Pituitary Pars Intermedia Dysfunction (PPID)

In this episode of Current Vet, Dr. Lottie talks about pituitary pars intermedia dysfunction, what it actually is, the key clinical signs to be aware of and how it is different to EMS!

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Timeline:
00:00 Intro
01:30 Case
02:34 Aetiology & Pathogenesis
04:47 Clinical Signs
06:18 Diagnosis
10:24 PPID vs EMS
12:17 Treatment
15:50 Key Points
17:03 Outro

References

• McFarlane, D. (2011) ‘Equine Pituitary Pars Intermedia Dysfunction’, Veterinary Clinics: Equine Practice, 27(1), pp. 93–113. Available at: https://doi.org/10.1016/j.cveq.2010.12.007.
• McFarlane, D. (2014) ‘Pathophysiology and clinical features of pituitary pars intermedia dysfunction’, Equine Veterinary Education, 26(11), pp. 592–598. Available at: https://doi.org/10.1111/eve.12237.
• Durham, A.E. et al. (2014) ‘Pituitary pars intermedia dysfunction: Diagnosis and treatment’, Equine Veterinary Education, 26(4), pp. 216–223. Available at: https://doi.org/10.1111/eve.12160.
• Menzies-Gow, N.J. et al. (2024) ‘BEVA primary care clinical guidelines: Diagnosis and management of equine pituitary pars intermedia dysfunction’, Equine Veterinary Journal, 56(2), pp. 220–242. Available at: https://doi.org/10.1111/evj.14009.
• Tatum, R.C., McGowan, C.M. and Ireland, J.L. (2020) ‘Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review’, The Veterinary Journal, 266, p. 105562. Available at: https://doi.org/10.1016/j.tvjl.2020.105562.

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Any clinical cases discussed in this podcast are fictional, and are designed to reflect typical or likely clinical scenarios for educational purposes. They do not represent specific real-life cases, clients, or animals.

While every effort is made to ensure accuracy and alignment with current evidence at the time of publication, veterinary medicine is a rapidly evolving field, and recommendations may change over time.

Creators and Guests

Host

Dr. Lottie Wilkinson

Creator and host of the Current Vet podcast

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Intro

Hi, everyone, and welcome back to Current Vet. If you're new here, this is the podcast that makes vet med simple. I'm your host, Dr. Lottie, and today we are talking about PPID, which stands for pituitary pars intermedia dysfunction in horses.

Before we get into today's episode, I wanted to tell you more about the exciting launch we have coming up. So if you followed Vista and you've been on the podcast for a while, you know that the whole aim has always been to make vet med feel simpler and less overwhelming.

So this summer, we are launching our online platform that is built specifically for vets, especially vet students. The idea is to bring everything into one place. So we have things like fact sheets explaining different topics. Everything is referenced. We have quizzes and games, progress tracking for the quizzes so you know what's working, where to focus your revision.

And then we have a couple more tools to help revision feel a little bit more straightforward. And a big part of this is that we want to build it with students, not just for students. So our users will be able to request topics, vote on what gets added next, and help shape the platform as we grow.

If you're interested and you want revision to feel a little bit more simple, a bit more engaging, you can sign up to our waitlist now. I will include the link in the show notes, and we will be launching this summer

Case

So let's get straight into our case.

You're in equine ambulatory practice and you're called out to see Biscuit, who is a 19-year-old Welsh pony. His owner tells you that he's had two episodes of laminitis this year, despite being on restricted grazing. She's also noticed that his coat just isn't shedding properly anymore, and he's been really fluffy since last winter.

He also seems a little bit more lethargic than usual, and she wonders if old age is just getting to him. On exam, Biscuit is bright, but a little bit overweight. His coat is long, a little bit curly and patchy, especially over the neck and the hindquarters. His digital pulses are a little bit increased, and he's a bit footsore when turning.

Your top differentials in this presentation, we've got a bit of an overweight older pony, so we're going to be thinking of equine metabolic syndrome, PPID, and also maybe chronic laminitis for a endocrinopathic cause

Aetiology & Pathogenesis

So now we've got our case, let's talk about what PPID actually is. so as we said, PPID stands for pituitary pars intermediate dysfunction. It is also colloquially known as equine Cushing's. But unlike canine Cushing's, it is not primarily an adrenal disorder. It's a neurodegenerative disease that occurs in the hypothalamus and the pituitary gland. So in a normal horse, the pars intermedia of the pituitary gland is under dopaminergic inhibition from the hypothalamus.

This basically means that dopamine is released from the hypothalamus, dopaminergic neurons stimulate the pituitary gland from the hypothalamus,

so dopamine from the hypothalamus acts like a break to stop the pars intermedia in the pituitary gland from overproducing POMCs. And POMCs just stands for pro-opio melanocortin

So in PPID, there is degeneration of the dopaminergic neurones, which means there's a loss of that - inhibition on the pituitary gland, so the pars intermedia becomes overactive and it starts producing excessive amounts of , POMC, and its derived peptides. So POMC is cleaved into these peptides, which include ACTH, alpha MSH, and beta endorphins
So ACTH is gonna be the one that we measure clinically, but it's really important to remember that this is not identical to pituitary-dependent Cushing's in dogs because ACTH produced is biologically different and the disease is driven by dopamine loss and not a functional adenoma or hyperplasia that we see in dogs.

So essentially, in a nutshell, PPID means that there is degeneration of those dopaminergic neurons in the hypothalamus. There is a loss of dopamine inhibition on the pituitary gland. That means that the pituitary gland becomes overactive and the pars intermedia produces excess POMC peptides

Clinical Signs

So what clinical signs are we gonna see in horses with PPID? the most classic sign and the one you typically always have in your head is hypertrichosis, also called hirsutism, which is that long, curly, non-shedding coat, and that is very suggestive of PPID. But horses often present before this develops or before this becomes really obvious.

So a couple of earlier signs include recurrent laminitis, Delayed or incomplete hair shedding, lethargy, poor performance, muscle wasting, especially along the top line, weird fat distribution known as regional adiposity, and this is basically going to be concentrated areas of excess fat deposition, so it's especially in the neck, known as a cresty neck, and we also see it around the tail head especially as well.

Then we also see polyuria, polydipsia, and recurrent infections, so potentially things like sinusitis, dental infections, or parasitism. So if we go back to Biscuit, we have that older pony, we have recurrent amenorrhea, we have the abnormal coat shedding, and these are obviously going to be very classic and very indicative of PPID

Diagnosis

So how are we going to confirm this is what's going on in Biscuit?

In practice, diagnosis is based on clinical suspicion and then followed up with endocrine testing

So our first test is going to be a basal ACTH test, and it's a really simple blood test that just measures the plasma ACTH concentration. In horses with PPID, the ACTH levels are typically elevated, but we have to remember that ACTH levels in horses are seasonal. There is a physiological rise in ACTH around the autumn time, so it's really key to use seasonally adjusted reference ranges when you're doing these tests, or you risk getting false positives at specific times of the year

A second test is the thyrotropin-releasing hormone or TRH stimulation test. This is a bit more sensitive, especially useful in early-stage disease, and basically the method for this is that you measure a baseline ACTH, like the test we just did. You then administer the TRH injection. You measure ACTH again, usually 10, 20 minutes later, and in horses with PPID, you get an exaggerated ACTH response, so the ACTH level is going to be much higher than anticipated.

This test is very useful when the basal ACTH results are equivocal. They're a bit high, they're a bit suspicious, but they're not obviously wrong, and when clinical signs are subtle
Other findings that we might see on blood work, so hematology and biochemistry are going to be supportive, but not definitively diagnostic for PPID, but we might see hyperglycemia, hyperinsulinemia, especially if we have overlapping EMS, which is quite common in these horses, and we also possibly have stress leukogram We can do a dexamethasone suppression test, and this is when dexamethasone is administered and then cortisol is measured after. So in normal horses, cortisol will be suppressed. In PPID horses, it typically isn't or isn't as suppressed, but it isn't very commonly used anymore because it's less sensitive than the ACTH or TRH tests, and it also requires multiple samples and, timing.
It's a bit less practical

There is also technically tests available to detect the alpha-MSH, which stands for alpha-melanocyte-stimulating hormone. It's another one of those POMC derivatives like ACTH is. So there are a couple of tests that exist to test alpha-MSH, but it's not widely available, so it's not widely used in practice.

It is also recommended to test insulin in horses with suspected PPID, as so many of these animals also have concurrent insulin dysregulation or concurrent equine metabolic syndrome. So we can do a resting insulin level or an oral sugar test. These don't diagnose PPID, but they are detecting insulin dysregulation, and this is especially important because insulin dysregulation can drive laminitis, and also because many PPID horses, as we said before, also have EMS.

So this is going to guide different management approaches and treatment approaches, and it's really important to be aware of before starting any treatments

So for Biscuit, we're going to run a basal ACTH, making sure to interpret it with those seasonal reference ranges, and his ACTH comes back elevated, which is consistent with PPID

PPID vs EMS

I'm now just gonna take a moment to talk about the difference between PPID and EMS, I think a lot of students get really confused between the two. They're not the same disease, but they do often overlap or happen concurrently, so let's just break it down quickly. PPID is a neurodegenerative disease caused by degeneration of those dopaminergic neurons in the hypothalamus.

It's typically seen in older horses, more than kind of 15 years old, around that age bracket, and the classic clinical signs that are seen are gonna be those coat changes, so a curly, non-shedding coat, and laminitis. EMS, or equine metabolic syndrome, is a clinical syndrome of three different conditions, and that is obesity, insulin dysregulation, and increased risk of laminitis.

The condition is driven by the insulin dysregulation, and it's most seen in middle-aged horses or ponies, so around kind of 5 to 15 years old is that prime time for diagnosis. And the key clinical signs with this are gonna be obesity or regional adiposity and recurrent cases of laminitis

So the key thing here really is that they both can cause laminitis and some horses, potentially like Biscuit, can have both conditions at the same time. So in practice, if you are diagnosing or you suspect PPID, you also want to check the insulin regulation in the horse. And because insulin dysregulation is such a major driver of laminitis risk, it's really important to know about so we can carefully guide management approaches and let owners know what is good, what is not good practice for their horse

Treatment

Okay, let's now talk a bit about how to treat PPID. So pergolide is the mainstay of treatment here, and it is a dopamine agonist. So essentially, it is replacing the missing dopamine that
isn't being produced by the dopaminergic neurons anymore

This restores inhibition in the pars intermedia of the pituitary gland, and then there is reduced production of ACTH and other POMC derivatives. This is directly targeting the underlying problem, and it is a really effective treatment But remember that it is not a cure because there is no way to actually reverse the degeneration of those neurons, so it is going to need to be given for the rest of that horse's life

there are also a lot of different management approaches that we can include here, so let's go over some of the key areas. First of all is gonna be laminitis prevention. So we want strict dietary control to manage the horse's weight. We want a diet that is low in simple carbohydrates, so avoiding things like cereals, like high grain feeds, sweet feeds, anything with molasses in, and lush pasture because the

carbohydrate content and that can be really variable. Couple of things we can add to the diet is going to be hay, ideally tested

For the non-structural carbohydrate content, we're looking for a level of less than 10 to 12% of non-structural carbohydrates. We can soak the hay because that helps to reduce the sugar content, helps to dissolve sugars into the water and reduce it from the hay. We can give straw if we really need to add forage and bulk, and we can look for special low NSC balances or feeds to give these horses.

We can also restrict grazing if needed with a grazing muzzle if the horse is out on pasture
Or a hay net with smaller mesh for stabled horses Clipping the coat helps to manage the hypertrichosis and improves thermoregulation for these horses, so it just really helps to keep them comfortable. Good dental care is really important because we do have that immunosuppression, and there are a lot of dental problems that occur with aging in older horses, so it's important to stay on top of good oral health.

Parasite control because that increases susceptibility to infections. And then of course, routine monitoring, so keeping an eye on the weight, keeping an eye on their body condition, and checking those clinical signs, are they improving? We can also recheck the ACTH levels after starting pergolide, And if there isn't much of a response, we can adjust the dose based on clinical signs and those blood work, results.

So for Biscuit, we're gonna start pergolide, adjust his diet, and implement a stricter laminitis prevention plan, get rid of a few of those treats. And at a recheck visit three months later, his owner reports that his energy has improved, he is less lethargic, he has much better coat shedding, and there are no further laminitis episodes

Key Points

So before we finish, these are the key points that you need to know about PPID. PPID is a neurodegenerative disease caused by a loss of dopaminergic inhibition from the pituitary pars intermedia It is particularly common in older horses, more than kind of 15 years old, they typically present with coat changes, so that curly, non-shedding coat and recurrent laminitis.

Basal ACTH tests are often used, but always make sure to interpret the results with seasonal reference ranges. TRH stimulation tests are also available and are especially useful if the ACTH results are equivocal. Pergolide is the treatment of choice, and it is a dopamine agonist, so works by restoring that dopamine level.

Always assess insulin levels and the possibility of overlap with EMS, because insulin dysregulation from the EMS is going to further drive risk of laminitis. And remember that management changes are just as important as medication, so focusing on the diet, that weight control, and managing hypertriglycerides.

Outro

And that is PPID. Thank you so much for listening to Current Vets. If you found this episode helpful, follow or subscribe wherever you listen to podcasts and share it with someone who needs to hear this topic as well. You'll find all the resources in the show notes, and if you have any requests for topics or episodes that you want to hear next, let us know in the comments, or come and find us on TikTok and Instagram at veterinaryvista.

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