Síndrome de zolinger - Elison / Syndrome of Zolinger - Elison

Resumen:El síndrome de Zollinger - Ellison es una endocrinopatía que fue descrita en 1955 por los doctores Robert Zollinger y Edwin Ellison, quienes propusieron la triada diagnóstica que incluye hipersecreción gástrica ácida, úlcera péptica y gastrinoma. Esta enfermedad predomina en mujeres entre los 50 y 60 años de edad. Según su etiología, este síndrome se clasifica en una forma esporádica o asociada a neoplasia endocrina múltiple tipo 1 (NEM - 1).Más de la mitad de los gastrinomas se localizan en la pared duodenal, el páncreas es la segunda ubicación en frecuencia. Existen localizaciones ectópicas en ovario, mesenterio, hígado y ducto biliar. A nivel histopatológico se encuentran células tumorales redondas, con núcleos pequeños y nucléolos prominentes. La hipersecreción ácida gástrica está asociada a un defecto en la inhibición del retrocontrol negativo de la somatostatina sobre las células G antrales productoras de gastrina. Clínicamente, los pacientes manifiestan dolor abdominal, diarrea, pirosis, náuseas y vómitos; relacionados principalmente a la formación de úlceras pépticas. El diagnóstico debe incluir una medición en los niveles séricos de gastrina y valores de pH gástrico. El tratamiento de primera línea es la terapia antisecretora, principalmente con inhibidores de la bomba de protones. Los estudios de imágenes son deutilidad para detectar metástasis y evaluar la enfermedad quirúrgicamente resecable. Se debe hacer diagnóstico diferencial con otros tumores neuroendocrinos y causas de hipergastrinemia.

Abstract:Zollinger - Ellison syndrome is an endocrinopathy that was first described in 1955 by doctors Robert Zollinger and Edwin Ellison, who proposed the diagnostic triad that includes gastric acid hypersecretion, peptic ulcer and gastrinoma. This disease predominates in women between 50 and 60 years old. Based on the etiology, the syndrome is classified in sporadic or associated with multiple endocrine neoplasia type 1 (NEM - 1). Over half of gastrinomas are located in the duodenal wall, the pancreas is the second frequency location. There are ectopic locations, such as ovary, mesentery, liver and bile duct. Round cells, small nuclei and prominent nucleoli, are the main hispathologycal characteristics. Gastric acid hypersecretion is associated with a defect in the negative feedback inhibition of somatostatin on G antral gastrin-producing cells. Clinically, patients present abdominal pain, diarrhea, heartburn, nausea and vomiting; primarily related to the development of peptic ulcers. Diagnosis includes a measurement in serum gastrin levels and gastric pH values. The first line treatment is the antisecretory therapy, primarily proton-pump inhibitor. Imaging studies are useful to detect metastases and evaluate the surgically resectable disease. Neuroendocrine tumors and hypergastrinemia causes are the main differential diagnoses, the clinician should consider.

Effects of Proton Pump Inhibitors on Atrophic Gastritis and Gastric Cancer: Safe Perspective / 대한내과학회지

Proton pump inhibitors (PPIs) are widely used over 20 years for management of symptoms due to acid related diseases such as peptic ulcer and reflux esophagitis. Serious adverse events are extremely rare for short-term PPIs use. Recently, as long-term PPIs use increase, diverse reports have been reported on adverse event related with long-term PPIs use. Long-term PPIs use is generally referred as use of PPIs more than 1 year. Secondary hypergastrinemia after long-term PPIs use is associated with development of fundic gland polyps (FGP) and hyperplasia of enterochromaffin-like cell (ECL) that might be concerned with gastric carcinoid tumor. Furthermore, several studies have posed the relationship between the risk of gastric cancer and long-term PPIs use with co-existing H. pylori infection. The present review summarize the recent accumulated evidence on neoplasm associated with secondary hypergastrinemia after long-term PPIs use.

Sequelae of hypergastrinemia due to long-term administration of proton pump inhibitors and its management / 中国临床药理学与治疗学

Proton pump inhibitor (PPI) is considered as the standard treatment for acid-related disorders. However, its long-term use, especially in patients with gastroesophageal reflux disease, would cause potential risks, such as hypergastrinemia along with reduced gastric acidity, hyperplasia of enterochromaffin cells (ECL), gastric neoplasms, rebound gastric acid hypersecretion when PPI treatment is stopped, increased oxyntic gastritis in patients with H. pylori infection, and the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia. Each of these trends has led to numerous studies and evaluations on the potential risk-benefit ratio of the long-term use of PPIs, and countermeasures are being proposed for these problems.

Effect of Endogenous Gastrin on Pancreatic Growth and Regeneration in Rat

PURPOSE: Gastrin is a candidate for the growth regulatory factors of the pancreas and may solve the problem of pancreatic atrophy after partial pancreatectomy. The purpose of this study was to evaluate the effect of endogenous gastrin on the normal growth and regeneration of the pancreas (after partial pancreatectomy) in rat. METHODS: Sixty Sprague-Dawley rats (200-230 g) were divided into 6 groups. Group (G)-I and II received sham operation (splenectomy only), and G-III, IV, V, VI received both 66% partial pancreatectomy (PPx) and splenectomy. Endogenous hypergastrinemia was induced in G-II, IV, VI by stomach gavage of 30 mg/kg.day of Lansoprozole (LSP) for 3 weeks. In G-V and VI, L365,260 (ML lab, UK) was given continuously in a dose of 50 microgram/kg/hour intraperitoneally using osmotic mini pump. The rats were sacrificed 3 weeks later, and serum gastrin, the weight and the amount of DNA, RNA, and protein in the remnant pancreas or corresponding part were checked. RESULTS: Serum gastrin concentration was 3-4 times higher in the groups received LSP. LSP stimulated growth of the pancreas (G-I: 11921 vs. G-II: 14220 mg/100 g body weight, p=0.047), and the effect was even greater in partial pancreatectomy groups (G-III: 14616 vs. G-IV: 17318 mg/100 g body weight, p=0.007). Total DNA, RNA, and protein amount in the remnant pancreas showed the same trends as the pancreas weight. The effect of LSP was totally abolished by L365,260 (G-V: 13517 vs. G-VI: 14313 mg/100 g body weight, p>0.047). CONCLUSION: Endogenous gastrin has a stimulatory effect on normal growth, and a much stronger effect on the regeneration of the rat pancreas after partial pancreatectomy. Further investigations including clinical trial should be needed.

An Inhibitory Mechanism of Gastric Acid Secretion in Patients with Hyperthyroidism / 대한내분비학회지

BACKGROUND: Although hypochlorhydria, hypergastrinemia and antiparietal cell antibody have been well documented in the patients with hyperthyroidism, a cause of hypochlorhydria or hypergastrinemia is unknown at the present time. Therefore, in order to clarify an inhibitory mechansim of gastric acid secretion in the patients with hyperthyroidism, interrelationship among hypochlorhydria, hypergastrinemia and antiparietal cell antibody was investigated in this study. METHODS: The gastric secretory function, fasting and postprandial plasma concentrations of gastrin and titer of antiparietal cell antibody in the plasma were determined in the patients with hyperthyroidism and normal subjects. Immunoblot analysis was performed to identify the gastric membrane protein, a possible gastric antigen to antiparietal cell antibody. Using a immunocytochemical technique with electron microscopy, intracellular structure of the parietal cell reacted with antiparietal cell antibody was observed. RESULTS: The basal and pentagastrin-stimulated maximal acid output were reduced in the patients with hyperthyroidism. The fasting and postprandial plasma concentrations of gastrin were markedly elevated in the patients. The plasma gastrin concentration in the patients with the antiparietal cell antibody was higher than that of the norrnal subjects as well as the patients without the antibody not only in the fasting state but also in the postprandial state. However, the plasma gastrin concentration of the patients without the antiparietal cell antibody was elevated in the fasting state only. There was no difference in the gastrin content of the antral mucosa between the norrnal subjects and the patients. The antiparietal cell antibody was detected in 5 (38.5 %) out of 13 patients by using the indirect immunofluorescence method. Patient IgG dose-dependently inhibited rabbit gastric H (+),K (+)-ATPase activity. Among proteins of the rabbit gastric mucosa membrane, four high molecular weight proteins (91, 140, 170 and 210 K dalton) were reacted to the patient IgG. The patient IgG positive peroxidase-antiperoxidase (PAP) activity was electron microscopically detected on the intracellular cannalicular membrane of the parietal cell CONCLUSION: We conclude that hypochlorhydria and hypergastrinemia in the patients with hyperthyroidism are partially related to the antiparietal cell antibody and that the antigen to the antiparietal cell antibody may be H (+),K (+)-ATPase in the intracellular canalicular membrane of the parietal cell.