EQUINE PITUITARY PARS INTERMEDIA DYSFUNCTION (PPID): PATHOPHYSIOLOGY AND A SURGICAL APPROACH TO TREATMENT

Equine pituitary pars intermedia dysfunction (PPID) is a common endocrine disease of the older horse. First described in 1932, and likened to human Cushing’s disease, it is associated with an enlargement of the pituitary gland that was classically termed an adenoma. The underlying mechanism is attributable to a lack of dopaminergic inhibition of the pars intermedia. Treatment methods have remained essentially unchanged for 30 years and the prevalence data have mainly stemmed from Eastern Australia and the USA. The general objective of this thesis was to explore the feasibility of developing a targeted cell-specific approach for the treatment of equine PPID. The specific aims were to confirm the need for this advanced therapy by determining the prevalence of PPID in horses globally; to continue the investigation of the underlying cellular mechanism of PPID by confirming the role of pro-hormone convertases, and sequence the equine pro-opiomelanocortin, prohormone convertase 1 and 2 genes; and to investigate the methodology for site-specific applications of future therapy for equine PPID. These aims were met by reporting the prevalence data from a worldwide audience of veterinarians using an internet-based survey tool; by describing partial gene sequences of the equine proopiomelanocortin and prohormone convertase enzymes and their expression in normal and PPID horses; and by showing how low-volume contrast enhancement of the brain using computed tomography can delineate the margins of the pituitary gland, showing how general anesthesia effects the pulsitility and concentration of adrenocorticotrophic hormone, and finally, modifying a previously reported technique, by developing a novel surgical approach to the treatment of this classical condition