Age-Related Patterns of Organ-Specific Iron Distribution in Non-Transfusion-Dependent Thalassemia: A Multicenter MRI Study.

Objectives: This multicenter cross-sectional study investigated the relationship between age and organ-specific iron burden and characterized multi-organ iron phenotypes across different age groups in adults with non-transfusion-dependent thalassemia (NTDT). Methods: We retrospectively evaluated 96 adults with NTDT enrolled in the multicenter Italian Extension-Myocardial Iron Overload in Thalassemia network. Hepatic, pancreatic, and cardiac iron burden were assessed by quantitative magnetic resonance imaging (MRI). Results: The median age was 41.64 (36.08-53.92) years. Hepatic iron overload (IO) was present in 59.4% of patients and pancreatic IO in 29.2%, whereas no patient exhibited myocardial IO. Age was not associated with liver iron concentration (LIC) or cardiac R2*. A weak positive correlation was observed between age and pancreatic R2* (R = 0.215, p = 0.035), although this association was no longer significant after the exclusion of one extreme value. LIC and pancreatic R2* were not correlated. Across age groups (<40, 40-59, and ≥60 years), the prevalence of pancreatic IO increased (22.9%, 28.6%, and 50.0%, respectively), whereas hepatic IO remained stable. Isolated hepatic IO was the most common phenotype overall, while combined hepatic and pancreatic IO was more frequent among patients aged ≥60 years. Conclusions: In adults with NTDT, age was not associated with greater hepatic or cardiac iron burden, whereas older patients showed a higher prevalence of pancreatic iron accumulation and combined hepatic-pancreatic iron involvement. These findings highlight the organ-specific heterogeneity of iron distribution in NTDT and support the role of multi-organ MRI assessment beyond LIC evaluation, particularly in older patients.