Achlorhydria Workup

Updated: Jul 15, 2016
  • Author: Divyanshoo Rai Kohli, MD; Chief Editor: BS Anand, MD  more...
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Laboratory Studies

Although not all patients with suspected achlorhydria need documentary evidence of a lack of acid production, the most important study to prove the presence of the condition is measurement of basal acid secretion.

For practical purposes, gastric pH at endoscopy should be done in patients with suspected achlorhydria. Older testing methods using fluid aspiration through a nasogastric tube can be done. These procedures can cause significant patient discomfort and are less efficient in obtaining a diagnosis. It has been proposed that fasting gastric pH can be predicted noninvasively using an equation based on the serum pepsinogen I level and the presence/absence of H pylori.

See Procedures.

Antiparietal cell antibody testing should be ordered because a strong association exists between achlorhydria and so-called autoimmune conditions. If achlorhydria is confirmed, patients should have a hydrogen breath test to check for bacterial overgrowth. Iron indices, calcium, prothrombin time, vitamin B-12, vitamin D, and thiamine levels should be checked to exclude deficiencies. Complete blood count with indices and peripheral smears can be examined to exclude anemia. Elevation of serum folate is suggestive of small bowel bacterial overgrowth. Indeed, bacterial folate can be absorbed into the circulation.

H pylori infection can be inferred from the presence of immunoglobulin G (IgG) antibodies directed against H pylori. If endoscopy is performed, the most convenient biopsy-based test is the urease enzyme test, which is based on a change in color of an indicator dye due to urea degradation. Histologic examination of biopsy specimens is the most sensitive test, provided that a special stain (eg, a modified Giemsa or silver stain) permitting optimal visualization of H pylori is used. Culture of H pylori is the most specific test but is difficult.

A complete profile of gastric acid secretion is best obtained during a 24-hour gastric pH study.

Achlorhydria may also be documented by measurements of extremely low serum levels of pepsinogen A (PgA) (

High serum gastrin levels (>500-1000 pg/mL) may support a diagnosis of achlorhydria.

Litmus paper is readily available to examine the pH of gastric secretions and, in contrast to the pH electrode, is less expensive while providing equally reliable results.



Upper gastrointestinal endoscopy

To exclude gastric carcinoids at the time of diagnosis, an upper GI endoscopy may be indicated. Extensive literature examines the utility of upper GI endoscopy to screen patients with diabetes mellitus and antiparietal cell antibodies for gastric carcinoid tumors. Because of the low incidence of gastric carcinoid tumors, there is no evidence that upper GI endoscopy in screening these patients is of clinical benefit.

Gastric acid output measurement

Gastric acid output measurement consists of a timed collection of acid production; results are reported in mEq/h.

The patient is placed in the left lateral decubitus position. A nasogastric tube is passed into the antrum after an overnight fast. Fluoroscopy can be used to guide accurate tube placement.

The initial aspirated fluid is discarded. A specimen is collected for 1 hour (at 15-min intervals) to assess fasting basal acid output (reference range, 1-6 mEq/h). Acid secretion is then stimulated by administration of intravenous pentagastrin (2 U/kg). Four subsequent specimens in 15-minute aliquots are collected to determine maximal acid output (reference range,

Acidity is measured either by titration with the chemical indicator methyl red or by use of a pH electrode. Patients with achlorhydria do not respond with an increase of acid output after pentagastrin stimulation.

Intragastric pH measurements

Intragastric pH measurements during endoscopy may be a valuable screening method.

A pH electrode for titration of H+ is passed through the biopsy channel of the endoscope. If the pH is found to be 4.0 or higher (and if no further decrease in pH occurs over time), patients may undergo a pentagastrin stimulation test.

More than 50% of patients whose initial stomach pH is 4.0 or higher are hypochlorhydric or achlorhydric.


Histologic Findings

Gastric atrophy leads to achlorhydria. The subsequent increase of blood gastrin levels may lead to enterochromaffin hyperplasia with the possible, though rare, development of carcinoid tumors after achlorhydria. Patients with multiple endocrine neoplasia type 1 syndrome may develop carcinoids at some stage of their disease.

Another consequence resulting from gastric atrophy includes the development of benign gastric polyps. Conversely, patients who have gastric polyps have a high incidence of otherwise unsuspected achlorhydria and of unsuspected vitamin B-12 malabsorption (50%). In addition, gastric atrophy is considered a predisposing condition for adenocarcinoma of the stomach, especially in those patients who develop intestinal metaplasia.