Childhood survivors of cancer are prone to a number of adverse sequelae related to the therapeutic interventions used. Growth hormone deficiency (GHD) is common after cranial irradiation, and it is unclear to what extent GHD contributes to the abnormalities observed in adult survivors of childhood cancer, and whether GH replacement can reverse these anomalies. We compared 27 GHD survivors of childhood cancer with 27 adult age- and sex-matched controls, and went on to replace GH in the patient group to determine if GH improved the baseline abnormalities.
The GHD survivors of childhood cancer had an adverse lipid profile (TC, 5.4 vs 4.6 mmol/l, P=0.004; HDL-C, 1.05 vs 1.6 mmol/l, P<0.001; and TG, 1.3 vs 1.0 mmol/l, P<0.001); osteopenia (lumbar spine z-score, -1.53 vs -0.31 SDS, P<0.001; femoral neck z-score, -1.23 vs -0.27 SDS, P=0.02); and, the female subgroup had an increased percentage body fat (43.6 vs 32.8% P=0.016). In keeping with the selection criterion, quality of life in the patient cohort relative to the healthy controls was severely impaired (AGHDA, 15.5 [range 8-25] vs 1 [range 0-19], P<0.0001; PGWB, 67.5 [range 18-86] vs 89.0 [range 51-104], P<0.0001).
Following 12 months GH replacement small but significant improvements occurred in body composition in the male subgroup (WHR, 0.871 vs 0.863, P<0.05) and in the female cohort TC (6.0 vs 5.2 mmol/l, P=0.01) and TG (2.1 vs 1.4 mmol/l, P=0.01) levels fell. BMD improved in only one of the four sites studied (ultradistal radius, -1.21 vs -1.09, P=0.048) after a median duration of GH therapy of 18 months. Quality of life improved dramatically by 3 months (AGHDA, 15.5 vs 10.0, P<0.001) and the improvement was maintained at 12 months (AGHDA, 15.5 vs 9.0, P<0.001). Importantly, there was no clinical suggestion of tumour recurrence during the 12 months of GH replacement.
The minor improvements observed in body composition, the lipid profile, and BMD in GHD adult survivors of childhood cancer following 12-18 months GH replacement suggest that GHD may not be the major aetiological factor in their pathogenesis; the converse appears to be true for the quality of life status of these individuals. We propose that as in patients with GHD due to pituitary disease, the main indication for GH replacement in GHD survivors of childhood cancer should be severe impairment of quality of life.
03 - 04 Dec 2001
Society for Endocrinology