Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

Abstract

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Hormone replacement in survivors of childhood cancer and brain tumors: safety and controversies

“…Nevertheless, in-vitro and in-vivo proliferative and pro-mitogenic properties of GH and insulin-like growth factor-I (IGF-I), which is produced following stimulation by GH, have raised concerns regarding potential associations between hGH use and the risk for tumor recurrence or subsequent malignancy in treated childhood cancer and brain tumor survivors. This concern has prompted the publication of over the past 3 decades many reports and reviews on the topic including a recent consensus statement from the GH Research Society (6,17).…”

“…The primary limitation of the SAGhE cohort data is the reliance on comparison of adverse health outcomes and mortality among patients treated with hGH to data from the general population (27). The absence of a non-GH treated CCS control group curtails investigator ability to identify a specific effect of hGH, beyond risks that are already conferred by the primary cancer or tumor and their treatments (6). Nevertheless, a recent report from this cohort reassuringly showed that the occurrence of meningioma in CCS did not correlate with the dose or duration of treatment with hGH (26).…”

“…Benefits of treatment with hGH have been deemed to outweigh potential risks in GH deficient children who achieve remission from cancer or CNS tumors (6). However, areas of uncertainty remain including whether treatment with hGH should be delayed by 1 year after completion of tumor / cancer therapy (28), whether the dosing of hGH should be different in this population and whether the overall reassuring safety data are truly applicable to GH deficient children with cancer predisposing syndromes (6).…”

“…Benefits of treatment with hGH have been deemed to outweigh potential risks in GH deficient children who achieve remission from cancer or CNS tumors (6). However, areas of uncertainty remain including whether treatment with hGH should be delayed by 1 year after completion of tumor / cancer therapy (28), whether the dosing of hGH should be different in this population and whether the overall reassuring safety data are truly applicable to GH deficient children with cancer predisposing syndromes (6). The safety of hGH in patients who require maintenance treatment with targeted chemotherapy for disease control, such as children on TKI, and the use of long acting hGH preparations are additional areas of uncertainty given the lack of long-term data (6).…”

“…Furthermore, recommendations have varied according to the regional or national bodies that have formulated them (2)(3)(4). For these reasons, gaps in knowledge of the true risk conferred by hormone replacement therapy in CCS continue to represent a challenge, as best illustrated by the controversy surrounding the use of GH in this population (2)(3)(4)(5)(6). This review offers a summary of current evidence pertaining to hormone replacement using GH, thyroid hormone, and sex hormones in CCS and their potential association with tumor progression or recurrence as well as the risk for subsequent neoplasms in order to facilitate patient counseling and treatment decisions.…”