eMedicine Feature Series

Gastroesophageal Reflux Disease Newsletter _________Series 1, Issue 10, 2007

GASTRIC ACID HYPERSECRETORY DISORDERS

Praveen K Roy MD
University of Missouri-Columbia

Abhishek Choudhary, MD
University of Missouri-Columbia

Mohamed O Othman, MD
University of New Mexico

INTRODUCTION

Gastric acid hypersecretion is seen in several disorders, including duodenal ulcers, Zollinger-Ellison Syndrome (ZES), Helicobacter pylori–associated gastritis, gastric outlet obstruction, short gut syndrome, antral exclusion, gastric G-cell hyperfunction, systematic mastocytosis, basophilic leukemia, gastric carcinoids with carcinoid syndrome, and non–gastrin producing pancreatic tumors. Most incidences of gastric acid hypersecretion are idiopathic. As gastric acid secretion is not routinely measured, the diagnosis of a gastric acid hypersecretory state can often be missed in many cases.

CLINICAL FEATURES

The clinical features of gastric acid hypersecretion are typically due to ulcerations of the intestinal mucosa caused by acid hypersecretion. If the volume of gastric acid is high, diarrhea can occur. The ulcers caused by acid hypersecretion can be single or multiple and are usually located in the duodenum. They can also occur in unusual locations, such as the jejunum; the risk of perforation or bleeding of the ulcer is higher in these patients.

DIAGNOSIS

The diagnosis of a gastric acid hypersecretory state is established by measuring acid output, which is currently performed in few centers. Gastric acid hypersecretion is generally defined as a basal acid output (BAO) level of >10 mEq/h, though some use a BAO level of >15 mEq/h. In patients who have undergone prior gastric surgery, a BAO level >5 mEq/h defines acid hypersecretion.¹ Patients are required to fast the night before undertaking an acid output test, and, ideally, the patient should have stopped taking gastric acid antisecretory medications (4-7 days for H₂-receptor antagonists and 7 days for proton pump inhibitors). On the day of the test, a clinician places a nasogastric tube to aspirate gastric fluids for 1-2 hours. Gastric volume and pH levels are measured, and the BAO level is calculated.

Patients with ZES are often required to complete both a gastric analysis and an upper endoscopic examination. Unfortunately, many patients express dissatisfaction after enduring the typically lengthy conventional gastric analysis. However, 2 groups have recently reported success with 2 different modified approaches for gastric acid secretory studies that allow them to be completed in less time. Roy et al reported that gastric acid secretion studies produce accurate results over a shorter 30 minute duration,¹ and Oh et al found that assessing gastric acid hypersecretion during endoscopy was an effective means of obtaining accurate results, thereby eliminating the need to also test the patient’s gastric acid output.²

TYPES OF HYPERSECRETORY STATES

Idiopathic gastric acid hypersecretion

Idiopathic gastric acid hypersecretion is the most common cause of gastric acid hypersecretion. In these cases, most patients present with duodenal ulcers, which have a high risk of bleeding, and some patients report diarrhea and heartburn. BAO levels are high and can be as high as those found in ZES. The exact prevalence is unknown; however, idiopathic gastric acid hypersecretion typically – 80% of diagnosed cases – occurs in men, and patients are usually aged 20-30 years.^3-5

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Gastric acid hypersecretion with hypergastrinemia

Helicobacter pylori gastritis

Some patients with gastric H pylori infection have gastric acid hypersecretion and high gastrin levels.^6,7 These patients also have an increase in antral-G cells, a hypersensitivity of these cells to gastrin-releasing peptide, and a decrease in antral somatostatin levels. Eradication of H pylori infection resolves these abnormalities, including gastric acid hypersecretion.

Zollinger-Ellison syndrome

ZES is rare, occurring in about 1-5 cases per million per year.⁸ ZES is caused by an autonomous hypersecretion of gastrin due to an islet cell tumor, usually located in the pancreas or duodenum.⁹ Most cases are sporadic. About 25% of patients with ZES also have multiple endocrine neoplasia type 1 (MEN 1) syndrome.⁹ The most common symptoms of ZES are abdominal pain and diarrhea, and gastrointestinal bleeding can occur in 20% of patients.⁹ Although diagnosis of ZES only requires a high index of suspicion, the introduction of PPIs has led to a delay in diagnosis of this syndrome.

Measuring BAO can be useful in the diagnosis of ZES. BAO levels ≥15 mEq/hr are suggestive of ZES, having a sensitivity of 85%.¹ Among patients with a prior gastric acid–reducing surgery, a BAO level ≥5 mEq/hr is used for the diagnosis of ZES.¹ Investigators from the National Institutes of Health (NIH) reported that gastric acid volume output of ≥140 mL/hr and a pH level ≤2 have a >80% sensitivity for ZES.¹

Chronic gastric outlet obstruction

Although acid hypersecretion is not seen in acute gastric outlet obstruction, chronic gastric outlet obstruction can lead to gastric acid hypersecretion.¹⁰ The etiology of acid hypersecretion in chronic gastric outlet obstruction is not known, but reflex stimulation of gastrin and gastric acid by gastric distension and food material in the stomach is one possibility. Symptoms of both hypergastrinemia and acid hypersecretion resolve with continuous nasogastric suction. In some cases, the clinical presentation of chronic gastric outlet obstruction may be confused with ZES.

Antral exclusion (retained gastric antrum syndrome)

Antral exclusion is a rare complication of antrectomy and Billroth II gastrojejunostomy caused by a small cuff of antrum left attached to the duodenal bulb.¹¹ This extraneous piece of antrum is bathed in alkaline intestinal secretions instead of acidic fluid, which disrupts the normal negative-feedback loop in which gastrin release is inhibited by acidic gastric contents. This disruption leads to hypergastrinemia and acid hypersecretion. Antral exclusion causes patients to develop acid-peptic disease postoperatively, but secretin stimulation tests return negative results. Surgical resection of the retained antral stump is curative.

Short gut syndrome

Massive resection of the small intestine can result in a transient hypergastrinemia and acid hypersecretion.¹² This can last a few weeks to a few months. The loss of inhibitory control of gastrin release is thought to cause short gut syndrome.

Gastric acid hypersecretion with hyperhistaminemia

Systemic mastocytosis

Systemic mastocytosis is a rare condition characterized by abnormal accumulation of mast cells in the different organs in the body.¹³ Gastrointestinal manifestations can occur in about 80% of patients with systemic mastocytosis and include nausea, diarrhea, abdominal pain, and malabsorption.¹³ Excessive histamine release leads to gastric acid hypersecretion, which may cause duodenal ulcerations. Acid hypersecretion is present in 20-40% of patients with systemic mastocytosis.¹³

Basophilic leukemia

Basophilic leukemia is a rare cause of acid hypersecretion.^14,15 Symptoms and physical findings at the time of presentation are very heterogeneous. The basophil granules, which contain acid mucopolysaccharides such as heparin or histamine, may be responsible for some of the specific symptoms recorded. High blood levels of histamine may give cutaneous signs including pruritus, edema, urticarial rashes, areas of hyperpigmentation, and gastrointestinal symptoms such as nausea, vomiting, diarrhea, dyspeptic symptoms, abdominal distension, or ulcers. The released heparin may also interfere with coagulation.

Carcinoid syndrome with gastric carcinoid

Gastric carcinoids can also produce histamine.¹⁶ In some patients with carcinoid syndrome, release of histamine occurs and could lead to excessive acid secretion and peptic ulcer disease.

CONCLUSION

Several common and uncommon disorders result in gastric acid hypersecretion. They include duodenal ulcers, ZES, H pylori–associated gastritis, gastric outlet obstruction, short gut syndrome, antral exclusion, gastric G-cell hyperfunction, systematic mastocytosis, basophilic leukemia, gastric carcinoids with carcinoid syndrome, and non–gastrin producing pancreatic tumors. Even with this lengthy list of possible diagnoses, most cases of gastric acid hypersecretion are idiopathic, and the diagnosis can often be missed because of the difficulty of measuring gastric acid secretion, which is currently performed in a relatively few centers around the country and established through conventional gastric analysis or an upper endoscopy. The clinical features of gastric acid hypersecretion include diarrhea, the development of ulcers, (usually in the duodenum), perforation, and bleeding.

REFERENCES

1. Roy PK, Venzon DJ, Feigenbaum KM, et al. Gastric secretion in Zollinger-Ellison syndrome. Correlation with clinical expression, tumor extent and role in diagnosis--a prospective NIH study of 235 patients and a review of 984 cases in the literature. Medicine (Baltimore). 2001;80(3):189-222.

2. Oh DS, Wang HS, Ohning GV, Pisegna JR. Validation of a new endoscopic technique to assess acid output in Zollinger-Ellison syndrome. Clin Gastroenterol Hepatol. 2006;4(12):1467-73.

3. Collen MJ, Jensen RT. Idiopathic gastric acid hypersecretion. Comparison with Zollinger-Ellison syndrome. Dig Dis Sci. 1994;39(7):1434-40.

4. Lewis JH. Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders. Aliment Pharmacol Ther. 1991;5 Suppl 1:15-24.

5. Collen MJ, Sheridan MJ. Definition for idiopathic gastric acid hypersecretion. A statistical and functional evaluation. Dig Dis Sci. 1991;36(10):1371-6.

6. el-Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology. 1995;109(3):681-91.

7. Olbe L, Hamlet A, Dalenbäck J, Fändriks L. A mechanism by which Helicobacter pylori infection of the antrum contributes to the development of duodenal ulcer. Gastroenterology. 1996;110(5):1386-94.

8. Jensen RT, Niederle B, Mitry E, et al. Gastrinoma (duodenal and pancreatic). Neuroendocrinology. 2006;84(3):173-82.

9. Roy PK, Venzon DJ, Shojamanesh H, et al. Zollinger-Ellison syndrome. Clinical presentation in 261 patients. Medicine (Baltimore). 2000;79(6):379-411.

10. Hangen D, Maltz GS, Anderson JE, Knauer CM. Marked hypergastrinemia in gastric outlet obstruction. J Clin Gastroenterol. 1989; 11(4):442-4.

11. Rabago Torre LR, Gea Rodriguez F, Mora Sanz P, et al. The retained antrum, its endoscopic diagnosis and clinical significance [article in Spanish]. Rev Esp Enferm Dig. 1992;81(3):200-3.

12. Lord LM, Schaffner R, DeCross AJ, Sax HC. Management of the patient with short bowel syndrome. AACN Clin Issues. 2000;11(4):604-18.

13. Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14(3):579-623.

14. Duchayne E, Demur C, Rubie H, Robert A, Dastugue N. Diagnosis of acute basophilic leukemia. Leuk Lymphoma. 1999;32(3-4):269-78.

15. Olinger EJ, McCarthy DM, Young RC, Gardner JD. Hyperhistaminemia and hyperchlorhydria in basophilic granulocytic leukemia. Gastroenterology. 1976;71(4):667-9.

16. Burkitt MD, Pritchard DM. Review article: Pathogenesis and management of gastric carcinoid tumours. Aliment Pharmacol Ther. 2006;24(9):1305-20.

AUTHOR SPOTLIGHT

	Praveen K Roy, MD Chief of Gastroenterology Harry Truman Memorial VA Hospital University of Missouri-Columbia
	Abhishek Choudhary, MD Internal Medicine Resident Department of Internal Medicine University of Missouri-Columbia
Photo not available	Mohamed O Othman, MD Gastroenterology Fellow Division of Gastroenterology University of New Mexico

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