ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Endocrinol Invest. 2020 Feb;43(2):209–217. giulia.rodari@unimi.it

Growth hormone deficiency (GHD) is the most common endocrine late effect in children with tumours involving the hypothalamus-pituitary (HP) area or exposed to cranial, craniospinal or total body radiotherapy (RT). The location of brain tumours in continuity with the sellar/suprasellar area and HP radiation doses ≥18 Gy represent the most important risk factors for GHD.

This retrospective study analysed 87 childhood cancer survivors (CCS) treated with recombinant GH (rhGH). Patients were divided into 2 groups: A) children treated with cranial radiotherapy or affected by non-irradiated tumours of the HP area; B) children treated with craniospinal or total body irradiation. Overall height (HT) gain after 1 and 2 years of rhGH therapy was 0.38 ± 0.35 SDS and 0.18 ± 0.30 SDS, respectively. No differences were found between the 2 groups during the first year of treatment, but group B showed a poorer response to treatment during the second year. Mean final height (FH) was in the normal range, but not significantly different from HT SDS at baseline; 67% of children failed to reach their mid parental height (MPH).

Spinal, craniospinal or total body irradiation, precocious or early puberty contribute to the suboptimal growth response to rhGH in CCS. The administration of rhGH after craniospinal RT may result in an exaggeration of the skeletal disproportion often observed also in GH untreated CCS, due to the specific radiation-induced damage to the spine. For all of these reasons, final height of CCS often falls below MPH. In this study, the major determinants of FH were height at rhGH start and lag time between the end of antineoplastic treatments and rhGH start. GHD in these patients tends to present with progressive linear growth deceleration, rather than with significant short stature, which underlines the importance of early initiation of rhGH therapy as soon as height velocity decreases. rhGH therapy aims to prevent further linear growth deceleration, even if it is expected that it cannot normalize height. Treatment, although failing to induce catch-up growth, prevents progressive height loss, leading to a FH within the normal range, even if still below MPH.

References:

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3. Beckers D, Thomas M, Jamart J, Francois I, Maes M, Lebrethon MC, De WK, Tenoutasse S, De SJ. Adult final height after GH therapy for irradiation-induced GH deficiency in childhood survivors of brain tumors: the Belgian experience. Eur J Endocrinol 2010;162:483–90.