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Dysmetabolic hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin

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Abstract

Hyperferritinemia is common in individuals with the metabolic syndrome (dysmetabolic hyperferritinemia), but its pathophysiology and the degree to which it reflects tissue iron overload remains unclear. We conducted a cross-sectional study evaluating ten cases with dysmetabolic hyperferritinemia for liver iron overload and compared their serum iron indices and urine hepcidin levels to healthy controls. Seven out of ten cases had mild hepatic iron overload by magnetic resonance imaging (MRI) (median, 75 μmol/g dry weight). Cases had higher serum ferritin than controls (median, 672 μg/L vs. 105 μg/L, p < 0.001), but the median transferrin saturation was not significantly different (38% vs. 36%, p = 0.5). Urinary hepcidin was elevated in dysmetabolic hyperferritinemia (median; 1,584 ng/mg of creatinine vs. 799 ng/mg of creatinine, p = 0.05). Dysmetabolic hyperferritinemia is characterized by hyperferritinemia with normal transferrin saturation, elevated hepcidin levels, and mild liver iron overload in a subset of patients.

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Conflict of interest

No authors have a conflict of interest to report.

Funding source

Internally funded study

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Authors and Affiliations

  1. Department of Medicine and Centre for Health Education Scholarship, University of British Columbia, Vancouver, BC, Canada

    Luke Y. Chen

  2. Department of Radiology, University of British Columbia, Vancouver, BC, Canada

    Silvia D. Chang

  3. Department of Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Vancouver, BC, Canada, V5Z 1M9

    Gayatri M. Sreenivasan, Peter W. Tsang, Raewyn C. Broady, Charles H. Li & Leslie N. Zypchen

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  1. Luke Y. Chen
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  2. Silvia D. Chang
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  3. Gayatri M. Sreenivasan
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  4. Peter W. Tsang
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  5. Raewyn C. Broady
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  6. Charles H. Li
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  7. Leslie N. Zypchen
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Corresponding author

Correspondence to Leslie N. Zypchen.

Additional information

All authors had access to the data and were involved in writing the manuscript. LC and LZ designed the study, collected and analyzed the data, and wrote the manuscript. SC analyzed the MRIs and wrote the manuscript. GS, CL, RB, and PT assisted in the study design, collected data, and wrote the manuscript.

Appendix

Appendix

MRI technique for measurement of body iron overload

The MRI examinations were performed with a 1.5 T unit (Signa Horizon, GE Healthcare). A body coil was used with a bandwidth of 1.25 KHz, a 256 × 128 matrix, a field of view of 40 cm and slick thickness of 10 mm. Five sequences were acquired to calculate the liver iron concentration with the following parameters: (1) T1-weighted gradient echo (GRE) sequence, repetition time (TR) = 120 ms, echo time (TE) = 4 ms; flip angle = 90°; (2) proton density-weighted GRE sequence, TR = 120 ms, TE = 4 ms; flip angle = 20°; (3) T2-weighted GRE sequence, TR = 120 ms, TE = 9 ms; flip angle = 20°, (4) moderately high T2-weighted GRE sequence, TR = 120 ms, TE = 14 ms; flip angle = 20°; and (5) highly T2-weighted GRE sequence, TR = 120 ms, TE = 21 ms; flip angle = 20°. Axial fast recovery fast spin echo T2 with fat saturation (TR = 2,000, TE = 95, 6-mm slice thickness) and coronal single shot fast spin echo T2 (TR = infinity, TE = 99, 8-mm slice thickness) sequences were also acquired.

For each patient, liver signal intensity was measured for all five GRE sequences by applying three regions of interest on the same image on the peripheral aspect of the right hepatic lobe taking care not to include the blood vessels. Muscle signal intensity was measured by placing two regions of interest, one on the right paraspinal muscle and the other on the left paraspinal muscle. The degree of hepatic iron overload was calculated using the software program established by Y. Gandon (http://www.radio.univ-rennes1.fr/Sources/EN/Hemo.html).

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Chen, L.Y., Chang, S.D., Sreenivasan, G.M. et al. Dysmetabolic hyperferritinemia is associated with normal transferrin saturation, mild hepatic iron overload, and elevated hepcidin. Ann Hematol 90, 139–143 (2011). https://doi.org/10.1007/s00277-010-1050-x

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  • DOI: https://doi.org/10.1007/s00277-010-1050-x

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