The links between insulin dysregulation (ID), PPID, and adrenocorticotropic hormone (ACTH)—the hormone targeted in PPID testing—are complex and need to be better understood, said Martin Sillence, BSc(Hons), PhD, professor of biological sciences at Queensland University of Technology, in Brisbane, Australia.
But in their latest study he and his team have untangled at least one critical point: Insulin dysregulation can coincide with high ACTH concentrations in the fall, even when an animal does not have PPID.
“We found that ACTH concentrations in the fall can be high in (equids)—particularly ponies—that show no clinical signs of PPID,” Sillence said.
Indeed, the lack of clinical signs of PPID in their study ponies over the course of three years suggests ACTH levels in autumn can be higher than the currently recommended cutoff value for PPID diagnosis, even in animals that don’t actually have PPID, he explained.
A Need to Clear Up Confusion About ACTH Concentrations
Previously, other research groups have questioned the accuracy of ACTH testing for PPID, because the results can differ depending on the method used, he said. Studies in other species have shown a link between the brain—which controls dopamine production, the central factor that’s deficient in PPID—and the pancreas—which produces insulin, the factor that’s produced in excess in ID and can cause laminitis. Based on these study results, chronically high insulin levels could contribute to the development of PPID, Sillence said.
These issues, in addition to his team’s “deep and long-standing interest in preventing laminitis,” led the researchers to investigate the connections between ID, PPID, and ACTH more thoroughly, he added.
They performed clinical exams on 24 healthy horses and ponies (aged 17 to 25 years) in spring and the following autumn. At the same time, they took blood samples before and two hours after giving the equids a dose of glucose. In the laboratory, they measured concentrations of insulin, glucose, ACTH, and cortisol.
Fall ACTH Levels Rise With Post-Glucose Insulin, Especially in Ponies
They found that in the spring, all pre-glucose insulin levels were normal, but 10 equids—mostly ponies—had high enough concentrations of insulin post-glucose to be considered insulin dysregulated, he said. The following fall, post-glucose insulin concentrations showed eight of those animals, plus two others that had been negative in spring, were insulin-dysregulated. Pre-glucose insulin levels in the fall were normal for all but one pony.
The researchers noticed a critical trend, said Sillence: In autumn, as post-glucose insulin levels increased, so did ACTH levels.
“ACTH concentrations in the autumn are disproportionately higher in ID animals,” he said. “In fact, based on current reference ranges for ACTH, six of 10 ID animals would have been judged as PPID-positive.”
The findings suggest veterinarians should be wary when interpreting ACTH measurements made in the fall, Sillence said. He pointed to the importance of observing clinical signs of PPID and the animal’s breed when making a diagnosis, as ponies can produce misleading results.
Six of the eight equids that had ACTH concentrations above the cut-off value for PPID diagnosis, despite showing no signs of PPID, were ponies, he said. Most of them also had insulin concentrations above the cutoff value for ID.
Confirming a Growing Suspicion
“Despite being aware of a possible connection between insulin and ACTH, we were still surprised to see such a strong correlation in autumn, as this has not been reported before,” Sillence told The Horse.
“Other scientists have since commented to us that our findings are consistent with their casual observations or anecdotal evidence, but I think it has largely been missed before now, because the correlation is only seen in the fall and because it is not clear if you rely only on basal insulin measurements,” he continued. “The correlation only stands out after a dynamic insulin test in which the subject is given glucose, syrup, or high-energy feed to consume before the blood is taken for testing.”
Reliable PPID and ID Testing: Aiming to Prevent Laminitis
Veterinarians can diagnose PPID based on a physical exam—looking for signs like hypertrichosis (excessive hair growth), abnormal fat distribution, muscle wasting, hyperhidrosis (increased sweating), evidence of past or present laminitis, polyuria/polydipsia (excessive urination and drinking, respectively)—and ACTH testing. They should not base a PPID diagnosis on ACTH testing alone, Sillence said.
“It is reasonable to think that because ACTH levels are high in PPID cases, the hormone could be used as a marker for early detection of PPID before clinical signs become apparent,” he said. “However, in our study we followed the horses and ponies for three years, and several ponies had high ACTH (relative to published reference ranges and diagnostic cutoff values that are not breed-specific) every fall but did not develop clinical signs. This suggests that fall ACTH measurements which are not adjusted for breed type may not be a useful marker of subclinical PPID in ponies, because there would be too many false-positives.”
Owners who suspect their older horses are at risk of laminitis should ask their veterinarians to run an oral sugar/glucose test to check dynamic insulin levels, Sillence said.
“If you suspect your animal has either ID or PPID, then have a dynamic insulin test performed (based on an oral sugar test), regardless of the ACTH results, as this will help to predict the level of laminitis risk,” he added.
Veterinarians should follow the guidelines published by expert bodies such as the Equine Endocrinology Group. “If you are uncertain, consult a specialist equine practice,” Sillence said. “And be aware that no blood test is infallible. Look carefully for possible clinical signs and record these observations when you can.”