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Zollinger-Ellison syndrome :

DESCRIPTION: | SIGNS AND SYMPTOMS: | CAUSES: | DIFFERENTIAL DIAGNOSIS: | LABORATORY: | PATHOLOGICAL FINDINGS: | IMAGING: | TREATMENT | DRUG(S) OF CHOICE | PRECAUTIONS: | ALTERNATIVE DRUGS: | PATIENT MONITORING: | POSSIBLE COMPLICATIONS: | MISCELLANEOUS

BASICS TOP

DESCRIPTION: TOP :

* 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)

SIGNS AND SYMPTOMS: TOP :

* 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

RISK FACTORS: TOP :

* MEN 1

* Family history of ulcer disease

* Over age 60

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS: TOP :

* 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

LABORATORY: TOP :

* 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

PATHOLOGICAL FINDINGS: TOP :

* 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

IMAGING: TOP :

* 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

TREATMENT: TOP

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

DRUGS OF CHOICE: TOP :

* 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

PRECAUTIONS: TOP :

* 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

ALTERNATIVE DRUGS: TOP :

* Chemotherapy regimens of streptozocin and fluorouracil have shown partial response

* Interferon

FOLLOWUP

PATIENT MONITORING: TOP :

* 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

POSSIBLE COMPLICATIONS: TOP :

* 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

MISCELLANEOUS TOP

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.

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