MANAGEMENT OF ENDOCRINE DISEASE: GH therapy and cancer risk in hypopituitarism: what we know from human studies

Abstract

It has been difficult to identify factors that affect the risk of cancer, but we know that people are at higher risk as they get older, or if they have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Early population-based and casecontrol studies suggested that higher serum levels of IGF1 could be associated with increased cancer risk. Since GH therapy increases IGF1 levels, concern has been raised regarding its potential role as a cancer initiation factor. Experimental evidence and some clinical studies showed that when GH/IGF1 secretion or action was inhibited, a decreased incidence and rate of progression of cancers occurred. However, human populations comprise a garden variety of genotypes that respond differently to the same kind of exposures. Human population studies frequently reveal only very small effects to these exposures. So, are GH and cancer guilty by association? After more than 20 years, leukemia, a major safety issue initially believed associated with GH treatment in children with GH deficiency (GHD), has not been confirmed but the risk of second malignancies in patients previously treated with irradiation has been detected or confirmed through the National Cooperative Growth Study. Overall, this large study confirmed the favorable overall safety profile of GH therapy in children with GHD, and also highlighted specific populations at potential risk. The risk of secondary malignancy following radiotherapy is surely related to radiotherapy more than GH therapy that may increase growth but is less likely to start the oncogenic process. In GH-deficient adults treated with GH, observational studies (KIMS, HypoCCS) have shown that when IGF1 levels were targeted within normal age-related reference ranges, the occurrence of malignancies was not higher than in the general population.

Carotid Intima-Media Thickness in Children Treated with Growth Hormone: A Follow-Up Study over Three Years

“…These findings suggest that GH treatment in children is not associated with cardiovascular changes measurable with cIMT. Our observation is in line with reports that adult mortality and morbidity is not higher in childhood-onset GH-deficient patients who received pediatric GH treatment [33,34] . Our study demonstrated a relationship between changes in cIMT, IGF-1, and IGFBP-3 in univariate analyses.…”

“…However, the univariate significant associations between IGF-1, IGFBP-3, and cIMT got lost in multiple linear regression analyses adjusted for multiple confounders questioning its relevance. It is important to notice that GH therapy was not associated with an elevated cardiovascular risk in adults, when IGF-1 concentrations were targeted within normal agerelated reference ranges [34] .…”

Growth hormone therapy and risk of recurrence/progression in intracranial tumors: a meta-analysis

“…Irrelevant risks of tumor recurrence/progression were acquired from pituitary adenomas, NFPA, and ependymoma. However, the fluctuation in serum levels of GH and IGF-1 was observed in neoplastic disease, which might affect tumor progression [28]. In addition, Renehan et al conducted a meta-regression analysis and demonstrated that high level of IGF-1 contributed to carcinogenesis in prostate, colorectal, and premenopausal breast cancers [29].…”

Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

“…Speculation remains that there may be an increased risk of neoplastic disease in growth hormone (GH)-treated patients (1,2). The mitogenic and proliferative actions of GH and insulin-like growth factors (IGFs) have been demonstrated by epidemiological and experimental analyses (3,4,5,6,7).…”