How do you differentiate primary from secondary iron overload?

Medical history helps- transfusion history, chronic hemolytic anemias, ESRD on HD, and inflammatory conditions increase the risk of secondary iron.

In my practice, I use MRI to help distinguish between primary and secondary iron overload. In primary iron overload, the iron will only be seen in the liver. In secondary iron overload, the liver and spleen will be dark on T2, indicating iron in both organs.

The definitive way to differentiate is a liver biopsy. In primary iron overload, there will be iron in hepatocytes only. In secondary iron overload, there will be iron in hepatocytes and Kupffer cells.