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Central European Journal of Medicine

, Volume 9, Issue 3, pp 424–430 | Cite as

Multiple endocrine neoplasia type 1: a case report and review of the literature

  • Audrius Šileikis
  • Edvinas Kildušis
  • Ramūnas Janavičius
  • Kęstutis Strupas
Case Report
  • 95 Downloads

Abstract

Multiple endocrine neoplasia syndrome, type 1 (MEN1) is an underdiagnosed autosomal dominant inherited cancer predisposition syndrome with inter- and intrafamilial variability without a known genotype-phenotype correlation. Disease is caused by mutations in the MEN1 gene located on chromosome 11, but other genes (CDKN1B, AIP) and mechanisms might be involved too. We performed retrospective case series study of MEN1 syndrome patient and his family and present our experience of management of genetically confirmed 9 MEN1 syndrome large family members from Lithuania with novel MEN1 gene mutation (MEN1 exon 6 — c. 879delT (p.Pro293Profs*76)) and delineate its clinical phenotype. At present the diagnosis of MEN1 syndrome must be established by direct mutation testing. MEN1 syndrome patients, their relatives and patients suspected of MEN1 are eligible for mutation testing. Patients with MEN1 have a shorter life expectancy than the general population. MEN1 patients and mutation carriers should be subjected to periodic screening in order to detect manifestations in an early stage. Early genetic diagnosis and subsequent periodic screening is associated with less morbidity and mortality at follow-up. Our study confirmed the absence of genotype-phenotype correlation and showed high intrafamilial clinical expression variability of the MEN1 syndrome.

Keywords

Multiple endocrine neoplasia type 1 Pancreatic neuroendocrine tumours Pituitary tumours Primary hyperparathyroidism 

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References

  1. [1]
    Pieterman C.R., Vriens M.R., Dreijerink K.M., van der Luijt R.B., Valk G.D., Care for patients with multiple endocrine neoplasia type 1: the current evidence base, Fam Cancer, 2011, 10, 157–171PubMedCrossRefGoogle Scholar
  2. [2]
    Arnold A., Drezner M.K., Raby B.A., Mulder J.E., Multiple endocrine neoplasia type 1: Definition and genetics, 2012, http://www.uptodate.com/contents/multiple-endocrine-neoplasia-type-1-definitionand-genetics Google Scholar
  3. [3]
    Erdheim J., Zur normalen und pathologischen Histologie der Glandula Thyreoidea, Parathyreoidea und Hypophysis, Beitr Pathol Anat, 1903, 33, 158–263Google Scholar
  4. [4]
    Underdahl L.O., Woolner L.B., Black B.M., Multiple endocrine adenomas; report of 8 cases in which the parathyroids, pituitary and pancreatic islets were involved, J Clin Endocrinol Metab, 1953, 13, 20–47PubMedCrossRefGoogle Scholar
  5. [5]
    Wermer P., Genetic aspects of adenomatosis of endocrine glands, Am J Med Sci, 1954, 16, 363–371CrossRefGoogle Scholar
  6. [6]
    Chandrasekharappa S.C., Guru S.C., Manickam P., Olufemi S.E., Collins F.S., Emmert-Buck M.R., et al., Positional cloning of the gene for multiple endocrine neoplasia-type 1, Science, 1997, 276, 404–407PubMedCrossRefGoogle Scholar
  7. [7]
    Kouvaraki M.A., Lee J.E., Shapiro S.E., Gagel R.F., Sherman S.I., Sellin R.V., et al., Genotypephenotype analysis in multiple endocrine neoplasia type 1, Arch Surg, 2002, 137, 641–647PubMedCrossRefGoogle Scholar
  8. [8]
    Bassett J.H., Forbes S.A., Pannett A.A., Lloyd S.E., Christie P.T., Wooding C., et al., Characterization of mutations in patients with multiple endocrine neoplasia type 1, Am J Hum Genet, 1998, 62, 232–244PubMedCentralPubMedCrossRefGoogle Scholar
  9. [9]
    Carty S.E., Helm A.K., Amico J.A., Clarke M.R., Foley T.P., Watson C.G., et al., The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1, Surgery, 1998, 124, 1106–13, discussion 1113–1114PubMedCrossRefGoogle Scholar
  10. [10]
    Trump D., Farren B., Wooding C., Pang J.T., Besser G.M., Buchanan K.D., et al., Clinical studies of multiple endocrine neoplasia type 1 (MEN1), QJM, 1996, 89, 653–669PubMedCrossRefGoogle Scholar
  11. [11]
    Dean P.G., van Heerden J.A., Farley D.R., Thompson G.B., Grant C.S., Harmsen W.S., et al., Are patients with multiple endocrine neoplasia type I prone to premature death?, World J Surg, 2000, 24, 1437–1441PubMedCrossRefGoogle Scholar
  12. [12]
    Doherty G.M., Olson J.A., Frisella M.M., Lairmore T.C., Wells S.A. Jr., Norton J.A., Lethality of multiple endocrine neoplasia type I, World J Surg, 1998, 22, 581–6, discussion 586–587PubMedCrossRefGoogle Scholar
  13. [13]
    Geerdink E.A., Van der Luijt R.B., Lips C.J., Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening?, Eur J Endocrinol, 2003, 149, 577–582PubMedCrossRefGoogle Scholar
  14. [14]
    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, 249–255PubMedCrossRefGoogle Scholar
  15. [15]
    Taguchi R., Yamada M., Horiguchi K., Tomaru T., Ozawa A., Shibusawa N., et al., Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs, Biochem Biophys Res Commun, 2011, 415, 378–383CrossRefGoogle Scholar
  16. [16]
    Arnold A., Drezner M.K., Mulder J.E., Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis, 2012, http://www.uptodate.com/contents/multiple-endocrine-neoplasia-type-1-clinical-manifestations-and-diagnosis Google Scholar
  17. [17]
    Guarnieri V., Baorda F., Corbetta S., Battista C., Spada A., D’Agruma L., et al., Identification and functional analysis of novel variants of CDKN1B (encoding p27Kip1) in sporadic parathyroid tumors from an Italian cohort, 113th International Workshop on Multiple Endocrine Neoplasia, Final Program & Abstract Book, 2012, 58Google Scholar
  18. [18]
    Circelli L., Ramundo V., Marciello F., Del Prete M., Marotta V., Carratù A.C., et al., CDKN1B V109G polymorphism as a new putative prognostic factor in multiple endocrine neoplasia type 1 (MEN 1) patients, 113th International Workshop on Multiple Endocrine Neoplasia, Final Program & Abstract Book, 2012, 58–59Google Scholar
  19. [19]
    Modlin I.M., Gustafsson B.I., Moss S.F., Pavel M., Tsolakis A.V., Kidd M., Chromogranin A — biological function and clinical utility in neuro endocrine tumor disease, Ann Surg Oncol, 2010, 17, 2427–2443PubMedCrossRefGoogle Scholar
  20. [20]
    Nikou G.C., Marinou K., Thomakos P., Papageorgiou D., Sanzanidis V., Nikolaou P., Kosmidis C., Moulakakis A., Mallas E, Chromogranin a levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours, Pancreatology, 2008, 8, 510–519PubMedCrossRefGoogle Scholar
  21. [21]
    O’Toole D., Grossman A., Gross D., Delle Fave G., Barkmanova J., O’Connor J., Pape U.F., Plöckinger U., Mallorca Consensus Conference participants, European Neuroendocrine Tumor Society, ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biochemical markers, Neuroendocrinology, 2009, 90, 194–120PubMedCrossRefGoogle Scholar
  22. [22]
    Sciortino G., Vitale G., Manfredi G., Guizzardi F., Persani L., Different phenotypes of multiple endocrine neoplasia type 1 (MEN1): a case report of an Italian family, 13th International Workshop on Multiple Endocrine Neoplasia, Final Program & Abstract Book, 2012, 62–63Google Scholar
  23. [23]
    Weisbrod A.B., Nilubol N., Weinstein L.S., Simonds W.F., Libutti S.K., Jensen R.T., et al., Association of Type-O Blood with Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1, 13th International Workshop on Multiple Endocrine Neoplasia, Final Program & Abstract Book, 2012, 50Google Scholar
  24. [24]
    Faggiano A., Tavares L.B., Tauchmanova L., Milone F., Mansueto G., Ramundo V., De Caro M.L., Lombardi G., De Rosa G., Colao A., Effect of treatment with depot somatostatin analogue octreotide on primary hyperparathyroidism (PHP) in multiple endocrine neoplasia type 1 (MEN1) patients, Clin Endocrinol (Oxf), 2008, 69, 756–762CrossRefGoogle Scholar
  25. [25]
    Burgess J.R., Greenaway T.M., Parameswaran V., Shepherd J.J., Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1), Implications for an integrated model of MEN-1 tumorigenesis, Cancer, 1999, 86, 2154–2159PubMedCrossRefGoogle Scholar
  26. [26]
    Ramage J.K., Ahmed A., Ardill J., Bax N., Breen D.J., Caplin M.E., Corrie P., Davar J., Davies A.H., Lewington V., Meyer T., Newell-Price J., Poston G., Reed N., Rockall A., Steward W., Thakker R.V., Toubanakis C., Valle J., Verbeke C., Grossman A.B., Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs), Gut, 2012, 61, 6–32PubMedCentralPubMedCrossRefGoogle Scholar
  27. [27]
    Arnold A., Snyder P.J., Drezner M.K., Mulder J.E., et al., Multiple endocrine neoplasia type 1: Treatment, 2012, http://www.uptodate.com/contents/multiple-endocrine-neoplasia-type-1-treatment Google Scholar
  28. [28]
    Lopez C.L., Waldmann J., Fendrich V., Langer P., Kann P.H., Bartsch D.K., et al., Long-term results of surgery for pancreatic neuroendocrine neoplasms in patients with MEN1, Langenbecks Arch Surg, 2011, 396, 1187–1196PubMedCrossRefGoogle Scholar
  29. [29]
    Huang L.C., Poultsides G.A., Norton J.A., Surgical Management of Neuroendocrine Tumors of the Gastrointestinal Tract, Oncology (Williston Park), 2011, 25, 794–803Google Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Audrius Šileikis
    • 1
    • 2
  • Edvinas Kildušis
    • 1
    • 2
  • Ramūnas Janavičius
    • 3
  • Kęstutis Strupas
    • 1
    • 2
  1. 1.Faculty of MedicineVilnius UniversityVilniusLithuania
  2. 2.Center of Abdominal SurgeryVilnius University Hospital Santariskiu KlinikosVilniusLithuania
  3. 3.Vilnius University Hospital Santariskiu Klinikos, Hematology, Oncology and Transfusion Medicine CenterVilniusLithuania

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