History and Physical Examination
The typical presentation of Zollinger-Ellison syndrome (ZES) is severe abdominal pain, with or without diarrhea. Most children present with complications of peptic ulcer disease (PUD), such as bleeding from an ulcer or duodenal perforation.
Abdominal pain
The abdominal pain is due to peptic ulcers, which can be found in the upper gastrointestinal (GI) tract in 90-95% of patients. These ulcers are often multiple (see the following image) or in unusual locations. In 70% of patients, single or multiple ulcers are found in the first part of the duodenum. However, ulcers in the second or third part of the duodenum or in the jejunum are highly suggestive of Zollinger-Ellison syndrome. Other characteristics of Zollinger-Ellison syndrome ulcers include a size larger than 2 cm and a refractory behavior to conventional therapy.
Diarrhea
The second most common symptom of Zollinger-Ellison syndrome ulcers is diarrhea, which is seen in 50-65% of patients. Diarrhea may be the only symptom; however, it can also precede or follow the ulcer formation. The diarrhea is due to mucosal damage by activated pepsinogens that result from excessive acid secretion. Other mechanisms of diarrhea in Zollinger-Ellison syndrome include inhibition of sodium and water absorption, bile acid insolubility, and inactivation of pancreatic enzymes, leading to both malabsorptive (steatorrhea) and secretory states. [12]
Other symptoms
Zollinger-Ellison syndrome may also manifest as symptoms of gastroesophageal reflux and, in severe cases, has been associated with esophageal stenosis or Barrett mucosa in adults.
Because Zollinger-Ellison may present with many vague, common GI symptoms, the correct diagnosis is often delayed by 4-6 years. [13, 14]
Physical findings
The physical examination findings in affected patients are often normal. These children may have abdominal tenderness and, in the case of perforation, they may have peritoneal signs. Patients who experience anemia due to bleeding ulcers may appear pale and may have tachycardia and/or fatigue.
Staging
Staging Zollinger-Ellison syndrome (ZES) is based on tumor size (>2-3 cm) and metastases to the lymph nodes, liver, or both. Metastases to the liver are associated with poor prognosis and have been reported to occur in roughly 60% of patients with pancreatic gastrinoma versus less than 10% in patients with duodenal gastrinoma. [15]
Tumor size does not relate to serum gastrin levels or the severity of symptoms.
Ectopic Cushing syndrome, tumor flow cytometry features, and overexpression of certain growth factors such as human epidermal growth factor receptor 2 (HER2/neu) are associated with aggressive gastrinomas and poor prognosis.
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Somatostatin receptor scintigraphy in a young patient with Zollinger-Ellison syndrome. Besides physiologic uptake in the kidneys and the spleen, 2 pathologic hot spots are present, one in the area of the duodenum and another next to the pancreas.
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Somatostatin receptor scintigraphy in a young patient with Zollinger-Ellison syndrome whose gastrinomas were resected. The LEFT (big) tumor was a periduodenal lymph node gastrinoma; the RIGHT tumor was a pancreatic gastrinoma. Despite negative findings on the scan, the patient remained hypergastrinemic, probably because of microscopic disease that escaped diagnostic imaging and surgical exploration.
