Multiple Endocrine Neoplasia Type 1 Patients Research Articles

The natural course of cystic pancreatic neuroendocrine tumours in MEN1

Introduction: Pancreatic neuroendocrine tumours (PanNETs) significantly impact life expectancy in Multiple Endocrine Neoplasia Type 1 (MEN1). Both solid and cystic pancreatic lesions are observed in MEN1, yet limited research has been focused on cystic lesions in MEN1. While solid PanNETs are generally considered to have an indolent course, the natural course of cystic lesions remains unclear. Objective: This study aims to provide more insight into the natural course of cystic PanNETs in MEN1. Methods: Patients with MEN1 and radiologically suspected PanNETs, treated at UMC Utrecht and Radboudumc between 2010 and 2023, were included. In the first part, we examined the characteristics of patients with tumours visible on imaging scans. In the second part we investigated outcomes of pathological examinations following resection of these lesions. Results: A total of 136 patients were included, comprising 60 men and 76 women. The median follow-up was 5.1 years. [68Ga]Ga-DOTATOC PET/CT scans showed that both cystic and solid lesions demonstrated [68Ga]Ga-DOTATOC PET/CT uptake. The median growth of cystic and solid PanNETs was similar. Pathological examination of 38 resected tumours confirmed that cystic lesions identified on imaging were indeed PanNETs. Cystic lesions had a median diameter of 26 mm at the time of resection, compared to 18 mm for solid lesions, with comparable Ki-67 indices and mitotic counts. Conclusion: Cystic and solid PanNETs in MEN1 patients appear to be morphological variations of the same entity, suggesting similar management approaches should be considered.

Up-to-Date Imaging for Parathyroid Tumor Localization in MEN1 Patients with Primary Hyperparathyroidism: When and Which Ones (A Narrative Pictorial Review).

Patients diagnosed with multiple endocrine neoplasia type-1 (MEN1) often initially present with primary hyperparathyroidism (pHPT), and typically undergo surgical intervention. While laboratory tests are fundamental for diagnosis, imaging is crucial for localizing pathological parathyroids to aid in precise surgical planning. In this pictorial review, we will begin by comprehensively examining key imaging techniques and their established protocols, evaluating their effectiveness in detecting abnormal parathyroid glands. This analysis will emphasize both the advantages and potential limitations within the clinical context of MEN1 patients. Additionally, we will explore integrated imaging approaches that combine multiple modalities to enhance localization accuracy and optimize surgical planning-an essential component of holistic management in MEN1 cases. Various imaging techniques are employed for presurgical localization, including ultrasound (US), multiphase parathyroid computed tomography (CT) scanning (4D CT), magnetic resonance imaging (MRI), and nuclear medicine techniques like single photon emission computed tomography/CT (SPECT/CT) and positron emission tomography/CT (PET/CT). US is non-invasive, readily available, and provides high spatial resolution. However, it is operator-dependent and may have limitations in certain cases, such as intrathyroidal locations, the presence of bulky goiters, thyroid nodules, and previous thyroidectomy. Four-dimensional CT offers dynamic imaging, aiding in the identification of enlarged parathyroid glands, particularly in cases of ectopic or supernumerary glands. Despite concerns about radiation exposure, efforts are underway to optimize protocols and reduce doses, including the use of dual-energy CT. MR imaging offers excellent soft tissue contrast without radiation exposure, potentially providing superior differentiation between parathyroid glands and the surrounding structures. Radionuclide imaging, especially PET/CT using radiopharmaceuticals like [18F]FCH, shows promising results in localizing parathyroid tumors, particularly in patients with MEN1. [18F]FCH PET/CT demonstrates high sensitivity and may provide additional information compared to other imaging modalities, especially in cases of recurrent HPT.

Sarcomas arising in MEN1 patients: demonstrating LOH of the MEN1 locus and loss of menin expression.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors, typically from parathyroid, pancreatic, or anterior pituitary origin. In addition, benign cutaneous soft tissue tumors are prevalent in MEN1 patients. Although sarcomas have been reported in MEN1 patients it is unclear if these tumors should be considered as part of the MEN1 syndrome. Here, five patients with a MEN1 syndrome and a sarcoma are described. In all five sarcomas loss of heterozygosity of the MEN1 gene and loss of expression of menin are shown, suggesting that sarcomas may be a phenotypic expression of MEN1 syndrome.

Genetic Landscape and Clinical Manifestations of Multiple Endocrine Neoplasia Type 1 in a Korean Cohort: A Multicenter Retrospective Analysis.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Neuroendocrine Tumors and Survival Rates in Multiple Endocrine Neoplasia Type 1 Patients: Impact of Gender Difference

Introduction: Multiple endocrine neoplasia type 1 (MEN-1) is the most common inherited syndrome associated with NET development and gender-specific differences are emerging in neuroendocrine tumors (NETs). This study aimed to analyze gender difference in a single cohort of MEN-1 patients focusing on duodeno-pancreatic (DP)-NET and survival rates. Methods: MEN-1 patients referred to the Endocrinology Unit of the “Federico II” University of Naples, ENETS CoE, were retrospectively evaluated. Results: Among 100 MEN-1 patients enrolled, 59 (59%) were female and 41 (41%) male, and mean age at diagnosis was 39.4 years (range 5–86). No statistically significant association was identified between MEN-1 clinical manifestations and gender (primary hyperparathyroidism [PHPT] p: 1.0, DP-NET p: 0.83, pituitary adenoma [PA] p: 0.84, lung NET p: 0.64, and thymic NET p: 0.10), and similarly, age at diagnosis of MEN-1 and its individual manifestations was similar between genders. Survival analysis revealed no statistically significant difference between genders in DP-NET patients regarding progression disease p: 1.0 and death p: 1.0. Mean progression-free survival (PFS) of patients with DP-NET was 98.6 months (range 3–288), and mean overall survival (OS) was 130.1 months (range 3–444 months), without differences between genders (PFS p: 0.67 and OS p: 0.60). The Kaplan-Meier survival curves for PFS and OS showed no differences between genders (PFS p: 0.92; OS p: 0.87). Conclusion: In this MEN-1 cohort, no gender differences in the occurrence of PHPT, PA, DP-NET, lung NET, and thymic NET, nor in survival outcomes including PFS and OS within the DP-NET subcohort, emerged. Therefore, this study supports similar screening and follow-up for both male and female MEN-1 patients.

12406 Epidemiology Of Multiple Endocrine Neoplasia Type 1 In South Korea: A Nationwide Cohort Study

Abstract Disclosure: K. Kim: None. Y. Hwang: None. M. Yu: None. S. Moon: None. N. Hong: None. Y. Rhee: None. Multiple Endocrine Neoplasia Type 1 (MEN1) is one of the rarest endocrine disorders, with a scarcity of comprehensive epidemiological data globally. This deficiency in data is even more pronounced in Asian populations, where MEN1 remains an under-researched area. Therefore, our aim is to identity the prevalence, demographic characteristics, and patterns of comorbidities associated with MEN1.This nationwide cohort study assessed likely MEN1 cases from the Korean National Health Insurance Service database (2003-2020), selected via two operational definitions: one requiring an ICD-10 code for MEN1 (D44.8) and the other mandating at least two related procedures for MEN1-associated conditions (Primary Hyperparathyroidism, Pituitary Adenomas, and Duodenopancreatic Neuroendocrine Tumors). Cases were 1:10 matched by age, sex, and index year with controls who did not have any MEN-1 associated tumors. Our study evaluated 412 patients with likely MEN1 (mean age 43.6 ± 15.8 years; 35.4% male) against an age-sex matched control group of 4,120. Baseline characteristics showed a higher prevalence of comorbidities in MEN1 patients, including diabetes mellitus (22.6% vs 4.8%), hypertension (38.1% vs 16.4%), and dyslipidemia (20.6% vs 11.2%), all with p<0.001. Cancer prevalence was markedly elevated in MEN1 patients across most types, compared to controls. Adrenal involvements were observed in 34.7% of MEN1 patients, with adrenal adenoma being the most common (31.6%). Parathyroid, pituitary, and duodenopancreatic involvements were identified in 58.6%, 22.3%, and 19.9% of MEN1 patients, respectively. Mortality analysis revealed MEN1 patients had a higher mortality rate (16.0 per 1000 person-years) and a younger mean age at death (60.1 years) compared to controls (68.0 years), with an adjusted mortality hazard ratio of 3.1. Additionally, mortality risk varied with organ involvement; parathyroid involvement showed an adjusted HR of 2.7, pituitary involvement 4.7, and duodenopancreas involvement 4.0. The risk increased significantly with multi-organ involvement, where patients affected in more than two organs had HRs from 2.8 to 7.3. Our findings indicate that MEN1 significantly impacts patient morbidity and mortality, necessitating improved surveillance and tailored management to enhance early detection and optimize care for this vulnerable patient group. These insights underscore the pressing need for further research into MEN1 and other rare diseases to advance patient care and outcomes. Presentation: 6/2/2024

Living with a RET gene mutation: patient perspectives.

Multiple endocrine neoplasia type 2 (MEN2) is the collective term for two distinct types of autosomal dominantly inherited neuroendocrine neoplasm syndromes: MEN2A and MEN2B (or MEN3). MEN2 is characterised by medullary thyroid cancer (MTC) (99%) and phaeochromocytoma (50%) and also other conditions according to specific genotype. MEN2A also includes a 25% risk of developing parathyroid hyperplasia and is now recognised as four separate syndromes: classic MEN2A, MEN2A with cutaneous lichen amyloidosis, MEN2A with Hirschsprung's disease and familial MTC. MEN2B accounts for around 5% of all MEN2 cases and predisposes patients to diffuse intestinal ganglioneuromatosis, mucosal neuromas and musculoskeletal abnormalities. MEN2 is autosomal dominantly inherited, meaning that several generations in a single family may be affected by the same syndrome. We present a mini review of four case studies (×2 MEN2A and ×2 MEN2B) that illustrate the advantages of RET testing, as well as some of the likely obstacles that must be overcome to receive a diagnosis of MEN2A or MEN2B. In addition, despite improved genotype/phenotype correlation in MEN2, we highlight that not all cases are 'typical', which emphasises the need for all MEN2 patients to be cared for in a centre of expertise and experience. Some of our case study patients or their parents also took this opportunity to personally tell us more about their lives with MEN2, illustrating the need for more research into the psychosocial impact of these hereditary diseases.

Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disease of autosomal dominant inheritance, with an estimated prevalence of 3-20/100 000. Its main feature is neuroendocrine neoplasia in the parathyroid glands, the endocrine pancreas, the duodenum, and the pituitary gland. In this article, we review the diagnostic and therapeutic options for MEN1-associated tumors. We present an analysis and evaluation of retrospective case studies retrieved from PubMed, guidelines from Germany and abroad, and our own experience. The disease is caused by mutations in the MEN1 gene. Mutation carriers should participate in a regular, specialized screening program from their twenties onward. The early diagnosis and individualized treatment of MEN1-associated tumors can prevent the development of life-threatening hormonal syndromes and prolong the expected life span of MEN1 patients from 55 to 70 years, as well as improving their quality of life. Surgical treatment is based on the location, size, growth dynamics, and functional activity of the tumors. The evidence for treatment strategies is derived from retrospective studies only (level III evidence) and the optimal treatment is often a matter of debate. This is a further reason for treatment in specialized centers. MEN1 is a rare disease, and, consequently, the evidence base for its treatment is limited. Carriers of disease-causing mutations in the MEN1 gene should be cared for in specialized interdisciplinary centers, so that any appreciable tumor growth or hormonal activity can be detected early and organ-sparing treatment can be provided.

Role of Nutrition in the Management of Patients with Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations of MEN1 are primary hyperparathyroidism (PHPT), duodenal-pancreatic neuroendocrine tumors (DP-NETs) and anterior pituitary tumors. Endocrine tumors in patients with MEN1 differ from sporadic tumors because of their younger age at onset, common multiple presentations and the different clinical course. MEN1 is characterized by a complex clinical phenotype; thus, patients should be followed by a multidisciplinary team of experts that includes an endocrinologist, a surgeon, a oncologist, a radiotherapist, and not least, a nutritionist. It is important to remember the fundamental role that diet plays as a primary prevention tool, together with a healthy and active lifestyle in preventing osteoporosis/osteopenia and reducing the risk of developing kidney stones due to hypercalciuria, two frequent clinical complications in MEN1 patients. Is very important for MEN1 patients to have an adequate intake of calcium, vitamin D, magnesium and phosphate to maintain good bone health. The intake of foods containing oxalates must also be kept under control because in combination with calcium they concur to form calcium oxalate crystals, increasing the risk of nephrolithiasis. Another aspect to consider is the management of patients with pancreatic neuroendocrine tumors undergoing major surgical resections of the pancreas that can lead to alterations in digestion and absorption mechanisms due to partial or total reduction in pancreatic enzymes such as amylase, lipase, and protease, resulting in malabsorption and malnutrition. Therefore, the nutritionist's aim should be to devise a dietary plan that takes into consideration each single patient, educating them about a healthy and active lifestyle, and accompanying them through various life stages by implementing strategies that can enhance their quality of life.

Syndromic MEN1 Parathyroid Adenomas Consist of Both Subclonal Nodules and Clonally Independent Tumors

Abstract Background Primary hyperparathyroidism with parathyroid tumors is a characteristic presentation in Multiple Endocrine Neoplasia Type 1 (MEN1), historically referred to as "primary hyperplasia." The question of whether these tumors signify a multi-glandular clonal disorder or hyperplasia remains inconclusive. Loss of Menin protein expression serves as a reliable surrogate marker for biallelic inactivation and indicates a mutation in the MEN1 gene. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, associated with MEN4, encodes the p27 protein, whose expression is inadequately explored in the context of syndromic MEN1. Aims The aim was to explore the molecular basis of syndromic MEN1 parathyroid adenomas, identifying hyperplasia, multiple independent clones, and the extent of Menin loss. Additionally, p27 expression was assessed to evaluate its potential in indicating a germline mutation, especially in distinguishing MEN4 as a clinical alternative to MEN1. Methods In this investigation, we examined histomorphology and protein expression of Menin and p27 in parathyroid adenomas from 25 patients in two independent, well-characterized MEN1 cohorts. Loss of heterozygosity (LOH) patterns were evaluated using fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Furthermore, next-generation sequencing (NGS) was conducted on eleven nodules from four MEN1 patients. Results Morphologically, the majority of MEN1 adenomas displayed multiple distinct nodules, characterized by predominantly lost Menin expression and reduced p27 protein expression. FISH analysis indicated that most nodules exhibited MEN1 loss, with or without centromere 11 loss. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors. Conclusion Syndromic MEN1 parathyroid adenomas, therefore, consist of multiple clones with subclones, aligning with the current framework of the novel WHO classification of parathyroid tumors (2022). The observed loss of p27 expression in a significant fraction of MEN1 parathyroids emphasizes the need for caution when inferring MEN4 solely based on p27 expression.

Appendiceal NET in an 18-year-old woman, the youngest case of MEN4 with neuroendocrine manifestation: case report and review of the current literature

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. It is caused by loss-of-function mutation of the MEN1 gene, and characterized by variable association of primary hyperparathyroidism, pituitary adenomas and neuroendocrine tumours (NETs). Up to 3% of MEN1-like syndromes present a loss-of-function mutation in the tumour-suppressor gene CDKN1B, and therefore constitute MEN4 syndrome. Data on MEN4 clinical behaviour, penetrance and associated manifestations are still incomplete. We report the case of a young woman diagnosed with a rare NET G1 of the appendix at the age of 18 years. Genetic analysis revealed a germline missense mutation (c.397C>A), present in heterozygosity, of codon 133 in the CDKN1B gene. To date only 26 mutations of CDKN1B have been described in association with a MEN4 phenotype. Subsequently, the patient’s sister, father and paternal uncle were found to be carriers of the same mutation but showed no clinical or biochemical signs of disease. This is currently the youngest case of MEN4 with a gastrointestinal tract NET reported in the literature, and the first with appendiceal involvement. Despite the absence of disease within the proband’s family, ongoing screening would seem to be warranted, along the lines of that described by other authors for MEN1 patients. KEY WORDS: MEN4, CDKN1B mutations, youngest case of NET in MEN4, appendiceal NET, MEN4 review.

A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1.

Multiple Endocrine Neoplasia Type-1 (MEN1) is thought to increase the risk of meningioma and ependymoma. Hereby, we aimed to describe the frequency, the incidence and specific clinical and histological features of CNS tumors in the MEN1 population (except pituitary tumors). The study population included patients harboring CNS tumors diagnosed with MEN1 syndrome after 1990 and followed-up in the French MEN1 national cohort. Standardized incidence rate (SIR) was calculated based on the French Gironde CNS tumors registry. Genomic analyses were performed on somatic DNA from 7 CNS tumors including meningiomas and ependymomas from MEN1 patients, then in 50 sporadic meningiomas and ependymomas. Twenty-nine CNS tumors were found among the 1498 symptomatic patients (2%) (incidence=47.4/100'000 person-years; SIR=4.5), including 12 meningiomas (0.8%) (incidence=16.2/100'000; SIR=2.5), 8 ependymomas (0.5%) (incidence=10.8/100'000; SIR=17.6), 5 astrocytomas (0.3%) (incidence=6.7/100'000; SIR=5.8), and 4 schwannomas (0.3%) (incidence=5.4/100'000; SIR=12.7). Meningiomas in MEN1 patients were benign, mostly meningothelial, with 11 years earlier onset compared to the sporadic population and an F/M ratio of 1/1. Spinal and cranial ependymomas were mostly classified WHO grade 2. A biallelic MEN1 inactivation was observed in 4/5 ependymomas and 1/2 meningiomas from the MEN1 patients, whereas MEN1 deletion in one allele was present in respectively 3/41 and 0/9 sporadic meningiomas and ependymomas. Incidence of each CNS tumor was higher in the MEN1 population than in the French general population. Meningiomas and ependymomas should be considered part of the MEN1 syndrome, but somatic molecular data are missing to conclude for astrocytomas and schwannomas.

Does Genotype-Specific Phenotype in Patients with Multiple Endocrine Neoplasia Type 2 Occur as Current Guidelines Predict?

The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the RET proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the RET proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.

Individualized approach for MEN1-associated duodenopancreatic neuroendocrine neoplasms

Multiple endocrine neoplasia type 1 (MEN1)-associated duodenopancreatic neuroendocrine neoplasms (dpNEN) represent the most frequent syndrome-associated cause of death, but the adequate treatment is sometimes considered controversial. Presentation of possible diagnostic and therapeutic options for MEN1-associated dpNENs. In this review article retrospective case studies, expert recommendations, national and international guidelines as well as personal experiences were analyzed and evaluated. Due to early detection programs and the use of the most modern imaging techniques, dpNEN are nowadays diagnosed much earlier. Nonfunctional pNENs currently represent the most frequent dpNENs with about 70%, followed by gastrinomas and insulinomas. Regardless of their functional activity, dpNENs with asize of > 2 cm are generally an indication for surgery. The choice of the optimal treatment strategy, however, in most cases remains the subject of controversial discussions, although nowadays surgery should always be performed in an organ-preserving and minimally invasive way when feasible. Recurrences or new dpNENs are expected in more than 60% of cases, necessitating areoperation in up to 40% of these cases. Duodenopancreatic resections and reoperations can be carried out safely by experienced practitioners and with an acceptable level of risk. The planning of treatment requires careful consideration of the suitable timing, the extent of the operation, the risk of recurrence and potential morbidities. Furthermore, preserving pancreatic function and the quality of life is of utmost importance. In view of the complexity of the disease, MEN1 patients should be treated in specialized centers.

The risk of concurrent malignancies in patients with multiple endocrine neoplasia type 1: insights into clinical characteristics of those with multiple endocrine neoplasia type 1.

Summarize and analyze the characteristics of patients with Multiple Endocrine Neoplasia type 1 (MEN-1) who were diagnosed with malignant tumors that do not belong to MEN-1 components. Clinical data from patients with MEN-1 who visited Peking Union Medical College Hospital between April 2012 and April 2022 were collected. We compared the clinical characteristics of patients with malignant tumors outside of their MEN-1 components to those without additional tumors. MEN-1 gene testing was performed on most of these patients using Sanger sequencing, whole-exome sequencing, or MLPA. A total of 221 MEN-1 patients were diagnosed, of which 23 (10.40%) were found to have malignant tumors that did not belong to MEN-1 components, including papillary thyroid carcinoma (PTC) (4.52%), breast cancer (1.81%), urologic neoplasms (1.35%), primary hepatic carcinoma (PCC) (0.09%), meningeal sarcoma (0.05%), glioblastoma (0.05%), cervical cancer (0.05%), and lung carcinoma (0.05%). MEN-1 gene mutations were identified in 11 patients, including missense mutations, frameshift mutations, and splice mutations. The prevalence of each endocrine neoplasm, particularly gastroenteropancreatic neuroendocrine tumor, was higher in MEN-1 patients with other malignant tumors compared to MEN-1 patients without malignant tumors. Our retrospective study revealed a higher incidence of non-MEN-1 component malignant tumors in MEN-1 patients, especially breast cancer, PTC, and urologic neoplasms. These patients also exhibit more severe clinical phenotypes of MEN-1.

Pancreatic Neuroendocrine Tumors in MEN1 Patients: Difference in Post-Operative Complications and Tumor Progression between Major and Minimal Pancreatic Surgeries.

Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries. No post-operative mortality was observed. Metastatic cancers were found in 12 cases, prevalently from duodenal gastrinoma. Long-term cure of endocrine syndromes, by the 38 major pancreatic resections, was obtained in 78.9% of gastrinomas and 92.9% of insulinomas. In only one patient, hepatic metastases, due to gastrinoma, progressed to death. Out of the 38 major surgeries, only one patient was reoperated for the growth of a new PNEN in the remnant pancreas. No functioning PNEN persistence was reported in the five minimal pancreatic surgeries, PNEN relapse occurred in 60% of patients, and 40% of cases needed further pancreatic resection for tumor recurrence. No significant difference in PNEN relapse-free survival time after surgery was found between major and minimal pancreatic surgeries.

Ultrasound-guided microwave ablation in the treatment of recurrent primary hyperparathyroidism in a patient with MEN1: a case report.

Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine syndrome caused by the mutation in the tumor suppressor gene MEN1. The recurrence rate of primary hyperparathyroidism (PHPT) in patients with MEN1 after parathyroidectomy remains high, and the management of recurrent hyperparathyroidism is still challenging. We reported a 44-year-old woman with MEN1 combined with PHPT who was diagnosed through genetic screening of the patient and her family members. After parathyroidectomy to remove one parathyroid gland, the patient suffered from persistent high levels of serum calcium and parathyroid hormone, which returned to normal at up to 8 months after ultrasound-guided microwave ablation (MWA) for bilateral parathyroid glands, suggesting an acceptable short-term prognosis. Ultrasound-guided MWA for parathyroid nodules may be an effective therapeutic strategy for recurrent PHPT in MEN1 patients.

Imaging surveillance in multiple endocrine neoplasia type 1: Ten years of experience with somatostatin receptor positron emission tomography.

Guidelines for multiple endocrine neoplasia type 1 (MEN1) recommend intensive imaging surveillance without specifying a superior regimen, including the role of somatostatin receptor imaging (SRI) with positron emission tomography (PET). The primary outcomes were to: (1) Assess change in treatment of duodenal-pancreatic neuroendocrine neoplasms (DP-NENs), bronchopulmonary NENs, and thymic tumors attributed to use of SRI PET/computed tomography (CT) and (2) estimate radiation from imaging and risk of cancer death attributed to imaging radiation. This was a retrospective single center study, including all MEN1 patients, who had had at least one SRI PET/CT. A total of 60 patients, median age 42 (range 21-54) years, median follow-up 6 (range 1-10) years were included. Of 470 cross sectional scans (MRI, CT, SRI PET/CT), 209 were SRI PET/CT. The additional information from SRI PET had implications in 1/14 surgical interventions and 2/12 medical interventions. The estimated median radiation dose per patient was 104 (range 51-468) mSv of which PET contributed with 13 (range 5-55) mSv and CT with 91 mSv (range 46-413 mSv), corresponding to an estimated increased median risk of cancer death of 0.5% during 6 years follow-up. SRI PET had a significant impact on 3/26 decisions to intervene in 60 MEN1 patients followed for a median of 6 years with SRI PET/CT as the most frequently used modality. The surveillance program showed a high radiation dose. Multi-modality imaging strategies designed to minimize radiation exposure should be considered. Based on our findings, SRI-PET combined with CT cannot be recommended for routine surveillance in MEN1 patients.

Recurrence After Surgery for Primary Hyperparathyroidism in 517 Patients With Multiple Endocrine Neoplasia Type 1: An Association Francophone de Chirurgie Endocrinienne and Groupe d'étude des Tumeurs Endocrines study.

To assess recurrence according to the type of surgery for primary hyperparathyroidism (pHPT) in multiple endocrine neoplasia type 1 ( MEN1 ) patients and to identify the risk factors for recurrence after the initial surgery. In MEN1 patients, pHPT is multiglandular, and the optimal extent of initial parathyroid resection influences the risk of recurrence. MEN1 patients who underwent initial surgery for pHPT between 1990 and 2019 were included. Persistence and recurrence rates after less than subtotal parathyroidectomy (LTSP) and subtotal parathyroidectomy (STP) were analyzed. Patients with total parathyroidectomy with reimplantation were excluded. Five hundred seventeen patients underwent their first surgery for pHPT: 178 had LTSP (34.4%) and 339 STP (65.6%). The recurrence rate was significantly higher after LTSP (68.5%) than STP (45%) ( P < 0.001). The median time to recurrence after pHPT surgery was significantly shorter after LTSP than after STP: 4.25 (1.2-7.1) versus 7.2 (3.9-10.1) years ( P < 0.001). A mutation in exon 10 was an independent risk factor of recurrence after STP (odds ratio = 2.19; 95% CI: 1.31; 3.69; P = 0.003). The 5 and 10-year recurrent pHPT probabilities were significantly higher in patients after LTSP with a mutation in exon 10 (37% and 79% vs 30% and 61%; P = 0.016). Persistence, recurrence of pHPT, and reoperation rate are significantly lower after STP than LTSP in MEN1 patients. Genotype seems to be associated with the recurrence of pHPT. A mutation in exon 10 is an independent risk factor for recurrence after STP, and LTSP may not be recommended when exon 10 is mutated.

Traits of Patients With Pituitary Tumors in Multiple Endocrine Neoplasia Type 1 and Comparing Different Mutation Status.

Recent studies suggest that the clinical characteristics and biological behavior of pituitary tumors (PITs) in patients with multiple endocrine neoplasia type 1 (MEN1) may not be as aggressive as previously reported. Increased imaging of the pituitary as recommended by screening guidelines identifies more tumors, potentially at an earlier stage. However, it is unknown if these tumors have different clinical characteristics in different MEN1 mutations. To assess characteristics of patients with MEN1 with and without PITs, and compare among different MEN1 mutations. Data of patients with MEN1 in a tertiary referral center from 2010 to 2023 were retrospectively analyzed. Forty-two patients with MEN1 were included. Twenty-four patients had PITs, 3 of which were invasive and managed with transsphenoidal surgery. One PIT enlarged during follow-up. Patients with PITs had a higher median age at MEN1 diagnosis than those without PITs. MEN1 mutations were identified in 57.1% of patients, including 5 novel mutations. In patients with PITs, those with MEN1 mutations (mutation+/PIT+ group) had more additional MEN1-associated tumors than those without (mutation-/PIT+ group). The mutation+/PIT+ group had a higher incidence of adrenal tumors and a lower median age at initial manifestation of MEN1 than the mutation-/PIT+ group. The most common neuroendocrine neoplasm was nonfunctional in the mutation+/PIT+ group and insulin-secreting in the mutation-/PIT+ group. This is the first study comparing characteristics of patients with MEN1 with and without PITs harboring different mutations. Patients without MEN1 mutations tended to have less organ involvement and it might be reasonable for them to receive less intensive follow-up.