medwireNews: Growth hormone deficiency (GHD) is common among childhood cancer survivors and is associated with the use of hypothalamic-pituitary radiotherapy, alkylating agents and intrathecal chemotherapy, as well as adverse health outcomes, say researchers.
Wassim Chemaitilly (St Jude Children’s Research Hospital, Memphis, Tennessee, USA) and colleagues report that among 3141 individuals who had cancer during childhood and were followed up for a median 24.1 years, the estimated prevalence of GHD was 22.2%.
This increased to 40.2% among the 1089 participants treated with hypothalamic-pituitary radiotherapy. For individuals who did not receive this treatment, GHD prevalence was 6.2%.
Multivariable analysis revealed that receiving a radiotherapy dose of 1–19 Gy to the hypothalamic-pituitary region was associated with a significant 4.16-fold increased likelihood of GHD relative to no radiotherapy. Furthermore, the odds for GHD increased 5.71-fold at a radiotherapy dose of 20–30 Gy and 21.43-fold at a dose above 30 Gy.
Other factors significantly associated with GHD included the use of intrathecal chemotherapy (odds ratio [OR]=2.38) and alkylating agents at cumulative equivalent doses of 8001–12,000 mg/m2 (OR=1.55) and above 12,000 mg/m2 (OR=1.79), as well as stroke (OR=1.73) and hydrocephalus with shunt placement (OR=2.74).
Further analysis, stratified by those who did and did not receive hypothalamic-pituitary radiotherapy, attenuated the association between alkylating agents and GHD in both groups, while the association with intrathecal chemotherapy remained significant only in individuals who did not receive hypothalamic-pituitary radiotherapy (OR=3.70).
Chemaitilly and team emphasise, however, that “the small number of participants available for this sub-analysis requires interpreting these data with caution.”
They continue: “Whether associations with alkylating agents and intrathecal chemotherapy are due to direct [hypothalamic-pituitary] toxicity or potentiation of radiotherapy related damage requires further study.”
In terms of physical health outcomes, individuals with GHD were significantly more likely to have short stature (OR=3.50), low bone mineral density (OR=2.16), frailty (OR=1.87) and poor exercise tolerance (OR=1.51) than those without.
Other hypothalamic-pituitary disorders observed among the cohort included thyroid stimulating hormone deficiency, luteinising hormone/follicle stimulating hormone deficiency, adrenocorticotropic hormone (ACTH) deficiency and central precocious puberty. These occurred in hypothalamic-pituitary radiotherapy-treated patients at rates of 11.1%, 10.6%, 3.2% and 0.9%, respectively, versus 0.7%, 0.5%, 0% and 0.3%, respectively, in those who did not receive the radiotherapy.
Hypothalamic-pituitary radiotherapy was significantly associated with all four of these disorders, albeit only at the highest dose for ACTH deficiency, with ORs ranging from 4.41 to 33.53.
Writing in The Journal of Clinical Endocrinology & Metabolism, Chemaitilly and co-authors say their study “demonstrates that survivors of childhood cancer are at increased risk for [hypothalamic-pituitary] disorders predominantly related to primary cancer location and radiotherapy involving the [hypothalamic-pituitary] region, but also to intrathecal chemotherapy and alkylating agents, and conditions associated with [central nervous system] injury including seizure, strokes and hydrocephalus.”
They add: “Challenges in current follow-up care include providing adequate screening and hormone replacement therapy of [hypothalamic-pituitary] disorders for all survivors at risk, as well as attention to the physical and psychosexual effects of these conditions.”
By Laura Cowen
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J Clin Endocrinol Metab 2019; doi:10.1210/jc.2019-00834