Skip to main content
SpringerLink
Log in

MEN1 in children and adolescents: Data from patients of a regional referral center for hereditary endocrine tumors

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

To retrospectively evaluate the age of onset of MEN1-associated lesions in a group of affected children and adolescents and to compare the clinical features of our series with the evidence derived from the literature.

Methods

The study population consisted of 22 Italian children and adolescents (age 6–31 years at the time of the inclusion in this study) all with a clinical and/or a genetic diagnosis of MEN1 performed before the age of 16 who have been followed-up regularly from 1998 to 2016 at the Regional Referral Center for Hereditary Endocrine Tumors. Clinical, biochemical, imaging and genetic data have been collected for each patient.

Results

Ten subjects (45.5%) have not yet presented any clinical/biochemical/radiological manifestation of MEN1 disease, whereas 12 patients (54.5%) developed at least one MEN1-associated endocrine manifestation. The second group of patients was significantly older than the first one. The most frequent manifestation was primary hyperparathyroidism (50%), followed by pituitary tumors (prolactinomas) (31.8%) and nonfunctioning pancreatic neuroendocrine tumors (9%). The earliest cases of primary hyperparathyroidism and prolactinoma were a 12-year-old girl and a 13-year-old boy, respectively.

Conclusions

MEN1 disease seems to present with different features in children and adolescents from those in adults. Our study confirms the fundamental importance of screening for tumors in young MEN1 patients beginning in early childhood, in order to avoid diagnostic and therapeutic delays.

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. A. Falchetti, F. Marini, F. Tonelli, M.L. Brandi, Lessons from genes mutated in multiple endocrine neoplasia (MEN) syndromes. Ann. Endocrinol. 66, 195–205 (2005)

    Article  CAS  Google Scholar 

  2. R.V. Thakker, P.J. Newey, G.V. Walls, J. Bilezikian, H. Dralle, P.R. Ebeling, S. Melmed, A. Sakurai, F. Tonelli, M.L. Brandi, Endocrine Society: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metab. 97, 2990–3011 (2012)

    Article  CAS  PubMed  Google Scholar 

  3. P. Goudet, A. Dalac, M. Le Bras, C. Cardot-Bauters, P. Niccoli, N. Lévy-Bohbot, H. du Boullay, X. Bertagna, P. Ruszniewski, F. Borson-Chazot, B. Vergès, J.L. Sadoul, F. Ménégaux, A. Tabarin, J.M. Kühn, P. d’Anella, O. Chabre, S. Christin-Maitre, G. Cadiot, C. Binquet, B. Delemer, MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’étude des tumeurs endocrines. J. Clin. Endocrinol. Metab. 100, 1568–1577 (2015)

    Article  CAS  PubMed  Google Scholar 

  4. C. Marcocci, M.L. Brandi, A. Scillitani, S. Corbetta, A. Faggiano, L. Gianotti, S. Migliaccio, S. Minisola, Italian Society of Endocrinology Consensus Statement: definition, evaluation and management of patients with mild primary hyperparathyroidism. J. Endocrinol. Invest. 38, 577–593 (2015)

    Article  CAS  PubMed  Google Scholar 

  5. N. Mitre, K. Mack, D. Babovic-Vuksanovic, G. Thompson, S. Kumar, Ischemic stroke as the presenting symptom of primary hyperparathyroidism due to multiple endocrine neoplasia type 1. J. Pediatr. 153, 582–585 (2008)

    Article  PubMed  Google Scholar 

  6. C.A. Stratakis, D.H. Schussheim, S.M. Freedman, M.F. Keil, S.D. Pack, S.K. Agarwal, M.C. Skarulis, R.J. Weil, I.A. Lubensky, Z. Zhuang, E.H. Oldfield, S.J. Marx, Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J. Clin. Endocrinol. Metab. 85, 4776–4780 (2000)

    CAS  PubMed  Google Scholar 

  7. Gan, H.W., Bulwer, C., Jeelani, O., Levine, M.A., Korbonits, M., Spoudeas, H.A: Treatment-resistant pediatric giant prolactinoma and multiple endocrine neoplasia type 1. Int. J. Pediatr. Endocrinol.2015, 15 (2015)

  8. G. Kontogeorgos, N. Kapranos, I. Tzavara, N. Thalassinos, D. Rologis, Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1. Clin. Endocrinol. (Oxf) 54, 117–120 (2001)

    Article  CAS  Google Scholar 

  9. W.F. Simonds, S. Varghese, S.J. Marx, L.K. Nieman, Cushing’s syndrome in multiple endocrine neoplasia type 1. Clin. Endocrinol. (Oxf) 76, 379–386 (2012)

    Article  CAS  Google Scholar 

  10. C. Nozières, P. Berlier, C. Dupuis, C. Raynaud-Ravni, Y. Morel, F.B. Chazot, M. Nicolino, Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature. Orphanet J. Rare Dis. 6, 67 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  11. M. Rix, N.T. Hertel, F.C. Nielsen, B.B. Jacobsen, A.S. Hoejberg, K. Brixen, J. Hangaard, J.P. Kroustrup, Cushing’s disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1. Eur. J. Endocrinol. 151, 709–715 (2004)

    Article  CAS  PubMed  Google Scholar 

  12. P.J. Newey, J. Jeyabalan, G.V. Walls, P.T. Christie, F.V. Gleeson, S. Gould, P.R. Johnson, R.R. Phillips, F.J. Ryan, B. Shine, M.R. Bowl, R.V. Thakker, Asymptomatic children with multiple endocrine neoplasia type 1 mutations may harbour nonfunctioning pancreatic neuroendocrine tumors. J. Clin. Endocrinol. Metab. 94, 3640–3646 (2009)

    Article  CAS  PubMed  Google Scholar 

  13. B.W. Scheithauer, K. Kovacs, V. Nose, M. Lombardero, Y.R. Osamura, R.V. Lloyd, E. Horvath, A. Pagenstecher, J.E. Bohl, D.S. Tews, Multiple endocrine neoplasia type 1-associated thyrotropin-producing pituitary carcinoma: report of a probable de novo example. Hum. Pathol. 40, 270–278 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. T. Cuny, M. Pertuit, M. Sahnoun-Fathallah, A. Daly, G. Occhi, M.F. Odou, A. Tabarin, M.L. Nunes, B. Delemer, V. Rohmer, R. Desailloud, V. Kerlan, O. Chabre, J.L. Sadoul, M. Cogne, P. Caron, C. Cortet-Rudelli, A. Lienhardt, I. Raingeard, A.M. Guedj, T. Brue, A. Beckers, G. Weryha, A. Enjalbert, A. Barlier, Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don’t forget MEN1 genetic analysis. Eur. J. Endocrinol. 168, 533–541 (2013)

    Article  CAS  PubMed  Google Scholar 

  15. T.D. Gonçalves, R.A. Toledo, T. Sekiya, S.E. Matuguma, F. Maluf Filho, M.S. Rocha, S.A. Siqueira, A. Glezer, M.D. Bronstein, M.A. Pereira, R. Jureidini, T. Bacchella, M.C. Machado, S.P. Toledo, D.M. Lourenço Jr, Penetrance of functioning and nonfunctioning pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 in the second decade of life. J. Clin. Endocrinol. Metab. 99, E89–96 (2014)

    Article  PubMed  Google Scholar 

  16. A. Sakurai, M. Yamazaki, S. Suzuki, T. Fukushima, T. Imai, T. Kikumori, T. Okamoto, K. Horiuchi, S. Uchino, S. Kosugi, M. Yamada, I. Komoto, K. Hanazaki, M. Itoh, T. Kondo, M. Mihara, M. Imamura, Clinical features of insulinoma in patients with multiple endocrine neoplasia type 1: analysis of the database of the MEN Consortium of Japan. Endocr. J. 59, 859–866 (2012)

    Article  PubMed  Google Scholar 

  17. H.C. Fabbri, M.P. Mello, F.C. Soardi, A.M. Esquiaveto-Aun, D.M. Oliveira, F.C. Denardi, A. Moura-Neto, H.M. Garmes, M.T. Baptista, P.S. Matos, S.H. Lemos-Marini, L.F. D’Souza-Li, G. Guerra-Júnior, Long-term follow-up of an 8-year-old boy with insulinoma as the first manifestation of a familial form of multiple endocrine neoplasia type 1. Arq. Bras. Endocrinol. Metabol. 54, 754–760 (2010)

    Article  PubMed  Google Scholar 

  18. E.B. Kwon, H.R. Jeong, Y.S. Shim, H.S. Lee, J.S. Hwang, Multiple endocrine neoplasia type 1 presenting as hypoglycemia due to insulinoma. J. Korean Med. Sci. 31, 1003–1006 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. R.T. Jensen, M.J. Berna, D.B. Bingham, J.A. Norton, Inherited pancreatic endocrine tumor syndromes: advances in molecular pathogenesis, diagnosis, management, and controversies. Cancer 113, 1807–1843 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  20. P. Goudet, A. Murat, C. Cardot-Bauters, P. Emy, E. Baudin, H. du Boullay Choplin, Y. Chapuis, J.L. Kraimps, J.L. Sadoul, A. Tabarin, B. Vergès, B. Carnaille, P. Niccoli-Sire, A. Costa, A. Calender, GTE network (Groupe des Tumeurs Endocrines): 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 (2009)

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by AIMEN 1 & 2.

Author information

Authors and Affiliations

  1. Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    Letizia Vannucci, Francesca Marini & Simone Ciuffi

  2. Department of Surgery and Translational Medicine, University of Florence, Largo Palagi 1, 50139, Florence, Italy

    Francesca Giusti, Francesco Tonelli & Maria Luisa Brandi

Authors
  1. Letizia Vannucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Marini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francesca Giusti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Simone Ciuffi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Tonelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Luisa Brandi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Luisa Brandi.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vannucci, L., Marini, F., Giusti, F. et al. MEN1 in children and adolescents: Data from patients of a regional referral center for hereditary endocrine tumors. Endocrine 59, 438–448 (2018). https://doi.org/10.1007/s12020-017-1322-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-017-1322-5

Keywords

Search

Navigation