[Is there a relationship between the growth hormone dose and tumoral or cardiovascular complications?]

Growth hormone (GH) affects protein (anabolism), lipid (lipolysis) and carbohydrate (hyperglycemia) metabolism and stimulates hepatic synthesis of insulin-like growth factor 1 (IGF1). IGF1 is believed to act as a postnatal growth factor. In addition to its effects on growth, IGF1 affects cell proliferation, differentiation and survival, and has anabolic effects on proteins, and also lipogenic and glucose-lowering effects. The increasing availability of biosynthetic pituitary GH has made it feasible to treat GH-deficient children and adults, and patients of short stature due to a variety of other causes (Turner's syndrome, anomalies of SHOX, intrauterine growth retardation (IUGR), chronic renal failure, Prader-Willi syndrome, or idiopathic short stature). The therapeutic dose has been increased in some situations in which the response is inadequate, particularly in patients with certain conditions such as IUGR. However, it has been reported that cancers and cardiovascular diseases are associated with high plasma concentrations of GH and IGF1, particularly in patients with acromegaly but also in large epidemiological studies of apparently healthy populations. These findings raise questions as to the safety of GH treatment. Some long-term follow-up studies have shown an increase in the risk of some kinds of cancer or cerebrovascular disease, but these findings have not been replicated by others. The results of these studies remain debatable, due to their small sample sizes, methodological weaknesses, nonexhaustive data collection and problems involved in comparing these patients with an appropriate control group. Finally, GH and IGF1 deficiencies are themselves associated with an increased risk of cardiovascular diseases, as is small stature/low weight at birth (due to IUGR). Recent studies have demonstrated a higher risk of cardiovascular disease in patients with both low and high plasma concentrations of GH and IGF1, these risks disappearing at average values. These findings suggest that the GH dose should be adjusted during treatment to ensure that plasma IGF1 concentrations remain within the physiological range.