Manejo Paliativo

The Physician's Guide to Laboratory Test Selection and Interpretation

Zollinger-Ellison Syndrome - Gastrinoma
Diagnosis
Indications for Testing • Refractory peptic ulcer disease, multiple peptic ulcers, familial peptic ulcer disease, peptic ulcer disease with diarrhea Laboratory Testing • Gastrin, serum fasting (elevated in 99-100% of Zollinger-Ellison syndrome [ZES] patients) • Usually >200pg/mL • >500-1,000 pg/mL virtually diagnostic • Elevated fasting serum gastrin in isolation is not diagnostic of ZES • Gastric acid analysis – increased basal acid output/secretion (BAO) ≥15 mEq (mmol/L)/hr or >5 mEq (mmol/L)/hr after acid-reducing surgery • If BAO measurement unavailable, measure pH of gastric fluid • pH ≥2 not consistent with ZES diagnosis • Secretin stimulation test (90%sensitive and specific) – best test to diagnose gastrinoma • Identify increase in serum gastrin after secretin administration • Not recommended for patients with acute pancreatitis • Avoid external effects on gastrin release • Must fast on day of study • Acid suppressive medications discontinued at least 7-10 days prior to test • Baseline serum gastrin samples • Taken 15 minutes before and again 1minute before secretin administration • Administration of pure porcine secretin (2 units/kg) intravenously over a 30-second time period • Serum gastrin samples • Initial samples at 2 and 5 minutes postinjection • Additional samples every 5 minutes for ≥20 minutes • Positive secretin stimulation test (increase in serum gastrin by >200 pg/mL) confirms the need to search for presence of gastrinoma •Pancreatic polypeptide – increased in 35-40% of patients • Genetic • Counseling and testing if MEN1 suspected Histology • Nested or trabecular arrangement of small- to medium-sized cells • Finely granular eosinophilic cytoplasm • Central, round to oval nuclei • Stippled chromatin (“salt and pepper”) • Immunohistochemistry – chromogranin A, synaptophysin, Ki-67 (Mib-1) • Tumor-specific confirmation –gastrin • Other available stains include neuron specific enolase, polyclonal (NSE P), and protein gene product (PGP) 9.5 Imaging Studies • CT scan/endoscopic ultrasound/MRI • Identify tumor location and confirm diagnosis • Endoscopic ultrasound – 67% sensitivity

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The Physician's Guide to Laboratory Test Selection and Interpretation

• Somatostatin-receptor scintigraphy – ~85% sensitivity Differential Diagnosis • Gastroesophageal reflux disease • MEN1 (Wermer syndrome) • Peptic ulcer disease • Helicobacter pylori infection • Gastric outlet obstruction •Pernicious anemia • Short bowel syndrome • Achlorhydria • Pancreatic cancer • Malabsorption syndromes • Use of proton pump inhibitors

Monitoring

• Secretin test may be repeated during follow-up of curative surgery • Consider chromogranin A

Clinical Background

Zollinger-Ellison syndrome (ZES) is characterized by refractory peptic ulcer disease, diarrhea, and gastric acid hypersecretion as aresult of a functional pancreatic or duodenal neuroendocrine tumor (NET). ZES is also referred to as gastrinoma. Epidemiology • Incidence – 1/1,000,000 • Age – diagnosis in 30s-40s • Sex – M:F, equal • Occurrence – second most common pancreatic NET Inheritance • Most tumors are sporadic, although 20-30% are genetic • Multiple endocrine neoplasia type 1 (MEN1, Wermer syndrome) – heritable disorderwith increased risk for NETs • Parathyroid gland hyperplasia or tumor, endocrine tumors of the pancreas or duodenum, and endocrine tumors of the pituitary gland • Autosomal dominant Pathophysiology • Neuroendocrine tumor that secretes gastrin • Gastrin stimulates parietal gastric cells to increase in number • Increased number of parietal cells increases basal and maximal acid secretion •...