Zollinger Ellison syndrome

Dx:

• 1. Fasting gastrin level. Usually <150 pg/mL. Virtually all gastrinoma patients will have a gastrin level of >150-200 pg/mL. Measurement of gastrin should be repeated to confirm the clinical suspicion. Other processes that can elevate fasting gastrin level: gastric hypochlorhydria or achlorhydria (most frequent), with or without pernicious anemia; retained gastric antrum; G cell hyperplasia; gastric outlet obstruction; renal insufficiency; massive small bowel obstruction; rheumatoid arthritis, vitiligo, DM, and pheochromocytoma. A decrease in acid production will subsequently lead to a failure of the feedback inhibitory pathway, resulting in net hypergastrinemia. Gastrin levels will thus be high in patients using antisecretory agents for the treatment of acid peptic disorders and dyspepsia. A fasting gastrin level of x 10 times is suggestive of ZES. 2/3rd of patient will have fasting gastrin levels lower than that.

  2. Assess acid secretion. Normal or elevated gastric acid output indicates further testing. A BAO (basal acid output)/MAO (maximal acid output) ratio of >0.6 is highly suggestive of ZES, but a ratio of <0.6 does not exclude the diagnosis. A basal gastric pH of >3 or more virtually excludes gastrinoma.

  3. Gastrin provocative tests: The most sensitive and specific gastrin provocative test for the diagnosis of gastrinoma is the secretin study. An increase in gastrin of >200 pg or more within 15 min of secretin injection has a sensitivity and specificity of >90% for ZES. Calcium infusion study may be done if the secretin study in inconclusive. (rise >400 pg/mL).

  4. Imaging: Octreoscan, EUS, MRI used for tumor localization once the biochemical Dx of gastrinoma has been confirmed

  5. Up to 50% of patients have metastatic disease at diagnosis. Once a biochemical diagnosis has been confirmed, the patient should first undergo an abdominal CT scan, MRI, or octreoscan to exclude metastatic disease.

Tx:

PPI

Octreotide

Surgery for sporadic disease.

Surgical therapy of gastrinoma patients with MEN I remains controversial because of the difficulty of rendering these patients disease free with surgery.

Metastatic disease: chemo with streptozotocin, 5FU, and doxorubicin, IFN-alpha, hepatic artery embolization. 111In-pentetreotide has been used in the therapy of metastatic neuroendocrine tumors. Radiofrequency ablation or cryablation of liver lesions and the use of agents that block the vascular endothelial growth receptor pathway (bevacizumab, sunitinib)

When to obtain a fasting serum gastrin level

• • Multiple ulcers

  • Ulcers in unusual locations, associated with severe esophagitis; resistant to therapy with frequent recurrences; in the absence of NSAID ingestion or H. pylori infection

  • Ulcer patients awaiting surgery

  • Extensive family history for PUD

  • Postoperative ulcer recurrence

  • Basal hyperchlorhydria

  • Unexplained diarrhea or steatoma

  • Hyperglycemia

  • Family history of pancreatic islet, pituitary, or parathyroid tumor

  • Prominent gastric or duodenal folds.