Pathophysiology and clinical features of pituitary pars intermedia dysfunction

Our understanding of the development and progression of equine pituitary pars intermedia (PI) dysfunction has expanded over the last decade, although much remains to be explained. Degeneration of the hypothalamic periventricular dopaminergic neurons results in disinhibition of the endocrine cells of the PI, the melanotropes. As a result, the PI enlarges, compressing the adjacent lobes, the pars distalis and pars nervosa. The disinhibited melanotropes overproduce pro‐opiomelanocortin peptides, including α‐melanocyte stimulating hormone, β‐endorphin, corticotrophin‐like intermediate lobe peptide and adrenocorticotropin. The excess in PI hormones, perhaps in concert with a deficiency in other pituitary hormones, results in clinical signs of pituitary PI dysfunction. Evidence suggests both oxidative stress and accumulation of misfolded neuronal proteins contribute to damage to the periventricular neurons, although it is not clear if these pathologies actually initiate the disease or are downstream events.