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Journal of Neuroendocrinology Apr 2023Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a... (Review)
Review
Zollinger-Ellison syndrome (ZES) is a distinct syndrome characterized by hyperchlorhydria-induced peptic ulcer disease and chronic diarrhea. It is the result of a gastrin-excess state caused by a duodenal or pancreatic neuroendocrine tumor referred to as gastrinoma. This gastrin-secreting neuroendocrine tumor is usually sporadic in nature, or part of multiple endocrine neoplasia type 1 syndrome. The high rate of malignancy associated with gastrinomas substantiates the need for early diagnosis. In order to diagnose ZES with laboratory tests, patients under antacid medication are required to stay off proton pump inhibitors for at least one week and H2 receptor antagonists for 48 h. Fasting serum gastrin level measurement serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99%. Gastrinoma patients will present with a gastrin level greater than 100 pg/mL, while a serum gastrin level higher than 1000 pg/mL, in the presence of gastric pH <2, is considered diagnostic. Since more common causes of hypergastrinemia exist in the setting of hypochlorhydria, ruling those out should precede ZES consideration. Such causes include atrophic gastritis, Helicobacter pylori (H. pylori)-associated pangastritis, renal failure, vagotomy, gastric outlet obstruction and retained antrum syndrome. The secretin stimulation test and the calcium gluconate injection test represent classic adjuvant diagnostic techniques, while alternative approaches are currently being introduced and evaluated. Specifically, the secretin stimulation test aids in differentiating ZES cases from other hypergastrinemic states. Its principle is based on secretin stimulation of gastrinoma cells to secrete gastrin, while inhibiting normal G cells. The rapid intravenous infusion of 4 μg/kg secretin over 1 min is followed by gastrin level evaluation at specific intervals post-infusion. Localization of the primary tumor and its metastases is the next diagnostic step when gastrinoma-associated ZES is either suspected or biochemically confirmed. Endoscopic ultrasound has showcased sensitivity as high as 83% for pancreatic gastrinomas and is considered the primary modality in such cases, although its tumor detection rates are substantially lower in duodenal lesions. Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, are currently setting the standard in tumor localization, enhancing traditional imaging techniques and showcasing high sensitivity and specificity. Although gastrinomas have been reported in various anatomic locations, the vast majority arise in a specific site named the "gastrinoma triangle", involving parts of the duodenum, pancreas and extra-hepatic biliary system. Proton pump inhibitors serve as the cornerstone of symptomatic ZES treatment. Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results. ZES in multiple endocrine neoplasia type 1 requires work-up for evaluation and treatment of hyperparathyroidism, while surgery might be an option for selected cases. In cases of advanced and metastatic disease, there is a variety of potential treatments, ranging for somatostatin analogs to chemotherapeutic drugs, liver-directed therapies and liver transplantation, while neither hepatic metastases, nor locally invasive disease necessarily preclude surgical management. This article thoroughly and critically reviews available literature and provides an extensive and multidimensional overview of ZES, along with current controversies regarding management of this disease.
Topics: Humans; Zollinger-Ellison Syndrome; Gastrinoma; Multiple Endocrine Neoplasia Type 1; Secretin; Gastrins; Proton Pump Inhibitors
PubMed: 37042078
DOI: 10.1111/jne.13267 -
Gan To Kagaku Ryoho. Cancer &... Jul 2019Multiple endocrine neoplasia(MEN)is an autosomal dominantly inherited tumor syndrome which develop tumors in multiple endocrine organs and its subtype, MEN1 and MEN2,...
Multiple endocrine neoplasia(MEN)is an autosomal dominantly inherited tumor syndrome which develop tumors in multiple endocrine organs and its subtype, MEN1 and MEN2, are well known. The causative gene for MEN1 is the MEN1 gene located on chromosome 11q13. Primary hyperparathyroidism, pancreatic gastroduodenal neuroendocrine tumor, pituitary tumor, adrenal cortical hyperplasia, or thymic neuroendocrine tumor are the typical features of MEN1 patients. Pathogenic variant of the MEN1 gene is distributed in exons 2-10. The causative gene for MEN2 is the RET gene located on chromosome 10q11.2. MEN2 is characterized by medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. MEN2 is divided into two clinical phenotypes, 2A and 2B. Pathogenic variant of the RET gene concentrated on exons 10, 11, 13-16 and there are strong association of the location of the pathogenic variant with disease phenotype. Recently, it is reported that the pathogenic variant of the CDKN1B gene located on chromosome 12p13 is the cause of MEN4. In this syndrome, MEN1- associated tumors of hyperparathyroidism, pituitary adenomas and neuroendocrine tumors of the pancreas or digestive tract with other endocrine tumors are found. The onset age is relatively high and it shows greater diversity of the tumors compared to MEN1.
Topics: Adenoma; Adrenal Gland Neoplasms; Humans; Multiple Endocrine Neoplasia; Pheochromocytoma; Pituitary Neoplasms
PubMed: 31296813
DOI: No ID Found -
Annales D'endocrinologie Sep 2019Multiple Endocrine Neoplasia Type 1 (NEM1) is related to mutations of the menin gene. It is an autosomal dominant disease. Its prevalence is about 1/30 000 with a hugh... (Review)
Review
Multiple Endocrine Neoplasia Type 1 (NEM1) is related to mutations of the menin gene. It is an autosomal dominant disease. Its prevalence is about 1/30 000 with a hugh penetrance. There is no genotype-phenotype correlation. This hereditary syndrome is characterized by the presence of tumors of the endocrine system (parathyroid, endocrine pancreas, pituitary and adrenal gland). Other disorders have also been described (bronchial and thymic carcinoid tumor, breast cancer, skin lesions). Management must take into account the specificities of these pathologies in NEM1 compared to sporadic forms (young age at diagnosis, multiple lesions within the same gland, multi-focal disease). © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.
Topics: Carcinoid Tumor; Congresses as Topic; Endocrinology; Gastrointestinal Neoplasms; Humans; Multiple Endocrine Neoplasia Type 1; Mutation; Neuroendocrine Tumors; Penetrance; Pituitary Neoplasms; Proto-Oncogene Proteins; Societies, Medical
PubMed: 31606058
DOI: 10.1016/S0003-4266(19)30113-1 -
Pancreas 2017
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Outcome Assessment, Health Care; Pancreatic Neoplasms
PubMed: 28426491
DOI: 10.1097/MPA.0000000000000825 -
Aging Jun 2019
Topics: Age Factors; Age of Onset; Humans; Multiple Endocrine Neoplasia Type 2a; Mutation; Prognosis; Proto-Oncogene Proteins c-ret
PubMed: 31188782
DOI: 10.18632/aging.102030 -
The Journal of Urology May 2018
Topics: Humans; Multiple Endocrine Neoplasia Type 1
PubMed: 29677893
DOI: 10.1016/j.juro.2018.02.032 -
Journal of Infusion Nursing : the... 2015Multiple endocrine neoplasia (MEN) is a term used to describe a group of hereditary carcinoma syndromes. Patients carrying a characteristic autosomal dominant gene... (Review)
Review
Multiple endocrine neoplasia (MEN) is a term used to describe a group of hereditary carcinoma syndromes. Patients carrying a characteristic autosomal dominant gene aberration exhibit various endocrine carcinomas, as well as other anatomical abnormalities. Unfortunately, familial endocrine carcinoma patients are too often unrecognized by primary care providers, resulting in delayed diagnosis and treatment, with profound consequences related to morbidity and mortality. This article will introduce the various MEN syndromes and the infusion nurse's role in the care of these individuals and their families.
Topics: Female; Humans; Male; Multiple Endocrine Neoplasia
PubMed: 26536410
DOI: 10.1097/NAN.0000000000000143 -
Endocrine-related Cancer Feb 2018
Topics: Animals; Humans; Multiple Endocrine Neoplasia Type 2a; Point Mutation; Proto-Oncogene Proteins c-ret
PubMed: 29348305
DOI: 10.1530/ERC-17-0488 -
Deutsche Medizinische Wochenschrift... Sep 2017Multiple endocrine neoplasia type 1 and 2 are hereditary cancer syndromes. They are characterized by the occurrence of many benign and malignant tumor types, in MEN1...
Multiple endocrine neoplasia type 1 and 2 are hereditary cancer syndromes. They are characterized by the occurrence of many benign and malignant tumor types, in MEN1 parathyroid tumors, pituitary tumors, and pancreas tumors, in MEN2 medullary thyroid carcinoma, pheochromocytoma, and parathyroid tumors. The autosomal dominant inherited tumor syndromes are caused by mutations in the MEN1 gene, a tumor suppressor gene, and mutations in the RET gene, an activated oncogene, in MEN2. The clinical expression of the different tumors can vary within and between families, with a good genotype-phenotype correlation in MEN2. Early diagnosis and therapy is possible by using biochemical and imaging screening in the families. Early thyroidectomy in young patients with MEN2 results in a high cure rate of MTC.
Topics: Early Detection of Cancer; Humans; Multiple Endocrine Neoplasia; Mutation; Proto-Oncogene Proteins; Thyroidectomy
PubMed: 28902384
DOI: 10.1055/s-0043-109522 -
Endocrine Dec 2023Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary... (Review)
Review
PURPOSE
Multiple endocrine neoplasia type 4 (MEN4) is a rare multiglandular endocrine neoplasia syndrome, associated with a wide tumor spectrum but hallmarked by primary hyperparathyroidism, which represents the most common clinical feature, followed by pituitary (functional and non-functional) adenomas, and neuroendocrine tumors. MEN4 clinically overlaps MEN type 1 (MEN1) but differs from it for milder clinical features and an older patient's age at onset. The underlying mutated gene, CDKN1B, encodes the cell cycle regulator p27, implicated in cellular proliferation, motility and apoptosis. Given the paucity of MEN4 cases described in the literature, possible genotype-phenotype correlations have not been thoroughly assessed, and specific clinical recommendations are lacking. The present review provides an extensive overview of molecular genetics and clinical features of MEN4, with the aim of contributing to delineate peculiar strategies for clinical management, screening and follow-up of the last and least known MEN syndrome.
METHODS
A literature search was performed through online databases like MEDLINE and Scopus.
CONCLUSIONS
MEN4 is much less common that MEN1, tend to present later in life with a more indolent course, although involving the same primary organs as MEN1. As a consequence, MEN4 patients might need specific diagnostic and therapeutic approaches and a different strategy for screening and follow-up. Further studies are needed to assess the real oncological risk of MEN4 carriers, and to establish a standardized screening protocol. Furthermore, a deeper understanding of molecular genetics of MEN4 is needed in order to explore p27 as a novel therapeutic target.
Topics: Humans; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Adenoma; Syndrome
PubMed: 37632635
DOI: 10.1007/s12020-023-03497-2