What Causes Both Hypokalemia and Iron Deficiency Anemia?
The most likely unifying diagnosis causing both hypokalemia and iron deficiency anemia is chronic gastrointestinal blood loss, particularly from conditions affecting the upper GI tract or colon, with villous adenomas being a classic culprit that can cause both through potassium-rich mucus secretion and occult bleeding.
Primary Mechanism: Gastrointestinal Pathology
The combination of hypokalemia and iron deficiency anemia strongly suggests a GI source, as:
- Gastrointestinal blood loss is the leading cause of iron deficiency anemia in men and postmenopausal women, with colorectal cancer, gastric cancer, peptic ulcer disease, and NSAID-induced mucosal damage being major sources 1, 2
- Villous adenomas of the colon are particularly notorious for causing both conditions simultaneously through:
- Chronic occult blood loss leading to iron deficiency anemia
- Secretion of potassium-rich mucus causing hypokalemia (can lose 3-4 liters/day of potassium-rich fluid)
Other GI Causes to Consider
Malabsorption syndromes can contribute to both conditions:
- Celiac disease is found in 3-5% of iron deficiency anemia cases and should be routinely screened 1, 2
- Celiac disease can cause hypokalemia through chronic diarrhea and malabsorption
- Previous gastrectomy, gastric atrophy, and chronic PPI therapy can impair iron absorption 1, 2
Chronic diarrheal states from any cause (inflammatory bowel disease, bacterial overgrowth) can produce:
- Iron malabsorption and chronic blood loss 2
- Potassium losses through stool
Investigation Algorithm
Step 1: Confirm both diagnoses
- Serum ferritin is the most powerful test for iron deficiency (typically <30 ng/mL) 3, 4
- Serum potassium with repeat testing to confirm hypokalemia
- Check for microcytic anemia on CBC 3
Step 2: Bidirectional endoscopy is mandatory
- Upper and lower GI investigations should be considered in all postmenopausal women and all men where iron deficiency anemia has been confirmed 3
- Colonoscopy has advantages over CT colonography and is preferable to barium enema 3
- Look specifically for villous adenomas, which may be large and sessile
Step 3: Screen for celiac disease
- All patients should be screened for celiac disease regardless of age 3, 1
- Tissue transglutaminase antibodies with duodenal biopsies during upper endoscopy
Step 4: Assess for chronic blood loss
- Approximately one-third of men and postmenopausal women with iron deficiency anemia have an underlying pathological GI abnormality 1, 2
- Multiple causes may coexist in the same patient, and finding one cause should not deter further investigation 1, 2
Critical Clinical Pitfalls
Do not assume menstruation explains everything in premenopausal women - while menstrual blood loss is the most common cause of iron deficiency anemia in this population 1, 2, it does not explain hypokalemia and warrants GI investigation if both are present.
Do not stop at finding one abnormality - the presence of NSAID use, H. pylori gastritis, or other common findings should not prevent complete evaluation when both electrolyte and hematologic abnormalities coexist 1, 2.
Consider medication effects - chronic laxative abuse or diuretic use can cause hypokalemia but would not typically cause iron deficiency anemia unless there is concurrent GI pathology.