Recent work suggests that a drug used to treat human Cushing`s disease may be beneficial in the management of the disease in horses. Equine Cushing`s Disease (ECD) is associated with excessive cortisol production by the adrenal gland. In almost all cases it is caused by a functional tumour ("adenoma") of the pars intermedia of the pituitary gland.
In normal horses, ACTH from the pituitary stimulates the release of cortisol from the adrenal glands. The blood cortisol level is controlled by a complex "feedback" mechanism. Basically, an increase in blood cortisol inhibits further ACTH release, which in turn causes the cortisol level to fall.
In horses with Cushing`s Disease the pituitary adenoma produces ACTH, and other similar molecules, some of which increase the "potency" of ACTH. In addition, the adenoma does not respond to the usual feedback controls. The signs associated with ECD are mostly due to the increased cortisol activity.
Drugs such as bromocriptine (Pergolide®) or cyproheptadine (Periactin ®) have been used to control the disease. These drugs act on the pituitary gland to reduce ACTH production.
A different approach has been investigated recently using trilostane (Modrenal ® , Stegram Pharmaceuticals, UK), a drug which blocks cortisol production within the adrenal gland itself.
Researchers at the Royal Veterinary College, led by Dr Cathy McGowan, carried out a trial to evaluate the value of the drug in the management of ECD. Twenty horses and ponies were included in the study. Most were ponies; there were twelve mares and eight geldings. Each animal showed at least three signs of Cushing`s disease - eg hirsutism (long curly coat) (20/20 cases), lethargy (19/20), laminitis (16/20), excessive drinking/urinating (11/20). The diagnosis of ECD was confirmed using the combined dexamethasone suppression / TRH stimulation test.
The horses were treated with trilostane (at doses between 0.4 and 1mg/kg) by mouth once a day. The response to treatment was assessed after 30 days and after 12 months.
"After 30 days treatment all horses showed an improvement in at least 1 of the clinical signs. All horses were less lethargic. Thirteen cases (81%) showed an improvement or no recurrence of laminitis. However, three severe cases of laminitis did not improve." reports Dr McGowan. "The eleven cases which had been drinking and urinating excessively, all showed a decrease towards normal . These improvements continued over the 12 months of the study. The treatment had no effect on the hirsutism - the horses remained hairy."
Three horses which were given the lower dose (0.4mg/kg) developed laminitis during the trial. The dose was increased to 1mg/kg and no further recurrence occurred.
Treatment with trilostane did not affect the results of the dexamethasone suppression test. But the response to the TRH stimulation test was more normal.
"The treatment seemed safe and efficacious. The best effect was seen at the 1mg/kg dose rate. We have not noticed any side effects. "Dr McGowan concludes "This is a useful therapy for the treatment of ECD, especially with respect to improving the quality of life. We think it merits further study"
source: British Equine Veterinary Association Congress 2001.