Growth and Endocrine Preservation in Transfusion-Dependent β-Thalassemia: Updated Pharmacologic and Genomic Interventions

Abstract Transfusion-dependent beta-thalassemia (TDT) is associated with growth impairment and frequent endocrinopathies due to chronic anemia and iron overload. Although transfusion and chelation therapy have improved survival, endocrine morbidity remains common. This review evaluates the effects of emerging disease-modifying and curative therapies on growth and endocrine outcomes. Longitudinal cohorts, Phase 2–3 trials, and gene therapy studies were reviewed. Outcomes included hematologic response, iron reduction, and endocrine parameters (GH–IGF-1 axis, gonadal function, and glucose metabolism). Conventional therapy reduces but does not eliminate iron-related damage, with growth failure and hypogonadism persisting in 40–50% of adults. Hydroxyurea and thalidomide provide modest benefits in selected pediatric responders. Luspatercept significantly lowers transfusion burden and iron intake, improving metabolic stability. Gene addition and CRISPR-based editing achieve transfusion independence in over 90% of treated patients. Early intervention appears to stabilize growth and pubertal progression, whereas established endocrine damage is often irreversible. The degree of hematologic correction and reduction in iron-loading rate are key predictors of endocrine preservation. Early disease modification offers the greatest potential for normalizing growth and preventing endocrine dysfunction in TDT. Future trials should incorporate standardized longitudinal endocrine and fertility outcomes.