Iron Malabsorption Associated with Elevated Serum Gastrin

Iron deficiency anemia (IDA) in the absence of gastrointestinal (GI) bleeding is a common cause for hematologic consultation.  During a 24 month period a single hematologist evaluated 36 patients for iron deficiency anemia which was unresponsive to oral iron replacement.  Patients who had active GI bleeding, bariatric or extensive gastric surgery, or menorrhagia were excluded from this study.

Hematologic testing included a serum gastrin level, Helicobacter pylori antibodies, and anti gliadin antibodies.  Serum cobalamin levels were not measured.

28 patients had elevated gastrin levels, 3 patients had positive anti gliadin antibodies, and 2 patients had positive anti Helicobacter antibodies.  One patient had both an elevated gastrin level and a positive anti gliadin antibody.  One patient had both an elevated gastrin level and an anti helicobacter antibody.  One patient had profound hypothyroidism (TSH>100) whose iron deficiency corrected with thyroid replacement. 

Proton pump inhibitors (PPI) raise the serum gastrin levels.  16 patients with an elevated serum gastrin level were taking PPI when the gastrin measurements were obtained. However, the remaining 14 patients were not taking a PPI when gastrin levels were measured. 

23 patients were women and 13 were men.  No patient was under 40 years old.  11 were between 45 and 59 years of age.  25 were between 63 and 88 years old.  26 patients were non Hispanic caucasians, 8 were Hispanic caucasians, and 1 patient was African American.

In the absence of a gastrin secreting tumor or use of a PPI an elevated gastrin suggests that autoimmune gastric atrophy is present which can cause both iron and vitamin B12 malabsorption.

Iron malabsorption does occur in gluten enteropathy which is diagnosed by positive anti gliadin antibodies.  Helicobacter infections are also associated with iron malabsorption.

Intravenous iron replacement with iron dextran was administered to 35 patients.  Two patients had minor reactions to iron dextran.  One subsequently received iron sucrose without incident, but the other patient did not tolerate iron sucrose, iron carboxymaltose, and ferric gluconate.

The 28 patients with an elevated gastrin has a complete response to intravenous iron replacement except the one patient who was intolerant to all intravenous iron preparations.  Those with celiac sprue and helicobacter infections responded incompletely to intravenous iron therapy and required dietary modification and anti helicobacter therapy.

An abnormal gastric biopsy was found in 3 of 28 patients with an elevated serum gastrin level.  None of the 4 patients with a Helicobacter infection, gluten enteropathy, or severe hypothyroidism had a diagnostic esophagogastroduodenoscopy.

In this small study no clear relationship between an elevated gastrin and either gluten enteropathy or a Helicobacter was present.

This study has two interesting conclusions.  First PPI therapy alone can cause iron deficiency anemia due to iron malabsorption.  Also autoimmune gastric atrophy is a probable cause of IDA even when the gastrointestinal evaluation does not demonstrate bleeding or gastric atrophy.  Both conditions are associated with an elevated serum gastrin.

Serum gastrin measurement should be obtained during an evaluation for iron deficiency of unclear etiology.