Updated: 10/22/2019

Zollinger-Ellison (ZE) Syndrome

Review Topic
4 4
4 4
  • A 42-year-old male executive complains of upper abdominal pain. He says he is under considerable stress at work and smokes a pack of cigarettes daily. He has no history of shortness of breath, swelling of the feet, chest pain, or allergies. Further history reveals that the pain is worse at night and often wakens him from sleep. It occurs between meals and is subsided by drinking milk and avoiding spicy foods. On 1 occasion he vomited blood. Testing reveals serum gastrin level of 1000 pg/ml (normal < 300 pg/ml).
  • Clinical definition
    • syndrome characterized by the secretion of gastrin by duodenal or pancreatic neuroendocrine tumors (gastrinomas) 
  • Epidemiology
    • demographics
      • annual incidence is 0.5-2 per million 
      • high incidence in men compared to women
    • only 25% of gastrinomas arise in the pancreas with the majority occurring in the duodenum
  • Pathogenesis
    • excessive gastrin secretion from gastrinoma leads to high gastric acid output
      • gastrin has trophic action on gastric parietal cells and histamine-secreting enterochromaffin-like cells  
    • high gastric acid secreting overwhelms the neutralizing capacity of pancreatic bicarbonate secretion, resulting in low pH of intestinal contents
      • the low pH inactivates pancreatic digestive enzymes and thus interferes with the emulsification of fat by bile acids
      • results in maldigestion and malabsorption
    • high serum gastrin concentrations inhibit the absorption of sodium and water by the small intestine
  • Associated conditions
    • multiple endocrine neoplasia type 1 (MEN1) 
  • Symptoms
    • peptic ulcer disease 
    • heartburn
    • weight loss
    • diarrhea
  • Physical exam
    • abdominal tenderness
  • Upper endoscopy 
  • Contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI)
  • Somatostatin receptor scintigraphy
  • Endoscopic ultrasound
    • usually indicated prior to surgical resection as it has greater sensitivity in detecting small tumors
  • Fasting serum gastrin concentration and gastric pH 
    • best initial test
    • serum gastrin value > 10 times the upper limit of normal (> 1000 pg/mL) in the presence of gastric pH < 2 is diagnostic
  • Secretin stimulation test
    • indicated in patients with elevated gastrin/low gastrin pH that do not meet the diagnostic criteria 
    • differentiates gastrinomas from other causes of hypergastrinemia (e.g., antral G-cell hyperplasia)
    • patients with gastrinomas will have a dramatic rise in serum gastrin following secretin stimulation (normal gastric G cells are inhibited by secretin)
  • Calcium infusion study
    • indicated in patients with strong clinical suspicion despite a negative secretin stimulation test
  • MEN1 evaluation
    • serum parathormone levels
    • ionized calcium levels
    • prolactin levels
  • Antral G-cell hyperplasia  
    • distinguishing factors
      • poor response to secretin stimulation ltest
      • absence of gastrinoma on imaging
  • First-line
    • medical management with proton pump inhibitors (e.g., omeprazole) and H2-receptor anatagonists (e.g., ranitidine)
    • surgical resection
      • eliminates need for antisecretory medical therapy and protects against the morbidity and mortality of metastasis
  • Second-line
    • octreotide (rarely required)
    • reoperation
      • indicated in patients with intractable symptoms who fails dietary and medical therapy
  • Stricture
  • Perforation  
  • Metastatic gastrinoma
    • liver is the most common site
    • most common cause of morbidity and mortality

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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(M1.GI.13.25) A 41-year-old female complains of frequent diarrhea and abdominal pain between meals. Endoscopy reveals a duodenal ulcer distal to the duodenal bulb. CT scan of the abdomen demonstrates a pancreatic mass, and subsequent tissue biopsy of the pancreas reveals a malignant islet cell tumor. Which of the following hormones is likely to be markedly elevated in this patient: Review Topic | Tested Concept

QID: 101082













Vasoactive intestinal peptide







L 1 E

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(M1.GI.13.174) A 45-year-old male patient with a history of recurrent nephrolithiasis and chronic lower back pain presents to the ER with severe, sudden-onset, upper abdominal pain. The patient is febrile, hypotensive, and tachycardic, and is rushed to the OR for exploratory laporotomy. Surgery reveals that the patient has a perforated gastric ulcer. Despite appropriate therapy, the patient expires, and subsequent autopsy reveals multiple ulcers in the stomach, duodenum, and jejunum. The patient had been complaining of abdominal pain and diarrhea for several months but had only been taking ibuprofen for his lower back pain for the past 3 weeks. What is the most likely cause of the patient's presentation? Review Topic | Tested Concept

QID: 101231

A gastrin-secreting tumor of the pancreas




A vasoactive-intestinal-peptide (VIP) secreting tumor of the pancreas




Cytomegalovirus infection




H. pylori infection




Chronic NSAID use



L 1 B

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