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Clinical aspects of multiple endocrine neoplasia type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.

Key points

  • MEN1 is a rare genetic disorder that predisposes patients to primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours and anterior pituitary tumours, as well as more than 20 endocrine and non-endocrine tumours.

  • Hyperparathyroidism is the most common manifestation of MEN1 and is associated with mild to moderate hypercalcaemia but considerably reduced bone mineral density.

  • Duodenopancreatic neuroendocrine tumours are usually small in size, and multiple tumours are almost always present; they represent the main cause of death in MEN1 owing to their malignant potential.

  • Non-functioning pancreatic neuroendocrine tumours ≤2 cm could be managed by active surveillance while surgery should be proposed for large tumours and patients who progress on serial imaging studies.

  • Thymic neuroendocrine tumours occur predominantly in male individuals with MEN1, are very aggressive tumours and severely impact the prognosis of patients with MEN1.

  • MEN1 negatively influences health-related quality of life, but more data are needed about this issue.

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Fig. 1: The broad spectrum of MEN1 germline mutations registered in the French database.
Fig. 2: Age-related penetrance of MEN1 and four main MEN1-related lesions and their clinical phenotypes.
Fig. 3: Imaging studies in a patient with MEN1.
Fig. 4: Cutaneous lesions of MEN1.

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The authors contributed equally to all aspects of the article.

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Correspondence to Philippe Chanson.

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A.A.-S. has worked as sub-investigator for Alnylam Pharmaceuticals, Ionis (Isis) Pharmaceuticals, Novartis, MedDay Pharmaceuticals, Auris Medical, Gilead Sciences, Euroscreen (Ogeda), Alexion, Faron Pharmaceuticals, Actelion (Idorsia) Pharmaceuticals and IPSEN. G.C. is member of advisory boards of AAA, Keocyt, Ipsen, Novartis and Pfizer. P.G. received research grant from IPSEN. P.C. has received unrestricted research and educational grants from Ipsen, Novartis, Novo-Nordisk and Pfizer as Head of the Department of Endocrinology and Reproductive Diseases, APHP Paris-Saclay. P.C. has served as investigator (principal or coordinator) for clinical trials funded by Novartis, Pfizer, Ipsen, Antisense and Prolor Biotech. P.C. is a member of advisory boards from Ipsen, Novartis, Pfizer and Tiburio. P.C. gave lectures for Ipsen, Novartis and Pfizer. All the fees and honoraria are paid to his Institution. A.C. declares no competing interests.

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Al-Salameh, A., Cadiot, G., Calender, A. et al. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol 17, 207–224 (2021). https://doi.org/10.1038/s41574-021-00468-3

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