Published in UAB Insight, Summer 2008
Treatment Strategies Address Tumors and Acid Hypersecretion
Zollinger-Ellison syndrome (ZES) is a rare condition in which gastrin-secreting neuroendocrine tumors form in the pancreas or duodenum. Hypergastrinemia induces chronic diarrhea, erosive esophagitis, and severe peptic ulceration in the esophagus, duodenum, and jejunum. Malabsorption and weight loss often accompany the disease.
"Symptoms often are subtle, and differential diagnosis is tricky," says UAB gastroenterologist C. Melbern Wilcox, MD. Patients may present with recurrent episodes of peptic ulcer disease, severe reflux esophagitis, and diarrhea that do not respond to standard treatment. Many patients will complain of diarrhea rather than ulcer-like symptoms.
Elevated serum gastrin is the first indication of ZES. An upper gastrointestinal tract endoscopy can determine peptic ulcer disease and allow for gastric acid analysis, which Wilcox believes is the best diagnostic tool. With equivocal results from the above tests, a secretin stimulation test can facilitate a definite diagnosis. "A CT scan is not necessary but can establish a baseline," Wilcox says, "as will an octreotide scan, which we use primarily to determine the extent of disease and presence and location of tumor."
In about 20% of ZES patients, gastrinomas are associated with multiple endocrine neoplasia type I (MEN I). Those with MEN I have multiple endocrine, parathyroid gland, pituitary gland, and other neuroendocrine tumors. "Endoscopic ultrasonography may help localize duodenal and pancreatic tumors, particularly those associated with MEN-1," Wilcox says.
Wilcox and UAB gastroenterologist Basil I. Hirschowitz, MD, individualize treatment to address tumor control and the extent of acid hypersecretion. "Surgery is curative in very few cases," Wilcox says. "Tumors are small, hard to locate, and usually multiple and metastasized. In our experience, acid hypersecretion recurs after surgery, and patients must resume proton pump inhibitors [PPIs]," he says. Surgery may be appropriate in specific situations, such as in localized gastrinoma and in patients with MEN-1 with tumors >2 cm (J Am Coll Surg. 2007;205[4S]:S34-S37).
"PPIs remain the most effective treatment for reducing acid in progressive metastatic gastrinoma," he says. PPIs at a 2- to 3-fold increased standard dose inhibit hypersecretion. Individualized dosing aims to reduce basal secretion (Clin Gastroenterol Hepatol. 2005;3[1]:39-48) to <5 mEq/h to prevent complications.
Hirschowitz and Wilcox are principal investigators for an ongoing study of lansoprazole in hypersecretors and patients with ZES. "Gastrinomas, even when metastasized, have an indolent growth pattern. We have followed patients for 18 years and have controlled the disease well with PPIs at doses as high as 450 mg/d. We titrate medication and monitor stomach acid until we maintain effective suppression," Wilcox says. "Although PPIs have been associated with gastrointestinal infections, we have not found an association in our cohort of ZE patients." (BMC Gastroenterol. 2008;8:18.)
Hirschowitz's research also linked long-term PPI use to vitamin B12 malabsorption showing that measuring serum B12 alone underestimates prevalence. B12 deficiency was 29% more frequent than detected by measuring only serum B12 (Aliment Pharmacol Ther. 2008;27[11]:1110-1121). "With careful monitoring and pharmacology, patients with ZES can live long, full lives," Wilcox says.
FOR MORE INFORMATION:
Dr. Mel Wilcox
Dr. Basil Hirschowitz
1.800.UAB.MIST
mist@uabmc.edu