The number of patients treated for malignant disease in childhood surviving into adulthood is increasing, but success is tempered by long-term side-effects of chemotherapy and radiotherapy; 40% develop one or more endocrinopathy. ALL is a common childhood malignancy treated with chemotherapy and cranial irradiation. The latter causes anterior pituitary hormone deficiencies, most frequently GH deficiency.
We have determined GH status in 13 patients treated using UKALL protocols including cranial irradiation (18-24Gy) aged 2-13 years. None had required GH replacement in childhood. Patients underwent insulin tolerance (ITT) and arginine stimulation (AST) tests and a fasting serum IGF-I was measured. Fat mass was determined using bio-impedance.
At the time of testing the median age of the subjects was 28 years (range 20-39); body mass index 26.2 Kg/m2 (20.5-32.9) and time since irradiation was 21 years (11-27). Ten patients demonstrated abnormalities of the GH-IGF-I axis. Four patients had severe GH deficiency (peak GH response <9mU\/L to two tests) and one patient had an abnormal response to the ITT and a low IGF-I, but had a discordant response to the AST. Five patients had GH insufficiency (GH peak to ITT >9, <15mU\/L). Three of those patients had a serum IGF-I below the normal range and five had values in the lower quartile of the normal range. There was no correlation between fat mass and the GH peak to the ITT or to AST or serum IGF-I indicating that the abnormal GH response was not caused by obesity.
These data suggest that patients that received relatively low doses of radiotherapy in childhood can develop GH deficiency in adult life; 30% had overt GH deficiency and 46% had GH insufficiency. There is a large population of patients treated for childhood leukaemia that may benefit from GH replacement therapy.
08 - 11 Apr 2002
British Endocrine Societies