Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of choice for gastric acid hypersecretion in MEN type I has now changed from total gastrectomy to the long-term administration of H2 receptor blockers or similar agents. However, the importance of parathyroidectomy for the concomitant hypercalcaemia is not fully realized. A case is reported of a subject with MEN type I, who was initially treated with parathyroidectomy and H2 receptor blockade. Following parathyroidectomy, there was a rapid fall of the markedly elevated gastrin levels to the upper limit of the normal range. During follow-up of 2.5 years, there has been no increase in serum gastrin, and the subject's gastric symptoms have resolved, despite the cessation of H2 blockade. Infusion of calcium to pre-operative levels and superimposed secretin stimulation after this period of time closely reproduced the pre-operative hypergastrinaemia. On screening, the subject's only child was found to have hypercalcaemia but normal serum gastrin levels and pituitary function; parathyroidectomy has been carried out. No abnormality of gastrin secretion has been found during follow-up. This case highlights the importance of early parathyroidectomy in this syndrome.
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PMID:Resolution of hypergastrinaemia after parathyroidectomy in multiple endocrine neoplasia syndrome type I (MEN type I). 288 48

We have described a case of MEN-I in association with a benign pulmonary carcinoid tumor. Two other members of our patient's family also had MEN-I and benign carcinoid or adenomatous lung tumors. Hormonal assays of our patient's carcinoid lesion showed the production of gastrin, gastrin-releasing peptide, neurotensin, and somatostatin, but not serotonin, a hormonal profile distinct from those previously reported in carcinoid lung tumors unassociated with MEN-I.
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PMID:Neuroendocrine (carcinoid) tumor of the lung and type I multiple endocrine neoplasia. 289 Nov 94

This study evaluates prospectively the effect of parathyroidectomy on basal acid output (BAO), maximal acid output (MAO), fasting serum gastrin, secretin-stimulated serum gastrin, and sensitivity to antisecretory medication in 10 consecutive patients with primary hyperparathyroidism (PHP), Zollinger-Ellison syndrome (ZES), and multiple endocrine neoplasia type I (MEN-I). After parathyroidectomy, 9 of 10 patients remained normocalcemic, and each had a lower BAO; 6 of 9 no longer had gastric acid hypersecretion (less than 15 mEq/hr). Seven of 9 normocalcemic patients had a lower MAO, and a decrease in fasting serum gastrin. Two patients showed no evidence of ZES, a normal BAO, normal fasting serum gastrin concentration, and a negative secretin response after parathyroidectomy. Parathyroidectomy also reduced the dose of histamine H2-receptor antagonist required to control gastric acid secretion in 60% of patients. After successful parathyroidectomy three patients were studied for drug sensitivity, and each had greater acid inhibition with a given dose of histamine H2-receptor antagonist than preoperatively. One patient remained hypercalcemic after surgery and had no change in BAO, MAO, or gastrin. All patients with postoperative normocalcemia will have a lower BAO, 80% a lower MAO, 80% a decreased fasting serum gastrin, and 33% a negative secretin test. Antisecretory medication dose can be reduced because patients have reduced BAO and increased sensitivity to histamine H2-receptor antagonist. The study supports parathyroidectomy as the initial surgical procedure of choice in patients with PHP, ZES, and MEN-I.
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PMID:Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. 289 Dec 1

One hundred four endocrine tumors found in the body and tail of the pancreas of a patient with the Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia (MEN-I) were investigated by immunohistochemistry for insulin, glucagon, somatostatin, pancreatic polypeptide (PP), and gastrin. The results for each tumor were scored into six grades according to the frequency of immunoreactive cells. Pancreatic polypeptide, glucagon, insulin, and somatostatin were demonstrated in 96, 80, 62, and 42 tumors, respectively. When only the higher scores of cell frequency (3-5) were considered, PP and glucagon (accounting for 71 and 49 tumors, respectively) differed markedly from insulin (two tumors) and somatostatin (0). The frequency of PP-immunoreactive cells was higher in tumors of large size whereas that of glucagon cells was higher in the smaller neoplasms. No significant associations of the tumoral hormonal expressions were found with the type of histologic structure (trabecular versus gyriform), the occurrence of stromal fibrosis, and the intrapancreatic location of the neoplasms, except for a higher number of somatostatin cells in fibrotic tumors. Gastrin-immunoreactive cells never were found in the tumors in spite of the concomitant hypergastrinemia. In conclusion, the nonrandom expression of the hormonal phenotype by the neoplastic islet cells, as shown by the immunohistochemical, semiquantitative analysis of a large number of tumors, suggests that in our MEN-I patient the genetically determined neoplasms also are affected by other mechanisms, possibly nongenetic.
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PMID:Nonrandom expression of polypeptide hormones in pancreatic endocrine tumors. An immunohistochemical study in a case of multiple islet cell neoplasia. 289 80

We tested plasma from 83 members of a large kindred with familial multiple endocrine neoplasia type 1 (FMEN1) for mitogenic activity on cultured bovine parathyroid cells. We evaluated the age dependency of parathyroid mitogenic activity (PMA) in plasma from affected and unaffected members of the kindred, and we analyzed the relation of plasma PMA to indices of activity of parathyroid, pancreatic islet, and anterior pituitary tissue. Plasma PMA was higher in members expressing the FMEN1 gene than in their unaffected first, second, third, or fourth degree relatives (P less than 0.05), and 10 of 20 members expressing the FMEN1 gene had plasma PMA above the 95% limit of the control range. Plasma PMA was not dependent on sex or age; the lack of age dependency and the high values in FMEN1 gene carriers suggested that plasma PMA is elevated in some FMEN1 gene carriers very early in life. Plasma PMA in known gene carriers varied significantly with one index of parathyroid function [plasma PMA was 2.5 times higher in the group with than in the group without prior parathyroidectomy (P less than 0.005), an indicator of more severe prior parathyroid disease] and correlated positively, although not significantly so, with indices of pancreatic islet function (serum gastrin by RIA) and anterior pituitary function (serum PRL by RIA). In summary, (1) plasma PMA levels are high in many known carriers of the FMEN1 gene, (2) the high plasma PMA levels in FMEN1 may precede overt endocrine hyperfunction; and (3) high plasma PMA levels vary with one index of parathyroid function, but do not correlate with indices of pancreatic islet or anterior pituitary function in members expressing the FMEN1 gene. The high plasma PMA levels in FMEN1 may be the direct cause of hyperfunction of the parathyroids, but the relation of high plasma PMA to hyperfunction of the pancreatic islets and anterior pituitary is uncertain.
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PMID:Mitogenic activity on parathyroid cells in plasma from members of a large kindred with multiple endocrine neoplasia type 1. 289 72

A 28-year-old woman presented with hypoglycemia and acromegaly associated with pituitary sellar enlargement. Preoperative plasma levels of insulin and growth hormone (GH) were markedly elevated and there was mild hyperprolactinemia. Laboratory tests suggested hyperparathyroidism. Partial pancreatectomy was performed and two tumors were found. Morphologic examination revealed two well-differentiated pancreatic endocrine neoplasms with distinct histologic, immunohistochemical, and ultrastructural features. Immunoreactivity for insulin was present in the larger tumor; the smaller tumor contained glucagon, gastrin, somatostatin, and pancreatic polypeptide. Both neoplasms demonstrated growth hormone-releasing hormone (GRH) immunopositivity and released GRH in vitro. Subsequent studies confirmed abnormally elevated preoperative plasma levels of GRH. Postoperatively, blood glucose, insulin, GRH, and GH normalized and there was regression of acromegalic features with significant reduction in sellar size. The clinicopathologic findings indicate that, in patients with multiple endocrine neoplasia type I (MEN-I), GRH production by pancreatic tumors can stimulate hypophysial somatotrophs resulting in GH excess and acromegaly due to a reversible pituitary lesion, most likely somatotroph hyperplasia.
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PMID:Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome. 289 85

The problem of hypergastrinemia in patients with the syndrome of multiple endocrine neoplasia (MEN type 1) has become increasingly controversial since the introduction of the antisecretory H2 antagonists for the treatment of the Zollinger-Ellison syndrome (ZES). One of the questions in the management of ZES is whether the malignant potential of the gastrinomas or the recurrent complications of ulcer will be the ultimate cause of death. Another problem is whether the association of MEN is a favorable or unfavorable factor to the prognosis of patients with ZES. Hypercalcemia contributes to excessive gastrin secretion, thereby casting doubt on the diagnosis of ZES in the presence of MEN. Patients with MEN are also more likely than patients with ZES not to have gastrinoma on an exploratory laparotomy. The existing controversy concerns the choices of therapy in instances of progressive ZES associated with MEN or when there is a failure to detect a primary gastrinoma when exploration is performed. To highlight the debate, the clinical courses of two patients, observed during two and three decades, respectively, are presented. These patients were receiving high doses of cimetidine; in addition, conventional surgical treatment for ulcer and repeated biopsies for gastrinoma were performed. After total gastrectomies (as life saving procedures), both patients are well.
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PMID:The progressive Zollinger-Ellison syndrome in multiple endocrine neoplasia. 290 96

A case of multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I (MEN I) is reported. The patient was a 41-year-old woman who had a past history of thyroid cancer (papillary carcinoma) and hyperparathyroidism due to parathyroid adenoma. Later, a nonfunctional pituitary tumor and five nonfunctional pancreatic tumors were found simultaneously and the patient was finally diagnosed as having MEN I. Following surgical enucleation, the pancreatic tumors were histopathologically diagnosed as benign islet cell tumors. One of them (tumor 3) exhibited a solid nodular pattern while the others showed gyriform patterns. They were divided histochemically and immunohistochemically into three types: two (tumors 1 and 2) produced a single hormone (glucagon), one (tumor 3) produced five (insulin, glucagon, somatostatin, gastrin and pancreatic polypeptide) and the remaining two (tumors 4 and 5) produced two (glucagon and pancreatic polypeptide). Electron microscopically, three types of endosecretory granules were found in the tumor cells of tumor 3 but only one type was found in tumor 4. However, in the tumor 4 extract, glucagon, pancreatic polypeptide, C-peptide, somatostatin, vasoactive intestinal peptide and growth hormone releasing factor were detected by radioimmunoassay. These findings suggest that these pancreatic tumors were both multicellular and multihormonal.
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PMID:Multiple nonfunctional pancreatic islet cell tumor in multiple endocrine neoplasia type I. A case report. 290 67

A diagnostic and therapeutic strategy for the management of patients with Zollinger-Ellison syndrome has been developed, based on the review of a large personal experience and the most recent literature. The mainstay of a modern ZES management is the eradication of tumoral processes whenever feasible. Diagnosis is centred upon gastric acid and gastrin secretion measurements both in basal conditions and on secretin stimulation. Recognition of other endocrine involvement and familial inheritance is of the utmost importance in distinguishing sporadic ZES patients from those who have the condition known as multiple endocrine neoplasia type I. Blood calcium and phosphorus levels, parathyroid hormone concentration, combined if necessary with urinary cyclic AMP excretion measurement, should be performed routinely once ZES diagnosis is established or highly suspected. Localization of the tumour is the next essential step, and this has been considerably facilitated by the recent development in imaging techniques: it involves computerized axial tomography and selective abdominal angiography, a combination of which allows tumour detection in 60-70% of sporadic gastrinoma patients, with a maximal sensitivity for well-developed hepatic metastases. In sporadic ZES exploratory laparotomy is legitimate when preoperative localization of the tumour has failed; this laparotomy will allow further detection and then eradication of gastrinomas in a significant number of patients. Control of gastric acid secretion is mandatory throughout the work-up period; modern antisecretory agents are efficacious in most cases; total gastrectomy, when control of acid hypersecretion has failed, is now exceptional. Eradication of the tumour should be attempted in cases of sporadic ZES in the absence of recognizable liver involvement. The chance of a definite cure provided by surgery when performed by an experienced surgeon varies from 20% to 60% in pancreatic and ectopic gastrinomas respectively. In ZES patients with MEN I, exploratory laparotomy is seldom indicated (other than for symptomatic associated endocrine secretion), as the chance of a definite cure by surgery is very rare. Parathyroid surgery is often indicated and should take place before any form of abdominal surgery. In cases of hepatic metastases, chemotherapy with streptozocin and fluorouracil is indicated and soon, perhaps, chemo-embolization.
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PMID:Diagnosis and treatment of Zollinger-Ellison syndrome. 304 57

The Zollinger-Ellison syndrome, although uncommon, is not rare, and most patients with the disorder present with clinical manifestations similar to those of patients with common peptic ulcer. Early studies emphasized death due to complications of massive gastric acid hypersecretion. However, with the availability of potent antisecretory agents to control acid secretion, death is now more frequently associated with the metastatic potential of slowly growing but malignant gastrinomas. Therefore, physicians should maintain a high degree of suspicion of the Zollinger-Ellison syndrome in assessing patients with either chronic peptic ulcer or unexplained secretory diarrhea. An evaluation aimed at early diagnosis of the Zollinger-Ellison syndrome should be instituted in such patients and should begin with a determination of the fasting serum gastrin level. At least 50 percent of patients with gastrinoma will have nondiagnostic serum gastrin concentrations and will therefore require provocative testing to establish the correct diagnosis. After the presence of the syndrome is established, patients should be treated with a potent antisecretory agent in doses sufficient to reduce basal acid output to less than 10 mmol in the hour preceding administration of the next dose. Although some patients may be maintained satisfactorily in this manner for extended periods, an approach aimed at tumor localization and extirpation is recommended in most patients. Preoperative evaluation should begin with CT scanning with intravenous contrast material. Selective angiography, and occasionally, portal venous sampling for gastrin, should be performed if the location and extent of tumor remain in question. If metastatic disease is demonstrated, or if MEN-I is present, surgery aimed at tumor resection, although it is occasionally effective, will probably be unsuccessful. Because of the considerable morbidity and mortality associated with pancreatoduodenectomy, it should not be performed for unresectable tumor in the head of the pancreas. In other patients with the Zollinger-Ellison syndrome, exploratory surgery should be performed; this should include a careful search for, and resection of, all pancreatic and extrapancreatic gastrinomas. With this approach, it is likely that at least 20 percent of all patients with the Zollinger-Ellison syndrome can be cured.
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PMID:Zollinger-Ellison syndrome. Current concepts in diagnosis and management. 330 61


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