Elevations of serum ferritin levels can be due to inflammatory states

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 55-year-old man is evaluated during a routine examination. He feels well other than mild knee pain. He drinks six to eight cans of beer per night. He has no personal history of liver disease, but his older brother was recently diagnosed with hereditary hemochromatosis.

On physical examination, vital signs are normal; BMI is 24. He is tanned on sun-exposed body surfaces. Cardiac examination is normal. Abdominal examination reveals hepatomegaly. Bilateral bony hypertrophy of the knees is noted.

Laboratory studies:

Alanine aminotransferase	70 U/L
Aspartate aminotransferase	160 U/L
Ferritin	592 ng/mL (592 µg/L)
Transferrin saturation	40%

Genetic testing for hemochromatosis reveals heterozygosity for C282Y. Abdominal ultrasound reveals a change in liver echotexture consistent with fatty changes.

Which of the following is the most appropriate treatment?

A: Administer deferoxamine
B: Perform phlebotomy
C: Repeat serum iron tests now
D: Stop alcohol intake

MKSAP Answer and Critique

The correct answer is D: Stop alcohol intake.

This patient has alcohol-induced liver disease, and the most appropriate treatment is to stop alcohol intake. In alcohol-induced liver disease, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are typically elevated two to six times the upper limit of normal but AST levels above 500 U/L and ALT levels above 200 U/L are uncommon. An AST/ALT ratio above 2 to 3 is typical for alcoholic liver disease.

Hereditary hemochromatosis is an autosomal recessive disease, and homozygosity for C282Y is generally required to cause iron overload. The initial step in evaluating patients with suspected hemochromatosis is a serum transferrin saturation measurement, which is the most sensitive test in diagnosing this condition. Elevated serum transferrin saturations suggest hemochromatosis, and further assessment is advised, usually with serum ferritin measurement and hemochromatosis gene testing. Serum ferritin, although not usually used as an initial diagnostic study for suspected hemochromatosis, is a surrogate measure of iron stores; values greater than 1000 ng/mL (1000 µg/L) in the absence of an inflammatory state or another cause for liver disease suggest hemochromatosis. Serum ferritin measurement is therefore used as a follow-up study for elevated transferrin saturation levels. A liver biopsy specimen stained for iron confirms tissue iron overload. This patient is heterozygous for C282Y and has a slightly elevated serum ferritin level but a normal transferrin saturation; these findings do not support the diagnosis of hemochromatosis. Isolated elevations of serum ferritin, as seen in this patient, can be due to inflammatory states such as liver injury from another cause, including alcohol-induced liver disease. Phlebotomy (the treatment of choice for hemochromatosis) and iron chelation with deferoxamine (the typical treatment for secondary iron overload conditions) are not necessary at this time.

Repeating serum iron tests now will not add much useful information at this time; however, repeat testing should be performed later after the patient decreases his alcohol intake, as iron overload may result in some patients despite an absence of homozygosity for C282Y.

Key Point

Isolated elevations of serum ferritin levels can be due to inflammatory states such as liver injury from another cause, including alcohol-induced liver disease.′

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