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Gastrin, Zollinger-Ellison Syndrome

February 29, 2024Chemical pathologyLab Tests

Table of Contents

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  • Gastrin Level
        • What sample is needed for Gastrin Level?
        • What are the Indications for Gastrin Level?
        • What precautions are needed for Gastrin Level?
        • How will you define Gastrin?
        • How will you describe normal gastrin physiology?
        • What are the stimuli of the Gastrin secretion?
        • How will you discuss the pathophysiology of Gastrin?
        • How will you interpret gastrin action?
        • How will you describe the Gastrin functions:
        • What is the normal Gastrin Level?
        • Gastrin Level and its relation to diseases:
        • What are the conditions where gastrin level is Increased?
        • What are the conditions where gastrin level is decreased?
  • Zollinger-Ellison syndrome
        • How will you define Zollinger-Ellison syndrome?
        • How will you discuss the pathophysiology of Zollinger-Ellison syndrome?
        • How will you describe the signs and symptoms of Zollinger-Ellison syndrome?
        • How will you diagnose Zollinger-Ellison syndrome?
      • Questions and answers:

Gastrin Level

What sample is needed for Gastrin Level?

  1. Collect the venous blood to prepare the serum.
  2. A fasting sample is taken (at least for 12 hours of fasting).
  3. If the patient is not fasting, then the values will be different.
    1. The lowest values are between 3.00 a.m. and 7.00 a.m.
  4. Freeze the sample if the test is not done immediately.

What are the Indications for Gastrin Level?

  1. Gastrin level done in hyperacidity conditions.
  2. It is done to diagnose Zollinger-Ellison syndrome.
  3. This test also diagnoses G-cell hyperplasia.
  4. It is done to diagnose gastrinoma.

What precautions are needed for Gastrin Level?

  1. A high protein diet can increase gastrin levels 2 to 5 times the normal level.
  2. Diabetic patients on insulin may give a false raised level of gastrin.
  3. Patients with stomach surgery will have alkaline pH, a strong stimulant to gastrin.
  4. Drugs like antacids, H2-blockers (cimetidine, ranitidine), and hydrogen pump inhibitors (Omeprazole) will increase the gastrin level.
  5. Anticholinergic and tricyclic antidepressant drugs decrease the gastrin level.
  6. Avoid alcohol for at least 24 hours.

How will you define Gastrin?

  1. Gastrins are a group of peptide hormones secreted by the antrum of the stomach, and these are powerful inducers of the gastric secretion of HCL.
  2. Food in the stomach produces Gastrin secretion in response to mechanical stress or high pH.
  3. Gastrin stimulates parietal cells to produce HCL.

How will you describe normal gastrin physiology?

  1. When food enters the stomach, it changes pH to alkaline.
  2. This alkaline pH stimulates gastrin secretion to produce acid from parietal cells.
  3. Now, low pH stops further production of Gastrin.
    1. Secretion of gastrin:
      1. Maximal at Antral pH of 5 to 7.
      2. Reduced by 80% at a pH of 2 to 5.
      3. Inhibited at pH of 1.
Gastrin Level: Gastrin secretion and role of food

Gastrin Level: Gastrin secretion and role of food

  1. Zollinger Ellison syndrome is a gastrin-producing tumor of pancreatic origin with a high serum level of gastrin.
    1. Zollinger-Elison syndrome is due to non-beta cell tumors of the pancreas, which produce a large amount of gastrin.
  2. G-cell hyperplasia leads to high serum gastrin levels.
    1. Both conditions lead to an aggressive peptic ulcer.
  3. Gastrin level will be normal in the routine peptic ulcer.
  4. The Patient with antacid therapy or atrophic gastritis has a high gastrin level.
  5. A gastrin stimulation test is done by giving calcium or secretin.

What are the stimuli of the Gastrin secretion?

  1. Partially digested food.
  2. Alcohol and caffeine.
  3. Insulin-induced hypoglycemia.
  4. The smell of food, swallowing, and chewing.
  5. Calcium.
  6. Amino acids like glycine, tryptophan, and phenylalanine.
  7. Pancreatic islet tumors (non-β cells) produce large amounts of gastrin.
    1. Gastrin values follow a circadian rhythm and fluctuate physiologically to meals.

How will you discuss the pathophysiology of Gastrin?

  1. Gastrin is a hormone produced by:
    1. Pancreatic delta cells.
    2. Duodenal G-cells.
    3. Stomach mucosa’s antral cells (G-cells).
Gastrin producing cells and stimulus

Gastrin-producing cells and stimulus

  1. There are different forms of gastrin as biologically active forms that differ only in the length of the chain of the N-terminal end  like:
    1. Small gastrin has 17 amino acids polypeptide (little gastrin G17).
    2. Big gastrin comprises 34 amino acid polypeptides (Big gastrin G34).
    3. Mini gastrin has 14 amino acids (G14).
  2. Little and big gastrin are found in the gastric antrum and duodenum.
  3. Gastrin stimulates gastric acid secretion, pepsinogen, intrinsic factor, and secretin, stimulates intestinal mucosal growth,  and increases gastric and intestinal motility.
  4. Gastrin is produced from pregastrin, which has 101 amino acids and cleaves into gastrin.
  5. Gastrin from the three sources goes into circulation and then to the liver.
    1. The liver stimulates parietal cells to produce hydrochloric acid (HCl).
Gastrin sources

Gastrin sources

How will you interpret gastrin action?

  • Gastrin is in the normal range for peptic ulcers without Zollinger-Ellison syndrome.
Clinical presentation  Intragastric administration of 0.1 N HCL Serum gastrin level
Peptic ulcer without Zollinger-Ellison syndrome Normal
Zollinger- Ellison syndrome No change Highly raised
Pernicious anemia Marked decrease Raised may reach Zollinger-Ellison syndrome level

How will you describe the Gastrin functions:

  1. Stimulates gastric acid production (potent stimulator).
  2. Gastrin overproduction causes ulcers in the upper gastrointestinal tract.
  3. Regulate antral motility.
  4. Control secretion of pepsin.
  5. Control secretion of intrinsic factors.
  6. Secretion from the intestinal mucosa.
  7. Stimulate hepatic bile secretion.
  8. Secretion of pancreatic HCO3- and enzymes.
  9. Gastrin increases:
    1. Gastric Motility.
    2. Intestinal motility.
    3. Mucosa growth.
    4. Blood flow to the stomach.
  10. Gastrin secretion has diurnal variation.
    1. Its lowest value is 3 a.m. to 7 a.m.
Gastrin functions

Gastrin functions

What is the normal Gastrin Level?

Source 1

Age pg/mL
Cord blood 20 to 290
0 to 4 days 120 to 183
Child <10 to 125
!6 to 60 years 25 to 90
>90 years <100

Source 2

  • Adult = 0 to 180 pg/mL or 0 to 180 ng/L.

Source 6

  • Adult = 0 to 180 pg/mL  (0 to 180 ng/L).
  • Child = 0 to 125 pg/mL.
  • Levels are higher in elderly patients.

Source 4

  • Adult = <25 to 100 pg/mL  (<12 to 48 pmol/L)
  • Children = 10 to 125 pg/mL  (5 to 60 pmol/L)
  • Postprandial = 95 to 140 pg/mL  (46 to 67 pmol/L)

Another source

  • Children = 10 to 125 pg/mL.
  • Postprandial = 95 to 140 pg/mL.
  • Levels are higher in elderly patients.

Another source

  • Child = <10 to 125 pg/mL
  • Adult 16 to 60 years = 25 to 90 pg/mL.
  • Over 60 years = <100 pg/mL.

Gastrin Level and its relation to diseases:

Gastrin level Causes (Interpretations)
  • >100 to <500 pg/mL
  1. Pheochromocytoma
  2. Malignant carcinoma of the stomach
  3. Peptic ulcer
  4. Cirrhosis of the liver
  5. Hyperthyroidism
  6. Hyperparathyroidism
  7. Renal failure
  8. Rheumatoid arthritis
  • >500 to <1000 pg/mL
  1. Pheochromocytoma
  2. Renal failure
  3. Hyperparathyroidism
  4. Zollinger Ellison syndrome
  5. Pernicious anemia
  • >1000 pg/mL
  1. Zollinger Ellison syndrome
  2. Pernicious anemia
  • Fasting gastrin level
  • Elevated in 95% of Gastrinoma

What are the conditions where gastrin level is Increased?

  1. Zollinger-Ellison syndrome.
  2. G-cell hyperplasia.
  3. Atrophic gastritis.
  4. The retained antral portion after gastric surgery.
  5. Gastric carcinoma.
  6. Pyloric obstruction (gastric outlet obstruction)
  7. Gastric and duodenal ulcer.
  8. Chronic renal failure.
  9. Pernicious anemia.
  10. Vagotomy without gastric resection.
  11. Hyperparathyroidism.

What are the conditions where gastrin level is decreased?

  1. Hypothyroidism.
  2. Anterectomy with a vagotomy.

Zollinger-Ellison syndrome

How will you define Zollinger-Ellison syndrome?

  1. This is a disorder of autonomous gastric acid hypersecretion caused by the gastrin-secreting tumor.
  2. This gastrin production may be from non-β-cells tumors often present in the pancreas.
  3. Tumors are malignant in 50% of the cases, and 34% have metastatic disease.
  4. Hyperplasia only occurs in 10% of the cases.

How will you discuss the pathophysiology of Zollinger-Ellison syndrome?

  1. This is a gastrin-producing pancreatic tumor.
  2. Non-beta cell tumors of the pancreas produce excessive gastrin.
  3. The G cell’s hyperplasia of the stomach can also give a picture of Zollinger-Ellison syndrome.
  4. The patient has aggressive peptic ulcer disease.
  5. These patients have recurrence and complications.

How will you describe the signs and symptoms of Zollinger-Ellison syndrome?

  1. These patients have multiple ulcers in the antrum,  the duodenum, and the jejunum.
  2. The ulcers are multiple.
    1.  There is abdominal pain.
    2. There is burning and discomfort in the upper abdomen.
    3. There are acid reflux and heartburn.
    4. The patient may have diarrhea.
    5. The patient may have nausea and vomiting.
    6. The patient may have bleeding in the GI tract.
    7. The patient may have weight loss and decreased appetite.
  3. The gastrin level is normal in routine peptic ulcers.
  4. The gastrin level is normal in routine peptic ulcer disease, while it is high in Zollinger Ellison syndrome and G-cell hyperplasia.
  5. The patients on antacid or peptic ulcer disease medicines, atrophic gastritis, and patients with peptic ulcer surgery have slightly raised gastrin levels.
Zollinger-Ellison syndrome signs/symptoms

Zollinger-Ellison syndrome signs/symptoms

How will you diagnose Zollinger-Ellison syndrome?

  1. Gastrin assay is the method of choice.
    1. Most patients have fasting gastrin levels>500 pg/mL or >500 ng/L (fasting level is elevated in more than 95% of the cases).
    2. The gastrin level may reach 400,000 pg/mL.
    3. Gastrin level may be >5 times the normal value (1,000 pg/mL or 1,000 ng/L). This value is diagnostic.
  2. Advise Gastrin stimulation test using calcium or secretin.
    1. It is advised when the fasting level is <1,000pg/mL (1,000 ng/L) to assist the differentiation from other conditions.
  3. 90% of the Zollinger-Ellison syndrome patients have borderline gastrin fasting levels of 100 to 500 pg/mL.
  4. In response to the secretin stimulation test, these patients will increase 100 pg/mL above the baseline. 
  5. When a calcium infusion test is given, gastrinoma patients have similar results.
Gastrin level in gastrinoma

Gastrin level in gastrinoma

  1. Gastrin stimulation test to diagnose Zollinger-Ellison syndrome:
  2. Secretin stimulation test:
    1. Give 2 units/Kg body weight (IV bolus).
    2. Estimate Gastrin level at baseline, 2, 5, 10, 15 minutes.
    3. Get >200 pg/mL (200 ng/L)over the baseline.
    4. Positive results were seen in 87% to 100% of Zollinger-Ellison syndrome.
  3. Calcium infusion test:
    1. Give calcium gluconate 10% as 5 mg/Kg/hour for 3 hours.
    2. Check gastrin as baseline, post-dose 120, 150, and 180 minutes.
    3. An increase >395 pg/mL (395 ng/L) occurs in 95% of Zollinger-Ellison syndrome.
    4. An increase of >3 times the baseline is seen in 85% of the cases.
    5. Response to the Calcium infusion test is less specific than a response to the secretin test.

Questions and answers:

Question 1: What are the functions of gastrin?
Show answer
Gastrin stimulates acid production. Control secretion of pepsin.
Question 2: What is the source of Gastrin?
Show answer
It is G-cells of the stomach antral mucosa G-cells, Duodenal G-cells, and Pancreatic delta cells.

Possible References Used
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