Abstract
The Multiple Endocrine Neoplasia (MEN1) is an autosomal dominant disease due to mutation in the MEN1 gene. MEN1, described by Paul Wermer in 1954, is characterized by a broad spectrum of clinical manifestations from which the tree cardinal lesions are primary hyperparathyroidism, pituitary adenomas, and neuroendocrine tumors. MEN1 is a life-threatening disease, because duodeno-pancreatic and thymic tumors may turn into aggressive neuroendocrine cancers without early detection.
The identification of the MEN1 gene in 1997 has modified the landscape of MEN1 diagnosis and disease. The identification of a MEN1 mutation in a young patient with an isolated lesion allows now rapid confirmation of the clinical suspicion. Consequently, the patients are identified as at risk for developing other MEN1- lesions and should be offered a program of combined clinical, biochemical, and radiological screening, according to clinical practice guidelines. Furthermore, the identification of MEN1 mutation in relatives is considered as a predictive test for developing MEN1 lesions. Such family members have therefore access to a screening program, specific to the MEN1 disease. Conversely, the family members who do not harbor the familial MEN1 mutation and their progeny can be reassured and avoid the anxiety provided before by the uncertainty of the appearance or not of MEN1 lesions.
Nevertheless, the pitfalls of genetic testing and the difficulties in the interpretation of MEN1 variants are the new challenges in 2018. Concerted efforts between geneticists and physicians have to be undertaken to resolve the interpretation of allelic variants of uncertain significance.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Agarwal SK, et al. Transcription factor JunD, deprived of menin, switches from growth suppressor to growth promoter. Proc Natl Acad Sci U S A. 2003;100(19):10770–5.
Balogh K, et al. Menin and its interacting proteins: elucidation of menin function. Trends Endocrinol Metab. 2006;17(9):357–64.
Bassett JHD, et al. Characterization of mutations in patients with multiple endocrine neoplasia type 1. Am J Hum Genet. 1998;62(2):232–44.
Bathiya C, et al. Pancreatology patient characteristics and clinical outcomes following initial surgical intervention for MEN1 associated pancreatic neuroendocrine tumours : a systematic review and exploratory meta-analysis of the. Pancreatology. 2019;19(3):462–71.
Bonadies DC, et al. Adverse events in cancer genetic testing. Cancer J. 2014;20(4):246–53.
Brandi ML, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–71.
Brierley KL, et al. Errors in delivery of cancer genetics services: implications for practice. Conn Med. 2010;74(7):413–23.
Cebrián A, et al. Mutational and gross deletion study of the MEN1 gene and correlation with clinical features in Spanish patients. J Med Genet. 2003;40:e72.
Cetani F, et al. Genetic analyses in familial isolated hyperparathyroidism: implication for clinical assessment and surgical management. Clin Endocrinol. 2006;64(2):146–52.
Chandrasekharappa SC, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science (New York, NY). 1997;276(5311):404–7.
Chen D, et al. JunD and JunB integrate prostaglandin E2 activation of breast cancer-associated proximal aromatase promoters. Mol Endocrin (Baltimore). 2011;25(5):767–75.
Costello RT. Subclinical adenoma of the pituitary gland. Am J Pathol. 1936;12:205–16.
Culver JO, et al. Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clin Genet. 2013;84(5):464–72.
Cuny T, et al. Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don’t forget MEN1 genetic analysis. Eur J Endocrinol. 2013;168(4):533–41.
Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of liège, belgium. J Clin Endocrinol Metabol. 2006;91(12):4769–4775.
de Laat JM et al. MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC Med. 2016;14(1):182.
Den Dunnen JT, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37(6):564–9.
Doherty GM. Multiple endocrine neoplasia type 1: duodenopancreatic tumors. Surg Oncol. 2003;12(2):135–43.
Dreijerink KMA, et al. Breast-cancer predisposition in multiple endocrine neoplasia type 1. N Engl J Med. 2014;371(6):583–4.
Dumitrescu CE, et al. McCune-Albright syndrome. Orphanet J Rare Dis. 2008;3(1):12.
Falconi M, et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):153–71.
Farook S, et al. MEN-1 mosaic: the founder of a family. Endocr Abstr. 2011;25:P196.
Friedman E, et al. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N Engl J Med. 1989;321(4):213–8.
Georgitsi M, et al. Large genomic deletions in AIP in pituitary adenoma predisposition. J Clin Endocrinol Metabol. 2008;93(10):4146–51. http://www.ncbi.nlm.nih.gov/pubmed/18628514. Accessed 26 Mar 2018
Goudet 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.
Goudet P, et al. Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d’etude des Tumeurs Endocrines. Eur J Endocrinol. 2011;165(1):97–105.
Goudet P, et al. MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’étude des Tumeurs Endocrines. J Clin Endocrinol Metab. 2015;100(4):1568–77.
Heppner C, et al. Somatic mutation of the MEN1 gene in parathyroid tumours. Nat Genet. 1997;16(4):375–8.
Iacobone M, et al. Hereditary hyperparathyroidism – a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbeck’s Arch Surg. 2015;400(8):867–86.
Jarvik GP, Browning BL. Consideration of cosegregation in the pathogenicity classification of genomic variants. Am J Hum Genet. 2016;98(6):1077–81.
Kim H, et al. Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex. Cancer Res. 2003;63(19):6135–9.
Klein RD, et al. Clinical testing for multiple endocrine neoplasia type 1 in a DNA diagnostic laboratory. Genet Med. 2005;7(2):131–8.
Lairmore TC, Piersall LD, DeBenedetti MK, Dilley WG, Mutch MG, Whelan AJ, Zehnbauer B. 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 645–7.
Lecomte P, et al. Histologically proven bronchial neuroendocrine tumors in MEN1: a GTE 51-case cohort study. World J Surg. 2018;42(1):143–52.
Lemmens I, et al. Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet. 1997;6(7):1177–83.
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.
Lim LC, et al. Thymic carcinoid in multiple endocrine neoplasia 1: genotype-phenotype correlation and prevention. J Intern Med. 2006;259(4):428–32.
Lourenço DM Jr, et al. The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1. Clinics. 2007;62(4):465–70.
Lourenço DM, et al. The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1. Clinics (Sao Paulo). 2007;62(4):465–76.
Marini F, et al. Multiple endocrine neoplasia type 1. Orphanet J Rare Dis. 2006;1(1):38.
Marx S, et al. Multiple endocrine neoplasia type 1: clinical and genetic topics. Ann Intern Med. 1998;129(6):484.
Nakamura Y, et al. Localization of the genetic defect in multiple endocrine neoplasia type I within a small region of chromosome 11. Am J Hum Genet. 1989;44(5):751–5.
Nell S, et al. Management of MEN1 related nonfunctioning pancreatic NETs. Ann Surg. 2018;267(6):1155–60.
Newey PJ, et al. Asymptomatic children with multiple endocrine neoplasia type 1 mutations may harbor nonfunctioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2009;94(February):3640–6.
Newey PJ, et al. Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors. Hum Mutat. 2010;31(3):295–307.
Nozières C, et al. p.Ala541Thr variant of MEN1 gene: a non deleterious polymorphism or a pathogenic mutation? Ann Endocrinol. 2014;75(3):133–40.
Pannett AAJ, et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol. 2003;58(5):639–46.
Pellegata NS. MENX and MEN4. Clinics (Sao Paulo). 2012;67(Suppl 1):13–8.
Pieterman CRC, et al. Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of genetic screening on clinical outcome. Clin Endocrinol. 2009;70(4):575–81.
Pieterman CRC, et al. Primary hyperparathyroidism in Men1 patients: a cohort study with longterm follow-up on preferred surgical procedure and the relation with genotype. Ann Surg. 2012;255(6):1171–8.
Poncin J, et al. Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Hum Mutat. 1999;13(1):54–60.
Powell AC, et al. The utility of routine transcervical thymectomy for MEN1 related hyperparathyroidism. Surgery. 2008;144(6):878–84.
Ramundo V, et al. Clinical and prognostic implications of the genetic diagnosis of hereditary NET syndromes in asymptomatic patients. Horm Metab Res. 2011;43(11):794–800.
Richards S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.
Romanet P, et al. UMD-MEN1 database: an overview of the 370 MEN1 variants present in 1676 patients from the French population. J Clin Endocrinol Metabol. 2019a;104(3):753–64.
Romanet P, et al. Proposition of adjustments to the ACMG-AMP framework for the interpretation of MEN1 missense variants. Hum Mutat. 2019b;40(6):661–74.
Sakurai A, et al. Thymic neuroendocrine tumour in multiple endocrine neoplasia type 1: female patients are not rare exceptions. Clin Endocrinol. 2013;78(2):248–54.
Sallinen V, et al. Surveillance strategy for small asymptomatic non-functional pancreatic neuroendocrine tumors – a systematic review and meta-analysis. HPB. 2017;19(4):310–20.
Schaaf L, et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. Exp Clin Endocrinol Diabetes. 2007;115(8):509–17.
Teh BT, et al. Thymic carcinoids in multiple endocrine neoplasia type 1. Ann Surg. 1998;228(1):99–105.
Teramoto A, et al. Incidental pituitary lesions in 1,000 unselected autopsy specimens. Radiology. 1994;193(1):161–4.
Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386(1–2):2–15.
Thakker RV, et al. Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med. 1989;321(4):218–24.
Thakker RV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011.
Tham E, et al. Clinical testing for mutations in the MEN1 gene in Sweden: a report on 200 unrelated cases. J Clin Endocrinol Metab. 2007;92(9):3389–95.
Thevenon J, et al. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d’etude des Tumeurs Endocrines (GTE) cohort study. Hum Mol Genet. 2013;22(10):1940–8.
Thevenon J, et al. Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d’étude des Tumeurs Endocrines study. Eur J Endocrinol. 2015;173(6):819–26.
Thomas-Marques L, et al. Prospective endoscopic ultrasonographic evaluation of the frequency of nonfunctioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol. 2006;101(2):266–73.
Triponez F, et al. Long-term follow-up of MEN1 patients who do not have initial surgery for small ≤2 cm nonfunctioning pancreatic neuroendocrine tumors, an AFCE and GTE study. Ann Surg. 2018;268(1):158–64.
Turner JJO, et al. Diagnostic challenges due to phenocopies: lessons from multiple endocrine neoplasia type1 (MEN1). Hum Mutat. 2010;31(1):E1089.
Uchino S, et al. Screening of the Men1 gene and discovery of germ-line and somatic mutations in. World J Surg. 2000;24(11):1409–17.
Vargas-Poussou R, et al. Familial hypocalciuric hypercalcemia types 1 and 3 and primary hyperparathyroidism: similarities and differences. J Clin Endocrinol Metab. 2016;101(5):2185–95.
Warner J, et al. Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet. 2004;41:155–60.
Wermer P. Genetic aspects of adenomatosis of endocrine glands. Am J Med. 1954;16(3):363–71.
Yao JC, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–72.
Yeh MW, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metabol. 2013;98(3):1122–9.
Zerbini LF, et al. JunD-mediated repression of GADD45α and γ regulates escape from cell death in prostate cancer. Cell Cycle. 2011;10(15):2583–91.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this entry
Cite this entry
Romanet, P., Goudet, P., Barlier, A. (2021). Multiple Endocrine Neoplasia Type 1. In: Colao, A., Jaffrain-Rea, ML., Beckers, A. (eds) Polyendocrine Disorders and Endocrine Neoplastic Syndromes. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-89497-3_8
Download citation
DOI: https://doi.org/10.1007/978-3-319-89497-3_8
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-89496-6
Online ISBN: 978-3-319-89497-3
eBook Packages: MedicineReference Module Medicine