Background: Conflicting outcomes have been reported about the role of low IGF1 levels in predicting irradiation-dependent GHD in CCS. IGF1 <−2SD had a sensitivity between 28 and 47% in different studies, but these results were drawn from small samples of patients or from mixed cohorts including patients with GHD due to different aetiologies.
Objective: Our aim was to analyse the screening role of low IGF1 levels in CCS at risk of developing GHD (GH peak after stimulation test<7 μg/L) after radiotherapy involving the hypothalamic-pituitary area (HPA).
Method: We performed a retrospective analysis on 158 survivors of childhood brain tumours or leukaemia started on GH replacement treatment between 2003 and 2017 in our centre.
Results: 141/158 patients received either cranial, cranio-spinal or total body irradiation (TBI), with or without surgery and/or chemotherapy. To describe the specific detrimental role of irradiation on GH secretion, we identified 117 irradiated patients diagnosed with tumours not directly involving the HPA and who did not undergo surgery in the HPA. In this group, IGF1 levels <−2SD had a sensitivity of 31.9%. However, in 27/117 patients with severe childhood GHD (GH peak <3 μg/L), IGF1 levels <−2SD were statistically more frequent (P-value 0.0023) and had a higher sensitivity (45.6%). Among 14/117 leukaemic patients exposed to TBI without cranial boost, IGF1 <−2SD had a sensitivity of 7.1%, statistically lower than subjects with brain tumours treated with higher radiation doses. 38/117 patients underwent a reassessment of GH status at final height, and GH peak <3 μg/L was statistically more frequent both in patients with IGF1 <−2SD at diagnosis of childhood GHD (P-value: 0.0026) and in subjects with IGF1 <−2SD at final height (P-value=0.006). IGF1 <−2SD at final height had a sensitivity of 35.0% and a specificity of 100% in patients with a GH peak <3 μg/L. Finally, pre-treatment IGF1 values showed a weak but statistically significant negative correlation with the outcome of GH replacement therapy expressed as Δheight SDS between final height and height at diagnosis (Spearmanns rho: −0.31, P-value: 0.041) but no correlation with the number of pituitary hormones in those with multiple pituitary deficiencies.
Conclusions: Our study confirmed that IGF1<−2SD has a low sensitivity at predicting irradiation-induced GH deficiency. Lower IGF1 levels in childhood are associated with more severe GHD both at childhood and adulthood assessment and correlate with a better response to GH treatment at final height.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology