J Clin Endocrinol Metab. 2020; 105: e373041. https://pubmed.ncbi.nlm.nih.gov/32706856/
This retrospective analysis of the Pfizer International Growth Database (KIGS) included 1149 cancer survivors with growth hormone deficiency (GHD) who had received growth hormone therapy (GHT) for at least 5 years. Patients with craniopharyngioma had the best 5-year growth response to GHT with a delta height SD score of 1.6, compared to 0.9 in patients with medulloblastoma. By contrast, delta height SD score was only 0.3 in patients with leukemia who received TBI, and 0.5 in patients with leukemia without RT.
Many patients with craniopharyngioma already present at diagnosis with poor linear growth, suggesting that GHD was a direct result of tumor location in the hypothalamic-pituitary region. On the contrary, GHD following medulloblastoma or leukemia is an effect of treatment (i.e. RT). GHT is often started in craniopharyngioma survivors by 1 year after surgery, but is often delayed in survivors of medulloblastoma or leukemia. Several small studies have observed that vertebral growth is significantly impaired after spinal RT or TBI and contributes to disproportionate short stature.
In this study, leukemia survivors who had received conditioning regimen with TBI for bone marrow transplantation experienced the most severely impaired growth response to GHT at 1 and 5 years. In general, patients who were pubertal at GHT start showed a better height growth response than those who were prepubertal at GHT start, probably because the pubertal spurt enhanced the response to GHT. However, pubertal patients with leukemia receiving TBI, were an exception in that they showed a worse growth response than prepubertal patients. All these data support the hypothesis that TBI impairs the pubertal spurt by direct damage to the epiphyses and bony matrix.
The large sample size in each tumor group and the long GHT duration are clear strengths of this study. Nevertheless, the retrospective analysis of registry data lacks details of imaging, treatment modalities, body proportions, onset and tempo of puberty, and other pituitary hormone disfunctions. Details about body proportions would be particularly useful in evaluating the response to GHT in medulloblastoma patients who are treated with craniospinal RT. These patients may exhibit suboptimal height gains as well as disproportionately poor growth of the trunk relative to the legs, due to a direct radiation damage to the spine.