Multiple endocrine neoplasia, type

C. Eng. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung s disease. Seminars in medicine of the Beth Israel Hospital, Boston. NEn J Med, 335 (13), 943-951, 1996. 

Eisenhofer G, Lenders JW, Linehan WM, Walther MM, Goldstein DS, Reiser HR. Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. N Engl J Med 1999 340 1872-9. 

Eisenhofer G, Walther MM, Huynh TT, Li ST, Bornstein SR, Vortmeyer A, et al. Pheochromocy-tomas in von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 display distinct biochemical and clinical phenotypes. J CUn Endocrinol Metab 2001 86 1999-2008. 

Multiple endocrine neoplasia type I with pituitary and pancreatic tumors... 

Multiple endocrine neoplasia type II with medullary thyroid carcinoma and pheochroniocytoma Malignancy... 

Calcitonin is secreted by the parafollicular or C cells, which arise from the neural crest and are distributed throughout the thyroid gland. These cells are included in the APUD (cmine precursor uptake and decarboxylation) family, which explains the association of medullary thyroid carcinoma (a tumor of the C cells) and other tumors of the APUD family in multiple endocrine neoplasia type 2A and -2B (MEN-2A and MEN-2B). Release of calcitonin is stimulated by calcium, and it has been used pharmacologically as an inhibitor of bone resorption. 

Decker RA, Peacock ML, Borst MJ, Sweet JD, Thompson NW. Progress in genetic screening of multiple endocrine neoplasia type 2A is calcitonin testing obsolete Surgery 1995 118 257-64. 

Gagel RE. Multiple endocrine neoplasia type II and familial medullary thyroid carcinoma impact of genetic screening on management. Cancer Treat Res 1997 89 421-41. 

Kaplan MM, Stall GM, Cmnmings T, MacAulay A, MacAulay A, Motte P, Wolfe HJ, et al. High-sensitivity serum calcitonin assays applied to screening for thyroid C-celi disease in multiple endocrine neoplasia type 2A. Henry Ford Hosp Med J 1992 40 227-31. 

Wells SA Jr, Donis-Keller H. Current perspectives on the diagnosis and management of patients with multiple endocrine neoplasia type 2 syndromes. Endocrmol Metab Clin North Am 1994 23 215-8. 

J. R. Hansford and L. M. Mulligan Multiple endocrine neoplasia type 2 and RET from neoplasia to neurogenesis. Journal of Medical Genetics 37, 817 (2000). 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

Multiple endocrine neoplasia type 2 RET proto-oncogene... 

Kovacs CS, Mase RM, Kovacs K, et al. Thyroid medullary carcinoma with thyroglobulin immunoreactivity in sporadic multiple endocrine neoplasia type 2-B. Cancer. 1994 74 928-932. 

C cells in normal glands have an exclusive intrafollicular topography and are concentrated at the junctions of the upper and middle thirds of the lobes (Fig. 10.19). In patients with multiple endocrine neoplasia, type 2 (MEN2), C-cell hyperplasia has been recognized as the precursor of medullary thyroid carcinoma. Detailed immunohistochemical studies have shown that C-cell hyperplasia is characterized by increased numbers of C cells within the follicles in the same regions of the gland where C cells normally predominate (Fig. 10.20). These relationships are maintained in areas of more advanced C-cell hyperplasia, where C cells often completely encircle and displace the follicular epithelium centrally. Nodular hyperplasia is characterized by the complete obliteration... 

Le Bodic M-F, Heyman M-F, Lecomete M, et al. Immuno histochemical study of 100 pancreatic tumors in 28 patients with multiple endocrine neoplasia type I. Am J Surg Pathol. 1996 20 1378-1384. 

About 5% to 10% of GI neuroendocrine tumors are associated with a hereditary disease. The inherited syndromes and their associated genes include multiple endocrine neoplasia type I MENl gene), neurofibromatosis type 1 NFl gene), von Hippel-Lindau disease VHL gene), and the tuberous sclerosis complex TSCl or TSC2 gene).406... 

Komminoth P. Review multiple endocrine neoplasia type 1, sporadic neuroendocrine tumors, and MENIN. Diagn Mol Pathol. 1999 8 107-112. 

Shan L, Nakamura Y, Nakamura M, et al. Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. Lab Invest. 1998 78 471-475. 

MENl Multiple endocrine neoplasia type 1 locus transcripts... 

In some cases, a point mutation changes a normal RTK Into one that dimerizes and is constitutively active in the absence of ligand. For instance, a single point mutation converts the normal Her2 receptor into the Neu oncoprotein, which Is an Initiator of certain mouse cancers (Figure 23-14, lefi). Similarly, human tumors called multiple endocrine neoplasia type 2 produce a constitutively active dimeric Glia-derived neurotrophic factor (GDNF) receptor that results... 

Note-. Aetiological factors linked to the development of thyroid cancer. MEN2A, multiple endocrine neoplasia type 2A MEN2B, multiple endocrine neoplasia type 2B MTC, medullary thyroid carcinoma. 

The clinical presentation of patients with endocrine pancreatic tumors will vary according to the type of hormone released. Hyperinsulinism manifested with diarrhea, abdominal pain, and low levels of glucose will be found in the majority of patients. Nesidioblastosis is a primitive pancreatic B cells hyperplasia. Approximately 5% of patients with hyperinsulinism may have this type of tumor. Hunger, jitteriness, lethargy, apnea, and seizures are common manifestations in newborns with nesidioblastosis, while older children may show diaphoresis, confusion, or unusual behavior. Zollinger-Elli-son syndrome will present with intractable peptic ulcers. Patients with vipomas will have watery diarrhea, hypokalemia, and achlorhydria, while multiple endocrine neoplasias have been reported with multiple endocrine neoplasia type 1 (MEN 1). 

Hyperganglionosis is described as having two distinct patterns ganglioneuromas (nodular proliferations of ganglion cells often associated with multiple endocrine neoplasia type 2B and not seen in children) and intestinal neuronal dysplasia (NID). NID is a controversial entity but a consistently described feature is of increased density of the submucosal ganglia. Patients may present with intestinal dysmotility clinically indistinguishable from Hirschsprung s disease. 

The RET proto-oncogene located on chromosome 10 codes for a transmembrane tyrosine kinase. Mutations at codon 634 are directly associated with multiple endocrine neoplasia type 2A and medullary thyroid carcinoma. If children are diagnosed to carry such a mutation, cancer can be prevented by removal of the thyroid gland. Accuracy and reliability of the diagnostic assay is critical here as in... 

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