Endocrine complications in patients with β-thalassemia major receiving iron-chelation therapy

β-Thalassemia major patients are frequently vulnerable to endocrine dysfunction due to iron overload from chronic transfusions. This impairs growth, thyroid function, glucose metabolism, and bone health, ultimately compromising quality of life and long-term outcomes.

This study investigates the prevalence and pattern of endocrine dysfunction in β-thalassemia major patients receiving iron-chelation therapy and explores associations with iron overload markers.

This case-control study involved 60 β-thalassemia major patients and 20 age- and sex-matched controls. Hormonal and biochemical parameters were measured and linked to iron status.

Among β-thalassemia major patients (7-35 years), 73.3% (n = 44/60) were splenectomized; 36 received deferiprone, 19 deferasirox, and 5 deferoxamine. Concerning iron status, both splenectomized and non-splenectomized patients had significantly higher iron and ferritin and lower haptoglobin levels compared to controls. No significant differences were found in hepcidin or hemopexin levels. Regarding thyroid function, about 15% (n = 9/60) of β-thalassemia major patients had subclinical primary hypothyroidism. Ferritin negatively correlated with free thyroxine (r = -0.330, p = 0.010). As for glycemic status, 51.7% (n = 31/60) of β-thalassemia patients had glycated hemoglobin (HbA1c) ⩾6.5% and 38.3% (n = 23/60) showed impaired fasting blood sugar. With respect to metabolic markers, splenectomized patients had higher fibroblast growth factor 21 (FGF21) than the control (p = 0.042), while no significant group differences were found in galectin-1 or sortilin. Ferritin correlated significantly and positively with FGF21 levels (r = 0.353, p = 0.006). With respect to calcium-parathyroid-vitamin D axis, hypoparathyroidism and hyperparathyroidism were each found in 11.7% (n = 7/60) of β-thalassemia patients. Vitamin D levels were significantly lower in the β-thalassemia groups compared to controls (p = 0.0001) with 71.7% (n = 43/60) deficient despite 43.3% (n = 26/60) receiving supplements. Non-splenectomized patients had higher Procollagen Type I C-Peptide, a bone formation marker, compared to controls.

Endocrine disturbances are common in β-thalassemia major despite chelation therapy. Incorporating endocrine assessment into routine practice is essential for early detection and management.