Natural History of MEN1 GEP‐NET: Single‐Center Experience After a Long Follow‐Up

Giudici, Francesco; Cavalli, Tiziana; Giusti, Francesca; Gronchi, Giorgio; Batignani, Giacomo; Tonelli, Francesco; Brandi, Maria Luisa

doi:10.1007/s00268-017-4019-2

Cited by 21 publications

(22 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yamazaki et al reported delays of MEN1 diagnosis from -2.9 to 5.3 years, depending on different signs, tumours and proband/family member status [24]. Giudici et al observed 5.7 years of delay from GEP-NET to MEN1 diagnosis, which is significantly longer than observed in our database [27]. Leeuvaarde et al described markedly longer delays in diagnosis of particular lesions, but the authors analysed only non-index cases, and the delays decreased in the course of time [23].…”

Section: Discussioncontrasting

confidence: 56%

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

Soczomski

Jurecka‐Lubieniecka

Rogozik

et al. 2019

Endokrynologia Polska

View full text Add to dashboard Cite

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.

show abstract

Section: Discussioncontrasting

confidence: 56%

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

Soczomski

Jurecka‐Lubieniecka

Rogozik

et al. 2019

Endokrynologia Polska

View full text Add to dashboard Cite

show abstract

“…Bone metastasis are reported in 4-12% of NET patients, but the real incidence is probably higher [13][14][15][16]. However, except for those patients who have a metastatic disease associated with shorter survival [13], patients with NET usually have good long-term survival [10,17]. It has been demonstrated that NET patients have a greater clinical burden of disease than matched control subjects, with increased risk of cardiovascular, hepatic, and gastrointestinal diseases, as well as osteopenia and osteoporosis [18].…”

Section: Introductionmentioning

confidence: 99%

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

Altieri¹,

Dato

Modica

et al. 2020

Nutrients

View full text Add to dashboard Cite

Patients affected by gastroenteropancreatic–neuroendocrine tumors (GEP–NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP–NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP–NET, focusing on vitamin D and its role in GEP–NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.

show abstract

“…Of the three major manifestations, PHPT has the highest penetrance and is considered to appear first in MEN1, although it often remains unrecognised [5]. Recent publications show, that functionally active GEP-NETs, initially frequently diagnosed as sporadic ones, lead to diagnosis of MEN1 in a remarkable proportion of patients [6]. Compared to sporadic tumors, MEN1-associated GEP-NETs are diagnosed 10 years earlier and often in a multiple form [5, 7], and their penetrance is as high as 80–90%, reaching nearly that of the parathyroid adenomas [6].…”

Section: Introductionmentioning

confidence: 99%

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome

et al. 2019

View full text Add to dashboard Cite

Purpose Multiple endocrine neoplasia type 1 is a rare tumor syndrome caused by germline mutations of MEN1 gene. Phenotype varies widely, and no definitive correlation with the genotype has been observed. Mutation-negative patients with MEN1-associated tumors represent phenocopies. By comparing mutation-positive and mutation-negative patients, we aimed to identify phenotype features predictive for a positive genetic test and to evaluate the role of MEN1 mutations in phenotype modulation. Methods Mutation screeening of MEN1 gene by Sanger sequencing and assessment of clinical data of 189 consecutively enrolled probands and relatives were performed at our national and European Reference Center. Multiple ligation probe amplification analysis of MEN1 gene and Sanger sequencing of CDKN1B were carried out in clinically suspicious but MEN1 -negative cases. Results Twenty-seven probands and twenty family members carried MEN1 mutations. Five mutations have not been described earlier. Pronouncedly high number of phenocopies (>70%) was observed. Clinical suspicion of MEN1 syndrome emerged at significantly earlier age in MEN1 -positive compared to MEN1 -negative probands. Gastroenteropancreatic neuroendocrine tumors developed significantly earlier and more frequently in carriers compared to non-carriers. Probands with high-impact (frameshift, nonsense, large deletions) mutations, predicted to affect menin function significantly, developed GEP-NETs more frequently compared to low-impact (inframe and missense) mutation carriers. Conclusions MEN1 phenocopy is common and represents a significant confounder for the genetic testing. GEP-NET under 30 years best predicted a MEN1 mutation. The present study thus confirmed a previous proposal and suggested that GEP-NET under 30 years should be considered as a part of the indication criteria for MEN1 mutational analysis.

show abstract

Natural History of MEN1 GEP‐NET: Single‐Center Experience After a Long Follow‐Up

Cited by 21 publications

References 56 publications

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

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

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

True MEN1 or phenocopy? Evidence for geno-phenotypic correlations in MEN1 syndrome

Contact Info

Product

Resources

About