eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Zollinger-Ellison Syndrome: Treatment & Medication

Author: Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Coauthor(s): Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Dec 1, 2008

Treatment

Medical Care

Since the introduction of effective antisecretory medications such as histamine H2-receptor antagonists and proton pump inhibitors (PPIs), treatment paradigms for Zollinger-Ellison syndrome (ZES) have changed. Medical therapy is also indicated before surgery when patients present with metastatic disease and in patients who refuse or cannot undergo surgical resections. Measures are designed to prevent peptic ulcer disease (PUD) due to gastric acid hypersecretion.

• PPIs have become the first-line treatment in Zollinger-Ellison syndrome since their approval in 1988-1989. They are the most effective antisecretory medication available because they block the hydrogen potassium/adenosine triphosphate (ATPase) pump, the final common pathway, regardless of the stimulus.
  • The acid environment in the stomach allows for the release of the prodrug granules, which are then absorbed in the duodenum. Once in the systemic circulation, they are taken up by gastric parietal cells and diffuse into the extracellular canaliculus. The PPI then covalently and irreversibly binds to the proton pump. PPIs require acid for accumulation and activation, which is why they are most efficacious on an empty stomach.
  • PPIs are rapidly and almost completely absorbed. The peak plasma concentration is reached in 1-3 hours. The prodrug is quickly metabolized by the liver, primarily by cytochrome P-450 isoenzyme CYP2C19, resulting in a half-life of roughly 1 hour.
  • Despite the short half-life of PPIs, the irreversible covalent bonding to the proton pump provides sustained antisecretory effects; therefore, the effect is not due to plasma concentration of the drug but rather the area under the plasma concentration curve.
  • Little information about the metabolism and distribution of PPIs in children is available, but some data suggest decreased metabolism in newborns, a metabolic rate in children aged 1-9 years that is higher than that of adults, and more rapid absorption and clearance in children.
• H2-receptor antagonists are no longer indicated because PPIs provide more effective antisecretory effects and prolonged use of H2-receptor antagonists leads to tachyphylaxis.
• Somatostatin analogues such as octreotide decrease gastrin and gastric acid secretion and can be used to treat the symptoms associated with gastrinoma. Small studies in adults using weekly subcutaneous octreotide acetate for 1-48 months led to a decrease in abdominal pain and diarrhea in most patients.
• Because patients with multiple endocrine neoplasia type 1 (MEN-1) and Zollinger-Ellison syndrome are at risk for developing enterochromaffinlike (ECL) cell tumors, they require regular gastroscopy with multiple biopsies of all parts of the stomach and systematic biopsies of all mucosal lesions to detect these carcinoids. Both the clinical and laboratory factors and the biopsy results can be used to identify a subgroup of patients that need to be followed more closely because they have a higher risk for developing carcinoids.

Surgical Care

Total gastrectomy was the standard of care until at least the mid 1970s, when the first histamine H2-receptor antagonists were introduced. Surgery is now focused on staging (when gastrinomas are not revealed by imaging) and reducing tumor burden to decrease metastases and improve disease-free survival.

Even in cases in which no tumor is identified before surgery, an exploratory laparotomy is indicated because it offers the only chance of cure.

• The surgical exploration includes a careful bidigital palpation of the liver, pancreas, stomach, and lymph node groups along the pancreas and duodenum after mobilization of the duodenum and pancreatic head by a Kocher maneuver. Some authorities recommend a duodenotomy because it allows full exploration through palpation of the duodenal wall. However, others argue that duodenotomy-related complications, such as leakage and fistula formation, do not justify the procedure.
• Local tumor excision is currently the procedure of choice.
• Major surgical resections, including duodenopancreatectomy, have been performed in adults but not in children. The subgroup of patients that may benefit from extensive resections has not yet been identified.
• Total gastrectomy is no longer recommended because medical therapy with PPIs is effective in virtually all patients.
• Some investigators report that intraoperative endoscopic transduodenal illumination of the duodenum is helpful in discovering additional gastrinomas of the duodenal wall.
• Intraoperative ultrasonography of the pancreas may help to localize small tumors in the pancreas.

Consultations

• Because gastrinomas in children are extremely rare, only pediatric institutions should deal with the disease.
• Children with Zollinger-Ellison syndrome benefit from a multidisciplinary approach that involves pediatric gastroenterologists, surgeons, endocrinologists, and radiologists.

Diet

• Special diets are not required for children with Zollinger-Ellison syndrome.
• Special considerations may be necessary for children with severe diarrhea or symptoms who are unable to take in essential calories for normal growth on a regular diet.
• Although some studies indicate decreased vitamin B-12 levels in patients who receive long-term PPI therapy, no evidence of clinical significance has been reported.
• Current data are insufficient to support administration of cobalamin.

Activity

• Children who are receiving appropriate medication can pursue normal activities.

Medication

Inhibition of gastric acid secretion with proton pump inhibitors (PPIs) is mandatory to prevent complications of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome (ZES). PPIs have proven to be safe, without side effects even after long-term use. The goal is to reduce basal acid output (BAO) to levels less than 10 mEq/h 1 h prior to the next dose in patients without gastric acid–reducing surgery and less than 5 mEq/h in patients with prior acid-reducing gastric surgery.

Proton pump inhibitors

These agents are used to reduce gastric acid hypersecretion. Dosing should be adequate to achieve a BAO of less than 10 mEq/h. Dosing may vary in each patient. Children may require relatively higher doses per kilogram than adults.

Lansoprazole (Prevacid)

A substituted benzimidazole that covalently and irreversibly binds the hydrogen potassium/ATPase, thereby inhibiting acid secretion. It is available as IV, oral caps, or solutabs. Strawberry-flavored solutabs can be dissolved in water for easy administration to children. Dissolve 15-mg solutab in 4 mL water and 30-mg solutab in 10 mL water.

Omeprazole (Prilosec, Zegerid Oral Suspension)

A substituted benzimidazole that suppresses acid secretion by specific inhibition of hydrogen potassium/ATPase at the secretory surface of the parietal cell.

Pantoprazole (Protonix)

A substituted benzimidazole that suppresses acid secretion by specific inhibition of hydrogen potassium/ATPase at the secretory surface of the parietal cell.

Somatostatin Analogues

These agents are synthetic analogues of somatostatin that inhibit GH secretion, thereby leading to a decrease in chloride secretion, sodium absorption, and decreased fluid losses. They are used to treat secretory diarrhea in Zollinger-Ellison syndrome.⁵

Octreotide (Sandostatin)

Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides. Controls diarrhea in 80% of patients. Progressive increases in dosage may be necessary. In adults, Mozell et al reported success with 100 mcg SC 3 times/wk for 1-48 mo.

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