Search Results
Search for other papers by V G Pluimakers in
Google Scholar
PubMed
Search for other papers by M van Waas in
Google Scholar
PubMed
Search for other papers by C W N Looman in
Google Scholar
PubMed
Search for other papers by M P de Maat in
Google Scholar
PubMed
Search for other papers by R de Jonge in
Google Scholar
PubMed
Search for other papers by P Delhanty in
Google Scholar
PubMed
Search for other papers by M Huisman in
Google Scholar
PubMed
Search for other papers by F U S Mattace-Raso in
Google Scholar
PubMed
Search for other papers by M M van den Heuvel-Eibrink in
Google Scholar
PubMed
Section Endocrinology, Department of Medicine, Erasmus MC, Rotterdam, The Netherlands
Search for other papers by S J C M M Neggers in
Google Scholar
PubMed
Purpose:
Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography.
Methods:
The NCEP-ATPIII MetS-components, 14 additional serum biomarkers and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment effects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations.
Results:
After 27.5 years of follow-up, MetS occurred more often in survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value.
Conclusions:
Long-term childhood nephro- and neuroblastoma survivors frequently develop MetS. Additional assessment of biomarkers identified in PCA – adiponectin, LDL, apoB, and uric acid – may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Internal Medicine, Lillebaelt Hospital, Kolding, Denmark
Search for other papers by Simon Chang in
Google Scholar
PubMed
Search for other papers by Arkadiusz J Goszczak in
Google Scholar
PubMed
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Anne Skakkebæk in
Google Scholar
PubMed
Search for other papers by Jens Fedder in
Google Scholar
PubMed
Search for other papers by Anders Bojesen in
Google Scholar
PubMed
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Search for other papers by M Vakur Bor in
Google Scholar
PubMed
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Haematology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
Search for other papers by Moniek P M de Maat in
Google Scholar
PubMed
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Claus H Gravholt in
Google Scholar
PubMed
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Search for other papers by Anna-Marie B Münster in
Google Scholar
PubMed
Objective
Klinefelter syndrome (KS) is associated with increased risk of thrombosis. Hypogonadism and accumulating body fat in KS have a potential impact on fibrinolysis. In this study, we assessed the fibrinolytic system and the association with testosterone levels in KS.
Design
This study is a cross-sectional comparison of men with KS and age-matched male controls.
Methods
Fibrin clot lysis was evaluated by turbidity measurements and by measuring levels of individual fibrinolytic proteins in plasma samples. Fibrin clot structure was evaluated by scanning electron microscopy. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Body fat was evaluated by dual-energy X-ray absorptiometry.
Results
In this study, 45 men with KS and 45 age- and education-matched controls were included. Men with KS had a 24% reduction in fibrin clot lysis compared with controls (46.2 ± 17.1 vs 60.6 ± 18.8 %/h, P = 0.0003) and higher levels of fibrinogen, factor XIII (P ≤ 0.01), and plasminogen activator inhibitor type 1 (P = 0.04). Men with KS had lower total testosterone (P = 0.008) and higher body fat (P = 0.001). In KS, reduced fibrin clot lysability was associated with higher fibrinogen and body fat related to decreasing total testosterone and hypogonadism among men with KS. Fibrin clot structure was not different compared to KS and controls.
Conclusions
Fibrin clot lysis in KS was markedly reduced, potentially contributing to a prothrombotic state and increasing thrombotic risk. Hypogonadism in KS was associated with increased fibrinogen and total body fat, predicting reduced fibrin clot lysis.
