Neuroendocrine Tumours – Iron

What is Iron?

Iron is an essential mineral required for oxygen transport, energy production, and cellular metabolism. It exists in two main dietary forms:

• Haem iron — from animal sources; highly bioavailable
• Non‑haem iron — from plant sources; absorption varies with diet and gut health

Iron is stored mainly in the liver, spleen, and bone marrow. Because the body has no active excretion pathway, iron balance depends entirely on absorption and losses — making deficiency relatively common.

What does Iron do?

• Forms haemoglobin for oxygen transport
• Supports myoglobin in muscle tissue
• Enables mitochondrial energy production
• Supports immune function
• Participates in DNA synthesis

Deficiency

Iron deficiency is the most common micronutrient deficiency worldwide. It may result from:

• Inadequate intake
• Chronic inflammation
• Malabsorption
• Chronic blood loss
• Gastrointestinal disease

Functional iron deficiency occurs when iron stores are adequate but unavailable due to inflammation‑driven hepcidin elevation.

Symptoms

• Fatigue and reduced exercise tolerance
• Shortness of breath
• Restless legs
• Hair loss
• Cold intolerance
• Pale skin
• Pagophagia (ice craving)
• Brittle nails / koilonychia
• Cognitive fog / reduced concentration

Iron deficiency anaemia

Occurs when iron stores are exhausted and haemoglobin production falls.

Testing

Common tests include:

• Serum ferritin — reflects iron stores; low ferritin indicates deficiency unless inflammation is present
• Transferrin saturation (TSAT) — indicates available iron; particularly useful in chronic disease or inflammation
• Serum iron — fluctuates; less useful alone
• Full blood count (FBC) — microcytic anaemia in deficiency

Inflammation can raise ferritin, masking deficiency.

Sources & Absorption

• Haem iron — red meat, poultry, fish
• Non‑haem iron — legumes, whole grains, nuts, seeds, leafy greens

Absorption is enhanced by Vitamin C and inhibited by:

• Tea/coffee (polyphenols)
• Calcium
• Phytates (whole grains, legumes)
• Some medications (PPIs)

Iron is best absorbed on an empty stomach, though taking it with food may reduce side effects.

Supplements & Toxicity

Supplements

• Ferrous salts (sulfate, fumarate, gluconate) — widely used, effective
• Polysaccharide iron — gentler on the stomach
• IV iron — for severe deficiency or malabsorption

Side effects of oral iron include nausea, constipation, and dark stools.

Emerging evidence suggests that alternate‑day dosing may improve absorption and reduce side effects.

Toxicity

Iron overload is uncommon without:

• Hereditary haemochromatosis
• Repeated transfusions
• Excessive supplementation

Symptoms include joint pain, fatigue, liver dysfunction, and skin pigmentation.

NET‑Specific Considerations

Iron deficiency is common in people with NETs due to several mechanisms:

• Chronic diarrhoea reducing nutrient absorption
• Small bowel NETs or resection impairing iron uptake It primarily occurs due to chronic, occult (hidden) blood loss from fragile tumour tissues in the stomach, duodenum, or small intestine. Malabsorption can also contribute.
• Duodenal NETs (duodenum/jejunum)
• Gastric NETs or atrophic gastritis reducing acid → impaired iron absorption
• Chronic bleeding (e.g., from small bowel lesions)
• Inflammation causing functional iron deficiency (hepcidin‑mediated)
• Mesenteric fibrosis affecting motility or causing intermittent bleeding
• SIBO contributing to both iron and B12 deficiency

Iron deficiency may coexist with B12 deficiency, especially after ileal resection or in SIBO.

See my coverage of Vitamin B12 (Cobalamin)