The role of soluble transferrin receptor levels in the differential diagnosis of iron deficiency anemia and anemia of chronic disease in patients with gastrointestinal malignancy

Öz

Aim: Anemia is a common complication in patients with gastrointestinal malignancies. This study aimed to investigate the role of serum soluble transferrin receptor (sTfR), sTfR/log ferritin index, and hepcidin levels in the differential diagnosis of iron deficiency anemia (IDA) and anemia of chronic disease (ACD) in anemic patients with gastrointestinal malignancies. Material and Methods: The study included 126 anemic patients with gastrointestinal malignancies followed at Ankara Numune Training and Research Hospital. Serum iron, total iron-binding capacity, ferritin, vitamin B12, folic acid, sTfR, and hepcidin levels were measured, and the sTfR/log ferritin index was calculated. Based on transferrin saturation, patients were classified into two groups: IDA (transferrin saturation ≤20%) and ACD (transferrin saturation >20%). The diagnostic performance of sTfR and sTfR/log ferritin index was assessed using ROC analysis. Results:The sTfR level and sTfR/log ferritin index were significantly higher in the IDA group compared to the ACD group (p < 0.001). The sensitivity and specificity of sTfR for identifying IDA were 77.1% and 67.9%, respectively, with a cutoff value of 1.65 mg/L. Ferritin showed lower sensitivity (57.1%) but higher specificity (76.8%). No significant difference was found in hepcidin levels between the two groups. Conclusion: sTfR and the sTfR/log ferritin index are useful parameters for distinguishing IDA from ACD in patients with gastrointestinal malignancies. Hepcidin levels may not be effective due to their acute-phase reactant properties. Standardization of sTfR measurement and further large-scale studies are needed to determine optimal cutoff values for different patient populations.

Anahtar Kelimeler

• Soluble transferrin receptor (sTfR)
• sTfR/log ferritin index
• Hepcidin
• Gastrointestinal ma-lignancy

Gastrointestinal sistem maligniteli hastalarda demir eksikliği ve kronik hastalık anemisi ayırıcı tanısında soluble transferrin reseptör düzeylerinin yeri

Öz

Amaç: Anemi, gastrointestinal malignite hastalarında sık görülen bir komplikasyondur. Bu çalışma, anemik gastrointestinal maligniteli hastalarda serum soluble transferrin reseptör (sTfR), sTfR/log ferritin indeksi ve hepsidin seviyelerinin demir eksikliği anemisi (DEA) ile kronik hastalık anemisi (KHA) ayırıcı tanısındaki rolünü araştırmayı amaçladı. Gereç ve Yöntemler: Çalışmaya Ankara Numune Eğitim ve Araştırma Hastanesi’nde takip edilen gastrointestinal maligniteli 126 anemik hasta dahil edildi. Serum demir, total demir bağlama kapasitesi, ferritin, vitamin B12, folik asit, sTfR ve hepsidin seviyeleri ölçüldü ve sTfR/log ferritin indeksi hesaplandı. Transferrin saturasyonuna göre hastalar DEA (transferrin saturasyonu ≤ %20) ve KHA (transferrin saturasyonu > %20) olarak iki gruba ayrıldı. sTfR ve sTfR/log ferritin indeksinin tanısal performansı ROC analizi ile değerlendirildi. Bulgular: sTfR düzeyi ve sTfR/log ferritin indeksi DEA grubunda KHA grubuna kıyasla anlamlı derecede yüksekti (p < 0,001). sTfR'nin DEA’yı belirlemede duyarlılığı %77,1 ve özgüllüğü %67,9 olarak bulundu (1,65 mg/L kesim noktası). Ferritin için duyarlılık %57,1, özgüllük ise %76,8 olarak hesaplandı. Hepsidin düzeyleri açısından iki grup arasında anlamlı fark bulunmadı. Sonuç: sTfR ve sTfR/log ferritin indeksi, gastrointestinal maligniteli hastalarda DEA ile KHA ayırıcı tanısında faydalı parametrelerdir. Hepsidin seviyeleri, akut faz reaktanı özelliği nedeniyle ayırıcı tanıda etkili olmayabilir. sTfR ölçümünün standardizasyonu ve farklı hasta grupları için optimal kesim noktalarının belirlenmesi amacıyla daha geniş çaplı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Soluble transferrin receptor (sTfR)
• sTfR/log ferritin index
• Hepcidin
• Gastrointestinal ma-lignancy

Destekleyen Kurum

Araştırmacıların herhangi bir çıkar ilişkisi bulunmamaktadır.

Etik Beyan

Bu çalışma için, Ankara Numune Eğitim ve Araştırma Hastanesi Klinik Araştırmalar Etik Kurulu tarafından 27.07.2011 tarih ve 211/2011 karar numarası ile onay verilmiştir.

Kaynakça

1. Ge JN, Yu JC, Kang WM, Ma ZQ, Gu YC. Investigation of tumor related anemia in 10,218 patients with cancer in the digestive system. Chin J Gastrointest Surg 2011; 14: 340-2.
2. Centers for Disease Control and Prevention. CDC recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep 1998; 47: 1-29.
3. Cook JD, Baynes RD, Skikne BS. The physiological significance of circulating transferrin receptors. In: Ailen L, King J, Lönnerdal B, eds. New York: Plenum Press; 1994. p.119-26.
4. Fleming DJ, Jacques P, Tucker K, Massaro J, Wilson P. Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores. Am J Clin Nutr 2001; 73: 638–46.
5. Joosten E, Van Loon R, Bilen J, Blanckaert N, Fabri R, Pelemans W. Serum transferrin receptor in the evaluation of the iron status in elderly hospitalized patients with anaemia. Am J Hematol 2002; 69: 1-6.
6. Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997; 89: 1052-7.
7. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005; 352: 1011.
8. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003; 102: 783-8.

9. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron-regulatory hormone hepcidin. J Clin Invest 2004; 113: 1271-6.
10. Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci USA 2005; 102: 1906-10.
11. Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL. Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 1990; 322: 1689-92.
12. Suominen P, Mottonen T, Rajama A, Irjala K. Single values of serum transferrin receptor and transferrin receptor–ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum 2000; 43: 1016-20.
13. Wians FH Jr, Urban JE, Keffer JH, Kroft SH. Discriminating between iron deficiency anemia and anemia of chronic disease using traditional indices of iron status vs transferrin receptor concentration. Am J Clin Pathol 2001; 115: 112–8.
14. Lee MH, Park E, Lee J, et al. Cutoff values of serum ferritin and TIBC saturation for the evaluation of gastrointestinal neoplasms in adult anemic patients. Int J Hematol 2012; 96: 214-21.
15. Berlin T, Meyer A, Rotman P, Natur A, Levy Y. Soluble transferrin receptor as a diagnostic laboratory test for detection of iron deficiency anemia in acute illness of hospitalized patients. Isr Med Assoc J 2011; 13: 96–8.
16. Infusino I, Braga F, Dolci A, Panteghini M. Soluble transferrin receptor (sTfR) and sTfR/log ferritin index for the diagnosis of iron-deficiency anemia: a meta-analysis. Am J Clin Pathol 2012; 138: 642–9.
17. Koulaouzidis A, Said E, Cottier R, Saeed AA. Soluble transferrin receptors and iron deficiency, a step beyond ferritin: a systematic review. J Gastrointestin Liver Dis 2009; 18: 345–52.
18. Pasricha SR, McQuilten Z, Westerman M, Keller A, Nemeth E, Ganz T, Wood E. Serum hepcidin as diagnostic test of iron deficiency in premenopausal female blood donors. Haematologica 2011; 96: 1099-105.
19. Thomas C, Kobold U, Thomas L. Serum hepcidin-25 in comparison to biochemical markers and hematological indices for the differentiation of iron-restricted erythropoiesis. Clin Chem Lab Med 2011; 49: 207–13.
20. Goodnough LT. Iron deficiency syndromes and iron-restricted erythropoiesis (CME). Transfusion 2012; 52: 1584–92.