%0 Journal Article
%T Hypothalamic Obesity following Craniopharyngioma Surgery: Results of a Pilot Trial of Combined Diazoxide and Metformin Therapy
%A Jill K Hamilton
%A Louise S Conwell
%A Catriona Syme
%A Alexandra Ahmet
%A Allison Jeffery
%A Denis Daneman
%J International Journal of Pediatric Endocrinology
%D 2011
%I BioMed Central
%R 10.1155/2011/417949
%X Craniopharyngiomas constitute 9% of childhood intracranial tumors. They are histologically benign, arising from embryonal remnants in the sellar region [1, 2]. In addition to endocrine deficiencies, obesity is common following surgical resection of the tumor, with a significant increase in long-term cardio- and cerebrovascular mortality observed [3¨C5]. Data from our group, in 17 obese youth with craniopharyngioma, show significantly more features of the metabolic syndrome (66% versus 15%), higher acute insulin secretion in response to an oral glucose tolerance test (OGTT), and a higher prevalence of glucose intolerance (40% versus 0%) compared to age- and BMI-matched controls [6].The mechanisms contributing to hypothalamic obesity following surgery for craniopharyngioma, likely include one or both of the following: (i) damage to hypothalamic nuclei and neuronal circuits involved in appetite and body weight regulation and (ii) a primary defect of insulin hypersecretion due to hypothalamic damage-induced vagal efferent stimulation with increased weight gain and compensatory insulin resistance [7, 8].Given the serious challenges posed by the ongoing weight gain and the lack of effective interventions, we developed a novel therapeutic approach with combination therapy aimed both at decreasing insulin secretion using diazoxide and simultaneously enhancing insulin action through the use of metformin.Neither metformin nor diazoxide the combination has been tested previously in children with hypothalamic obesity due to intracranial damage. The oral route of medication administration, safety profile, decreased cost, and their mechanisms of action support their use in combination in this situation. We hypothesized that the combined metformin and diazoxide therapy would lower insulin secretion while minimizing the risk of hyperglycemia, leading to weight loss and improvement in metabolic status.An open-label, 6-month duration, pilot treatment trial of combined diazoxide-metfor
%U http://www.ijpeonline.com/content/2011/1/417949