Endocrine complications in Β-thalassemia represent a prominent cause of morbidity. Above all, dysfunction of GH-IGF-1 axis is of a major concern because of its pathogenic role on cardiac and bone disease, frequently described in this clinical setting. The aim of this paper is to analyze GH-IGF-1 axis in a cohort of 25 adult patients affected by Β-thalassemia. We found that GH deficiency was present in only 8% of our patients if diagnosis was based on GH peak below 9μg/L to two GH provocative tests instead of only one, and was mainly related to iron overload. On the contrary, IGF-1 production was impaired in a higher percentage of patients (72%), without significant correlation with iron burden. Of note, patients with hepatitis C virus infection showed lower IGF-1 concentrations than uninfected subjects despite a normal GH reserve, suggesting that partial GH insensitivity at the post-receptor level may play a key role in IGF-1 deficiency described in thalassemic patients.