Cushing’s Disease and a New Potential Surgical Cure

Cushing’s disease in horses, also known as equine pituitary pars intermedia dysfunction (PPID), is caused by excessive hormone secretion from a tumour in the brain’s pituitary gland. It is often diagnosed in senior horses, and is characterized by abnormal hair growth, a change to fat deposit patterns (including a “cresty” neck) and laminitis.

Currently, the only treatment for Cushing’s is daily drug therapy, but researchers at the Western College of Veterinary Medicine (WCVM) are working on a long-term, surgical solution.

The pituitary gland sits below the hypothalamus, the part of the brain responsible for hormone regulation. The pituitary gland’s primary function is to produce and release hormones into the circulatory system.

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Pituitary hormone production is normally regulated by chemicals, such as dopamine, from the hypothalamus. In PPID-affected horses, neurons of the hypothalamus degenerate. As a result, the hypothalamus releases less dopamine. A tumour develops, and hormone production in the pituitary gland increases.

To combat this process, the drug pergolide must be given daily (in oral paste or tablet form), as it imitates dopamine, acting as a replacement and decreasing the clinical signs of disease.

“[It’s] a chronic, incurable disease of the aging horse that is relatively common,” said Dr. James Carmalt, a large animal surgeon and researcher at the WCVM.

Dr. Carmalt is proposing a drastic shift in veterinarians’ approach to treating equine PPID. The end goal of his research is to develop a surgical cure that will improve on the current standard of treatment. As he pointed out, when humans or dogs suffer from pituitary-dependent Cushing’s disease, the gold standard for care is surgery. So, “why not [surgery for] the horse?”

Surgical destruction of equine pituitary tumours could provide a long-term cure for PPID and eliminate the need for daily drug therapy.

Dr. Carmalt noted that the PPID diagnosis and treatment are difficult for the veterinarian and the horse owner. “The common veterinary problem of questioning the diagnostic tests, agonizing over whether to treat and then finally having someone treat the horse every day for the rest of its life has to become something of the past,” he said.

The first step in this research project is examining biomarkers of PPID – measurable indicators of the severity or presence of the disease. Association of a reliable chemical pattern with PPID may permit veterinarians to conduct more accurate and predictive testing. Particularly, the aim is to identify horses that are developing PPID, but show no distinctive disease signs.

Current laboratory work involves evaluating pituitary tissue samples for gene expression – measurements that may help to define the mechanistic effect of diminished dopamine regulation.

Another part of the research team’s plan is to sequence genes of interest. This process could detect differences in hormone modification that exist between normal and PPID-affected horses.

Dr. Carmalt’s collaborator is Dr. Suraj Unniappan of the Laboratory of Integrative Neuroendocrinology at the WCVM. The project has received financial assistance from the veterinary college’s Equine Health Research Fund.

Early detection of PPID and a long-term cure for the disease may ultimately sustain a horse’s career and allow horses to enjoy a longer, useful life, said Dr. Carmalt. He acknowledged that his goals are ambitious, but said, “The status quo will remain as such unless someone somewhere makes a radical, paradigm shift in the thinking process surrounding this disease.”