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Atherosclerosis represents a disease that begins in childhood and in which LDL cholesterol plays a pivotal role for the development of the pathology. Children and adolescents with high cholesterol levels are more likely than their peers to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet should begin at the age of 2 yr and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development, and psychological aspects in children and adolescents limiting total and saturated fat intake. Pharmacotherapy should be considered in children over 10 yr of age when LDL cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple risk factors are present. The only lipid-lowering drugs recommended up to now for childhood and adolescence are resins reported to be effective and well tolerated, although compliance is very poor because of unpalatability. The use of statins is increasing and seems to be effective and safe in children, even if studies enrolled a small number of patients and evaluated efficacy and safety for short-term periods. Recently, an interesting drug represented by ezetimibe has been found that may provide cholesterol-lowering additive to that reached with statin treatment. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence.

a-Melanocyte-stimulating-hormone (a-MSH) is a peptide derived from a two steps cleavage of Pro-opiomelanocortin (POMC) and produced in adults by a residual zona of the original intermediate lobe. It has recently been shown that a-MSH is not only detectable in healthy adult subjects, but also that plasma levels change during menstrual cycle, concomitantly with sex steroids modification. In addition it has been demonstrated that the peptide secretion is controlled by a dopaminergic inhibitory tore. In order to evaluate whether plasma a-MSH levels vary with advancing pubertal development and the dopaminergic tone influence the peptide release in children, 12 prepubertal and 15 pubertal subjects of both sexes underwent a domperidone stimulation (i.v. bolus dose of 0.3 mg/kg, max 10 mg). a-MSH and ACTH 1-13 plasma levels were determined before and after domperidone administration. Both peptides were measured by RIA after plasma extraction on Seppak Cartridges and reverse phase HPL-C fractionation. In prepubertal children basal a-MSH (2.8±0.8 fmol/ml) and ACTH 1-13 (6.0±1.6 fmol/ml) levels were lower, though not significantly, than those in pubertal subjects (4.8±0.9 and 8.2±1.4 respectively). After domperidone both a-MSH (8.1±2.5) and ACTH 1-13 (20.7±5.2) plasma levels significantly (p 0.05) increased in prepubertal subjects, whereas no changes were detected in pubertal ones. The results of the present study demonstrate that: 1) plasma a-MSH levels are detectable troughout childhood; 2) a functional activity of pituitary neurointermediate lobe is more evident in prepubertal than in pubertal subjects, suggesting a modified dopaminergic tone and/or anatomical changes during puberty.

An increased opioidergic tone has been demonstrated in obese subjects and ascribed to the metabolic derangements of obesity. Based on the different beta-endorphin (ß-EP) responses to oral (OGTT) and intravenous (IVGTT) glucose tolerance test, it has been suggested that the increased ß-EP levels detected in obese adult patients are not only originated from the pituitary but also from peripheral sites as the gastrointestinal tract. To assess whether ß-EP levels are affected by the hyperglycemia and/or hyperinsulinemia obtained by the enteral or parenteral administration of glucose in children, 24 obese children (14 F and 10 M, aged 6-17 yr) underwent either an OGTT (1.75 g/kg of glucose) or IVGTT (0.5 g/kg of glucose). Blood samples were obtained before and 0,30,60,90 and 120 min after the po glucose administration and -15, -1, before and 1,3,5,7,10,15,30,60, min after the iv glucose dose for measurements of blood insulin, ß-EP and glucose levels. Insulin plasma levels significantly increased following both tests. In contrast, ß-EP blood concentration did not vary after either the po cr iv administration of glucose. No significant correlation between insulin and ß-EP plasma levels was found. The results of the present study suggest that ß-EP secretion of obese children is not influenced by metabolic factors such as hyperglycemia and/or hyperinuslinemia as that of obese adult subjects.