Zollinger‑Ellison Syndrome (Gastrinoma) in Children
Overview
Zollinger‑Ellison syndrome (ZES) is a rare disorder caused by one or more gastrin‑producing tumors called gastrinomas. These tumors are usually located in the pancreas or duodenum and secrete excessive amounts of the hormone gastrin, which overstimulates gastric acid production. The resulting hyperacidity leads to severe peptic ulcers, intestinal inflammation, and a host of gastrointestinal (GI) symptoms.
While ZES is most often diagnosed in adults (average age 40–50 years), it can occur in children and adolescents. In the pediatric population, the condition is extremely uncommon, representing less than 1 % of all gastrinomas and accounting for roughly 0.1 % of all pediatric ulcer disease cases.1
Most childhood cases are linked to an inherited condition called multiple endocrine neoplasia type 1 (MEN‑1). Sporadic (non‑hereditary) gastrinomas also occur, but they are even less frequent.
Symptoms
Because excess gastric acid damages the lining of the stomach and small intestine, children with ZES typically present with a combination of the following signs. The intensity can vary from mild discomfort to life‑threatening bleeding.
Gastrointestinal Symptoms
- Recurrent abdominal pain – often epigastric, worsens after meals.
- Severe or persistent heartburn – may be misdiagnosed as gastro‑esophageal reflux disease (GERD).
- Frequent nausea and vomiting – especially vomiting of “coffee‑ground” material, indicating digested blood.
- Peptic ulcers – multiple, deep, and often located beyond the duodenum (e.g., jejunum) which is atypical for simple H. pylori infection.
- Diarrhea – acidic chyme can inactivate pancreatic enzymes, leading to malabsorption.
- Weight loss or failure to thrive – due to chronic pain, malabsorption, and decreased intake.
Systemic / Extra‑intestinal Symptoms
- Fatigue or anemia – from chronic GI bleeding.
- Bone pain or fractures – long‑standing hyperacidity can impair calcium absorption.
- Elevated serum calcium – if associated with MEN‑1 (parathyroid hyperplasia).
Causes and Risk Factors
ZES results from uncontrolled secretion of gastrin by neuroendocrine tumor cells. Understanding the underlying cause helps determine both treatment and family counseling.
Primary Causes
- Gastrinoma (neuroendocrine tumor) – 80–90 % arise in the duodenum, 10–20 % in the pancreas.
- Multiple endocrine neoplasia type 1 (MEN‑1) – an autosomal‑dominant mutation in the MEN1 gene; up to 25 % of pediatric ZES cases are linked to MEN‑1.2
Risk Factors
- Family history of MEN‑1 – children of an affected parent have a 50 % chance of inheriting the mutation.
- Previous gastric ulcer disease – may mask the early presentation of ZES.
- Exposure to radiation – rare, but abdominal radiation can increase neuroendocrine tumor risk.
Diagnosis
Because the signs overlap with common GI disorders, a high index of suspicion is essential, especially in children with refractory ulcers or unexplained diarrhea.
1. Clinical Evaluation
- Detailed history (frequency of ulcers, family MEN‑1, medication use).
- Physical exam focusing on abdominal tenderness, signs of anemia, and growth parameters.
2. Laboratory Tests
- Fasting serum gastrin level – a level > 1000 pg/mL (normal < 100 pg/mL) is strongly suggestive, especially if gastric pH < 2.
- Secretin stimulation test – a rise in gastrin > 120 pg/mL after IV secretin is diagnostic in borderline cases.
- Complete blood count (CBC) for anemia, serum calcium, and vitamin D levels if MEN‑1 is suspected.
3. Imaging Studies
- Endoscopic ultrasound (EUS) – high sensitivity for small duodenal gastrinomas.
- Somatostatin receptor scintigraphy (Octreoscan®) or 68Ga‑DOTATATE PET/CT – detects both primary tumors and metastases.
- CT or MRI of the abdomen – evaluates tumor size, location, and possible liver involvement.
4. Endoscopy
Upper endoscopy (EGD) is performed to document ulcer number, size, and location, and to obtain biopsies ruling out H. pylori infection or malignancy.
5. Genetic Testing
If MEN‑1 is suspected, sequencing of the MEN1 gene is recommended for the child and, if positive, for at‑risk relatives.
Treatment Options
Management aims to control acid hypersecretion, eradicate tumors when feasible, and address nutritional deficits.
1. Acid‑Suppressive Medications
- High‑dose proton pump inhibitors (PPIs) – e.g., omeprazole 2 mg/kg/day divided BID; titrated to symptom control. PPIs are the cornerstone and often needed lifelong.
- H2‑receptor antagonists – may be added for breakthrough symptoms, but are less effective