Long-term safety of growth hormone replacement after CNS irradiation.
ABSTRACT Radiotherapy is a central component in the treatment of many brain tumors, but long-term sequelae include GH deficiency and increased risk of secondary neoplasms. It is unclear whether replacement therapy with GH (GHRT) further increases this risk.
The objective of the study was to assess the effect of GHRT on the incidence of secondary tumors and tumor recurrence after cranial irradiation.
We conducted a retrospective matched-pairs analysis of previously irradiated patients, with and without GHRT, attending a tertiary center between 1994 and 2009. Patients: We reviewed the records for all patients undergoing GHRT at our institution over the study period. Patients were included if they had received cranial irradiation, GHRT for at least 12 months, and records of serial magnetic resonance imaging data and data for dose and fractionation of irradiation were available. GH-naïve control patients were selected from a radiotherapy database of patients attending the same hospital. Patients were matched for date of radiotherapy, age, site of primary diagnosis, radiation dose, and fractionation.
The primary outcome measure was risk of tumor recurrence or secondary tumor.
Matched controls were identified for 110 GH-treated patients. Median follow-up was 14.5 yr. No significant differences were apparent in the number of tumor recurrences (six vs. eight, GHRT vs. control group) or secondary tumors (five vs. three, respectively) between groups.
Our study demonstrates no increased risk for recurrent or secondary neoplasms in patients receiving GHRT, thus supporting a high safety profile of GHRT after central nervous system irradiation.
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ABSTRACT: Objective The potential involvement of growth hormone therapy in tumor promotion and progression has been of concern for several decades. Our aim was to assess systematically the association between growth hormone therapy and all-cause, cancer and cardiovascular mortality, cancer morbidity and risk of second neoplasm mainly in patients treated during childhood and adolescence. Design A systematic review of all articles published until September 2013 was carried out. The primary efficacy outcome measures were the all-cause, cancer and cardiovascular standardized mortality ratios (SMR). The secondary efficacy outcome measures were the standardized incidence ratio (SIR) for cancer and the relative risk (RR) for second neoplasms. The global effect size was calculated by pooling the data. When the effect size was significant in a fixed model we repeated the analyses using a random model. Results The overall all-cause SMR was 1.19 (95% CI 1.08–1.32, p < 0.001). Malignancy and cardiovascular SMRs were not significantly increased. Both the overall cancer SIR 2.74 (95% CI 1.18–5.41), and RR for second neoplasms 1.99 (95% CI 1.28–3.08, p = 0.002), were significantly increased. Conclusion The results of this meta-analysis may raise concern on the long-term safety of GH treatment. However, several confounders and biases may affect the analysis. Independent, long-term, well-designed studies are needed to properly address the issue of GH therapy safety.Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 01/2014; · 2.35 Impact Factor
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ABSTRACT: Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.Journal of Molecular Medicine 09/2013; · 4.77 Impact Factor
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ABSTRACT: Due to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant endpoints seems feasible. In this Review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and non-fatal cardiovascular disease (CVD) and stroke, fractures, fatal and non-fatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and non-fatal malignancies were not more prevalent in GH treated adults compared to the general population. However, follow up time is still relatively short. The studies on diabetes are difficult to interpret and more evidence is awaited. In clinical practice a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile, and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes. This article is protected by copyright. All rights reserved.Clinical Endocrinology 04/2014; · 3.40 Impact Factor