Pathogenesis and diagnosis of equine Cushing's disease (Proceedings)
Apr 01, 2010
CVC IN WASHINGTON, D.C. PROCEEDINGS
In humans and dogs, Cushing's disease is most commonly attributed to a corticotroph adenoma in the pars distalis of the pituitary gland. These adenomas are thought to arise spontaneously. In contrast, Cushing's disease in horses is almost exclusively attributed to hyperplasia or adenoma formation in the pars intermedia that appears to be due to loss of hypothalamic innervation. Abnormal pars intermedia tissue in horses contains markedly reduced amounts of dopamine, about 10% that of normal pars intermedia tissue, consistent with a specific loss of hypothalamic dopaminergic innervation. Recent evidence suggests that this loss of dopaminergic innervation is due to oxidant-induced injury to hypothalamic tissue. Thus, a risk factor for affected horses may be reduced anti-oxidant defense mechanisms in neural tissue. Further, insoluble aggregates of the neural protein α-synuclein have been found in dopaminergic nerve terminals of PPID-affected horses. These protein aggregates are also found in humans with Parkinson's disease suggesting that the two neurodegenerative disorders may share a similar pathogenesis. However, the population of neurons affected in horses, as compared to humans, appears to be somewhat different leading to the difference in clinical signs observed in each species.Abnormal pars intermedia cells produce excessive amounts of pro-opiomelanocortin (POMC) and a number of POMC-derived peptides including adrenocoticotropin (ACTH). Also unlike Cushing's disease in humans and dogs, adrenocortical hyperplasia accompanying equine Cushing's disease is relatively uncommon, occurring in ~20% of affected horses. These differences in location and pathophysiology between human, canine, and equine pituitary adenomas have lead several authors to suggest that the disease in horses should not be called equine Cushing's disease; rather, pituitary pars intermedia dysfunction (PPID) has been advanced as a more appropriate descriptor.
Chronic, insidious-onset laminitis is perhaps the major clinical complication of PPID with more than 50% of horses affected in most reports. Although the condition is more amenable to management in ponies due to their lower body weight, chronic or recurrent pain with exacerbation of laminitis or associated foot abscesses is often the reason for euthanasia. Polydipsia and polyuria (PU/PD) develops in about one-third of horses with PPID. Equids with PPID tend to have delayed wound healing and are frequently affected with secondary infections. Commonly recognized infections include skin infections (e.g., refractory "scratches" and fistulous tracts), recurrent subsolar abscesses, conjunctivitis, sinusitis (Figure 2, right), gingivitis, alveolar periostitis, and bronchopneumonia.
Other signs that have been reported in horses with PPID include persistent mammary secretions and infertility. Central nervous system (CNS) dysfunction, including ataxia, blindness, and seizure-like activity, are occasionally observed in equids with PPID. A major complication of hypercortisolism in affected human patients is osteoporosis. Although occurrence of this complication has not been investigated in horses, it is interesting to note that euthanasia of horses with PPID has been reported due to development of pelvic, pedal bone, mandibular, and multiple rib fractures.