How is hypergastrinemia managed?

From the Guidelines

Hypergastrinemia management should focus on treating the underlying cause while controlling acid hypersecretion, with options including endoscopic resection, observation, or octreotide for symptom control in patients with gastrinoma and Zollinger-Ellison syndrome, as recommended by the most recent guidelines 1.

Key Considerations

• For patients with Zollinger-Ellison syndrome, proton pump inhibitors (PPIs) are the mainstay of treatment, with dosing adjusted to maintain basal acid output below 10 mEq/hr or symptom control 1.
• Gastrinomas are typically managed with surgical resection for localized tumors, while unresectable or metastatic disease may require somatostatin analogs (octreotide 100-500 mcg subcutaneously three times daily or long-acting formulations) 1.
• In cases of antral G-cell hyperplasia, antrectomy may be curative, and for medication-induced hypergastrinemia from chronic PPI use, gradual tapering rather than abrupt discontinuation is recommended to avoid rebound hyperacidity 1.

Management Strategies

• Hypergastrinemic patients with tumors 2 cm or smaller and either solitary or multiple can be managed with endoscopic resection, observation, or octreotide for symptom control in patients with gastrinoma and Zollinger-Ellison syndrome 1.
• Patients with nonmetastatic gastric NETs and normal gastrin levels (type 3) have more aggressive tumors and are usually treated with radical resection of the tumor with regional lymphadenectomy 1.
• Regular monitoring of serum gastrin levels and endoscopic surveillance for gastric carcinoids is important in long-standing hypergastrinemia, as chronic elevation of gastrin can lead to enterochromaffin-like cell hyperplasia and potential malignant transformation 1.

Treatment Options

• Proton pump inhibitors (PPIs) such as omeprazole 60-120 mg/day or equivalent doses of other PPIs like esomeprazole 40-80 mg twice daily 1.
• Somatostatin analogs (octreotide 100-500 mcg subcutaneously three times daily or long-acting formulations) for unresectable or metastatic disease 1.
• Antrectomy for antral G-cell hyperplasia or to remove the source of gastrin production in patients with type 1 gastric carcinoids 1.

From the FDA Drug Label

During lifetime exposure of rats with up to 150 mg/kg/day of lansoprazole dosed seven days per week, marked hypergastrinemia was observed followed by ECL cell proliferation and formation of carcinoid tumors, especially in female rats Serum Gastrin Effects In over 2100 patients, median fasting serum gastrin levels increased 50 to 100% from baseline but remained within normal range after treatment with 15 to 60 mg of oral lansoprazole Hypergastrinemia Management:

• The FDA drug label does not provide direct guidance on managing hypergastrinemia.
• However, it is noted that increased gastrin causes enterochromaffin-like cell hyperplasia and increased serum CgA levels 2.
• The label also mentions that serum gastrin levels increased after treatment with lansoprazole, but remained within normal range 2.
• No conclusion can be drawn on how to manage hypergastrinemia based on the provided drug labels.

From the Research

Management of Hypergastrinemia

Hypergastrinemia can be managed through various approaches, depending on the underlying cause.

• In cases of Zollinger-Ellison syndrome (ZES), proton pump inhibitors serve as the cornerstone of symptomatic treatment 3.
• Surgery is routinely performed in localized sporadic ZES, irrespective of imaging results 3.
• For ZES in multiple endocrine neoplasia type 1, work-up for evaluation and treatment of hyperparathyroidism is required, and surgery might be an option for selected cases 3.
• In cases of advanced and metastatic disease, potential treatments range from somatostatin analogs to chemotherapeutic drugs, liver-directed therapies, and liver transplantation 3.

Diagnostic Testing

Diagnostic testing for hypergastrinemia includes:

• Fasting serum gastrin level measurement, which serves as an initial and fundamental diagnostic test, boasting a sensitivity of 99% 3.
• The secretin stimulation test, which aids in differentiating ZES cases from other hypergastrinemic states 3.
• Endoscopic ultrasound, which has showcased sensitivity as high as 83% for pancreatic gastrinomas 3.
• Gallium-68 radiotracers, especially DOTATOC with positron emission tomography, which are currently setting the standard in tumor localization 3.

Predictors of Hypergastrinemia

Predictors for the development of hypergastrinemia in maintenance treatment for mild gastroesophageal reflux disease using a half-dose proton pump inhibitor include:

• Old age 4.
• High baseline serum gastrin levels 4.
• Low baseline pepsinogen (PG) ratios 4.
• Helicobacter pylori infection 4.

Hypergastrinemia and Proton Pump Inhibitors

Proton pump inhibitors (PPIs) can induce hypergastrinemia, and long-term use of PPIs may increase the risk of developing gastric carcinoids (g-NETs) 5.

• The risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses 5.
• Those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk 5.