Albertine Donker

Summary 341 10 with ferritin and transferrin saturation (TSAT). Serum hepcidin levels, hepcidin/ferritin and TSAT/hepcidin ratios were similar for both sexes. Serum hepcidin and hepcidin/ ferritin ratio substantially declined after the age of 12 years, TSAT/hepcidin ratio gradually increased with increasing age. Corroborating with data in adults, we found that serum ferritin was the most significant correlate of serum hepcidin in our study population, explaining 15.1 % and 7.9 % of variance in boys and girls, respectively. Multivariable linear regression analysis including age, blood sampling time, iron parameters, ALT, CRP and BMI as independent variables showed a statistically significant negative association between age as dichotomous variable (≤ 12 years versus >12 years) and log-transformed serum hepcidin levels in both sexes. With this study we demonstrated that serum hepcidin relative to indicators of body iron is age dependent in children, suggesting that the set point of serum hepcidin relative to stored and circulating iron changes during childhood. In Chapter 8 we described a study assessing the value of the TSAT/hepcidin ratio in discriminating IRIDA from iron deficiency anemia due to acquired causes, e.g. gastro-intestinal or vaginal blood loss of malabsorption. We included 21 IRIDA patients from various hospitals in the Netherlands and 39 IDA controls from the Gastroenterology, Gynecology and Emergency Department of the Máxima Medical Center, Veldhoven, the Netherlands. We measured serum hepcidin-25 levels in all patients by an isotope dilution mass spectrometry assay and calculated the TSAT/ hepcidin ratio. We observed that the TSAT/hepcidin ratio was significantly lower in IRIDA patients compared to IDA controls. Area under the receiver operating characteristic (ROC) curve for the TSAT/hepcidin ratio was 0.991 with a specificity of 100% (95% Confidence Interval, 93-100%), a sensitivity of 95% (95% CI, 79-100%) at an optimal cut-off point of 5.9%/nM to distinguish IRIDA from IDA because of other reasons. We therefore concluded that the TSAT/hepcidin ratio is able to differentiate between IRIDA and IDA-controls due to other reasons with high specificity in a broad iron-deficient population, provided inflammation is absent and no recent iron therapy has been given. PART III: DISCUSSION, SUMMARY AND ADDENDA In Chapter 9 we discuss our main findings and reflect upon the implications for clinical practice. We comment on the strengths and limitations of the studies and consider future research challenges. In the current Chapter 10 we summarize this thesis. Chapter 11 contains the addenda of this paper.