Iron Overload


Hereditary Hemochromatosis

Secondary Iron Overload


EXTREMELY HIGH FERRITIN LEVELS — Extremely high ferritin levels (ie, >10,000 ng/mL) in the absence of genetic or transfusional iron overload may be found in a number of conditions, such as juvenile idiopathic arthritis, systemic lupus erythematosus, and hemophagocytic lymphohistiocytosis (HLH). It is important that HLH be considered in this context, as this condition can be fatal if not diagnosed and treated in an urgent manner. (See “Pathophysiology and diagnosis of iron overload syndromes”, section on ‘High levels of ferritin in the absence of iron overload’ and “Clinical features and diagnosis of hemophagocytic lymphohistiocytosis”, section on ‘Serum ferritin levels’.)

## Physiology

In normal subjects there is no mechanism to regulate iron loss from the body, which averages about 1 mg/day in adult men from sweat, shed skin cells, and gastrointestinal losses. Premenopausal adult women lose an additional 0.5 to 1.0 mg/day because of menses. Therefore, to insure normal stores of iron within the body, iron absorption must be tightly regulated. A simple calculation will make this clear. If iron absorption is increased in an individual by as little as 1.5 mg/day above the amount needed to achieve homeostasis, this will result in the accumulation of 5.5 grams of iron every decade, 16 grams in 30 years and 33 grams in 60 years. This latter figure corresponds to the amount of iron (30 to 40 g) usually found in patients with clinically detected hereditary hemochromatosis (HH) and explains both the delayed time for the clinical appearance of this disease in men and its rarity in premenopausal women. (See “Regulation of iron balance”.)

As a result of the inability to increase iron loss, iron overload is an inevitable response to increased iron entry into the body. This can occur by one of three mechanisms (table 1):

●A massive increase in iron intake

●An increase in iron absorption when iron intake is normal

●The parenteral administration of iron, as with transfusional overload