Effects of intensive iron chelation therapy on glucose abnormalities in beta-thalassemia major patients

Sohair Elsiddig; Ashraf Soliman; Fawzia Alyafei; Nada Alaaraj; Noor Hamed; Shayma Ahmed

doi:10.1530/endoabs.110.EP1044

JOINT725

Background: Beta-thalassemia major is a transfusion-dependent condition characterized by chronic iron overload, leading to glucose abnormalities, endocrine dysfunctions, and impaired growth. This study evaluates the impact of intensive iron chelation therapy on these complications using real-world evidence from published literature.

Methods: A systematic review of 23 studies published between 2007 and 2023 involved 2,385 patients with beta-thalassemia major or intermedia. The studies assessed the effectiveness of iron chelation therapy using metrics such as serum ferritin, MRI-derived liver and pancreatic iron burden, glucose tolerance tests (OGTT), and endocrine outcomes.

Results: • Iron Chelation Therapy Impact:.

• Glucose Abnormalities: Improvements were observed in 44% of patients with glucose tolerance abnormalities following intensive chelation therapy. Pancreatic T2* MRI proved superior to serum ferritin in predicting glucose abnormalities.

• Insulin Sensitivity: Increased insulin sensitivity was reported in patients achieving reduced liver and pancreatic iron burden, with an estimated improvement in 68% of cases.

• Endocrine Dysfunction:.

• Hypogonadism: Prevalence was reduced in 50% of patients after chelation adjustments guided by pituitary MRI findings.

• Growth Hormone Deficiency: Limited improvement in growth-velocity, with only 25% of patients showing significant catch-up growth due to irreversible damage in late-diagnosed cases.

• Delayed Puberty: Onset normalized in 38% of patients, particularly in those who received early and aggressive therapy.

• MRI Utility: MRI assessments were consistently better at correlating iron burden with glucose and endocrine outcomes compared to serum ferritin. Pituitary and pancreatic iron deposition strongly predicted dysfunctions.

• Emerging Therapies: The data remains preliminary.

Table 1. Real Impact Table from Big Table Data.
Outcome	Observed Change	Patients Impacted (% Real)	Comments
Glucose Abnormalities	Improvement in glucose tolerance	44%	*Pancreatic T2 MRI outperformed serum ferritin in predicting improvements.**
Insulin Sensitivity	Increased in patients with reduced liver/pancreatic iron	68%	Strongly linked to early chelation therapy.
Hypogonadism	Reduction in prevalence	50%	Residual dysfunction remained in severe cases.
Growth Hormone Deficiency	Limited improvement in growth velocity	25%	Late diagnoses resulted in irreversible axis damage.
Linear Growth	Slight height catch-up	33%	Most effective in children receiving early therapy.
Delayed Puberty	Onset normalized	38%	Early chelation showed greater efficacy in mitigating pubertal delays.

Conclusions: Intensive iron chelation therapy significantly improves glucose tolerance, insulin sensitivity, and some endocrine dysfunctions in beta-thalassemia major patients. However, limitations remain in reversing severe growth impairments. MRI is indispensable for accurate organ-specific iron monitoring and guiding treatment adjustments. The integration of advanced therapies, including gene therapy, may further enhance long-term outcomes.

Endocrine Abstracts

EP1044