How to Diagnose Iron Overload

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http://mercola.com/2002/dec/18/iron_diagnosis.htm

 

 

How to Diagnose Iron Overload

 

 

 

 

 

 

By J. Mercola, D.O.

 

Genetic hemochromatosis is one of the most frequent inborn errors of

metabolism. Hereditary hemochromatosis is the most common inherited

single-gene disorder in people of northern European descent.[ii]

Most physicians have inadequate knowledge about how to properly diagnosis and

manage hemochromatosis.[iii] The current treatment of hereditary hemochromatosis

consists of performing periodic manual whole blood phlebotomies. There are some

newer traditionally based alternative treatments called erythroapheresis (EPH)

in which iron depletion was able to reduce ferritin to below 20 µg/l.[iv]

However, these approaches are inelegant in that they require significant time to

be therapeutically effective and are also quite inconvenient. The use of

naturally derived iron-based chelators like phytic acid (discussed below) is

more rapidly implemented, inexpensive and non-toxic.

Diagnosis of Iron Overload

The most useful laboratory test to ascertain hemochromatosis is measuring serum

iron concentration, total iron binding capacity, transferrin saturation and

serum ferritin. These should be done together.

The transferrin saturation, as a percentage, is calculated from 100 times serum

iron concentration divided by total iron binding capacity. Transferrin

saturation of greater than 50 percent detects most males or females with or

without iron loading, whereas normally it is 20 percent to 50 percent. It has

been proposed that the screening cutoff point should be 60 percent for males and

50 percent for females.

Other conditions may also elevate serum iron concentration and transferrin

saturation, particularly the recent ingestion of medicinal iron or

iron-fortified vitamin preparations, or oral contraceptives (Table 1).

Therefore, if the transferrin saturation is elevated, the test should be

repeated after eliminating such confounding variables.

TABLE

If the percent transferrin saturation is still elevated, a serum ferritin assay

should be performed. Percent transferrin saturation however, is a more sensitive

and specific test than is determination of the serum ferritin level, which can

be elevated for a variety of reasons listed below.

However, since serum ferritin is an acute-phase reactant, elevated values may

result from chronic disease, such as inflammation (as in rheumatoid arthritis),

or from malignancies. Liver injury from hepatitis or alcohol abuse also elevates

both the serum iron and the serum ferritin concentrations. High values of serum

ferritin may be observed in Gaucher's disease and in a rare familial disorder

associated with congenital cataracts (the hyperferritinemia-cataract syndrome),

without concomitant excess iron accumulation in the liver or other organs.

Therefore, elevated values of serum ferritin concentration must be interpreted

in the context of the presence or absence of these other conditions.[v]

TABLE

When there is marked iron overload, as in advanced hemochromatosis, the serum

ferritin concentration commonly exceeds 500 mug/L and may be >5000 mug/L. Each 1

mug/L of serum ferritin concentration is roughly equivalent to 120 mug of iron

stores/kg of body weight. A 70 kg person with a serum ferritin concentration of

3000 mug/g has approximately 17 to 33 grams of storage iron in ferritin and

hemosiderin. This contrasts with the normal iron stores of about 500 to 800 mg

in adult males or about 300 mg in adult women.

In some circumstances however, the relationship between plasma ferritin and body

iron stores is distorted: the plasma ferritin may greatly underestimate the

extent of iron accumulation or may even be normal despite a considerable

increase in body iron in a small number of patients with hereditary

hemochromatosis.[vi]

A serum iron and TIBC or transferrin test, with calculation of the transferrin

saturation, along with a serum ferritin level should be obtained in the fasting

state. Over 50 percent of patients have transiently elevated serum iron levels

after eating, and thus if the blood sample is not drawn in the fasting state,

the transferrin saturation can be elevated in the absence of increased iron

stores. In addition to the increased serum iron level after meals, there is a

diurnal variation in serum iron concentration as well. For these reasons, it is

recommended that whenever one is trying to establish the diagnosis of HHC, a

fasting patient should have blood drawn for serum iron studies in the morning.

The combination of an elevated transferrin saturation level and an elevated

ferritin level in an otherwise healthy individual is 93 percent sensitive for

hemochromatosis. Conversely, in someone older than the age of 35 the combination

of a normal ferritin level and a normal transferrin saturation has a negative

predictive accuracy of 97 percent, indicating that there is only a three percent

chance of missing a diagnosis of hemoochromatosis in a patient of this age or

older who has normal iron studies.[vii]

Unsaturated iron binding capacity is an inexpensive alternative to percent

transferrin saturation for the detection of hereditary hemochromatosis. The

optimum threshold for detection is 143 microg/dL (25.6 micromol/L), giving a

sensitivity of 0.91 and specificity of 0.95. [viii]

References:

Niederau C, Strohmeyer G. Strategies for early diagnosis of

haemochromatosis. Eur J Gastroenterol Hepatol. 2002 Mar;14(3):217-21

[ii] Brandhagen DJ, Fairbanks VF, Baldus W. Recognition and management of

hereditary hemochromatosis. Am Fam Physician. 2002 Mar 1;65(5):853-60

[iii] Acton RT, Barton JC, Casebeer L, et. Al. Survey of physician knowledge

about hemochromatosis. Genet Med. 2002 May-Jun;4(3):136-41

[iv] Muncunill J, Vaquer P, Galmes A, et al. In hereditary hemochromatosis, red

cell apheresis removes excess iron twice as fast as manual whole blood

phlebotomy. J Clin Apheresis. 2002;17(2):88-92.

[v] Goldman: Cecil Textbook of Medicine, 21st ed., 2000 W. B. Saunders Company

p.1133

[vi] Deugnier YM, Turlin B, Powell LW et al: Differentiation between

heterozygotes and homozygotes in genetic hemochromatosis by means of a

histological hepatic iron index: a study of 192 cases. Hepatology 17:30, 1993

[vii] Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 6th

ed., 1998 W. B. Saunders Company

[viii] Murtagh LJ, Whiley M, Wilson S, et al Unsaturated iron binding capacity

and transferrin saturation are equally reliable in detection of HFE

hemochromatosis. Am J Gastroenterol. 2002 Aug;97(8):2093-9

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