Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007095 (carcinoid)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of multiple carcinoid tumors of the duodenum accompanied by familial multiple endocrine neoplasia is reported. A 46-year-old man with duodenal polyps discovered during a mass screening was followed up for 5 years. In August 1994, a histological examination revealed carcinoid tumors, and he was thus referred to our hospital for surgery. He underwent a parathyroidectomy and cholecystectomy for primary hyperparathyroidism and cholecystolithiasis, respectively. The patient's sister had also undergone a parathyroidectomy and distal pancreatectomy for primary hyperparathyroidism and insulinoma of the pancreas. In addition, his two children were also followed up for hypercalcemia. A serum examination of the patient revealed high levels of somatostatin and pancreatic polypeptide, but normal levels of gastrin and serotonin. In November 1994, a pancreaticoduodenectomy with a D2 lymph node dissection was performed. The macroscopic findings of the resected specimen showed multiple polypoid lesions with delles on the top, measuring 3 to 15 mm in size throughout the duodenum. A microscopic examination revealed the tumor to have infiltrated into the submucosa extensively, and an immunohistochemical analysis also demonstrated the tumor cells to be positive for somatostatin, but not for pancreatic polypeptide. After surgery, the serum level of somatostatin returned to normal but the pancreatic polypeptide remained high. The post-operative course was uneventful, and the patient remains in good health.
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PMID:Multiple carcinoids of the duodenum accompanied by type I familial multiple endocrine neoplasia. 968 14

In 1983 a large family with MEN-1 (designated Tasman 1) was identified in Tasmania. Kindred screening and case follow-up over the subsequent 15 years has yielded data on over 160 MEN-1-affected patients. Hyperparathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathological finding. Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gastrinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients, respectively. Metastatic gastroenteropancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitary disease developed in 19% of patients. Prolactinoma and 'nonfunctioning' adenoma account for 76 and 24%, respectively, of pituitary abnormalities. Prolactinomas exhibit clustering within branches of the Tasman 1 kindred. Adrenal adenomas occur in 36% of patients. The majority of adrenal lesions are benign and nonsecretory and develop in association with pancreatic neoplasia. Carcinoid tumours are uncommon but important malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to recognition of MEN-1 in Tasman 1, complications of hyperparathyroidism and malignancy accounted for the majority of patient mortality. Since commencement of prospective screening, malignant GEP tumours and cardiovascular disease have become the most prevalent causes of death amongst MEN-1-affected patients.
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PMID:Expression of the MEN-1 gene in a large kindred with multiple endocrine neoplasia type 1. 968 44

In vitro studies have shown that gastroenteropancreatic tumors, with the exception of insulinomas, have a high density of somatostatin receptors and can be imaged in vivo using somatostatin receptor scintigraphy (SRS) with either [123I-Tyr3]octreotide or [111In DTPA,DPhe1]octreotide. However, the sensitivity in relation to conventional imaging studies (ultrasound, CT, MRI, angiography) remains unclear. To address this question, we performed a prospective study of 80 patients with gastrinomas where SRS was compared with other conventional imaging techniques for detecting extrahepatic gastrinomas or liver metastases. Extrahepatic gastrinomas were identified by SRS in 58 percent of patients, whereas conventional imaging studies detected gastrinomas in 9 percent to 48 percent of patients. In detecting hepatic metastases in 24 patients with histologically-proven metastases, SRS was positive in 92 percent; ultrasound, CT or angiography in 42 percent to 62 percent; and MRI in 71 percent of patients. These results are compared with other studies in detecting gastrinomas as well as series including other PETs, excluding insulinomas, with insulinomas alone, and with carcinoid tumors. An analysis of the ability of SRS to identify gastrinomas found in different sites at surgery was performed. The role of endoscopic ultrasound (EUS) in detecting various PETs, in comparison to that of SRS, is yet to be established, particularly for extrapancreatic PETs. Therefore, the results of EUS in various studies containing patients with PETs are compared to those with SRS and conventional imaging studies. These data suggest that EUS is the first choice of localization methods for detecting insulinoma, which is an intrapancreatic tumor in almost all cases. In other PETs there still is not sufficient data to establish the relative roles of EUS and SRS.
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PMID:Comparative analysis of diagnostic techniques for localization of gastrointestinal neuroendocrine tumors. 982 78

A malignant insulinoma (LOHG-I), a carcinoid of the lung (LOHG-L), a parathyroid adenoma (LOHG-NSA), and a fibroma (LOHG-F) were obtained from a patient with multiple endocrine neoplasia type 1 (MEN1). Long-term cultures were established. Essential neurobiological properties of the cell lines were proven immunocytochemically and by electron microscopy. Molecular analysis of the germline DNA showed a 4 bp deletion in exon 3 of the MEN1 gene. Cytogenetic and CGH analyses of the tumors/tumor cell lines revealed diploidy and balanced and unbalanced structural aberrations different for each tumor. Chromosomes 6q21, 11q and 17q were most frequently involved in clonal structural aberrations.
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PMID:Cytogenetic and CGH studies of four neuroendocrine tumors and tumor-derived cell lines of a patient with multiple endocrine neoplasia type 1. 1037 92

Multiple endocrine neoplasia type 1 (MENI) is a promising model to understand endocrine and other tumors. Its most common endocrine expressions are tumors of parathyroids, entero-pancreatic neuro-endocrine tissue, and anterior pituitary. Recently, collagenomas and multiple angiofibromas of the dermis also have been recognized as very common. MEN1 can be characterized from different perspectives: (a) as a hormone (parathyroid hormone, gastrin, prolactin, etc.) excess syndrome with excellent therapeutic options; (b) as a syndrome with sometimes lethal outcomes from malignancy of entero-pancreatic neuro-endocrine or foregut carcinoid tissues; or (c) as a disorder than can give insight about cell regulation in the endocrine, the dermal, and perhaps other tissue systems. The MEN1 gene was identified recently by positional cloning, a comprehensive strategy of narrowing the candidate interval and evaluating all or most genes in that interval. This discovery has opened new approaches to basic and clinical issues. Germline MEN1 mutations have been identified in most MEN1 families. Germline MENI mutations were generally not found in families with isolated hyperparathyroidism or with isolated pituitary tumor. Thus, studies with the MENI gene helped establish that mutation of other gene(s) is likely causative of these two MEN1 phenocopies. MEN1 proved to be the gene most frequent L4 mutated in common-variety, nonhereditary parathyroid tumor, gastrinoma, insulinoma, or bronchial carcinoid. For example, in common-variety parathyroid tumors, mutation of several other genes (such as cyclin D1 and P53) has been found, but much less frequently than MEN1 mutation. The majority of germline and somatic MEN1 mutations predicted truncation of the encoded protein (menin). Such inactivating mutations strongly supported prior predictions that MEN1 is a tumor suppressor gene insofar as stepwise mutational inactivation of both copies can release a cell from normal growth suppression. Menin is principally a nuclear protein; menin interacts with junD. Future studies, such as discovery of menin's metabolic pathway, could lead to new opportunities in cell biology and in tumor therapy.
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PMID:The gene for multiple endocrine neoplasia type 1: recent findings. 1042 35

MEN1 is a syndrome of parathyroid adenomas, gastrinomas, prolactinomas, and other endocrine tumors. Collagenomas and facial angiofibromas are newly recognized but common skin expressions. Many tumors in MEN1 are benign; however, many entero-pancreatic neuroendocrine tumors and foregut carcinoid tumors are malignant. MEN1 is thus the expression of a cancer gene but without available prevention or cure for malignancy. Hereditary (as compared to sporadic) endocrine tumors show early onset age and multiplicity, because each cell of the body has "one hit" by inheritance. Multiple neoplasia syndromes with endocrine tumor(s) all include nonendocrine components; their known defective genes seem mainly to disturb cell accumulation. Hereditary neoplasia/hyperplasia of one endocrine tissue reflects a defect that is tissue selective and directed at cell secretion. Though the hereditary endocrine neoplasias are rare, most of their identified genes also contribute to common sporadic endocrine neoplasms. Hereditary tumors may be caused by activation of an oncogene (e.g., RET) or, more often, by inactivation of a tumor suppressor gene (e.g., P53, MEN1). Recently, MEN1 was identified by positional cloning. This strategy included narrowing the gene candidate interval, identifying many or all genes in that interval, and testing the newly identified candidate genes for mutation in MEN1 cases. MEN1 was identified because it showed mutation in 14 of 15 MEN1 cases. NIH testing showed germline MEN1 mutations in 47 of 50 MEN1 index cases and in seven of eight cases with sporadic MEN1. Despite proven capacity to find germline MEN1 mutation, NIH testing found no MEN1 mutation among five families with isolated hyperparathyroidism, suggesting that this often arises from mutation of other gene(s). Analogous studies in Japan found that familial isolated pituitary tumors also did not show MEN1 germline mutation. MEN1 mutation testing can now be considered for cases of MEN1 and its phenocopies and for asymptomatic members of families with known MEN1 mutation. Germline MEN1 testing does not have the urgency of RET testing in MEN2a and 2b, as MEN1 testing does not commonly lead to an important intervention. Somatic MEN1 mutation was found in sporadic tumors: parathyroid adenoma (21%), gastrinoma (33%), insulinoma (17%), and bronchial carcinoid (36%). For each of these, MEN1 was the known gene most frequently mutated. MEN1 has a widely expressed mRNA that encodes a protein (menin) of 610 amino acids. The protein sequence is not informative about domains or functions. The protein was mainly nuclear. Menin binds to JunD, an AP-1 transcription factor, inhibiting JunD's activation of transcription. Most of the germline and somatic MEN1 mutations predict truncation of menin, a likely destructive change. Inactivating MEN1 mutations in germline and in sporadic neoplasms support prior predictions that MEN1 is a tumor suppressor gene. Germline MEN1 mutation underlies all or most cases of MEN1 (familial or sporadic). Somatic MEN1 mutation is the most common gene mutation in many sporadic endocrine tumor types.
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PMID:Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neoplasias. 1054 85

We reviewed our 8.5 year experience with magnetic resonance imaging (MRI) in the demonstration of neuroendocrine tumors of the pancreas using precontrast fat-suppressed T1-weighted, fat-suppressed T2-weighted, and serial post-gadolinium T1-weighted images, to describe the spectrum of appearances of these tumors. All MR examinations of patients with histologically proven neuroendocrine tumors were retrospectively reviewed. Histological type, tumor location, tumor diameter, signal intensity on precontrast images, enhancement patterns, and presence and appearance of metastases were determined. Twenty-two patients had histologically proved neuroendocrine tumors detected by MRI over the 8.5 year period. Histological types were gastrinoma (n = 8), insulinoma (n = 3), glucagonoma (n = 2), somatostatinoma (n = 1), VIPoma (n = 1), ACTHoma (n = 1), carcinoid (n = 1), and five untyped tumors. Primary tumors ranged in diameter from 1 to 6.2 cm. There was one histopathology-proven false-positive neuroendocrine tumor. The positive predictive value for MRI in the detection of these tumors was 96%. The most common appearance on precontrast images was low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, which was observed in tumors in 18 of 22 patients. Moderate or intense early enhancement of all or portions of the primary tumors was observed in tumors in 19 of 22 patients either as uniform homogeneous, ring, or diffuse heterogeneous enhancement. Enhancement was minimal on these images in the other three patients. Gastrinomas enhanced in a ring pattern in 7 of 8 patients whereas the majority (9 of 11 patients) of noninsulinoma-nongastrinoma and untyped tumors enhanced in a diffuse heterogeneous fashion. Liver metastases were present in 13/22 patients including 3/8 with gastrinoma and 9/11 with noninsulinoma-nongastrinoma tumors. Most neuroendocrine tumors of the pancreas are low signal intensity on fat-suppressed T1-weighted images and moderately high in signal intensity on fat-suppressed T2-weighted images, although variations do exist. Tumors most often enhance in an early moderately intense fashion. Gastrinomas are often different in appearance than other neuroendocrine tumors in that they usually enhance in a ring fashion whereas nongastrinoma-noninsulinoma tumors usually enhance in a heterogeneous fashion.
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PMID:Neuroendocrine tumors of the pancreas: spectrum of appearances on MRI. 1071 46

The preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.
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PMID:Anesthetic implications for surgical patients with endocrine tumors. 1081 14

MEN-1 is an autosomal dominantly inherited disorder, characterised by the occurrence of multiple tumours, particularly in the parathyroid glands, the pancreatic islets, the pituitary gland and the adrenal glands, as well as by neuroendocrine carcinoid tumours. Various clinical manifestations are presented by description of three patients harbouring a MEN1 gene germline mutation. A 44-year-old man had symptoms of hyperparathyroidism and in addition to parathyroid adenomas proved to have tumours in the thymus, adrenal and pituitary glands. A 48-year-old woman from a family with MEN-1 had suffered since her 40th year from headache and heartburn; she appeared to have adenomas in the parathyroid glands and gastrinomas in the pancreas, leading to a Zollinger-Ellison syndrome. One of her relatives, a man aged 29, had suffered from childhood from convulsions due to attacks of hypoglycaemia, and an insulinoma was assessed. In all patients, surgical and/or medical treatment alleviated symptoms. Clearly, the position or nature of the mutations in the MEN1 gene do not correlate with the clinical expression of the disease. Family investigation, DNA analysis and periodic examination improve quality of life and the life expectancy.
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PMID:[Diverse expression of multiple endocrine neoplasia type 1]. 1115 52

The study describes the results of Octreoscan SPET (OCTSPET) qualitative and semi-quantitative evaluation in 38 patients with suspected pancreatic neuroendocrine tumors. SPET studies were acquired at 4 and 24 hours after the injection of 111-220 MBq of 111-In-pentetreotide (Octreoscan). Qualitative and semi-quantitative evaluations were performed. The semi-quantitative approach was based on the time course of Tumor/Non Tumor ratios (TNTinc) from 4 and 24 hours. The OCTSPET results were true positive in 18 of 19 patients (10 gastrinoma, 5 insulinoma, 1 neuroendocrine tumor, 1 glucagonoma and 1 carcinoid) and false negative in one insulinoma. Besides, 20 of 38 patients (52%) had clinical plans modified after OCTSPET; OCTSPET was the only positive diagnostic test in 14 of 19 patients (73%) and guided the surgery decision in 14 of 25 patients (56%). In conclusion, these data indicate that Octreoscan represents an excellent tool for the diagnosis of pancreatic neuroendocrine tumors.
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PMID:Octreoscan SPET evaluation in the diagnosis of pancreas neuroendocrine tumors. 1178 28


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