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.

Keywords: Cancer survivor; Childhood cancer survivor; Growth hormone deficiency; Growth hormone safety.

Fig. 1

Diagrammatic representation of endocrine and paracrine effects of GH on mitogenesis, angiogenesis and apoptosis, either directly or by synergy with other growth factors. GH stimulates both IGF-I and IGBP3 [41]. While IGF-I and IGFBP proteases favors cell proliferation and inhibits apoptosis [43, 44, 47], IGFBP3 [46] and IGF-II receptors [47] act in the opposite direction, via an IGF-independent pathway. The result of these opposed forces in a tissue-specific environment might be critical for normal and abnormal cell growth [41]. Dotted lines: inhibition. Continuous line: stimulation. Adapted from Ref. [46, 48]