Cushing's disease has been around for a long time in people, horses, and other animals. For years, theories and information concerning the affliction all centered on one source for the problem–tumors of the pituitary gland, which is located at the base of the brain. In the case of horses, it was generally felt that benign tumors in the intermediate lobe of the horse's pituitary gland resulted in an inappropriate secretion of hormones, which brought on Cushing's disease. Nowadays, the correct term is pituitary pars intermedia dysfunction (PPID), since it has been discovered that degeneration of the hypothalamic dopaminergic neurons (those in the hypothalamus using dopamine as their neurotransmitter) is the primary cause.

There is an affliction that has some of the same characteristics as Cushing's, yet is different. At the same time, there is speculation that this syndrome, termed metabolic syndrome and previously called peripheral Cushing's syndrome, could be a factor in horses which develop Cushing's disease