Background
Survival in childhood craniopharyngioma (CP) is excellent, however survivors face many sequelae of the tumor and its treatment, mainly caused by hypothalamic-pituitary dysfunction. Growth hormone (GH) deficiency (GHD) is diagnosed in up to 92%. GH replacement therapy in children is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GH in GHD patients after CP treatment is still on debate and concerns regarding tumor progression/recurrence have been raised.

Methods
We performed a systematic review and cohort study aiming to evaluate the effect of GH treatment and its timing on tumor progression/recurrence, mortality and secondary tumors in childhood CP. Within our retrospective cohort, patients diagnosed with childhood CP between 2006 and 2021 were included, and patients receiving GH from ≤ 1 year of CP diagnosis were compared to those given GH from >1 year after CP diagnosis.

Results
In total 19 studies could be included in the literature review, reporting on 6603 childhood CP with GH treatment. No increased risk for tumor progression/recurrence was associated with GH or its timing. Four studies with low quality evidence, reported an increased risk for mortality, when compared to the general population. One study reported a higher observed than expected prevalence of secondary tumors, possibly confounded by radiotherapy.

In our retrospective cohort, of 59 childhood CP patients, 51 (86.4%) received GH for median of 4.13 years [0.27 – 13.80]. No difference was found for patients with or without GH on the progression/recurrence rate or on mean progression free survival (PFS), neither between patients who started GH ≤1 year after CP diagnosis compared to those who received GH > 1 year after diagnosis.

Conclusions
Current evidence suggests that there is no effect of GH in childhood CP on regrowth or recurrent disease and that there is no effect of timing of start of GH. These results support early initiation of GH in childhood CP patients aiming to optimize linear growth and metabolic outcome.