Tuesday, July 28, 2015

Cushings/PPID Primer, Part III

Welcome to Part III of the Cushings/PPID primer. In this part we'll discuss what you can do after your horse has been diagnosed with PPID. If you have not already done so it will be helpful to read the first two posts on the topic:

I want to remind everyone that we are presenting information in layman's terms and as simply as possible for ease of understanding in all of these posts. 

As we discussed in Part II, diagnosing a horse with PPID isn't always straightforward. At this point in time the general consensus is there is NO test available at this time that is sensitive enough to catch early cases, or even all cases that are not early, of PPID.  There is general agreement among veterinarians and researchers that if your horse presents with clinical symptoms of PPID but a negative test, it is best to assume the horse has PPID and you should manage the horse accordingly. 

PPID is not a curable disease. Once your horse has PPID he/she has it for life. The goal is to manage PPID and keep the symptoms minimized as much as possible. When it is caught extremely early it is significantly easier to manage symptoms. We see a big difference in mitigation of symptoms in horses that begin treatment sooner rather than later. 

A critical step in managing PPID is drug therapy. As we discussed in Part I, PPID is a metabolic condition, or a disorder of the endocrine system. PPID is initiated when hypothalamic dopamine producing neurons fail. When this failure occurs the suppression mechanism of the pars intermedia fails. 

The failure of the suppression mechanism leads to an increased hormone production in the pars intermedia. The result of this increased hormone production means the hormone levels within the pars intermedia, including ACTH, can be up to 100 times higher than that in a horse that does not have PPID. There are a lot of  side effects to these dramatically increased hormone levels. The classic PPID sign is the long and/or non-shedding hair coat. Other symptoms include being very prone to skin infections or other infections, drinking extremely excessive amounts of water, muscle loss, abnormal fat deposits, excessive or abnormal sweating, and laminitis. These are all things you want to get under control as best you can.

Pergolide mesylate, marketed under the brand name Prascend, is the medication used for controlling PPID. Prascend/pergolide mesylate is used to manage the lack of dopamine in horses with PPID. The pergolide mesylate attaches to dopamine receptors within the pars intermedia lobe of the pituitary gland and mimics the actions of dopamine. When the drug binds to the dopamine receptors it decreases the secretion of hormones by the pars intermedia. Since it is the excess of hormones being releasted by the pars intermedia that causes PPID this makes drug therapy with pergolide mesylate/Prascend a crucial factor in managing PPID. 

In our experience we generally start seeing improvements in PPID horses treated with Prascend somewhere between 30 days and a few months. It really varies from horse to horse. Ideally we will re-test the horse at the 90 day mark to see if the dosage needs to be adjusted. We will also re-test when a horse that has been on the same dose of Prascend for a period of time with no change in symptoms starts exhibiting a change/increase in symptoms. If the horse had very mild symptoms and was diagnosed and began treatment early the symptoms will often virtually disappear. In other cases we're happy if we keep the symptoms contained to about the same level of presentation without progressing, and of course other horses fall somewhere in between. PPID presents and responds to management very differently in each horse.

The standard dose of Prascend/pergolide mesylate is 1.0mg per day for an average sized horse. We have learned that it is best not to begin treatment at this dose. The most common side effect we see when we begin treatment with Prascend/pergolide mesylate is a loss of appetite and/or a lethargic attitude. Some people refer to this as the Pergolide Veil. 

Most horses do not experience the Pergolide Veil, however in our experience the ones that do really do. Thus, we generally start at 0.5/mg per day which is the equivalent of half of a Prascend tablet, If the horse is sensitive to that dose we stop treatment for about 10 days and then start at 0.25mg per day, or a quarter tablet of Prascend. We stay on this dose for 4 weeks, then alternate between that and a half tablet (0.5mg) for a few days before moving up to a half tablet for four weeks, and proceed accordingly until we reach 1 tablet (1mg) per day. 

With the horses that prove to be very sensitive to the pergolide it can take 2 or 3 months to work them up to the 1mg dose.  We have found that if you really take your time working up to the 1mg dose that the Pergolide Veil symptoms can be kept at bay. With these sensitive horses we sometimes re-test when we are at 0.5mg or or 0.75mg per day to see if this dose is sufficient to bring ACTH levels within normal limits instead of waiting until we get to the standard 1mg per day.

We find that a lot of people think Prascend is a new drug. It is "new" in the sense that Boehringer Ingelheim received FDA approval to be the sole marketer of pergolide mesylate about four years ago. Many people see this and automatically assume it is a new drug and new method of treatment. In reality it is the same pergolide mesylate that has been used to manage PPID in horses for a long.long time. 

We used to have to get pergolide mesylate through compounding pharmacies as they were the only suppliers, but now we have Prascend. It was easily shown during the approval process that the dosages of pergolide mesylate made by the compounding pharmacies were very inconsistent. Your 1mg/scoop of pergolide powder may have actually been 0.7mg/scoop or 1.1mg per scoop as an example. Compounding pharmacies have their place but it is no secret that they can certainly have their issues. Thus we were happy to have a more controlled source being held to higher standards from which to purchase the pergolide when Prascend came on the market.

In addition to drug therapy with Prascend movement is extremely important in managing a horse with PPID. Note that I did not say turnout, I said movement. When your horse is turned out in a dry lot and parked at his hay the entire time that isn't movement. When your horse goes out in a beautiful but small grassy paddock and basically slowly turns on his haunches while he stuffs his face that isn't movement. Both of those examples are "turnout" but they don't produce movement.

Every part of a horse's body depends on movement. Their endocrine system, their digestive system, their joints, healthy hooves - everything - works better when the horse gets continual, low impact movement. A good 45 minute ride helps, but constant casual walking with friends around a large pasture will do far more good for the horse. If you can do both that is even better. Many horses that test positive for PPID also test positive for IR (insulin resistance). Interestingly at our farm, of all the horses that have tested positive for PPID through the years, only one of them has also tested positive for IR. One. And that one horse doesn't currently show any IR symptoms which is pretty impressive given that the horses live on good grass many months out of the year. Movement is crucial for a horse, it is critical, and it can never be understated. A no turnout lifestyle is about the worst thing there is for a horse as it goes against all of their body's natural workings. Limited or no turnout is really bad for a horse with any metabolic disorder.

Diet also needs to be considered when managing a PPID horse, or any metabolic horse.  We aim for a diet that is reasonably low in NSCs (non structural carbohydrates). Forages, be it grass or hay, that come from warm season grasses are generally lower in NSCs than forages from cool season grasses. Feed as little grain as necessary (none if it isn't needed) and keep it low NSC as well. We are able to manage our horses on grass because they live in groups in big pastures so they naturally keep each other moving around. A few years ago we put pedometers on some of them and they were walking several miles per day, up to 10 in some cases. If this were not the case we would try using grazing muzzles to restrict grass intake. If you cannot feed hay that tests low in NSCs, soaking the hay in water and then draining the water off will help a lot. I'm not a big fan of dry lots just because they are so mentally unstimulating for a horse and don't encourage movement, but they are a tool used by many with success. I like the idea of paddock paradise set-ups better than regular dry lots.

You will occasionally come across people pushing Chastetree Berry as a treatment for PPID. Although there is evidence to support the idea that Chastetree Berry helps control the presentation of some symptoms, mainly the haircoat, there isn't any evidence that it offers meaningful clinical management. A couple of extremely limited and very small in scope studies on Chastetree Berry (the only studies done to date) showed that the effects of Chastetree Berry on ACTH and insulin levels were quite varied and inconsistent. I would need to see some more credible research done that involved more than 10 horses before I was convinced of its efficacy. I'm not opposed, the clinical and even anecdotal evidence simply isn't there.

That brings us to the end of our series of posts in the Cushings/PPID primer. I want to remind everyone again that we are presenting this information in layman's terms and as simply as possible. These posts are not meant to be published in a veterinary journal. I hope some of you have found them useful. As always, if you have questions we will be happy to answer them if we can!


Lofty, Asterik and Romeo


Faune and Flyer

Stormy, Walon, Johnny, Oskar and Donovan

Sam, Sebastian and Alex

Nemo and B-Rad

Timbit, Griselle, Sparky and Bonnie

Homer, Leo and Chance (Moe hiding behind the trees)

Ritchie (Grand in the background)


Johnny and Toledo

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