medwireNews: Children who receive total body irradiation (TBI) or craniospinal radiation for cancer may have a reduced response to growth hormone (GH) therapy if they later require it, say researchers.
Children given TBI to treat leukaemia achieved a median estimated height standard deviation score (SDS) of just –1.74 after 5 years of GH therapy, whereas those with craniopharyngioma who received cranial radiation achieved a median of –0.17, report Susan Rose (Cincinnati Children’s Hospital Medical Center, Ohio, USA) and co-researchers.
The team used the Pfizer International Growth Database (KIGS) to identify cancer survivors who subsequently received GH therapy for at least 5 years. These included 431 who had craniopharyngioma, 251 of whom received cranial radiation; 224 with medulloblastoma who all received craniospinal radiation; and 134 with leukaemia, 72 of whom underwent TBI.
The differences in growth response to GH therapy according to tumour and radiation type remained evident after accounting for factors including mid-parental height SDS, puberty status, age and height SDS at GH initiation and GH dose.
Overall, the median 5-year change in height SDS was greatest in children with craniopharyngioma who did not receive radiation, at 1.6. However, receipt of cranial radiation alone had no effect on growth response to GH in these patients; those who received the treatment achieved a median 5-year height SDS change of 1.5.
The researchers say this is probably because GH deficiency in this patient subgroup is often a cause of the craniopharyngioma rather than of its treatment. This means GH deficiency is frequently detected and replacement therapy started soon after treatment of the tumour and before growth has markedly slowed, whereas for other cancer survivors there may be a significant period of poor growth before GH deficiency is diagnosed.
The poorest response to GH therapy was seen in children with leukaemia who underwent TBI, at a median height SDS increase of just 0.4.
However, the response of leukaemia patients who did not receive TBI remained poorer than that of the craniopharyngioma group, at a median increase of 1.0 and “suggests long term effects on growth potential by other factors in leukemia therapy (such as steroids or chemotherapy)”, write the researchers in The Journal of Clinical Endocrinology & Metabolism.
Children who received craniospinal radiation for medulloblastoma also had a relatively poor response to GH therapy, achieving a median 0.9 increase in height SDS.
Rose and team stress that the reduced GH response in some subgroups of cancer survivors “does not contravene use of GH [therapy]”, noting that factors such as gonadotropin-releasing hormone analogue therapy may be brought into play in some cases to prolong the GH treatment window and maximise response.
“It is important for clinicians to give patient-families realistic expectations of response to GH [therapy] so they can make appropriate, well-informed risk-benefit decisions (and also help prevent loss of adherence to GH [therapy] from disappointment that height is not increasing as anticipated)”, they say.
“Those with history of spinal [radiation therapy] should be prepared for suboptimal height increases as well as disproportionate elongation of legs relative to trunk.”
By Eleanor McDermid
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J Clin Endocrinol Metab 2020; doi:10.1210/clinem/dgaa478