Gastrin Level, Zollinger-Ellison Syndrome

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 fast).
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)

1. Gastrin level basically 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 lead to an increase in gastrin level 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 antacid, H2-blocker (cimetidine, ranitidine), and hydrogen pump inhibitor (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 the presence of food in the stomach.
3. Gastrin stimulates parietal cells to produce HCL.

Pathophysiology of Gastrin

1. Gastrin is a hormone produced by the stomach mucosa’s antral cells (G-cells).
   1. Other sources of production are the G-cell of the duodenum and the delta cells of the pancreas.

2. 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).
3. Little and big gastrin are found in the gastric antrum and duodenum.
   1. Gastrin stimulates gastric acid secretion, pepsinogen, intrinsic factor, 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. From liver stimulates parietal cells to produce hydrochloric acid (HCl)

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 80% at a pH of 2 to 5.
      3. Inhibited at pH of 1.
         

         Gastrin secretion and role of food

4. 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.
5. G-cell hyperplasia leads to high serum gastrin levels.
   1. Above both conditions leads to an aggressive peptic ulcer.
6. Gastrin level will be normal in the routine peptic ulcer.
7. The Patient with antacid therapy or atrophic gastritis has a high gastrin level.
8. 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

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 yreas = 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

Pathophysiology:

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

Signs and symptoms:

1. These patients have multiple ulcers in the antrum,  the duodenum, and even the jejunum.
2. The ulcers are multiple.
   1.  There is abdominal pain.
   2. There are burning and discomforts 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 the 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.

Diagnosis:

1. 1. Advise Gastrin stimulation test using calcium or secretin.
   2. The patients mostly have fasting gastrin levels>500 pg/mL or >500 ng/L.
   3. The gastrin level may reach 400,000 pg/mL.
   4. 90% of the Zollinger-Ellison syndrome patients have borderline gastrin fasting levels 100 to 500 pg/mL.
   5. And these patients will show an increase of 100 pg/mL above the baseline in response to secretin stimulation. 
   6. Similar results are seen in patients with gastrinomas when a calcium infusion test is given.
      

      Gastrin level in gastrinoma 

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