ENDOCRINE MANAGEMENT IN PRADER-WILLI SYNDROME

Prader Willi syndrome (PWS) is a genetic disorder (15q11-q13) characterized by short stature, hypogonadism leading to osteoporosis, delayed puberty, central hypocorticism and the most life threatening, excessive appetite which is followed by morbid obesity. Patients with PWS present reduced GH secretion, hypogonadotropic hypogonadism, abnormal appetite control and high pain threshold suggesting hypothalamic-pituitary dysfunction. However, all high resolution imaging studies are normal; due to changes in Chr 15, the hypothalamic function is disrupted. All patients with PWS show severe disturbances in appetite control resulting in hyperphagia and obesity. Peptides involved in hypothalamic appetite control as ghrelin. leptin, NPY/AGRP, POMC, and their cognate receptors, are involved in developmental processes, determine the threshold for signals of body fat below which increases in energy intake and reductions in energy expenditure. In addition, low GH and IGF1 level, central hypothyroidism, delayed puberty and central hypogonadism may impact upon the body composition. Despite the detailed knowledge about obesity mechanisms regulated at hypothalamic level, the pharmacological intervention is limited currently to substitution of proven endocrine deficiencies and GH treatment. The PWS brain seems "wired" for a positive energy balance, and very few pathways can counterbalance this genetic imprinting.