2. INTRODUCTION
• ZOLLINGER-ELLISON SYNDROME IS A CONDITION IN WHICH THE BODY
PRODUCES TOO MUCH OF THE HORMONE GASTRIN. MOST OF THE TIME, A
SMALL TUMOR (GASTRINOMA) IN THE DUODENUM , PANCREAS , STOMACH
• GASTRINOMAS ARE RARE, WITH AN INCIDENCE OF 0.5 TO 3 PER MILLION PER
YEAR.
• SPORADIC 75% - SINGLE TUMOR
• FAMILIAL 25% - MULTIPLE TUMOR ASSOCIATED WITH MEN1 SYNDROME
3.
4. PATHOPHYSIOLOGY
• GASTRIN WORKS ON THE PARIETAL CELLS OF THE GASTRIC GLANDS, CAUSING THEM TO
SECRETE MORE HYDROGEN IONS INTO THE STOMACH LUMEN.,
• HYDROGEN ION SECRETION IS CONTROLLED BY A NEGATIVE FEEDBACK LOOP BY
GASTRIC CELLS TO MAINTAIN A SUITABLE PH.
• THE NEUROENDOCRINE TUMOR THAT IS PRESENT IN INDIVIDUALS WITH ZOLLINGER–
ELLISON SYNDROME HAS NO REGULATION, RESULTING IN EXCESSIVELY LARGE
AMOUNTS OF SECRETION, THERE IS AN INCREASE IN THE NUMBER OF ACID-SECRETING
CELLS, AND EACH OF THESE CELLS PRODUCES ACID AT A HIGHER RATE.
• THE INCREASE IN ACIDITY CONTRIBUTES TO THE DEVELOPMENT OF PEPTIC ULCERS IN
THE STOMACH, DUODENUM (FIRST PORTION OF THE SMALL BOWEL) AND
OCCASIONALLY THE JEJUNUM (SECOND PORTION OF THE SMALL BOWEL), THE LAST OF
WHICH IS AN 'ATYPICAL' ULCER
5. CAUSES
• ZOLLINGER-ELLISON SYNDROME IS CAUSED BY TUMORS. THESE GROWTHS ARE
MOST OFTEN FOUND IN THE HEAD OF THE PANCREAS AND THE UPPER SMALL
INTESTINE. THE TUMORS ARE CALLED GASTRINOMA. HIGH LEVELS OF GASTRIN
CAUSE PRODUCTION OF TOO MUCH STOMACH ACID.
• GASTRINOMA OCCUR AS SINGLE TUMORS OR SEVERAL TUMORS. ONE HALF TO
TWO THIRDS OF SINGLE GASTRINOMA ARE CANCEROUS (MALIGNANT) TUMORS.
THESE TUMORS OFTEN SPREAD TO THE LIVER AND NEARBY LYMPH NODES.
• MANY PEOPLE WITH GASTRINOMA HAVE SEVERAL TUMORS AS PART OF A
CONDITION CALLED MULTIPLE ENDOCRINE NEOPLASIA TYPE I (MEN I) AD
INHERITED. TUMORS MAY DEVELOP IN THE PITUITARY GLAND (BRAIN) AND
PARATHYROID GLAND (NECK) AS WELL AS IN THE PANCREAS.
6. The Gastrinoma Triangle (of Stabile) is bound by the junction of 1) the common and cystic ducts
(superiorly), 2) the second and third portions of the duodenum (inferiorly), and 3) the head and neck of
the pancreas (medially). Most primary (sporadic) gastrinomas are single and arise in the duodenal wall
as depicted. In MEN-1 syndrome, duodenal primaries are commonly multiple. Occasionally, solitary
sporadic primary lesions develop in the pancreas (within the triangle defined above).
7. SYMPTOMS
• CHRONIC DIARRHEA, INCLUDING STEATORRHEA (FATTY STOOLS)
• NAUSEA
• MALNOURISHMENT
• LOSS OF APPETITE
• MALABSORPTION
• REFLUX
• HEARTBURN
• NAUSEA AND VOMITING
• ABDOMINAL PAIN
• BLEEDING AND PERFORATION
8. DIAGNOSIS
• UPPER GI ENDOSCOPY : MULTIPLE DUODENAL ULCER / ATYPICAL ( 2ND PART OF
DUODENUM / GIANT ULCERS )
• PUD USUALLY SEEN IN 1ST PART OF DUODENUM
• CT , MRI SHOW METASTATIS HEPATIC , PANCREAS AND STAGING AND MEDICAL
THERAPY
• PTH ASSAY , SERUM CALCIUM,PANCREATIC POLYPEPTIDE, PROLACTIN LEVELS
• INVESTIGATION OF CHOICE :
• SECRETIN STUDY
• CHECK FASTING GASTRIN X10 TIMES ELEVATED 1000 PG/ML
9. • FALSELY ELEVATED FASTING GASTRIN LEVEL SEEN IN : PPI , H.PYLORI, GASTRIC
OUTLET OBSTRUCTION
• BASAL ACID OUTPUT > 15MEQ/HOUR
• USEFUL TO DETERMINE THE PH OF THE GASTRIC JUICE WHICH CAN BE OBTAINED
DURING ENDOSCOPY OR THROUGH A NASOGASTRIC TUBE. IF THE GASTRIC PH IS >2
IN THE ABSENCE OF ANTISECRETORY THERAPY, THE PATIENT IS HYPOCHLORHYDRIC
AND, THEREFORE, ZES CAN BE EXCLUDED
• BASAL ACID OUTPUT / MAX . ACID OUTPUT > 0.6
• GASTRIN PROVACTIVE TEST : SECRETIN STIMULATING TEST – INJECT SECRITIN –
AFTER 15 MIN – MEASURE GASTRIN LEVEL - > 120PG – ZES
• FALSE POSITIVE SECRITIN TEST : PPI INDUCED STOP PPI 1 WEEK BEFORE
10. • CALCIUM AND MEAL TESTS ARE LESS USEFUL THAN SECRETIN FOR DETECTING
ZES.
• TUMOR LOCALIZATION – ENDOSCOPIC ULTRASOUND
• MC SITE DUODENUM > PANCREAS > STOMACH AND ALSO IN MESENTERY ,
OVARY OR HEART
• IMAGING FOR METASTATIC ZES : SOMATOSTATIN SCINTIGRAPHY
11. • ENDOSCOPY OF THE SECOND PORTION OF THE DUODENUM (A) SHOWING NECROTIC
ULCERATIONS (YELLOW ARROWS), WHICH BEGAN TO BLEED WHEN LIGHTLY TOUCHED WITH
THE ENDOSCOPE (WHITE ARROW) AND THE DUODEUNOJEJUNAL FLEXURE (B) WITH MORE
NECROTIC ULCERS (WHITE ARROWS).
13. Somatostatin receptor scintigraphy: anteroposterior (A) and posteroanterior (B)
view four hours after contrast administration demonstrating intense focal uptake
in the area of the third portion of the duodeunum.
14.
15. TREATMENT
• PROTON PUMP INHIBITORS : OMEPRAZOLE ,ESOMEPRAZOLE, LANSOPRAZOLE, PANTOPRAZOLE,
DEXLANSOPRAZOLE, RABEPRAZOLE .
• H2 RECEPTOR ANTAGONISTS ARE NO LONGER THE DRUGS OF CHOICE FOR PATIENTS WITH ZES
POOR CONTROL OF THE GASTRIC ACID HYPERSECRETION AND SOMETIMES THE NEED FOR HIGH
AND FREQUENT DOSES OF THE DRUG
• OMEPRAZOLE 60 – 100MG
• OCTREOTIDE – CONTROL GASTRIN SECRETION , TUMOR GROWTH AND METASTATIS
• SURGERICAL REMOVAL OF TUMOR GREATER THAN 2CM
• ZES MEN 1 HYPERPARATHYROIDISM WITH HYPERCALCALCEMIA – PARATHYRODECTOMY DONE IT
REDUCE FASTING SERUM LEVEL OF GASTRIN AND BAO
• CHEMOTHERAPHY
