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:

Cushings/PPID Primer Part I - What is PPID

Cushings/PPID Primer Part II - Diagnosing PPID

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!

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Lofty, Asterik and Romeo

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)

Hemi

Johnny and Toledo

Cushings/PPID Primer, Part II

Welcome to Part II of the Cushings/PPID primer. If you have not already read the first post on this subject it would be very helpful to read it first before continuing with this post. You can find Part I of the Cushings/PPID primer here, and in that post I explained what Cushings/PPID is. I also want to emphasize again that I am grossly oversimplifying my explanations in order to make the big picture easier to understand. This series of posts will not be submitted to a veterinary journal.

Now that we know what PPID is how do we recognize the signs? As I mentioned in the first post there is a lengthy list of signs that can point to PPID. Many of them are easily attributable to other causes so it is easy to to miss the early signs of PPID. I also find that when these signs are seen in younger horses people often do not want to test because in the past PPID/Cushings has always been thought of as an "old horse" disease. This assumption is patently false. It has now been clinically proven that PPID can occur in horses as young as five years old. 

This meme makes me giggle. As soon as I tell someone I think their horse should be tested for PPID (or any other disease) the emails with all the internet theories often start.  I understand why, I've presented my small animal vet with a lot of internet theories. The problem with internet theories in regards to PPID is that a lot of old theories about PPID in horses have been shown to be false (hence the name change in horses from Cushings to PPID). Thus, much of the information someone is reading on the internet is not current, even articles from vet journals that are only a few years old. The irony that I am posting this picture on the internet with some information about PPID is not lost on me.

One reason that PPID was thought of as a disease only for older horses was the lack of a test sensitive enough to give a positive result if PPID was still in the early stages in a horse. It wasn't that many of the younger horses that tested negative for PPID didn't actually have the disease, it was simply that there was no test sensitive enough to diagnose them, and many would maintain there still isn't a test sensitive enough. As one of our vets once said, the tests we have for PPID don't give us a positive result until the disease has essentially reached Stage 4 cancer in many horses.

For us, the most common sign that tips us off that a horse should be tested for PPID is abnormalities with the haircoat. The hair doesn't shed properly, the horse sheds very late, the hair is very long and dry, or maybe all of the above. The second most common symptom we see is excessive water consumption. We've had more than one horse whose only sign of PPID was their constant trips to the water trough. Their coats looked good, they had shiny hair, they shed normally, but they drank an excessive amount of water. Other symptoms we've seen have included muscle loss, abnormal fat deposits, excessive sweating and/or abnormal sweat patterns, lethargic attitude and symptoms one might associate with a suppressed immune system such as chronic skin issues or runny eyes. Laminitis is also a common symptom of PPID although it isn't one we've dealt with.

Maybe you have noticed that your horse is exhibiting one or more of these symptoms. What should you do? Call your horse and get them tested for PPID by your veterinarian. But before you do that have an understanding of the tests that a vet might choose to use. There are some tests even older than the ones I discuss below, but for the most part any vet is going to mention one of the following three tests.

1. The DST or Dexamethasone Suppression Test - In the dex suppression test blood is drawn to measure blood cortisol levels. The horse is then injected with dexamethasone and blood is drawn again 19 hours later to measure cortisol levels. A normal horse should respond with a very low blood cortisol concentration after injection of dexamethasone. This is due to negative feedback whereby high circulating levels of steroids (from the dexamethasone) signal the body to suppress the release of cortisol. Horses with PPID lack this normal response and will continue to have normal to elevated cortisol concentrations (failure to suppress).

There are a lot of weaknesses to the DST. Number one is the test cannot be accurately performed during the fall because cortisol levels in the horse are naturally higher at that time. Also the test is not sensitive and will give false negative results in early onset cases. If this is the only test your vet is using to diagnose PPID at this time then they are not current on diagnosing PPID.

Negatives aside this test was used for a long time because it was the test we had. Then the baseline ACTH test came along. However it could only be done during certain times of the year at first. Thus, depending on the season horses were tested using the DST or a baseline ACTH test. We no longer use the dex suppression test test at our farm.

2.  Baseline ACTH Test or Plasma ACTH Concentration - These two terms are often used interchangeably to describe the same test. For a baseline ACTH reading your vet will draw blood in EDTA (purple top) tubes. The blood is chilled then the plasma is separated from the blood cells and sent for testing. 

In horses positive for PPID the plasma concentration of ACTH is considerably higher than in non-affected horses. For a few years there wasn't enough reference data to perform the ACTH test year round. Thankfully that eventually changed and the test can now be done at any time of the year. In our experiences we saw fewer false negatives with this test as compared to the Dex Suppression Test. However we still had horses with negative results to this test that showed clear clinical signs of PPID. 

3.  TRH Stimulation Test (our test of choice) - TRH stands for thyrotropin-releasing hormone.  To perform the TRH stim test your vet will first draw blood to measure baseline ACTH levels as described above. Your vet will then administer TRH via IV injection, wait ten minutes, and then collect another blood sample that will be used to measure the post-TRH level of ACTH. Thus you get two ACTH levels with this test, a baseline reading and a post-TRH reading.

In our experience the TRH stim test appears to be the most sensitive test for PPID available at this time. Horses at our farm that have presented with a negative result after a baseline ACTH test have tested positive using the TRH stim test. Thus, this test is our test of choice at this time. The big drawback is that, just like it used to with the baseline ACTH test, there is currently only enough reference data to perform this test in the months of December through June. Outside of those months we have to settle for the baseline ACTH test, and if we get a negative result will retest using the TRH stim test during the December - June period.

Researchers in the field of PPID freely admit that there is still not a test sensitive enough at this time to pick up many of the early stage cases of PPID. Thus, if your seven year old horse has clinical signs and a negative test, he probably has PPID. This theory has been proven true through necropsies of young horses with clinical signs but negative tests. 

What happens if your horse does test positive for PPID? I'll cover that in my next post on the topic.

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Apollo and Hemi

Asterik and Gus

Homer and Levendi

Mick and Lighty

Moe

Rubrico

Grand, Elfin and Rip

Hesse, Remmy, Duesy and Merlin

Cushings/PPID Primer, Part I

Cushings Disease is something that we have a lot of experience with. In fact we have so much experience in identifying, treating and managing Cushings horses we have spent the last few months participating in a clinical study with one of our veterinarians and the manufacturer of the drug Prascend. Many people get confused when they hear the name Prascend, however the actual drug in Prascend is pergolide mesylate, which has been the drug of choice for treating Cushings in horses for many years.

Since we test, treat and live with so many horses with Cushings (more appropriately known as PPID now) we spend a lot of time discussing this with our vets and our clients. I decided it was time to write a series of blog posts that contained the answers to the questions we get asked over and over. Keep in mind in these posts that I will be attempting to explain things in layman's terms, thus I am grossly oversimplifying many of these explanations to allow for ease in understanding of the big picture. In today's post, Part I, am going to attempt to explain what this disease is.

Cushings is one of the most common metabolic disorders, or disorder of the endocrine system, in horses. Cushings disease is now officially called PPID (Pituitary Pars Intermedia Dysfunction) in horses, although most people generally still refer to it as Cushings. In horses Cushings is now referred to as PPID since it was discovered that the mechanism of the disease is different of that in people in dogs. 

PPID causes the pituitary gland to overproduce hormones. The pituitary gland, which is sometimes referred to as the master gland, is located at the base of the brain and is made up of three lobes in a horse: pars distalis, pars intermedia, and pars tuberalis. PPID  specifically affects the pars intermedia lobe of the pituitary gland, hence the name Pituitary Pars Intermedia Dysfunction.

Under normal circumstances the pars intermedia acts to regulate and suppress the secretion of certain hormones. One of the hormones that is kept regulated via a suppression mechanism is ACTH. 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. The cells in the pars intermedia divide and enlarge without regulation, causing the pars intermedia to increase greatly in size.  At the same time that the pars intermedia lobe of the pituitary gland is expanding, it forces the other two lobes of the gland to become compressed.  

Thus a PPID horse has a greatly enlarged pars intermedia lobe that is busy over producing hormones. This overproduction leads to a variety of symptoms in horses, and rarely do two PPID horses present with exactly the same symptoms. The most common initial symptom we see are issues with the haircoat. The hair is overly long and/or very dry, or the hair doesn't shed properly or shedding is delayed, or some combination of these. The second most common symptom we see is an over-consumption of water. The third most common symptom we see are a poorly functioning immune symptom, or better put as an increased susceptibility to infection. The horses might be prone to skin infections, have chronically puffy and/or runny eyes, and other such symptoms that are easy to write off and attribute to weather and other factors. There are a lot of other symptoms we've seen as well including irregular fat deposits, a lethargic attitude, muscle wasting, etc. 

We've seen these symptoms presented very subtly and sometimes in very obvious ways. Sometimes the horse might have only one subtle symptom, other horses start presenting more than one symptom, and some pretty much scream at you "I have PPID, begin treatment now." We've had horses in their early teens test positive as well as older horses. One extremely common misconception is that PPID/Cushings is an "old horse" disease. This has been soundly disproven clinically. As a horse ages the odds of having PPID continue to increase, but PPID has now been clinically verified in many horses as young as five.

In my next post on the topic I'll discuss testing and treatment. I want to state again that in an effort to make my explanations easy to understand I am grossly oversimplifying many things. My point isn't to turn all of us into clinical experts on all aspects of PPID, but simply to help us all understand what it is, how to test for it, treat it and manage horses with it. I hope the information will be helpful to at least a few people!

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Lofty and Faune having a particularly relaxing day with George, Gibson and Flyer

a closer look at Lofty and Faune (and George)

Dutch, Blu and Murphy . . . 

. . . didn't bother to lift their heads as the turkeys strolled past them

Kennedy and Oskar

Duesy and Remmy (Bruno in the background)

Gibson

Walden, Hesse and O'Reilly

pony power; Norman, Traveller and Cuff Links

Donovan, Oskar and Johnny

Rocky, Largo and Clayton