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M. Casale et al.
the age of 12 years is certainly related to different factors, such as the current inability to recognize hypogonadism prior to puberty; the effect of hypogonadism on bone metabolism due to the impact of steroids on bone miner- alization; the delay between the start of iron damage in the gland tissues and the onset of overt clinical complica- tions, e.g., diabetes.4,11-13 Furthermore, adolescence is also marked by less physical activity and more adverse body habitus and nutrition that worsen insulin sensitivity. For all these reasons, children are not protected by iron damage in endocrine glands and conversely, they require more aggressive prophylaxis to avoid pituitary and pancreatic iron accumulation which will be clinically manifested only years later, when the functional reserve has been destroyed. Different chelation goals (such as transferrin desaturation and the use of direct endocrine imaging) and alternative chelation strategies are necessary to better pro- tect endocrine glands.
In conclusion, although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is consider- able risk variation and the burden of these complications remains high. This is the first study providing a practical tool for physicians to identify patients at higher risk of developing endocrine complications. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory pre- dictors, including the assessment of direct endocrine MRI.
Disclosures
Università degli Studi della Campania “Luigi Vanvitelli” spon- sored the study (VALERE project) and received a partial financial support to trial costs from and Novartis Farma SpA which had no role in study design, data collection, data analysis, data interpreta- tion, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication; MC received speaker honoraria and advisory board fees from Novartis Farma SpA; GLF received advisory board fees from Novartis Farma SpA; MP received con- sulting fees and advisory board fees from Novartis Farma SpA; SP received grant support paid to his institution, advisory board fees and speaker honoraria from Novartis Farma SpA. No other poten- tial conflict of interest relevant to this article was reported. All other authors declare no conflict of interests of any kind.
Contributions
MC, SP, and AIL designed the study. Each author collected the data from his/her own center and takes responsibility for the accu- racy of the data provided. AIL carried out the statistical analysis; MC and AIL drafted the manuscript. All authors contributed to the interpretation of the data and approved the manuscript. The cen- ters in Naples, Genoa, Milan, and Padua are part of the European Reference Network on Rare Hematological Diseases (ERN- EuroBloodNet). All centers involved in the study are part of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) and pediatric centers are part of the Italian Association of Pediatric Hematology and Oncology.
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