More horses than ever are developing conditions that used to be considered rare complications of old age. And, in part, that's a good thing. Whereas once the equine lifespan topped off in the late teens, advances in medical care, parasite control, pharmaceuticals and nutrition now make unprecedented longevity possible. The price, of course, is an upswing in the incidence of aging-related problems. And Cushing's disease leads that list.
The basic facts about Cushing's have been known practically since the disorder was first identified some 70 years ago: A malfunction of the pituitary gland, the marble-size organ at the base of the brain, causes the release of excessive levels of the hormone adrenocorticotropin (ACTH). This, in turn, triggers the adrenal gland to increase the production of cortisol, and the resulting hormonal imbalances lead to the hallmarks of Cushing's: a long, shaggy hair coat, loss of muscle mass, laminitis and susceptibility to infection.
No one knows for sure how many aged horses are affected by pituitary dysfunction, but it was the most common specific diagnosis in a 2003 study of 467 horses aged 20 or older admitted to the Tufts University clinic. In related research, a survey of 218 horse owners revealed that 30 percent of their horses had signs associated with Cushing's even though only 8 percent of the cases had been diagnosed.
But research has focused on far more than the incidence of Cushing's. Over the past decade or so, studies have illuminated the complex processes underlying the disorder, and along the way several false assumptions have fallen by the wayside. As a result, Cushing's horses today have a better prognosis than ever before, and with proper treatment and management they can enjoy long and productive lives.
Why the New Name?
Originally, equine Cushing's shared the name of similar pituitary disorders in people and dogs, which are both known as Cushing's syndrome. Nowadays, however, experts prefer to call the equine condition "pituitary pars intermedia dysfunction" (PPID), which more accurately reflects its nature.
In horses, the intermediate lobe of the pituitary gland is affected; in human and canine Cushing's, the anterior lobe malfunctions. Dianne McFarlane, DVM, PhD, assistant professor at Oklahoma State University, has done pioneering research on PPID. In a recent study, McFarlane's team investigated the role of the hypothalamus, the portion of the brain connected to the pituitary by neurons. Although the pituitary is often referred to as the "master gland" because it controls the endocrine system, the hypothalamus actually regulates the pituitary's release of hormones.
In recent studies, McFarlane has found that PPID begins when hypothalamic neurons degenerate and produce less dopamine, the substance that restrains pituitary secretion. "This has been suggested in literature since the 1980s; recently we were able to confirm this finding," she says. Without a steady supply of dopamine, the pituitary cells secrete uncontrolled levels of hormones, including ACTH, and the adrenal gland responds by releasing high levels of cortisol. ACTH plays an important role in PPID, says McFarlane, but it's likely that a combination of hormones are responsible for the variable signs of illness.
"We don't know precisely how each hormone is involved," she says. "It's possible, for example, that another hormone known as a-MSH is responsible for a decreased immune response and a susceptibility to infection, but we don't know for sure. The clinical signs probably result from a combination of these different hormones."
A Similar Disorder
Although research findings show that PPID is different from Cushing's in people, they also suggest a similarity to another human illness: Parkinson's, a neurologic disease believed to be caused by deterioration of the brain cells that produce dopamine. "PPID and Parkinson's are both associated with the degeneration of dopamine neurons," says McFarlane, but they are not identical--different neurons are affected with Parkinson's. What causes the degeneration is unclear.
A leading theory holds that the neurons are damaged by free radicals, byproducts of the oxidative processes of metabolism that are known to damage cells, proteins and DNA by altering their chemical structure. "It's possible that horses who get this disease are more susceptible to oxidative stress in this part of the brain," says Harold Schott, DVM, PhD, an associate professor at Michigan State University who published a study called "The Michigan Cushing's Project" in 2001. McFarlane agrees: "We haven't proven oxidative stress causes PPID, but there's been a strong association of oxidative stress to the neurons in these horses compared to normal aged horses."
Also under investigation are the physical changes within the pituitary gland. What was once thought to be a tumor of the pituitary is now better described as an enlargement, although a collection of benign tumors called adenomas may also contribute to PPID. "In severe cases, part of the pituitary can become enlarged and compress the other lobes--even the hypothalamus--and you can lose function of those structures, which also can contribute to clinical signs," says McFarlane.