Thursday, July 2, 2015

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

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