Introduction: Insulin-like growth factor 1 (IGF-1) is a key peptide involved in cell growth and protein turnover, acting as the primary mediator of many of the responses regulated by growth hormone (GH) in tissues. Signs and symptoms of adult GH deficiency (AGHD) in patients with β-thalassaemia major (TM) may be subtle and overlap with those of the disease itself; therefore, the diagnosis may be missed or delayed, with potentially serious consequences. The diagnosis of AGHD requires an appropriate clinical setting and is confirmed through biochemical testing. The aim of this study was to measure IGF-1 values and other clinical data in a large number of adult patients with TM and to evaluate whether an IGF-1 concentration 2 SDs below normative values could be used as an effective index supporting the probable presence of AGHD.Patients and Methods: A cohort of 120 adult patients with TM was studied for plasma levels of IGF-1. Plasma total IGF-1 was determined by chemiluminescent immunometric assay (CLIA) method. In eleven patients (4 males) the GH response during glucagon stimulation test (GST) was also evaluated. Results: Fifty percent of patients (33 males and 27 females) had IGF-1 levels <- 2 SDs below normative values for healthy subjects matched for age and sex. In these patients endocrine complications and elevations of aminotransferases (ALT) were more common compared to TM patients with IGF1 > -2SDs. In multivariate regression analyses, height, weight, BMI, serum ferritin, ALT, HCV serology and left ventricular ejection fraction (LVEF) were not significantly related to IGF-1, but a significant correlation was found in females between HCV-RNA positivity and IGF-1, ALT and serum ferritin (p= 0.043).AGHD was diagnosed in 6 (4 males) out of 11 patients (54.5%) who had glucagon stimulation tests and in 5 out of 8 (62.5%) with IGF-1 <-2SD. The mean age of patients with GHD was 39.3 years (range: 25-49 years) versus 35.8 years (range: 27-45 years) in non-GHD patients. A positive correlation between GH peak after GST and IGF-1 level was found (r: 0.6409; p: < 0.05).Conclusions: On the basis of the present results and data from the literature, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) recommends a GH stimulation test in adults with TM in the presence of very low IGF-1 levels (<-2SDs of normative values for healthy individuals matched for age and sex) especially in patients with childhood onset of GHD with pituitary iron deposition and/or atrophy. In addition the presence of short stature (HtSDS <-2.5), severe and/or prolonged iron overload, and severe osteoporosis strengthens the indications for a GH stimulation test in adult patients with TM.