Hypothalamic Obesity and Wasting Syndromes

Abstract

Since the early animal lesional and electric brain stimulation experiments of Hetherington and Ranson, it has been appreciated that lesions in certain parts of the hypothalamus can induce profound phenotypes of morbid obesity or dramatic wasting. These and other findings led to the postulation of hypothalamic “satiety” and “feeding” centers. Subsequent clinical observations in humans including characterization of children with morbid obesity associated with entities such as the Prader-Willi and Frohlich syndromes as well as Simmonds’ cachexia demonstrated that similar hypothalamic dysfunction phenotypes existed in human hypothalamic disease. The discovery of leptin and the subsequent better characterization of the hypothalamic basis for modulation of satiety, hunger, and energy balance as well as the discovery of various adipo- and enterocytokines with central hypothalamic modulatory effects crystallized hypothalamic obesity and wasting as distinct and important clinical entities. This manuscript seeks to provide a comprehensive overview of the causes, presentation, and basic pathophysiology of these two disparate but functionally related clinical syndromes.