire, Nantes, France

    Arnaud Murat

  4. INSERM CIE1, Centre d’Investigation clinique-Epidémiologie clinique, Centre Hospitalier Universitaire, Dijon, France

    Christine Binquet, Annie Costa & Claire Bonithon-Kopp

  5. Service de Médecine interne et Endocrinologie, Clinique Marc Linquette, Centre Hospitalier Régional et Universitaire, Lille, France

    Christine Cardot-Bauters

  6. Service de Gastro-entérologie, Groupement Hospitalier Universitaire Nord, Hôpital Beaujon, Clichy, France

    Philippe Ruszniewski

  7. Service d’Endocrinologie, Diabète et Maladies métaboliques, Centre Hospitalier Universitaire La Timone, Marseille, France

    Patricia Niccoli

  8. Service de Chirurgie Générale, Viscérale et Endocrinienne, Groupement Hospitalier Universitaire Est, Hôpital de la Pitié, Paris, France

    Fabrice Ménégaux

  9. Service de Médecine interne et Nutrition, Centre Hospitalier Universitaire, Hôpital de Hautepierre, Strasbourg, France

    Georges Chabrier

  10. Service d’Endocrinologie, Centre Hospitalier Universitaire Est, Hôpital Wertheimer, Lyon, France

    Françoise Borson-Chazot

  11. Service d’Endocrinologie, Centre Hospitalier Universitaire, Hôpital du Haut Levêque, Pessac, France

    Antoine Tabarin

  12. Service d’Endocrinologie, Groupement Hospitalier Universitaire Est, Hôpital Saint Antoine, Paris, France

    Philippe Bouchard

  13. Service d’Endocrinologie, Centre Hospitalier Universitaire, Hôpital Robert Debré, Reims, France

    Brigitte Delemer

  14. Service d’Endocrinologie Clinique, Centre Hospitalier Universitaire de Liège, Liège, Belgium

    Alfred Beckers

Authors
  1. Pierre Goudet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Arnaud Murat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Binquet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christine Cardot-Bauters
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annie Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philippe Ruszniewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patricia Niccoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fabrice Ménégaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Georges Chabrier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Françoise Borson-Chazot
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Antoine Tabarin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Philippe Bouchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Brigitte Delemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Alfred Beckers
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Claire Bonithon-Kopp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre Goudet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goudet, P., Murat, A., Binquet, C. 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 34, 249–255 (2010). https://doi.org/10.1007/s00268-009-0290-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-009-0290-1

Keywords

Search

Navigation