Hypothalamo-Pituitary Dysfunction and Association with Pituitary Siderosis in Adult Subjects with...

Transfusion-dependent beta-thalassemia (TDT) is frequently associated with endocrine dysfunction secondary to hemosiderosis involving multiple organs. This study aimed to evaluate long-term endocrine dysfunction, neuroradiological manifestations, and biochemical markers of iron overload in adult TDT subjects, alongside analyzing associations between pituitary siderosis and endocrine deficits. A cross-sectional study was conducted on 63 adult TDT subjects treated at a tertiary care center in North India. Patient history, clinical examination, biochemical evaluation, and neuroimaging findings were recorded. Hormonal assessments included insulin-like growth factor-1 (IGF-1), growth hormone (GH), thyroid function, cortisol, adrenocorticotropic hormone, sex steroids, and gonadotropins. Dynamic hormone testing was conducted to assess GH status (n = 44) and adrenal reserve (n = 45). Iron deposition in the brain, liver, and heart was assessed radiologically using MRI. Sixty-three subjects (43 males), median age 27 years (IQR: 22-30), were analyzed. Most (59/63) had thalassemia major (TM); the remainder had thalassemia intermedia (TI). Endocrine deficits included low IGF-1 (75.8%), low DHEAS (73%), hypocortisolism (64.5%), hypogonadism (58%), growth hormone deficiency on provocation test (56%), and central hypothyroidism (24%). MRI revealed pituitary siderosis in 76.6%, hepatic siderosis in 53.4%, and cardiac siderosis in 38.2%. Calvarial thickening and diploic space widening in 81% each were common findings. No significant association was observed between pituitary siderosis, pituitary height, and endocrine deficits. Most TDT subjects experience hypothalamo-pituitary dysfunction despite chelation therapy, emphasizing the need for close monitoring. While MRI is valuable for assessing systemic hemosiderosis, its utility in predicting endocrine dysfunction is limited.

The online version contains supplementary material available at 10.1007/s12288-025-02179-5.