Safety of growth hormone replacement therapy in childhood-onset craniopharyngioma: a systematic review and cohort study.

Background Survival of childhood-onset craniopharyngioma (cCP) is excellent, however many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence. Methods A systematic review and cohort study were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis. Results Evidence of 18 included studies, reporting on 6603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression or recurrent disease. One study evaluated timing of GHRT and progression/recurrence free survival and found no increased risk with earlier initiation. One study reported a higher observed than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0 - 17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence free survival, or secondary tumors. Conclusions Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.