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      Cardiovascular Effects of Growth Hormone Treatment: Potential Risks and Benefits

      Hormone Research in Paediatrics

      S. Karger AG

      Heart, Growth hormone, Insulin-like growth factor-I, Acromegaly, Growth hormone deficiency

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          Growth hormone (GH) and insulin-like growth factor-I are involved in heart development and in maintaining cardiac structure and performance. Cardiovascular disease has been reported to reduce life expectancy both in GH deficiency (GHD) and in GH excess. Patients with GHD suffer from abnormalities of left ventricular performance, i.e. reduced diastolic filling and impaired response to peak exercise. Patients with GHD also have increased intima-media thickness at the common carotid arteries, associated with a higher occurrence of atherosclerotic plaques, which may further aggravate the haemodynamic conditions. This may contribute to increased cardiovascular and cerebrovascular risk. These cardiovascular abnormalities can be reversed, at least partially, with GH replacement therapy. In recent years, GH therapy has been used to increase cardiac mass in ischaemic or dilated cardiomyopathy, but the results have produced contradictory data.

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          Most cited references 53

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          Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor.

          Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone. We have examined the role of superoxide anion (O-2) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O-2 contributes significantly to the instability of EDRF.
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            Factors influencing mortality in acromegaly.

            Studies of acromegaly have shown a doubling of mortality compared with the general population. With the development of new modalities of treatment, it has become important to identify prognostic factors relating to mortality. Between 1964 and 2000, 208 acromegalic patients were followed for a mean of 13 yr at Auckland Hospital. Treatment was by surgery or radionuclide pituitary implantation, and all except 27 patients received pituitary radiation. Over the duration of the study, 72 patients died at a mean age of 61 +/- 12.8 yr. Those dying were significantly older at diagnosis, had a higher prevalence of hypertension and diabetes, and were more likely to have hypopituitarism. The observed to expected mortality ratio (O/E ratio) fell from 2.6 (95% confidence interval, 1.9-3.6) in those with last follow-up GH greater than 5 microg/liter to 2.5 (1.6-3.8), 1.6 (0.9-3), and 1.1 (0.5-2.1) for those with GH less than 5, less than 2, and less than 1 microg/liter, respectively (P < 0.001). Serum IGF-I, expressed as an SD score, was significantly associated with mortality, with O/E mortality ratios of 3.5 (95% confidence interval, 2.8-4.2) for those with an SD score greater than 2, 1.6 (0.6-2.6) for those with an SD score less than 2 (normal or low levels), and 1.0 (0.1-3) for those with an SD score less than zero. When assessed by multivariate analysis, last serum GH (P < 0.001), age, duration of symptoms before diagnosis (P < 0.03), and hypertension (P < 0.04) were independent predictors of survival. If IGF-I was substituted for GH, then survival was independently related to last IGF-I SD score (P < 0.02), indicating that GH and IGF-I act equivalently as predictors of mortality. These findings indicate that reduction of GH to less than 1 microg/liter or normalization of serum IGF-I reduces mortality to expected levels.
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              Association between premature mortality and hypopituitarism


                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                October 2004
                17 November 2004
                : 62
                : Suppl 3
                : 42-50
                Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Naples, Italy
                80498 Horm Res 2004;62(suppl 3):42–50
                © 2004 S. Karger AG, Basel

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                Page count
                Figures: 3, References: 86, Pages: 9
                GH Treatment – Potential Risks and Benefits


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