GH/IGF-1 axis in a large cohort of ß-thalassemia major adult patients: a cross-sectional study

Abstract

Purpose GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. Methods Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. Results Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. Conclusion GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

“…The keywords of research are “beta-thalassemia” in combination with one of the following: “endocrine”, “fertility”, respective “pregnancy”; but, also, “hypogonadism”, “thyroid”, “TSH”, “parathyroid”, “parathormone”, “stature”, “puberty”, “pituitary”, “diabetes”, “glycaemia”, “fracture”, “TBS”, “DXA”, “ACTH”, “osteoporosis”, “osteopenia”, or “adrenal”. Core endocrine descriptive analysis as displayed in Table 1 was restricted to clinical studies with different levels of statistical evidence, in both paediatric and adult population with major BTH, including more than 40 participants/study aiming two types of data: the ratio of EDs among the general panel of complications; and correlations between EDs and other specific parameters of evaluation in BTH (we included 1 longitudinal study, 15 cross-sectional studies, 1 retrospective analysis, 1 cohort study, 2 meta-analysis, and 2 surveys) [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] ( Table 1 ).…”

“…Patients with major BTH experience low GH levels as part of TED [ 20 ]. Children with GH deficiency and short stature are candidates for GH replacement.…”

“…Low IGF1 in populations with GH deficiency is identified in 94.4% and 93.6%, respectively, on persons without GH deficiency. Short stature is related to low GH/IGF1 values, but not exclusively, as low IGF1 is also found in patients without GH deficiency [ 20 ].…”

“…The patients took a GHRH (GH Releasing Hormone) + arginine test; 18 subjects were diagnosed with a GH deficiency during the test, not at baseline. This subgroup had a higher body mass index (BMI) and a more severe lipid profile ( p < 0.05), but with similar liver function when compared to BTH individuals without GH deficiency [ 20 ].…”

“…IGF1 production may be independent of GH control, for instance, in the relationship between liver status and IO [ 20 ]. Other than correlations with serum ferritin, we also identified transferrin saturation (TS) and EDs in the study [ 23 ].…”