open access

Vol 70, No 5 (2019)
Original Paper
Published online: 2019-06-12
Submitted: 2019-03-25
Accepted: 2019-05-16
Get Citation

Multiple endocrine neoplasia type 1 in Poland: a two-centre experience

Przemysław Soczomski, Beata Jurecka-Lubieniecka, Natalia Rogozik, Andrzej Tukiendorf, Barbara Jarząb, Tomasz Bednarczuk
DOI: 10.5603/EP.a2019.0031
·
Pubmed: 31274185
·
Endokrynologia Polska 2019;70(5):385-391.

open access

Vol 70, No 5 (2019)
Original Paper
Published online: 2019-06-12
Submitted: 2019-03-25
Accepted: 2019-05-16

Abstract

Introduction: Multiple endocrine neoplasia type 1 (MEN1) has been causing problems for clinicians since it was first described in 1954 by Wermer. Not only its rarity, but also its variable clinical manifestations and lack of genotype-phenotype correlation make it hard to establish evidence-based guidelines for the management of this syndrome. Nationwide registers and population-based research are the best means to improve knowledge about this rare disease. As yet, there is no example of such research in the Polish population of MEN1 patients.

Material and methods: We performed a retrospective analysis of clinical and genetic data of patients diagnosed with MEN1 syndrome and followed-up in two polish referral centres in the years 1994–2018.

Results: We analysed 79 patients, of whom the majority were women. The mean age of the patient population was 43 years, mean age at MEN1 diagnosis was 37.95 years, and mean interval from initial symptoms to MEN1 diagnosis was 6.93 years. Primary hyperparathyroidism (PHP), gastroenteropancreatic neuroendocrine tumour (GEP-NET), and pituitary adenoma (PA) developed in 90%, 52%, and 47% of patients, respectively. The dominance of insulinoma with low prevalence of gastrinoma is the most vivid difference, when compared to previously described populations. Moreover, we found 3.5-fold higher risk of developing a pituitary tumour in patients with a frameshift mutation with the STOP codon of the MEN1 gene. 

Conclusions: The Polish population of patients with MEN1 is different than previously described European and Asian populations, primarily in prevalence of functional NETs. A frameshift mutation with the STOP codon of the MEN1 gene significantly increases the risk of PA. Further studies with a larger cohort of patients are needed to fully describe the Polish population and improve diagnosis and management of the syndrome.

Abstract

Introduction: Multiple endocrine neoplasia type 1 (MEN1) has been causing problems for clinicians since it was first described in 1954 by Wermer. Not only its rarity, but also its variable clinical manifestations and lack of genotype-phenotype correlation make it hard to establish evidence-based guidelines for the management of this syndrome. Nationwide registers and population-based research are the best means to improve knowledge about this rare disease. As yet, there is no example of such research in the Polish population of MEN1 patients.

Material and methods: We performed a retrospective analysis of clinical and genetic data of patients diagnosed with MEN1 syndrome and followed-up in two polish referral centres in the years 1994–2018.

Results: We analysed 79 patients, of whom the majority were women. The mean age of the patient population was 43 years, mean age at MEN1 diagnosis was 37.95 years, and mean interval from initial symptoms to MEN1 diagnosis was 6.93 years. Primary hyperparathyroidism (PHP), gastroenteropancreatic neuroendocrine tumour (GEP-NET), and pituitary adenoma (PA) developed in 90%, 52%, and 47% of patients, respectively. The dominance of insulinoma with low prevalence of gastrinoma is the most vivid difference, when compared to previously described populations. Moreover, we found 3.5-fold higher risk of developing a pituitary tumour in patients with a frameshift mutation with the STOP codon of the MEN1 gene. 

Conclusions: The Polish population of patients with MEN1 is different than previously described European and Asian populations, primarily in prevalence of functional NETs. A frameshift mutation with the STOP codon of the MEN1 gene significantly increases the risk of PA. Further studies with a larger cohort of patients are needed to fully describe the Polish population and improve diagnosis and management of the syndrome.

Get Citation

Keywords

multiple endocrine neoplasia type 1; MEN1; Polish population; genotype-phenotype correlation

About this article
Title

Multiple endocrine neoplasia type 1 in Poland: a two-centre experience

Journal

Endokrynologia Polska

Issue

Vol 70, No 5 (2019)

Pages

385-391

Published online

2019-06-12

DOI

10.5603/EP.a2019.0031

Pubmed

31274185

Bibliographic record

Endokrynologia Polska 2019;70(5):385-391.

Keywords

multiple endocrine neoplasia type 1
MEN1
Polish population
genotype-phenotype correlation

Authors

Przemysław Soczomski
Beata Jurecka-Lubieniecka
Natalia Rogozik
Andrzej Tukiendorf
Barbara Jarząb
Tomasz Bednarczuk

References (34)
  1. Thakker RV, Newey PJ, Walls GV, et al. Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012; 97(9): 2990–3011.
  2. Marini F, Falchetti A, Del Monte F, et al. Multiple endocrine neoplasia type 1. Orphanet J Rare Dis. 2006; 1: 38.
  3. Dreijerink KMa, Lips CJm. Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1). Hered Cancer Clin Pract. 2005; 3(1): 1–6.
  4. de Laat JM, van der Luijt RB, Pieterman CRC, et al. MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC Med. 2016; 14(1): 182.
  5. Ito T, Igarashi H, Uehara H, et al. Causes of death and prognostic factors in multiple endocrine neoplasia type 1: a prospective study: comparison of 106 MEN1/Zollinger-Ellison syndrome patients with 1613 literature MEN1 patients with or without pancreatic endocrine tumors. Medicine (Baltimore). 2013; 92(3): 135–181.
  6. Van Be, et al. ‘Quality in, quality out’, a stepwise approach to evidence-based medicine for rare diseases promoted by multiple endocrine neoplasia type 1. Endocr Connect. 2018 Nov; 7(11): R260–R274. Endocr Connect. 2018; 7(11): R260–R274..
  7. van Leeuwaarde RS, Pieterman CRC, Bleiker EMA, et al. High Fear of Disease Occurrence Is Associated With Low Quality of Life in Patients With Multiple Endocrine Neoplasia Type 1: Results From the Dutch MEN1 Study Group. J Clin Endocrinol Metab. 2018; 103(6): 2354–2361.
  8. Berglund G, Lidén A, Hansson MG, et al. Quality of life in patients with multiple endocrine neoplasia type 1 (MEN 1). Fam Cancer. 2003; 2(1): 27–33.
  9. van Leeuwaarde RS, de Laat JM, Pieterman CRC, et al. The future: medical advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017; 24(10): T179–T193.
  10. Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015; 3(11): 895–905.
  11. Leeuwaarde RS, Herder WW, Valk GD. The need for national registries for rare endocrine tumor syndromes. Endocrine. 2017; 58(2): 205–206.
  12. Aymé S, Rodwell C. The European Union Committee of Experts on Rare Diseases: three productive years at the service of the rare disease community. Orphanet J Rare Dis. 2014; 9: 30.
  13. Sakurai A, Suzuki S, Kosugi S, et al. MEN Consortium of Japan. Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database. Clin Endocrinol (Oxf). 2012; 76(4): 533–539.
  14. Giusti F, Cianferotti L, Boaretto F, et al. Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine. 2017; 58(2): 349–359.
  15. Goudet P, Bonithon-Kopp C, Murat A, 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.
  16. Machens A, Schaaf L, Karges W, et al. Age-related penetrance of endocrine tumours in multiple endocrine neoplasia type 1 (MEN1): a multicentre study of 258 gene carriers. Clin Endocrinol (Oxf). 2007; 67(4): 613–622.
  17. Marini F, Giusti F, Brandi ML. Multiple endocrine neoplasia type 1: extensive analysis of a large database of Florentine patients. Orphanet J Rare Dis. 2018; 13(1): 205.
  18. Pieterman CRC, Schreinemakers JMJ, Koppeschaar HPF, et al. Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of genetic screening on clinical outcome. Clin Endocrinol (Oxf). 2009; 70(4): 575–581.
  19. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001; 86(12): 5658–5671.
  20. Buła G, Truchanowski W, Koziołek H, et al. A follow-up study of patients with MEN syndromes - five case reports. Endokrynol Pol. 2018; 69(2): 163–167.
  21. Debski MG, Makowska A, Bar-Andziak E. Insulinoma in a patient with MEN 1 syndrome — 9-year follow-up: case report. Endokrynol Pol. 2010; 61(2): 212–216.
  22. Krassowski J. Trudności w rozpoznawaniu i leczeniu MEN 1. Pol J Endocrinol. 2005; 3(56).
  23. van Leeuwaarde RS, van Nesselrooij BPM, Hermus AdR, et al. Impact of Delay in Diagnosis in Outcomes in MEN1: Results From the Dutch MEN1 Study Group. J Clin Endocrinol Metab. 2016; 101(3): 1159–1165.
  24. Yamazaki M, Suzuki Si, Kosugi S, et al. MEN Consortium of Japan. Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked. Endocr J. 2012; 59(9): 797–807.
  25. de Laat JM, van Leeuwaarde RS, Valk GD. The Importance of an Early and Accurate MEN1 Diagnosis. Front Endocrinol (Lausanne). 2018; 9: 533.
  26. 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. 2010; 34(2): 249–255.
  27. Giudici F, Cavalli T, Giusti F, et al. Natural History of MEN1 GEP-NET: Single-Center Experience After a Long Follow-Up. World J Surg. 2017; 41(9): 2312–2323.
  28. Donegan D, Singh Ospina N, Rodriguez-Gutierrez R, et al. Long-term outcomes in patients with multiple endocrine neoplasia type 1 and pancreaticoduodenal neuroendocrine tumours. Clin Endocrinol (Oxf). 2017; 86(2): 199–206.
  29. Ito T, Jensen RT. Imaging in multiple endocrine neoplasia type 1: recent studies show enhanced sensitivities but increased controversies. Int J Endocr Oncol. 2016; 3(1): 53–66.
  30. Lipiński M, Rydzewska G, Foltyn W, et al. Gastroduodenal neuroendocrine neoplasms, including gastrinoma — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol. 2017; 68(2): 138–153.
  31. Thevenon J, Bourredjem A, Faivre L, 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): 1940–1948.
  32. Bartsch DK, Slater EP, Albers M, et al. Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. J Clin Endocrinol Metab. 2014; 99(11): E2387–E2391.
  33. Christakis I, Qiu W, Hyde SM, et al. Genotype-phenotype pancreatic neuroendocrine tumor relationship in multiple endocrine neoplasia type 1 patients: A 23-year experience at a single institution. Surgery. 2018; 163(1): 212–217.
  34. Falchetti A. Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and what's old. F1000Res. 2017; 6.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Via MedicaWydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl