Chapter 21 Canine pituitary-dependent hyperadrenocorticism: a spontaneous animal model for neurodegenerative disorders and their treatment with 1-deprenyl

Abstract

Canine hyperadrenocorticism is a common disorder in the dog and probably the most common endocrinopathy encountered in geriatric patients. The majority of cases (90%) occur as the result of pituitary hypersecretion of ACTH [pituitary-dependent hyperadrenocorticism (PDH); Cushing's disease], which results in bilateral adrenal hyperplasia and an overproduction of cortisol. This chapter presents a spontaneous animal model for neurodegenerative disorders and their treatment with l-deprenyl that is based on canine pituitary-dependent hyperadrenocorticism. There are many similarities between canine PDH and human Parkinson's disease. Both are related to dopamine deficiency within specific areas of the brain, with attendant disruption of normal function. In canine PDH, dopaminergic depletion occurs in the median eminence and paraventricular nuclei associated with an increased secretion of POMC peptides (including ACTH) from polydipsia (PD) and pars intermedia (PI). The hypersecretion of ACTH results in the overproduction of cortisol and leads to the clinical signs and laboratory abnormalities characteristic of PDH. The use of I-deprenyl in dogs with PDH results in an amelioration of clinical signs and a return of post-dexamethasone (LDDS) cortisol levels towards or into the normal reference range. The administration of the dopaminergic neurotoxin, l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine, not only results in a parkinsonian state in man and dogs, but also results in a state of functional hyperadrenocorticism in normal dogs.