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Treatment of radiation-induced growth hormone deficiency with growth hormone-releasing hormone

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In children with hypothalamic causes for GH deficiency there are theoretical reasons why a GHRH analogue might be better than conventional GH therapy in promoting growth.

OBJECTIVEWe have aimed to determine the efficacy and safety of growth hormone-releasing hormone (GHRH) (1–29)-NH2 given as a twice daily subcutaneous injection in the treatment of growth failure in children with radiation-induced GH deficiency.

DESIGNA multicentre study comparing growth before and after 1 year of treatment with GHRH (1–29)-NH2, 15 g/kg twice daily, by subcutaneous injection in children with radiation-induced GH deficiency. On completion of the study year all children were treated with GH (05 U/kg/week) and growth parameters were documented over the next year.

PATIENTSNine children (six boys) with radiation-induced GH deficiency following cranial (n = 4) or craniospinal (n = 5) irradiation for a brain tumour distant from the hypothalamic–pituitary axis (n = 8) or prophylaxis against central nervous system leukaemia (n = 1) were studied. All were prepubertal when the study commenced, which was at least 2 years from radiotherapy.

MEASUREMENTSAnthropometry and pubertal staging were carried out at 3-monthly intervals and bone age estimations at 6-monthly intervals (TW2 method). Pretreatment standing height velocities were compared with values during the year of GHRH treatment and then after the first year of GH therapy. In those that had received craniospinal irradiation, 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.

RESULTSThere was a significant increase in height velocity from 33 (SD 11) cm/year before treatment, to 60 (SDS 15) cm/year after 1 year of GHRH treatment (P = 0004). GHRH maintained or improved the leg length SDS in children who had received craniospinal irradiation. Bone age increased by a mean of 11 years/chronological year during treatment with GHRH. Subsequent height velocity during 1 year of GH therapy was 75 (SD 15) cm/year. No adverse changes in biochemical or hormonal analyses were noted or adverse events that could be attributed to GHRH therapy. One child went into puberty during the GHRH study year and three were pubertal during the first year of GH therapy.

CONCLUSIONIn cranially irradiated children, GHRH was effective in increasing growth velocity but this was less than that seen in response to GH therapy, although it matched that in children with isolated idiopathic GH deficiency treated with the same dose and schedule of GHRH administration.
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Document Type: Research Article

Affiliations: 1: Department of Endocrinology, Christie Hospital NHS Trust, Manchester, 2: Department of Child Life and Health, University of Edinburgh, Edinburgh, 3: Division of Paediatric Endocrinology, St Bartholomew’s Hospital, London, 4: Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford, UK 5: Department of Paediatrics, Clarendon Wing, Leeds General Infirmary, Belmont Grove, Leeds,

Publication date: May 1, 1997

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