Laboratory Values Indicating Iron Overload in Women
In women, iron overload is indicated by transferrin saturation >45% and serum ferritin >200 μg/L, according to the most recent European Association for the Study of the Liver (EASL) guidelines. 1
Primary Diagnostic Parameters
Transferrin Saturation (TSAT)
- Women: >45% indicates iron overload 1, 2
- Calculated by dividing serum iron by total iron binding capacity (TIBC)
- Fasting samples are preferred as they eliminate circadian variations and reduce false-positive results by approximately 80% 1
- Should be measured before any iron parameter assessment is performed
Serum Ferritin
- Women: >200 μg/L indicates iron overload 1
- Post-menopausal women may follow the male threshold of >300 μg/L 1
Additional Laboratory Considerations
Interpretation Challenges
- Biological variability can limit the reliability of a single measurement
- Up to 33% of C282Y homozygotes (hereditary hemochromatosis) may be missed with a single TSAT measurement 3
- Repeat testing may be necessary when iron overload is suspected but initial values are borderline
Confounding Factors
- Several conditions can cause elevated ferritin without true iron overload:
- Inflammatory conditions (check C-reactive protein)
- Fatty liver disease (most common cause of elevated ferritin with normal TSAT)
- Alcoholic liver disease
- Metabolic syndrome
- Acute or chronic liver damage 2
Additional Testing When Iron Overload Is Suspected
- Complete iron studies panel including:
- Serum iron
- Total iron binding capacity (TIBC)
- Transferrin saturation
- Serum ferritin 2
- Liver function tests (ALT, AST)
- HFE gene testing for p.C282Y mutations, especially in patients with European ancestry 2
- MRI can detect and quantify hepatic iron excess with high sensitivity and specificity 2
Clinical Significance of Iron Overload Values
- Serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of increased iron stores across multiple ethnic populations 4
- Early identification and treatment of iron overload before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 2
- In women with C282Y homozygosity (hereditary hemochromatosis), 46.9% will have both elevated TSAT and ferritin values 5
Racial/Ethnic Considerations
- African Americans tend to have lower mean TSAT but higher mean serum ferritin compared to whites 5
- The prevalence of elevated serum ferritin >900 μg/L varies by ethnicity: 7 per 10,000 among Caucasians, 13 per 10,000 among Hispanics, 20 per 10,000 among African Americans, and 38 per 10,000 among Asians and Pacific Islanders 4
Remember that laboratory values should be interpreted in the clinical context, and a combination of elevated transferrin saturation and serum ferritin provides stronger evidence of iron overload than either parameter alone.