Cause of Death in Multiple Endocrine Neoplasia Type 1

Wilkinson, Stephen; Teh, Bin Tean; Davey, Kiah R.; McArdle, John P.; Young, Margot de; Shepherd, J. J.

doi:10.1001/archsurg.1993.01420180085016

Cited by 143 publications

(180 citation statements)

References 10 publications

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“…In series focusing on MEN1-related mortality, 5-9% of the MEN1-related deaths occurring before 1990 were attributed to pulmonary carcinoids (Wilkinson et al 1993, Goudet et al 2010, with no deaths due to pulmonary carcinoids reported after 1990 (Geerdink et al 2003, Wilson et al 2008, Goudet et al 2010. In line with these findings, pulmonary carcinoids do not give an increased risk of death in MEN1 patients (Goudet et al 2010).…”

Section: Natural History and Prognostic Factors: Pulmonary Carcinoidsmentioning

confidence: 59%

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

Endocrine-Related Cancer

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Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

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Section: Natural History and Prognostic Factors: Pulmonary Carcinoidsmentioning

confidence: 59%

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

Endocrine-Related Cancer

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“…In these studies, deaths from malignant pancreatic islet cell tumours account for only 9-13% of the deaths related to MEN-1. Wilkinson et al (26) were the first to conclude that neoplasm rather than peptic ulcer disease is the main cause of death in MEN-1. Other recent studies (10,27,28) have confirmed this conclusion.…”

Section: Discussionmentioning

confidence: 99%

Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening?

Geerdink

Luijt

Lips

2003

European Journal of Endocrinology

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Objective: To determine the benefit of periodical clinical screening of carriers of a mutation in the multiple endocrine neoplasia type 1 (MEN-1) gene, because any useful discussion requires more concrete data. Design and methods: Our study population consisted of all the patients with MEN-1 (n ¼ 58) who were treated at the University Medical Centre Utrecht, The Netherlands, during the period 1975 -2003, and their affected relatives (n ¼ 29). Records of affected individuals who died were analysed for morbidity, cause of death and age at death. We discuss our results in the light of the literature on MEN-1 regarding the benefit of screening. Results: Over a period of 28 years, we identified 87 individuals affected with MEN-1, from 16 families. A mutation in the MEN-1 gene was detected in 57%, 18% were obligate carriers, and in 24% the diagnosis was only clinically confirmed. Thirty individuals died, 17 from MEN-1-related causes, including malignancies (n ¼ 12: pancreatic islet cell tumours n ¼ 6 and carcinoid tumours n ¼ 6), the Zollinger-Ellison syndrome (n ¼ 4) and Cushing's disease (n ¼ 1). The remaining patients died of causes probably related to MEN-1 (n ¼ 3), unrelated to MEN-1 (n ¼ 7) or of unknown causes. Mean ages at death from MEN-1 were 55.4 years for men and 46.8 years for women, in both cases significantly lower than the mean age at death in the average Dutch population (P , 0.05). Conclusions: We feel that the significantly increased risk of premature death found in patients with MEN-1 justifies the periodical clinical screening of carriers of the MEN-1 gene mutation. Early detection and treatment of abnormalities will probably reduce this risk.

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“…Moreover, histopathological analysis of resected MEN1-pancreases has shown numerous micro-tumors that were not identified using imaging studies (Anlauf et al 2006), further emphasizing the diffuse involvement of the pancreas in patients with MEN1. Historically, NF tumors were diagnosed late because of local symptoms and were associated with a high lethality early in life (Wilkinson et al 1993, Doherty et al 1998, Goudet et al 2010, Ito et al 2013). Indeed, the mean age of death for patients who died because of NF-pNET was 43 in a previous registry-based study (comprising patients diagnosed with MEN1 in France from 1956 to 2003) and 46 in the study by Doherty and coworkers analyzing patients registered in the Washington University database (Doherty et al 1998).…”

Section: Non-functional Pancreatic Netsmentioning

confidence: 99%

The future: surgical advances in MEN1 therapeutic approaches and management strategies

Sadowski¹,

Cadiot²,

Dansin³

et al. 2017

Endocrine-Related Cancer

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Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disorder associated with numerous neuroendocrine tumors (NETs). Recent advances in the management of MEN1 have led to a decrease in mortality due to excess hormones; however, they have also led to an increase in mortality from malignancy, particularly NETs. The main challenges are to localize these tumors, to select those that need therapy because of the risk of aggressive behavior and to select the appropriate therapy associated with minimal morbidity. This must be applied to a hereditary disease with a high risk of recurrence. The overall aim of management in MEN1 is to ensure that the patient remains disease-and symptom-free for as long as possible and maintains a good quality of life. Herein, we review the changes that occurred in the last 20 years in the surgical management of MEN1-associated functional and non-functional pancreaticoduodenal NETs and thymic and bronchial NETs.

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Cause of Death in Multiple Endocrine Neoplasia Type 1

Cited by 143 publications

References 10 publications

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening?

The future: surgical advances in MEN1 therapeutic approaches and management strategies

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