AKT · Endocrine/Lipids, metabolic & inherited

Haemochromatosis

Iron overload (hereditary HFE / secondary) → multi-organ deposition

Overview

Iron overload — hereditary (autosomal-recessive HFE mutations, commonest in those of northern European descent) or secondary (repeated transfusion). Iron deposits in liver, pancreas, heart, joints, skin and gonads. Classic late triad: 'bronze diabetes' + hepatomegaly/cirrhosis. Diagnosed by raised ferritin and transferrin saturation; treated by venesection.

Recognise

Fatigue, arthralgia (2nd/3rd MCP joints), erectile dysfunction/loss of libido (hypogonadism)
Skin bronzing/slate-grey pigmentation, DIABETES ('bronze diabetes'), hepatomegaly → cirrhosis, cardiomyopathy/arrhythmia
Raised ferritin AND raised TRANSFERRIN SATURATION (the key early markers)

Red flags

Cirrhosis → hepatocellular carcinoma risk (surveillance); cardiomyopathy/arrhythmia
First-degree relatives need screening (HFE genetics + iron studies)

Differentials & how to tell them apart

Other causes of raised ferritinferritin is an acute-phase reactant — inflammation, alcohol, fatty liver raise it; transferrin saturation distinguishes true iron overload

Secondary iron overloadtransfusion-dependent anaemias (thalassaemia) — managed with chelation, not venesection

Wilson diseasecopper (not iron) overload — young, neuro/psychiatric + liver, low caeruloplasmin

Investigations

Transferrin saturation (raised, >45%) and ferritin (raised) → HFE genetic testing (C282Y/H63D). Liver assessment (LFTs, fibrosis/elastography, MRI/biopsy for iron/cirrhosis); glucose; cardiac/endocrine evaluation.

Management

Regular venesection (chelation if transfusion-related)

1Confirm with transferrin saturation + ferritin → HFE genetics; assess organ damage (liver, glucose, heart). Treat hereditary disease with regular VENESECTION to deplete iron.Gate: Ferritin alone is non-specific (acute-phase) — use TRANSFERRIN SATURATION to confirm true iron overload; secondary (transfusional) overload needs CHELATION, not venesection; screen first-degree relatives
2Maintenance venesection; HCC surveillance if cirrhotic; manage diabetes/cardiomyopathy/hypogonadism; screen and counsel family.

Venesection (regular phlebotomy) — first-line for hereditary haemochromatosis — removes iron; target ferritin/transferrin saturation

Iron chelation (desferrioxamine) — for secondary (transfusional) overload where venesection is unsuitable

Avoid iron/vitamin C supplements and excess alcohol — reduce iron loading/liver damage

Key points

Fatigue + arthralgia + bronze skin + diabetes + deranged LFTs = think haemochromatosis → transferrin saturation + ferritin → HFE → venesect. 'Bronze diabetes'. Don't be fooled by ferritin alone (acute-phase).

Monitor & prognosis

Ferritin/transferrin saturation; LFTs; HCC surveillance.

Normal life expectancy if treated before cirrhosis.

Source: BSG; Society for Endocrinology