Zollinger-Ellison syndrome (ZES)

Zollinger-Ellison syndrome (ZES) is characterized by peptic ulcers, diarrhea, and marked gastric acid hypersecretion in association with a gastrin-secreting non–β islet cell endocrine tumor (gastrinoma).

-The mean age of onset of symptoms is 41 years

-Multiple endocrine neoplasia syndrome type 1 (MEN 1) is present in approximately 20–25% of patients. It consists of pancreatic neuroendocrine tumors, pituitary tumors, and hyperparathyroidism.

-Most gastrinomas occur in the submucosa of the duodenum.

-Most patients have a typical duodenal ulcer.

Symptoms and Signs: Peptic ulcer disease, abdominal pain, and diarrhea, gastroesophageal reflux, nausea, weight loss, bleeding.  


When the diagnosis is suspected, a fasting gastrin is usually the initial test performed. Serum gastrin concentration >1000 pg/mL in combination with acidic stomach pH <2.0 is diagnostic.

The secretin stimulation test is the provocative test of choice used to differentiate patients with gastrinomas from other causes of hypergastrinemia and to establish the diagnosis of ZES.

In all patients with ZES, a serum PTH, Prolactin, LH, FSH, GH levels should be obtained to exclude MEN 1.

CT and MRI scans to identify the site of the primary tumor and whether there is metastasis.


Medical Treatment: PPIs are the drugs of choice, though H2 blocking drugs can also be used. Nasogastric aspiration of stomach acid stops the diarrhea.

-With long-term PPI use in ZES patients, vitamin B12 deficiency can develop; thus, vitamin B12 levels should be assessed during follow-up.

-Long-term PPI use may be associated with a number of side-effects including; an increased incidence of bone fractures;

Surgical Treatment: Tumor resection

In patients with MEN 1, surgical resection is recommended

Q: What are the most common symptoms experienced by ZES patients? Abdominal pain and diarrhea

Q: What do you suspect in patients who had peptic ulcers in unusual locations? ZES

Q: Who can have significant hypergastrinemia beside individuals with ZES? Patients taking PPIs, those with H pylori infection, chronic atrophic gastritis, pernicious anemia, hypochlorhydria

Q: What is the most sensitive method for identifying ZES? Demonstration of an increased fasting serum gastrin concentration.

Q: What is the most important predictor of survival in ZES?  The presence of hepatic metastases.

Complications of Peptic Ulcer Disease-

Complications of peptic ulcer disease include bleeding, ulcer perforation, penetration, and gastric outlet obstruction.

Bleeding: Most common complication. Treat with fluid resuscitation to correct hypovolemia; blood transfusions as necessary; early, high-dose intravenous PPI.

Ulcer Perforation:

Perforation usually elicits a sudden, severe upper abdominal pain. The patient appears severely distressed, lying quietly with the knees drawn up and breathing shallowly to minimize abdominal motion. Pain may radiate to the top of the right shoulder or to both shoulders.In the second phase (usually 2 to 12 hours after onset), abdominal pain may lessen. Board-like abdominal rigidity. Plain x-ray or CT scan of the abdomen reveals free subdiaphragmatic air. Up to 40% of ulcer perforations seal spontaneously; treat with fluids, nasogastric suction,IV PPIs, antibiotics.

Penetration: Ulcer perforates into contiguous structures such as pancreas. The pain becomes more severe and constant, may radiate to the back. Treat with IV PPIs, surgery.

Gastric Outlet obstruction: Least common complication; Presents with new onset of early satiety, nausea, vomiting, increase of postprandial abdominal pain, and weight loss. Prolonged vomiting and poor fluid intake may lead to prerenal azotemia, hyponatremia, and a hypokalemic, hypochloremic metabolic alkalosis.

On physical examination, a succussion splash may be heard in the epigastrium, which indicates retained fluid in the stomach.

Diagnosis: Nasogastric aspiration of a large amount of foul-smelling fluid; Endoscopy

Treat with dilation of the gastric obstruction by hydrostatic balloons passed through the endoscope, surgery. Malignancy is a more common cause of gastric outlet obstruction and must be excluded.

Q: What is the most common complication observed in PUD? GI bleeding.

Q: What is the most common cause of ulcer-related death? Bleeding

Peptic Ulcer Disease

A peptic ulcer is a defect in the gastric or duodenal mucosa that extends through the muscularis mucosa into the deeper layers of the wall.

Causes: H.pylori infection, NSAIDS, aspirin, Zollinger-Ellison syndrome, Hyperparathyroidism, Crohn disease, burns, head injury, organ failure

Symptoms and Signs: 70 percent of peptic ulcers are asymptomatic; Symptoms include epigastric pain, early satiety, nausea

Gastric Ulcer (GU): Occur later in life, 55-70 years; Eating exacerbates pain; Nausea and weight loss occur more commonly in GU patients than DU patients. Should be biopsied because 5% of gastric ulcers are malignant.

Duodenal Ulcer (DU): Younger age of onset, 30-55 years; Eating relieves pain; The typical pain pattern in DU occurs 90 min to 3 h after a meal and is frequently relieved by antacids or food. Awakens the patient at night. Do not require biopsy because DUs are virtually never malignant and do not require biopsy.

Q: What is the most discriminating symptom in DU? it awakes the patient from sleep (between midnight and 3 A.M)

Ulcer complications: Bleeding, gastric outlet obstruction, fistulization, perforation

Diagnosis: Upper endoscopy or radiologic studies, Testing for Helicobacter pylori: Urea breath test, stool antigen test, serologic testing


Removal of offending factors.

Antacids: rarely used by physicians. Most often used by patients. Aluminum hydroxide can produce constipation and phosphate depletion; magnesium hydroxide may cause loose stools.

H₂ receptor antagonists: cimetidine, ranitidine, famotidine, nizatidine. Cimetidine can cause reversible gynecomastia and impotence.

Proton Pump Inhibitors: Omeprazole, Esomeprazole, Lansoprazole, Rabeprazole, Pantoprazole etc

Cytoprotective agents: Sucralfate

Bismuth-Containing Preparations: Bismuth subsalicylate

Prostaglandin analogues: Misoprostol (contraindicated in women who may be pregnant)

Surgery: Vagotomy and drainage

H.pylori treatment:

Clarithromycin Triple: PPI + Clarithromycin + Amoxicillin for 14 days, Approved by FDA.

Bismuth Quadruple: PPI + Bismuth subsalicylate + Tetracycline + Metronidazole for 10-14 days, not approved by FDA

Levofloxacin Triple: PPI + Levofloxacin + Amoxicillin for 5-7 days, not approved by FDA.

-In patients treated for H. pylori, eradication of infection should be confirmed four or more weeks after the completion of therapy. Tests to confirm eradication: urea breath test, fecal antigen test, or upper endoscopy

-Approximately 60 percent of peptic ulcers heal spontaneously but with eradication of H. pylori infection, ulcer healing rates are >90 percent.

Potential Adverse effects of Proton Pump Inhibitor Drugs:

-Chronic kidney disease, acute kidney disease, acute interstitial nephritis, hypomagnesemia, Clostridium difficile, Community-acquired pneumonia, bone fracture

-Long-term acid suppression, especially with PPIs, has been associated with a higher incidence of community-acquired pneumonia as well as community and hospital acquired Clostridium difficile–associated disease.

– long-term use of PPIs was associated with the development of hip fractures in older women.

Q: What is the most commonly identified risk factor for peptic ulcer bleeding? NSAIDS use

Q: What is the most frequent finding on physical examination in patients with GU or DU? Epigastric tenderness.

Q: What is the procedure of choice for the diagnosis of duodenal and gastric ulcers? Upper Endoscopy  

Q: What are the antisecretory drugs of choice for treating NSAID-related ulcers? PPIs

Q: What is the most common complication associated with peptic ulcers? GI bleeding

T or F?The majority of patients with peptic ulcers may be asymptomatic.True