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Gastrin Level, and Zollinger-Ellison Syndrome

November 21, 2022Chemical pathologyLab Tests

Table of Contents

  • Gastrin Level
      • Sample for Gastrin Level
      • Purpose of the test (Indications) for Gastrin Level
      • Precautions for Gastrin Level
      • Definition of Gastrin
      • Pathophysiology of Gastrin
      • Interpretation of the gastrin:
      • Gastrin functions are:
      • Normal gastrin physiology:
      • Gastrin secretion stimuli are:
      • Normal Gastrin Level
        • Gastrin Level and its relation to diseases:
      • Increased gastrin level is seen in:
      • Decreased Gastrin level is seen in:
  • Zollinger-Ellison syndrome
      • Definition:
      • Pathophysiology:
      • Signs and symptoms of Zollinger-Ellison syndrome:
      • Diagnosis of Zollinger-Ellison syndrome:
      • Questions and answers:

Gastrin Level

Sample 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; to 7.00 a.m.
  4. Freeze the sample if not the test is not done immediately.

Purpose of the test (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.

Precautions 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-blocker (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.

Definition of 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. Gastrin secretion response to mechanical stress or high pH is produced by food in the stomach.
  3. Gastrin stimulates parietal cells to produce HCL.

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

Gastrin producing cells

  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.
    1. Gastrin stimulates gastric acid secretion, pepsinogen, intrinsic factor, and secretin, stimulates intestinal mucosal growth,  and increases gastric and intestinal motility.
  3. Gastrin is produced from pregastrin, which has 101 amino acids and cleaves into gastrin.
  4. Gastrin from the three sources goes into circulation and then to the liver.
    1. From liver stimulates parietal cells to produce hydrochloric acid (HCl)
Gastrin source and action

Gastrin source and action

Interpretation of the gastrin:

  • Gastrin is in the normal range in case of peptic ulcer 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

Gastrin functions are:

  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.

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 will 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.

Gastrin secretion stimuli are:

  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.

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 Pheochromocytoma
Malignant carcinoma of the stomach
Peptic ulcer
Cirrhosis of the liver
Hyperthyroidism
Hyperparathyroidism
Renal failure
Rheumatoid arthritis
>500 to <1000 pg/mL Pheochromocytoma
Renal failure
Hyperparathyroidism
Zollinger Ellison syndrome
Pernicious anemia
>1000 pg/mL Zollinger Ellison syndrome
Pernicious anemia

Increased gastrin level is seen in:

  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.

Decreased Gastrin level is seen in:

  1. Hypothyroidism.
  2. Anterectomy with a vagotomy.

Zollinger-Ellison syndrome

Definition:

  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.

Pathophysiology:

  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.

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 the 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

Diagnosis of 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 of 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. And these patients will show an increase of 100 pg/mL above the baseline in response to secretin stimulation. 
  5. Similar results are seen in patients with gastrinomas when a calcium infusion test is given.
Gastrin level in gastrinoma

Gastrin level in gastrinoma

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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