Endocrine dysfunction in transfusion-dependent and non-transfusion-dependent beta-thalassemia: a systematic review and meta-analysis.

INTRODUCTION: To systematically compare adrenal, thyroid, and growth hormone axes between transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) beta-thalassemia patients, and to quantify differences in hormone levels and prevalence of endocrine abnormalities. CONTENT: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. MEDLINE (PubMed), Embase, and Scopus were searched from inception to 2024. Studies reporting quantitative hormone data stratified by transfusion status were included. Primary outcomes were morning serum cortisol, thyroid hormones (TSH, T4), and growth hormone or IGF-1 levels. Random-effects meta-analysis was performed, and risk of bias was assessed using the Joanna Briggs Institute checklist. SUMMARY: Out of 217 records, four studies (n=427; 209 TDT, 218 NTDT) were included. Three studies were pooled for cortisol analysis, showing no significant difference between groups (SMD 0.27; 95 % CI -1.25 to 1.79; I2=91.6 %). Despite comparable basal cortisol levels, adrenal insufficiency prevalence was high (38-44 %) in both groups based on dynamic testing. Thyroid dysfunction was more frequent in TDT patients, though heterogeneity limited the meta-analysis. One paediatric study reported lower IGF-1 levels and higher growth impairment in TDT. Serum ferritin levels were consistently higher in TDT cohorts. Risk of bias was moderate to high in half of the studies. OUTLOOK: Basal cortisol levels were similar between TDT and NTDT patients; however, significant endocrine morbidity persists, particularly in TDT. These findings emphasize the need for comprehensive endocrine evaluation beyond basal hormone measurements across all thalassemia patients.