Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (415 page)

   Chronic hemodialysis

   Porphyria cutanea tarda (minor)

   Alcoholic liver disease (iron deposited in Kupffer cells) and other chronic liver disorders

   Following portosystemic shunts

   Who Should Be Suspected?

IOD should be suspected in individuals with a family history of HH, or in its absence, in those with chronic liver disease, skin hyperpigmentation, or diabetes without predisposing factors and in patients with unexplained arthritis, cardiomyopathy, or hypogonadism. Weakness and lethargy can also be presenting manifestations of HH. Individuals with the secondary form of IOD have usually a history of a disease predisposing to increased iron stores or of multiple RBC transfusions.

   Laboratory Findings

   The presence of IOD is established by the demonstration of increased body iron using serum iron studies, radiologic techniques (MRI using special techniques),
liver biopsy
, and assessment of response to phlebotomy if clinically indicated. When one of the hereditary forms is suspected, genetic studies are helpful.

   Transferrin saturation is the best method for screening populations of North European ancestry suspected for IOD. A persistent value of >45% starting early in life remains the best predictive phenotypic test for the homozygous C282Y mutation (see below). Percent transferrin saturation is frequently >70% and may reach 100%.

   Total iron binding capacity is an assay similar to transferrin saturation, and parallels it, increasing with increase in iron store.

   Increased serum ferritin is found in approximately two thirds of patients with IOD. Levels >300 μg/L in men and >200 μg/L in women with no evidence of inflammatory or autoimmune disease are the recommended thresholds for further screening for IOD. The serum ferritin is usually >1,000 μg/L at the time of diagnosis, and it indicates biochemical accumulation of tissue iron. The critical threshold associated with the development of liver cirrhosis is unknown.

   Serum iron is usually increased (>200 μg/dL in women and >250 μg/dL in men), but it is a less reliable test, especially if performed alone.

   Other laboratory tests explore damage to various organs: