Researchers aim for earlier detection of equine Cushing's disease - DVM
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Researchers aim for earlier detection of equine Cushing's disease


According to the theory, "increased HSD activity in the cells leads to increased cortisol within the tissues," Johnson explains. Increased HSD in a given tissue implies increased cortisol effect in that tissue. Exactly what cortisol is doing in that tissue is not always clear.

As a part of studies to better understand why laminitis sometimes occurs in the context of excess glucocorticoids (hypercortisolism), Johnson and his team, Drs. Seshu Ganjam and Nat Messer, developed a test for HSD in the tissues of horses. They then compared the level of HSD in the tissues of the skin and hoof of normal, healthy adult horses with the levels found in horses with laminitis. They were able to show that HSD could be identified both in the skin and hoof tissues and that the level of HSD was substantially elevated in the tissues of the foot and skin of horses with laminitis. They also hypothesized that skin/hoof HSD activity may be increased as a result of insulin resistance in some laminitic horses.

"Under some circumstances," says Johnson, "it appears that HSD is increased in the hoof tissues. The implication is that the action of cortisol is increased locally — cortisol does many different things to the cells. If HSD is increased locally, it could be either a result of laminitis or a contributing risk factor for laminitis. We do not know."

Nat Messer, DVM, Dipl. AVBP, University of Missouri at Columbia veterinary school, displayed results of experiments performed by Fabiana Farias and Seshu Ganjam investigating 11-beta HSD activity in adipose tissues from nonobese and obese/IR horses, and showed no differences between groups. Moreover, unlike the situation in humans and some other laboratory animal species, 11-beta HSD activity did not differ based on whether it was measured in subcutaneous fat compared with visceral fat.

"I think that the development of chronic insulin resistance (IR) is the major problem in horses," says Nicholas Frank, DVM, PhD, Dipl. ACVIM from the University of Tennessee.

"There is agreement that the development of insulin resistance is regarded as important in terms of risk of laminitis in obese horses,"Johnson says.

What the Missouri team has shown is that, "unlike the situation in humans that develop obesity-associated insulin resistance, heightened activity of the 11-beta HSD enzyme in visceral adipose tissue does not appear to be an important mediating link between accretion of obesity and development of insulin resistance. The role of heightened 11-beta HSD activity in skin and hoof lamellar interface tissues in the laminitis context points to a role for cortisol, but continues to lack a satisfactory explanation: specifically, is the increased 11-beta HSD a consequence of laminitis or was it there in such a manner as to predispose to laminitits?" Johnson asks.

Getting an early handle on PPID

"The most challenging question regarding PPID is the issue of mild/early disease," Frank says. It is relatively easy to diagnose advanced PPID because horses with hirsutism are easily recognized, he adds. However, if we want to match the situation with Parkinson's disease in human medicine, "we should be more focused upon slowing the development of disease or even preventing it," he says.

Dianne McFarlane, DVM, PhD, Dipl. ACVIM, Oklahoma State University veterinary school, has shown that PPID is a disorder that develops as dopaminergic neurons undergo oxidative damage. It is a degenerative process that occurs as horses age, but may also be accelerated under some circumstances.

Factors that determine the rate of degeneration might include genetics, diet, environmental exposure to oxidants or pre-existing conditions, such as chronic inflammatory or metabolic disease. "My work with obesity and insulin resistance leads me to believe that horses that are chronically affected by these conditions are predisposed to PPID," Frank says. For such horses, especially those placed in confinement (off good grass pasture) on poor-quality grass, hay supplemental vitamin E is advisable.

"Unfortunately, currently available diagnostic tests (with the possible exception of a new oral domperidone test under development) do not seem to detect early/mild PPID," Frank says. This leaves practitioners trying to decide whether to be aggressive and try to prevent the disease or wait until it gets severe enough to diagnose.


Source: DVM360 MAGAZINE,
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