DESCRIPTION: | SIGNS AND SYMPTOMS: | CAUSES: | DIFFERENTIAL DIAGNOSIS: | LABORATORY: | PATHOLOGICAL FINDINGS: | IMAGING: | TREATMENT | DRUG(S) OF CHOICE | PRECAUTIONS: | ALTERNATIVE DRUGS: | PATIENT MONITORING: | POSSIBLE COMPLICATIONS: | MISCELLANEOUS
* A triad of
>> Marked elevated gastric acid secretion
>> Peptic ulcer disease
>> A non-beta islet cell tumor of the pancreas (and sometimes other sites); frequently multifocal and small; one half are malignant with metastases into lymph nodes, liver and less frequently into the bone
* Gastrin producing tumor, single or multiple, large or small, benign or malignant: 80% sporadic, 20% associated with multiple endocrine neoplasia (MEN 1)
System(s) affected: Gastrointestinal, Endocrine/Metabolic
Genetics: 25-50% occur in association with the MEN 1 syndrome
Incidence/Prevalence in USA: 0.1% of patients with duodenal ulcer
Predominant age: Middle age (40-75)
Predominant sex: Male > Female (3:2)
* Abdominal pain
* Epigastric pain
* Reflux esophagitis
* Vomiting unresponsive to standard therapy
* 25% have diarrhea which persists with fasting
* Ulcer disease
* Complications of severe peptic ulcer disease (hemorrhage, perforation, obstruction)
* Signs related to MEN 1 (hyperparathyroidism, hypercalcemia)
* Weight loss
* Enlarged liver when metastasized
* Endoscopic (esophagitis, duodenal ulceration with multiple ulcers)
* Steatorrhea
CAUSES: TOP Gastrinoma - found in the gastric triangle in 90%; 80% arise in the pancreatic islets and are located in the pancreatic head; 10-15% arise in the G cells of the duodenum
* MEN 1
* Family history of ulcer disease
* Over age 60
DIAGNOSIS
* Elevated serum gastrin with hypochlorhydria/achlorhydria
>> Atrophic gastritis
>> Drug induced
>> Gastric cancer
>> Gastric ulcer
>> Pernicious anemia
>> Postvagotomy
>> Vitiligo
* Elevated serum gastrin with normal or increased gastric acid
>> Antral G-cell hyperfunction
>> Chronic renal failure
>> Gastric outlet obstruction
>> Pheochromocytoma (rare)
>> Retained gastric antrum
>> Rheumatoid arthritis
>> Small bowel resection
* Consider gastrinoma in all patients with:
>> Recurrent or refractory ulcer disease
>> Gastric hypertrophy and ulcers
>> Duodenal and jejunal ulcers
>> Ulcers and diarrhea
>> Kidney stones
>> Hypercalcemia
>> Pituitary disease
>> Family history of ulcer disease or endocrine tumors suggestive of MEN 1
* Elevated serum gastrin - fasting
* Elevated basal gastric acid output >15 mEq/hr (> 15 mmol/hr)
* Elevated maximal acid output >150 mEq/hr (> 150 mmol/hr)
* Gastric pH < 2.0
* Increased pancreatic polypeptides
* Check serum calcium, phosphorus, cortisol and prolactin levels
Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A
* Gastrinoma found in gastric triangle (60-70% in head of pancreas)
* 50% of tumors stain for VIP, ACTH, insulin, neurotensin
* In addition, 50% will have multiple metastases to liver, bone, lymph nodes, or with blood vessel invasion
* Duodenal ulcer
* Jejunal ulcer
* Gastric ulcer
SPECIAL TESTS:
* Secretion stimulation test - gastrin level increases > 200 pg/mL (> 200 ng/L)
* Calcium infusion test
* Used to localize tumor
* Abdominal CT scan
* Abdominal ultrasound
* Abdominal angiography
* Selective venous sampling of gastrin from portal venous tributaries
* Sella turcica imaging
DIAGNOSTIC PROCEDURES: TOP : Endoscopy to look for tumors
APPROPRIATE HEALTH CARE: Advise daily care based on symptoms
GENERAL MEASURES: TOP : Medical treatment alone in some cases; surgical correction if patient fails medical therapy
SURGICAL MEASURES:
* Medical treatment plus laparotomy to search for resectable tumors
* Definitive therapy - removal of gastrinoma when found
* Total gastrectomy (is no longer used in most patients)
* Vagotomy in some patients to reduce acid secretion and add to inhibitory effect of medication
* In MEN I - parathyroidectomy; associated gastrinomas are generally benign and not amenable to surgery
ACTIVITY: As tolerated
DIET: Restrict only foods which aggravate symptoms
PATIENT EDUCATION: Inform as to nature of disease and prognosis
MEDICATIONS
* Omeprazole first followed by H2 blockers. (Must correct hypercalcemia if caused by hyperparathyroidism.)
>> Note: Dosages may exceed maximum recommended daily dose. Start at the recommended doses as listed below, and titrate up to maximum as listed.
>> Omeprazole 60-120 mg/d
>> Cimetidine start 300 mg q6h, up to maximum of 1.25-5.0 gm/day
>> Ranitidine 150 mg q 12 hrs, up to maximum of 6 gm/day
>> Famotidine 20 mg at bedtime, up to maximum of 800 mg/day
Contraindications:
* H2-receptor antagonists - anti-androgen effects; drug interactions due to hepatic oxides system
* Omeprazole - none
* Appropriate dose adjustment for renal and geriatric patients
* Gynecomastia reported with high doses of cimetidine (> 2.4 gm/day)
Significant possible interactions: Refer to manufacturer's literature
* Chemotherapy regimens of streptozocin and fluorouracil have shown partial response
* Interferon
FOLLOWUP
* Close followup necessary following any surgical procedure
* Careful dose titration required with medical therapy
* Gastric analysis to measure acid secretion rates for dose adjustment of H2-receptor antagonists
PREVENTION/AVOIDANCE: Must screen first degree relatives of patients with MEN 1
* The complications of ulcer disease, e.g., bleeding or perforation
* Approximately two thirds of Zollinger-Ellison tumors are malignant with metastases
* Multiple hormone production and related syndromes such as Cushing's and others
EXPECTED COURSE AND PROGNOSIS:
* Survival rate - 5 year = 62-75%, 10 year = 47-53%
* Prognosis improves with complete resection
* If tumor inoperable due to metastases, 5 year = 43%, 10 year = 25%
* The presence of metastatic disease has decreased owing to the early detection
ASSOCIATED CONDITIONS:
* Hyperparathyroidism
* Prolactinoma
* Insulinoma
* Carcinoid tumors
AGE-RELATED FACTORS:
Pediatric: N/A
Geriatric:
* One third of patients with Z-E are over age 50
* Consider this diagnosis for any patient with persistent or recurring peptic ulcer disease
Others: N/A
PREGNANCY: N/A
SYNONYMS:
* Z-E syndrome
* Pancreatic ulcerogenic tumor syndrome
* Multiple endocrine neoplasia, partial
* Ulcerogenic islet cell tumor
ICD-9-CM:
251.5 Zollinger-Ellison syndrome (other codes based on related diagnosis)
SEE ALSO: N/A
OTHER NOTES: N/A
ABBREVIATIONS:
MEN = multiple endocrine neoplasia
REFERENCES:
* McGuigan JE: Zollinger-Ellison Syndrome (Gastrinoma). In: Braunwald E, Isselbacher KJ, Petersdorf RG, et al. Harrison's Principles of Internal Medicine. 13th Ed. Vol.2. New York, McGraw-Hill, Inc., 1994:1375-1377
* Spiro HM: Ulcerogenic Tumor of the Pancreas (Zollinger-Ellison Syndrome). In: Spiro HM, ed. Clinical Gastroenterology. 4th Ed. New York, McGraw-Hill, Inc.,1993:313-327
* McGuigan JE: The Zollinger-Ellison Syndrome. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease. 5th Ed. Philadelphia, W.B. Saunders Co.,1994:679-692
* Richardson CT: Zollinger-Ellison Syndrome. In: Wyngaarden JB, Smith LH, Bennett JC, eds. Cecil Textbook of Medicine. 19th Ed. Philadelphia, W.B. Saunders Co.,1992:665-667
Author(s):
Guy W. Neff, MD
Samuel Sim, MD
Ann Neff, MD
Copyright - Williams & Wilkins, 1997.