TREATMENT OF RADIATION-INDUCED GROWTH-HORMONE DEFICIENCY WITH GROWTH HORMONE-RELEASING HORMONE

In children with hypothalamic causes for GH deficiency there are theor etical reasons why a GHRH analogue might be better than conventional G H therapy in promoting growth. OBJECTIVE We have aimed to determine th e efficacy and safety of growth hormone-releasing hormone (GHRH) (1-29 )-NH2 given as a twice daily subcutaneous injection in the treatment o f growth failure in children with radiation-induced GH deficiency. DES IGN A multicentre study comparing growth before and after 1 year of tr eatment with GHRH (1-29)-NH2, 15 mu g/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On complet ion of the study year all children were treated with GH (0.5 U/kg/week ) and growth parameters were documented over the next year. PATIENTS N ine children (six boys) with radiation-induced GH deficiency following cranial (n=4) or craniospinal (n=5) irradiation for a brain tumour di stant from the hypothalamic-pituitary axis (n=8) or prophylaxis agains t central nervous system leukaemia (n=1) were studied. All were prepub ertal when the study commenced, which was at least 2 years from radiot herapy, MEASUREMENTS Anthropometry and pubertal staging were carried o ut at 3-monthly intervals and bone age estimations at 6-monthly interv als (TW2 method). Pretreatment standing height velocities were compare d with values during the year of GHRH treatment and then after the fir st year of GH therapy. In those that had received craniospinal irradia tion, a change in leg-length Standard deviation score (SDS) was noted before and after GHRH therapy. Changes in skin-fold thickness and bone age during the GHRH study year were documented. Adverse events and 3- monthly measurements of clinical chemistry, haematology, lipid profile and thyroid function were recorded. RESULTS There was a significant i ncrease in height velocity from 3.3 (SD 1.1) cm/year before treatment, to 6.0 (SDS 1.5) cm/year after I year of GHRH treatment (P=0.004). GH RH maintained or improved the leg length SDS in children who had recei ved craniospinal irradiation. Bone age increased by a mean of 1.1 year s/chronological year during treatment with GHRH. Subsequent height vel ocity during 1 year of GH therapy was 7.5 (SD 1.5) cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse eve nts that could be attributed to GHRH therapy. One child went into pube rty during the GHRH study year and three were pubertal during the firs t year of GH therapy. CONCLUSION In cranially irradiated children, GHR H was effective in increasing growth velocity but this was less than t hat seen in response to GH therapy, although it matched that in childr en with isolated idiopathic GH deficiency treated with the same dose a nd schedule of GHRH administration.