Zollinger-Ellison syndrome is caused by gastrin-secreting tumors called gastrinomas, which produce high levels of the hormone gastrin. This excess gastrin stimulates excess stomach acid production, leading to ulcers in the stomach and small intestine. Gastrinomas most commonly arise in the duodenum or pancreas. Treatment focuses on acid suppression with proton pump inhibitors to relieve symptoms and prevent new ulcers from forming. For malignant or metastatic gastrinomas, surgical removal can be attempted when possible, while other treatments like chemotherapy, somatostatin analogs, or targeted therapies may help control tumor growth.

1. ZOLLINGER ELLISON
SYNDROME
R.Anusha
Pharm D Vl Year
Roll no : 170514882007

2. DEFINITION
Zollinger-Ellison syndrome is due to gastrin-
secreting tumors called Gastrinomas which may be
duodenal or pancreatic endocrine tumors.
Non-beta cells of the pancreatic tumor produce a large
amount of gastrin and patients suffer from ulcers.
• Gastrin level is highly increased.
• The gastrin leads to increased production of the acid and
there is a high level of HCL which leads to multiple ulcers
in the stomach and small bowel.
Gastrinoma may occur in the stomach, pancreas, lymph
nodes mesentery.

4. PATHOPHYSIOLOGY
Gastrin is a potent hormone for the secretion of gastrin from
gastric G cells, Proximal duodenal G cells, and pancreatic
delta cells.
This is under the control of vagal stimulation.
Gastrin production:
o Endocrine cells (G cell) of the antral mucosa of the
stomach.
o The lesser amount of the G cells of proximal
duodenum.
o A small amount from delta cells in the pancreas.

6. Gastrin is secreted in response to :
Antral distension.
Meals.
Partially digested food (Proteins).
Free amino acids also stimulate gastrin.
Carbohydrates and Fats have little effect on gastrin secretion.
Other gastrin release stimulants are:
Alcohol.
Caffeine.
Insulin-induced hypoglycemia.
Calcium ingestion or I/V infusion.
Vagal stimulation by:Smell,Tasting,Swallowing,Chewing.

7. Increased fasting gastrin level is associated with increasing
age over 60 years.
Secretion of gastrin depends upon the pH of gastric acid
(HCl):
pH 5 to 7: Gastrin secretion is maximum.
pH 2.5: Gastrin secretion is reduced by 80%.
pH 1.0: Maximum suppression of Gastrin production.

8. •Most gastrinomas arise in the duodenum.
•Gastrinomas located in the pancreas carry a greater malignant
potential.
•Around 25% of the patient with gastrinoma have multiple
tumors as a part of a condition called Multiple endocrine
neoplasia types 1 (MEN-1)
MEN 1 has the tumors in the pituitary gland, and
parathyroid gland in addition to the tumor of the pancreas.

9. CLINICALPRESENTATION

10. Diagnosis of Gastrinoma
Raised level of Gastrin (Hypergastrinemia).
Fasting gastrin level is markedly raised from 2 to 2000 times
normal.
Gastrin level of 1000 ng/L (ng/L; greater than 481 pmol/L) is
diagnostic and the basal acid output (BAO) is more than or
equal to 15 mEq/h (more than or equal to 15 mmol/h).

11. Normal gastrin levels:
Fasting level-up to 100 ng/L.
Older people over 60 years = 100 to 800 ng/L.
Adult = 0 to 180 ng/L.
Child = 0 to 125 ng/L.
The level fluctuates during the day:
Highest during the daytime.
After the meal.
The lowest level from 3.00 to 7.00 am.

12. TREATMENT
•PPIs are now the drugs of choice for treating gastric acid
hypersecretion in patients with ZES because of their long
duration of action and potency.
•Many of the PPIs (omperazole, esomeprazole,
lansoprazole, esomeprazole, rabeprazole, and
pantoprazole) are effective in ZES.
•Initial doses of 80 mg/day for pantoprazole (or an
equivalent dose of other available PPIs) given every 8 to
12 hours is most effective at controlling gastric acid
hypersecretion and reliving symptoms. IV PPIs can be
used for those patients who do not tolerate oral therapy.

13. •PPIs must be dose adjusted in patients with ZES to normalize
BAO levels to less than 15 mEq/h (less than 15 mmol/h) or less
than 5 mEq/h (5 mmol/h) in patients with reflux esophagitis or
prior operations to reduce acid secretion, such as subtotal
gastrectomy.
•PPI therapy can be gradually decreased after adequate control of
hypersecretion is achieved.
•Since 60% to 90% of gastrinomas are malignant, management of
advanced disease may include surgical resection of primary and
metastatic gastrinomas.
•Nonsurgical therapy may include treatment with chemotherapy,
somatostatin analogues such as octreotide, interferon, and
targeted-molecular therapies such as a mTor inhibitor
(everolimus) or a tyrosine-kinase inhibitor (sunitinib).

14. •Octreotide inhibits gastric acid secretion and lowers serum
gastrin levels, its subcutaneous route of administration and side
effects make it less desirable in therapeutic setting.
•For ZES patients with MEN1,parathyroidectomy should be
considered because correction of hyper parathyroidism often
reduces serum calcium levels and lowers gastrin secretion and
acid out put.
•Patients with metastatic gastrinomas can be treated with
chemotherapeutic agents to inhibit the growth of these
tumours.Such chemotherapy is generally streptozocin
based,and involves using a combination of streptozocin,5
fluoracil and doxorubicin.
• Targeted therapy Everolimus and Sunitinib can be used for
advanced tumours.

15. REFERENCE
Joseph T Dipiro; Pharmacotherapy: A Pathophysiologic
Approach;10 edition, Zollinger-Ellison Syndrome;
Pg :1531-1533.
Labpedia.net (Zollinger Ellison Syndrome).
Zollinger Ellison Syndrome-NORD National organisation for
rare diseases.