Year-round diagnosis of pituitary pars intermedia dysfunction (PPID, also known as Cushing’s) just got easier, thanks to the joint efforts of equine researchers in England and mathematicians in Australia.
Caused by an enlarged and overactive pituitary gland, PPID is characterized by overproduction of adrenocorticotrophic hormone (ACTH). This hormonal imbalance can lead to a slew of complications, including a long-haired, slow-to-shed coat, muscle weakness and compromised immunity. PPID also increases susceptibility to laminitis. Although typically found in horses 15 years old or older, PPID can also occur earlier in life.
PPID diagnosis usually requires tests that measure the ACTH levels in a horse’s blood. These levels naturally fluctuate by season, however, which can make interpreting results difficult. “The pituitary gland controls several processes that are seasonally variable---such as reproductive hormones,” explains Andy E. Durham BVSc, MRCVS, of the Liphook Equine Hospital in England. “Exactly why the pars intermedia (a specific areas of the pituitary gland) changes activity through the year is not understood. It might be that this is a process that has simply remained during evolution and is of no value or benefit to the horse.”
Because ACTH levels are naturally elevated in the autumn, veterinarians used to avoid testing horses for PPID at that time of year. Eventually, more research led to a better understanding of seasonal changes and testing year-round became feasible, though week-to-week fluctuations in hormone levels still complicate the process. Clinicians must weigh the horse’s clinical signs and the test results in making a diagnosis.
To provide clinicians with more accurate baselines, Durham and his team gathered information on ACTH testing in 75,892 horses from across the United Kingdom over a four-year period. In addition to the test results and the exact date the blood was drawn, information from each case included whether the horse had high or low probability of PPID based on clinical signs. An older, laminitic horse with a non-shedding coat, for instance, would fall into “high suspicion” of having PPID group.
All of the data was then sent to a team of mathematicians at Murdoch University in Australia for a series of statistical calculations. “The mathematics part is essentially a rather clever method of examining a lot of ACTH data, some from normal horses and some from horses with PPID, and then working out the numerical characteristics---means and standard deviations---of the two different populations, allowing them to be separated out,” says Durham. “The big advantage of this method is that you don’t have to rely on clinical examination to decide whether they have PPID---the math can do this.”
The statistical model ultimately yielded weekly thresholds---ranges of normal ACTH readings---for each week of the year. With this information, available online through the published paper, veterinarians can make more accurate PPID diagnoses generally, and especially during times of the year when ACTH levels naturally rise. A comparison of the thresholds generated by the calculations to clinical descriptions of the study horses confirmed that the mathematical method was accurate, says Durham.
“Apart from a different way of determining thresholds for diagnosis, the other novel thing that we did was present different thresholds for different scenarios,” says Durham. “Where there is a very strong clinical suspicion of PPID (for instance, an elderly, hairy, laminitic horse) then it is valid to use the lower threshold, and where it is a highly speculative test it is best to use the higher threshold. For most scenarios somewhere between the two the balanced threshold can be applied.”
Although the study was based on ACTH levels among horses in England, Durham says the findings should be applicable to those in the United States as well. “There is some debate about a possible small effect of higher or lower latitudes on ACTH values, although the timing would not differ. I seriously doubt that would have much, if any, effect.”
Reference: “Clinically and temporally specific diagnostic thresholds for plasma ACTH in the horse,” Equine Veterinary Journal, May 2020