Low Ferritin in a Vegetarian Woman with Regular Menstruation
Most Likely Cause
The low ferritin levels (10-25 ng/mL) in this reproductive-aged vegetarian woman with regular menstruation are most likely due to inadequate dietary iron intake combined with ongoing menstrual blood loss, representing true iron depletion. 1, 2
Primary Diagnostic Considerations
Iron Deficiency from Combined Factors
Vegetarian diet significantly reduces bioavailable iron intake, as plant-based (non-heme) iron has lower absorption compared to heme iron from animal sources 1
Regular menstruation causes ongoing iron losses of approximately 0.5-1 mg daily in reproductive-aged women, and ferritin levels below 20 ng/mL are found in 22-26% of healthy menstruating women 2, 3
The combination of vegetarian diet and menstruation creates a particularly high-risk scenario for iron depletion, with studies showing 19% of vegetarians develop iron deficiency, classified as iron depletion (ferritin <20 ng/mL without anemia) 4
Normal TSAT and serum iron levels do NOT rule out iron deficiency - this patient has isolated ferritin depletion (stage 1 iron deficiency) before functional iron deficiency develops 5, 2
Acid Reflux as Contributing Factor
Proton pump inhibitor (PPI) use for acid reflux significantly impairs iron absorption by reducing gastric acid needed to convert ferric iron to absorbable ferrous form 5
Chronic gastritis or H. pylori infection associated with acid reflux can cause iron malabsorption and should be ruled out, as these are common non-genetic causes of oral iron resistance 5
Critical Tests to Order
Rule Out Malabsorption
Test for celiac disease with tissue transglutaminase (TTG) antibodies, as celiac disease causes iron malabsorption and can present with isolated low ferritin 6
H. pylori testing (stool antigen or urea breath test) to exclude infection-related malabsorption 5
Upper endoscopy if PPI use is chronic to evaluate for autoimmune atrophic gastritis, which impairs both iron AND B12 absorption 5
Assess for Occult Blood Loss
Fecal occult blood testing to rule out gastrointestinal bleeding beyond menstrual losses 6
Detailed menstrual history including duration, heaviness (number of pads/tampons per day), and presence of clots to quantify menstrual blood loss 2
Evaluate Nerve Pain Etiology
The B12 level of 372 pg/mL is in the low-normal range (normal typically >200-300 pg/mL), and vegetarians have significantly lower B12 levels with 40% developing deficiency 4
Methylmalonic acid (MMA) and homocysteine levels should be measured to detect functional B12 deficiency, as serum B12 can be falsely normal when tissue deficiency exists 4
The nerve pain in hands and lower arms could represent early B12 neuropathy, which can occur even with "normal" serum B12 levels if functional deficiency is present 4
Thyroid function tests (TSH, free T4) as hypothyroidism can cause both peripheral neuropathy and contribute to anemia 6
Fluctuating Ferritin Pattern Analysis
The ferritin fluctuations (10→25→13→14→21 ng/mL) are NOT consistent with hemochromatosis or inflammatory conditions, as the European Association for the Study of the Liver states that "unexpected changes in serum ferritin or transferrin saturation levels should always be investigated, as significant fluctuations are not a feature of haemochromatosis" 5
These fluctuations likely reflect variable dietary iron intake, intermittent iron supplementation attempts, or timing relative to menstrual cycle, as ferritin can rise temporarily after iron-rich meals or supplementation 1, 2
All values remain below 30 ng/mL, confirming persistent iron depletion regardless of minor fluctuations 2
Additional Workup Considerations
Inflammatory Markers
High-sensitivity C-reactive protein (hs-CRP) to exclude occult inflammation that could mask true iron status, as inflammation elevates ferritin independent of iron stores 1, 6
Normal liver enzymes (ALT, AST) and albumin argue against chronic liver disease as a cause of altered iron metabolism 6
Functional Iron Assessment
Reticulocyte hemoglobin content (CHr or RET-He) provides direct assessment of iron availability for erythropoiesis and can detect functional iron deficiency before anemia develops 7, 6
Soluble transferrin receptor (sTfR) is elevated in true iron deficiency but not affected by inflammation, helping distinguish iron deficiency from anemia of chronic disease 7, 6
Critical Pitfalls to Avoid
Do not assume normal TSAT excludes iron deficiency - ferritin depletion (stage 1) precedes low TSAT (stage 2) and anemia (stage 3) 5, 2
Do not overlook celiac disease screening - this is a common cause of refractory iron deficiency in young women and can present without gastrointestinal symptoms 6
Do not dismiss the B12 level as "normal" - vegetarians are at high risk for B12 deficiency, and the value of 372 pg/mL is low-normal with 40% of vegetarians developing deficiency 4
Do not attribute nerve pain solely to carpal tunnel or other mechanical causes without excluding B12 deficiency, as peripheral neuropathy is an early manifestation 4
Do not start iron supplementation without addressing PPI use - acid suppression will impair oral iron absorption and lead to treatment failure 5
Recommended Management Algorithm
Immediately check celiac panel (TTG-IgA with total IgA), H. pylori testing, MMA, and homocysteine 5, 4
If celiac and H. pylori are negative, consider trial of oral iron supplementation (ferrous sulfate 325 mg daily) taken with vitamin C and separated from PPI by at least 2 hours 5
If no response to oral iron after 4-6 weeks (ferritin remains <30 ng/mL), consider intravenous iron therapy as this bypasses gastrointestinal absorption issues 5
If MMA or homocysteine are elevated, initiate B12 supplementation (1000 mcg daily oral or intramuscular injections) regardless of serum B12 level 4
Reassess ferritin every 1-2 months during treatment until levels reach >50 ng/mL, then maintain with dietary counseling and periodic monitoring 5, 2