-
Endocrine Reviews Mar 2021Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for... (Review)
Review
Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics, and molecular biology specialists. There have been 2 major clinical practice guidance papers published in the past 2 decades, with the most recent published 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature, and those data are discussed in this review. The genetic and molecular interactions of the MEN1-encoded protein menin with transcription factors and chromatin-modifying proteins in cell signaling pathways mediated by transforming growth factor β/bone morphogenetic protein, a few nuclear receptors, Wnt/β-catenin, and Hedgehog, and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1-related conditions in germline MEN1 mutation-negative patients. There is rapidly accumulating knowledge about clinical presentation in children, adolescents, and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuroendocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.
Topics: Adolescent; Animals; Germ-Line Mutation; Humans; Mice; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Quality of Life; Signal Transduction
PubMed: 33249439
DOI: 10.1210/endrev/bnaa031 -
Internal Medicine Journal Aug 2019The multiple endocrine neoplasia (MEN) syndromes include MEN1, MEN2 (formerly MEN2A), MEN3 (formerly MEN2B) and the recently identified MEN4. Clinical presentations are... (Review)
Review
The multiple endocrine neoplasia (MEN) syndromes include MEN1, MEN2 (formerly MEN2A), MEN3 (formerly MEN2B) and the recently identified MEN4. Clinical presentations are varied and often relate to the overproduction of specific hormones. Understanding the genetics of each syndrome assists in determining screening timelines. Treatments for each manifestation are dependent on location, risk of recurrence or malignancy, hormone excess and surgical morbidity. Multidisciplinary management should include geneticists, genetic counsellors, endocrinologists and endocrine surgeons.
Topics: Combined Modality Therapy; Endocrine Surgical Procedures; Genetic Markers; Genetic Testing; Humans; Multiple Endocrine Neoplasia; Recurrence
PubMed: 31387156
DOI: 10.1111/imj.14394 -
Surgical Oncology Clinics of North... Oct 2015Early diagnosis of multiple endocrine neoplasia (MEN) syndromes is critical for optimal clinical outcomes; before the MEN syndromes can be diagnosed, they must be... (Review)
Review
Early diagnosis of multiple endocrine neoplasia (MEN) syndromes is critical for optimal clinical outcomes; before the MEN syndromes can be diagnosed, they must be suspected. Genetic testing for germline alterations in both the MEN type 1 (MEN1) gene and RET proto-oncogene is crucial to identifying those at risk in affected kindreds and directing timely surveillance and surgical therapy to those at greatest risk of potentially life-threatening neoplasia. Pancreatic, thymic, and bronchial neuroendocrine tumors are the leading cause of death in patients with MEN1 and should be aggressively considered by at least biannual computed tomography imaging.
Topics: Disease Management; Genetic Predisposition to Disease; Genetic Testing; Humans; Multiple Endocrine Neoplasia; Proto-Oncogene Mas; Risk Assessment
PubMed: 26363542
DOI: 10.1016/j.soc.2015.06.008 -
Seminars in Cancer Biology Feb 2022Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant... (Review)
Review
Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis and Hirschprung's disease and MEN 2B with MTC, phaeochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities. Germline RET variants causing MEN 2 result in gain-of-function; since the discovery of the genetic variants a thorough search for genotype-phenotype associations began in order to understand the high variability both between families and within family members. These studies have successfully led to improved risk classification of prognosis in relation to the genotype, thus improving the management of the patients by thorough genetic counseling. The present review summarizes the recent developments in the knowledge of these hereditary syndromes as well as the impact on clinical management, including genetic counseling, of both individual patients and families. It furthermore points to future directions of research for better clarification of timing of treatments of the various manifestations of the syndromes in order to improve survival and morbidity in these patients.
Topics: Carcinoma, Neuroendocrine; Digestive System Neoplasms; Ganglioneuroma; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Genotype; Germ-Line Mutation; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Prognosis; Proto-Oncogene Proteins c-ret; Risk Factors; Thyroid Neoplasms; Thyroidectomy
PubMed: 33812987
DOI: 10.1016/j.semcancer.2021.03.035 -
Nature Reviews. Endocrinology Apr 2021Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours... (Review)
Review
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.
Topics: Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Proto-Oncogene Proteins
PubMed: 33564173
DOI: 10.1038/s41574-021-00468-3 -
Thyroid : Official Journal of the... Jun 2015The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid... (Review)
Review
INTRODUCTION
The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association.
METHODS
The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document.
RESULTS
The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC.
CONCLUSIONS
The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Fine-Needle; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Disease Management; Genetic Testing; Hormone Replacement Therapy; Humans; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Proto-Oncogene Proteins c-ret; Radiotherapy; Societies, Medical; Thyroid Neoplasms; Thyroidectomy
PubMed: 25810047
DOI: 10.1089/thy.2014.0335 -
Clinical Endocrinology Oct 2022This review provides an overview of novel insights in the clinical management of patients with Multiple Endocrine Neoplasia Type 1, focusing on the last decade since the... (Review)
Review
This review provides an overview of novel insights in the clinical management of patients with Multiple Endocrine Neoplasia Type 1, focusing on the last decade since the last update of the MEN1 guidelines. With regard to Diagnosis: Mutation-negative patients with 2/3 main manifestations have a different clinical course compared to mutation-positive patients. As for primary hyperparathyroidism: subtotal parathyroidectomy is the initial procedure of choice. Current debate centres around the timing of initial parathyroidectomy as well as the controversial topic of unilateral clearance in young patients. For duodenopancreatic neuroendocrine tumours (NETs), the main challenge is accurate and individualized risk stratification to enable personalized surveillance and treatment. Thymus NETs remain one of the most aggressive MEN1-related tumours. Lung NETs are more frequent than previously thought, generally indolent, but rare aggressive cases do occur. Pituitary adenomas are most often prolactinomas and nonfunctioning microadenomas with an excellent prognosis and good response to therapy. Breast cancer is recognized as part of the MEN1 syndrome in women and periodical screening is advised. Clinically relevant manifestations are already seen at the paediatric age and initiating screening in the second decade is advisable. MEN1 has a significant impact on quality of life and US data show a significant financial burden. In conclusion, patient outcomes have improved, but much is still to be achieved. For care tailored to the needs of the individual patient and improving outcomes on an individual basis, studies are now needed to define predictors of tumour behaviour and effects of more individualized interventions.
Topics: Child; Female; Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Pituitary Neoplasms; Quality of Life
PubMed: 35319130
DOI: 10.1111/cen.14727 -
Neuroendocrinology 2021The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a... (Review)
Review
Multiple Endocrine Neoplasia Type 1 and the Pancreas: Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement.
The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.
Topics: Consensus; Duodenal Neoplasms; Humans; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms
PubMed: 32971521
DOI: 10.1159/000511791 -
Clinics in Dermatology 2021Dermal hyperneury (DN) is a rarely reported form of small nerve hypertrophy characterized by an exaggerated size and prominence of dermal nerve fibers. Clinically, it...
Dermal hyperneury (DN) is a rarely reported form of small nerve hypertrophy characterized by an exaggerated size and prominence of dermal nerve fibers. Clinically, it can present with or without visible lesions, within a syndrome or sporadically, and in solitary or multiple fashion. The syndromes most commonly associated with DN include multiple endocrine neoplasia 2B and 2A, neurofibromatosis type II, and Cowden syndrome. Patients with syndrome-associated DN have an increased risk for various malignancies. Sporadic DN has been reported either in association with cutaneous tumors/reactive lesions, such as nodular prurigo, or in idiopathic form, where it can present with multiple DN lesions. There is a morphologic overlap between mucocutaneous neuromas and DN, as the former can have the appearance of either bulkier circumscribed lesions or tortuous and hyperplastic nerves more akin to DN. Epithelial sheath neuroma also shares a similar appearance to DN, from which it can be distinguished by a squamoid-appearing and thickened perineurium.
Topics: Hamartoma Syndrome, Multiple; Humans; Multiple Endocrine Neoplasia; Neuroma; Skin Neoplasms
PubMed: 34272024
DOI: 10.1016/j.clindermatol.2020.10.008 -
Surgery Today Dec 2023In patients with multiple endocrine neoplasia type 1 syndrome (MEN 1) and Zollinger-Ellison syndrome (ZES), gastrinomas arise from the duodenum, about 60% are multiple,... (Review)
Review
In patients with multiple endocrine neoplasia type 1 syndrome (MEN 1) and Zollinger-Ellison syndrome (ZES), gastrinomas arise from the duodenum, about 60% are multiple, and about 15% of patients have coexisting pancreatic gastrinomas, which can be localized by the selective arterial secretagogue injection test (SASI test). The guidelines (GLs) by the Japanese Neuroendocrine Tumor Society (JNETS) recommend surgical resection for functioning duodenopancreatic neuroendocrine tumors (NETs), including gastrinomas, in patients with MEN1 (Grade A, 100% agreement among members). Conversely, the GLs of the National Comprehensive Cancer Network (NCCN) in the USA recommend observation and treatment with proton pump inhibitors (PPIs) or exploratory surgery for occult gastrinomas. An international Consensus Statement (ICS) from the European Union (EU) also does not recommend resection of gastrinomas in patients with MEN1, despite some surgeons having reported surgery being curative for gastrinomas in MEN1 patients. In this review, we discuss the serious side effects and tumorigenic effects of the prolonged use of PPIs and the safety and curability of surgery, supported by our results of curative surgery for gastrinomas in 20 patients with MEN1 over 30 years. We conclude that surgery should be the first-line treatment for gastrinomas in MEN1 patients.
Topics: Humans; Gastrinoma; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Proton Pump Inhibitors; Zollinger-Ellison Syndrome
PubMed: 36473964
DOI: 10.1007/s00595-022-02627-z