Hypothalamic obesity.

Following extensive suprasellar operations for excision of hypothalamic tumors, some patients develop morbid obesity, the so-called hypothalamic obesity (HyOb). HyOb complicates disorders related to the hypothalamus, including those that cause structural damage to the hypothalamus, pituitary macroadenoma with suprasellar extension, glioma, meningioma, teratoma, germ cell tumors, radiotherapy, Prader-Willi syndrome, and mutations in leptin, leptin receptor, POMC, MC4R and CART genes. It is conceivable that a subgroup of patients with 'simple obesity' also have HyOb. The hypothalamus regulates body weight by precisely balancing the intake of food, energy expenditure and body fat tissue. Orexigenic and anorexigenic hypothalamic centers (hyperphagia when impaired) play a central role, connecting to adipose tissue by means of an intricate efferent and afferent signals circuit. Other mechanisms by which the brain regulates adipose tissue and beta cells of the pancreas include the sympathetic nervous system, vagally mediated hyperinsulinemia and the endocrine system, namely growth hormone, thyroid-stimulating hormone and the hypothalamo-pituitary-adrenal axis. Corticotropin-releasing hormone, adrenocorticotropic hormone glucocorticoids and the 11beta-HSD-1 shuttle regulate lipolysis both directly and indirectly. All the above mechanisms may be impaired in HyOb. Management of HyOb targets the major manifestations: hyperphagia, autonomic dysfunction, hyperinsulinemia and impaired energy expenditure. Individual variation is considerable. Satisfactory therapy is currently unavailable.