Differentials
Atrophic gastritis
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
Gastric secretory analysis will show decreased acid secretion.
Peptic ulcer disease from Helicobacter pylori infection
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
Increased fasting serum gastrin in the presence of achlorhydria (due to H pylori).[39]
The exaggerated serum gastrin level response to food stops after H pylori eradication.
Idiopathic gastric hypersecretion
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
Post-prandial hypersecretion of acid without presence of gastrin-secreting tumour.[40]
Normal gastrin levels.
Antral G cell hyperfunction and hyperplasia
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
Secretin infusion test is positive in ZES but negative in antral G cell hyperfunction.[40]
Chronic renal failure
SIGNS / SYMPTOMS
Fatigue, weakness, dyspnoea, pleuritic pain, restless legs, and pruritus may be differentiating symptoms.
Pallor, brown nails, bruising, and oedema may be differentiating signs.
INVESTIGATIONS
Hypergastrinaemia is found in chronic renal failure. Gastrin levels are not affected by haemodialysis but will return to normal after renal transplant.[41][42]
Elevated serum creatinine and decreased glomerular filtration rate are found in chronic renal failure but are not associated with ZES.
Retained antrum syndrome
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
May be a history of prior Billroth I and II subtotal gastric resections.
INVESTIGATIONS
Negative secretin infusion test.[40]
Pernicious anaemia
SIGNS / SYMPTOMS
Common features include tiredness, dyspnoea, paraesthesia, sore red tongue, diarrhoea, and mild jaundice.
INVESTIGATIONS
Like ZES, pernicious anaemia is associated with raised gastrin levels.[43] These are appropriate, however, due to achlorhydria. Following treatment with cobalamin and correction of vitamin B12 levels, gastrin levels will normalise.
Systemic mastocytosis
SIGNS / SYMPTOMS
Urticarial skin lesions may occur.
INVESTIGATIONS
Biopsies of the gastric or intestinal mucosa may reveal an increase in mast cells.
Gastric outlet obstruction
SIGNS / SYMPTOMS
Common features include nausea, vomiting, and inability to tolerate oral feeding.
INVESTIGATIONS
Abdominal imaging could be suggestive or confirmatory.
Proton-pump inhibitor (PPI) use
SIGNS / SYMPTOMS
Difficult to differentiate clinically.
INVESTIGATIONS
PPI use can cause an appropriate fasting hypergastrinaemia due to negative feedback caused by hypochlorhydria. To diagnose ZES in patients on PPI therapy, a fasting serum gastrin level should ideally be repeated 1 week after discontinuation of PPI. However, guidelines recommend that PPI treatment should not be abruptly stopped in patients with overt clinical symptoms of gastrinoma and/or risks of complications (e.g., active ulcer disease) because of the potential for rapid development of severe acid-peptic problems.[15] In practice, the diagnosis of ZES cannot easily be established without stopping PPI treatment. It is therefore recommended that if the diagnosis is unclear (fasting serum gastrin <10-fold increased, gastric pH <2, no tumour seen on imaging), the patient should be referred to a specialist centre for further investigation. If this is not possible, PPI withdrawal should be cautiously performed (only in an asymptomatic patient in whom active acid-peptic disease or damage has been excluded by endoscopy), with adequate cover by histamine 2 receptor antagonists (H2 antagonists) and careful patient monitoring.[15]
Alternatively, basal acid output (BAO) measured on PPI therapy should be low (<15 mEq/hour), whereas BAO measured in patients with ZES must be high to make the diagnosis.
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