medwireNews: Around 70% of children who survive a brain tumour develop at least one form of endocrine dysfunction, suggests a long-term study of patients attending a hospital in Portugal.

Joana Maciel and co-workers, from Instituto Português de Oncologia de Lisboa Francisco Gentil in Lisbon, identified 242 children treated for a brain tumour between 1994 and 2018 at their institution and monitored the group for a median of 9.8 years (range 0.4–31.2 years).

Overall, 71.5% of patients were diagnosed with one or more endocrinopathies, a higher rate than the previously reported figures of 50.0–65.7% in studies of paediatric brain cancer survivors, the team remarks in the Journal of Endocrinological Investigation.

“This is probably due to the active surveillance that is applied in our center”, the researchers say, where all children are referred to an endocrinology clinic for monitoring within a year of completing cancer treatment, or earlier when specific concerns are raised.

And they note that endocrinopathies were significantly more common among children who received brain radiotherapy than those who received other treatment modalities (78.9 vs 57.0%).

The patients were aged a median 6.7 years at time of tumour diagnosis, with the majority of patients having pilocytic astrocytoma (33.5%) or medulloblastoma (26.9%). Brain tumours were most commonly found at the posterior fossa (38.4%) or sellar and suprasellar regions (28.9%).

The patients underwent surgery (79.8%), chemotherapy (76.0%), and cranial (66.5%) or craniospinal (36.4%) radiotherapy, with median radiation doses of 54.0 Gy and 30.6 Gy, respectively.

The most common endocrinopathy detected was growth hormone (GH) deficiency, affecting 52.9% of patients after a median 4.3 years of follow-up, at a median age of 12.1 years. The majority (69.5%) of patients were approved for somatropin therapy and 39.8% had achieved a final adult height at last follow-up with an average height standard deviation score (SDS) of –0.9, an improvement on the SDS of –1.5 before somatropin therapy.

The investigators note that the average final height SDS did not significantly differ between the 16 patients who had received cranial radiotherapy and the 29 patients who received craniospinal radiotherapy (0.0 vs –0.3) but that the final upper/lower segments ratio was significantly smaller in the latter group (1.0 vs 1.1).

“This is probably due to radiation-induced dimorphisms, like scoliosis, and to an inadequate GH response by the irradiated vertebral bone”, they postulate.

Nevertheless, the children given craniospinal radiotherapy did not significantly differ in final height SDS from their family targets, the researchers say.

A further 38.0% of patients were diagnosed with primary (23.6%) or central (14.5%) hypothyroidism and 25.2% had abnormalities of puberty, such as delayed (12.0%), precocious (8.7%) or accelerated puberty (4.5%). In addition, 25.2% of patients developed hypogonadism, most commonly central hypogonadism (21.9%), 10.3% adrenocorticotropic hormone deficiency and 12.0% diabetes insipidus.

The researchers conclude that their study “strengthens the importance to routinely monitor growth and pubertal development” of childhood brain tumour survivors and “highlights that, in addition to cranial [radiotherapy], craniospinal irradiation effects in this population must not be underestimated since they may contribute to skeletal dysmorphism.”

They therefore emphasize that “it is extremely important to establish a routine and systematic follow-up” for these patients and point to the “urgent need to delineate specific and detailed guidelines for this population.”

By Lynda Williams

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J Endocrinol Invest; doi:10.1007/s40618-021-01541-4

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