How should hyperferritinaemia be investigated and managed?

Ong, Sim Yee; Nicoll, Amanda; Delatycki, Martin B.

doi:10.1016/j.ejim.2016.05.014

Cited by 21 publications

(29 citation statements)

References 109 publications

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“…Serum ferritin concentrations are commonly used in the clinical routine as an indicator of body iron stores [7]. The MetS results in a complex dysregulation of iron homeostasis [8].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Stechemesser

Eder

Wagner

et al. 2017

Molecular Metabolism

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ObjectiveElevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways.MethodsIn a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach.ResultsSubjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites).ConclusionsOur data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

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“…Serum ferritin concentrations are commonly used in the clinical routine as an indicator of body iron stores [7]. The MetS results in a complex dysregulation of iron homeostasis [8].…”

Section: Introductionmentioning

confidence: 99%

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Stechemesser

Eder

Wagner

et al. 2017

Molecular Metabolism

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“…We selected a threshold of SF >1000 µg/L as an indicator for relevant iron overload, which is above the normal range, but was intended to increase the specificity in the context of inflammation.…”

Section: Methodsmentioning

confidence: 99%

“…This analysis was performed with SAS version 9.4. ROC analysis was used to compare the accuracy of SF and MR‐Fe in diagnosing relevant iron overload (we applied a threshold of SF >1000 µg/L, with reference to Ong et al). Spearman's ρ was used as a measure of their correlation.…”

Section: Methodsmentioning

confidence: 99%

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MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

Wurschi

Mentzel

Herrmann

et al. 2019

Pediatric Transplantation

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Multiple blood cell transfusions may cause iron overload or even liver fibrosis, requiring early diagnosis and intervention. SF is the standard for estimating iron levels in the body, but it also increases with inflammation. We hypothesized that T2* magnetic resonance (MR) relaxometry is a more accurate alternative for follow‐up in pediatric patients before and after allogenic SCT. Twenty‐three children (mean age 10.2 years, 10 female, 13 male) were evaluated prospectively before SCT as well as at least 1 year after SCT with T2* relaxometry on a 1.5 T MR‐scanner to estimate liver iron concentrations from the T2* values (“MR‐Fe”). The results were compared with SF, while also considering CRP, and correlated with the number of transfusions. Overall, 24.3 transfusions were administered in average, mainly within 100 days of SCT (mean 10.5 units). Both MR‐Fe and SF increased after SCT and decreased in the absence of new transfusions 1 year later without chelate therapy. This suggests regeneration of LP and iron loss, although the original states were not reached. Additionally, simultaneous peaks of CRP and SF were observed directly after SCT. MR‐Fe did neither reveal these peaks nor was it associated with CRP (P = .39). We postulate that these early CRP and SF peaks after SCT are probably related to inflammatory reactions and not to iron overload. Thus, SF is not reliable for iron overload diagnosis after SCT in every condition. Beside this interaction, SF and MR‐Fe revealed similar accuracy. MRI, however, has practical and economical disadvantages in routine estimation of iron.

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“…3,5 Although there is strong evidence to justify the need for pre-symptomatic detection of this condition, one of the problems faced by primary care physicians in identifying HH is that symptoms are often absent or mimic those found in other common conditions. 13,14 Previously undiagnosed C282Y homozygotes with SF values that remain <1000 μg/L are at low risk for developing HH signs and symptoms. 9,10 Abnormalities in iron biochemical assays are often the first indicator of HH, and it is widely accepted that transferrin saturation (TS) and SF are the best initial tests for HH.…”

Section: Introductionmentioning

confidence: 99%

Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing

O'Toole

Romeril

Bromhead

2017

Internal Medicine Journal

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How should hyperferritinaemia be investigated and managed?

Cited by 21 publications

References 109 publications

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

Using iron studies to predict HFE mutations in New Zealand: implications for laboratory testing

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