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Cushings/PPID

NB. We've kept this page separate from our EMS/IR Metabolic Horse page as Cushings/PPID has its own complex metabolic circumstances.

Updated May'21

Principal Body System: Endocrine

Definition: All glands that produce hormones.

Function: Regulates body activities through hormones transported by the cardiovascular system.

Think about all the problems that arise from just one bill getting lost in the mail. Your power could get turned off, you might lose your wifi for a while and be unable to work, and it could even end up affecting your credit. There are so many issues that can result from just one message not getting where it needed to go.

Now, imagine that process happening inside your body. And imagine that for every message that wasn’t properly delivered, another gets thrown off course. This is hormone imbalance in a nutshell.

Living longer can bring about health issues that than we didn’t need to consider in the past, and although age isn't always a factor with Cushing's, the endocrine system - made up of glands that make hormones - and specifically the pituitary gland, is adversely affected as we all age, whether human or horse.

If you're interested in the history, Cushing's Disease was named after Harvey Cushing, an eminent American neurosurgeon, who described the first (human) patients with Cushing's in 1912. Now also known (more appropriately) as PPID (Pituitary Pars Intermedia Dysfunction), our own personal experience with Equine Cushing's Disease first came out of the blue many years ago with husband's then very young daughter's first pony, Dinky.

We'd not long had Dinks - just 6-weeks; he was a lovely senior chap, perfect for a young child's lead-rein pony. Yet very unexpectedly on his daily walk, he went from happily walking out the previous day to seriously lame in all four hooves alongside very worryingly very laboured breathing – all typical signs of acute laminitis. This literally happened overnight - the previous day he'd been fine; the next, he wasn't.

Although we instantly alleviated him, there had been other niggling signs on the sidelines - even though we were still getting to know him, we were approaching summer and it was obvious that his winter coat wasn't shifting. He was also noticeably drinking excessively and saturating his stable. We suspected Cushing's and got him tested. It came back positive.

Cut to 2014, and my step-daughter's now third pony, Cookie, also developed the classic non-shedding curly coat, still holding onto it in August, alongside noticeable lethargy and, well, she was just so sad. She was 14 at the time. (Updated 2021 - Cookie's still very much with us, now aged 21.)

These days? Every spring and autumn, and a lot in-between, the number of Cushing's diagnoses increase disproportionately, as more of us are unsure whether our horse's coat is changing normally or not. And then there's ′′pseudo-Cushing's", where some horses show the classic Cushing's presentation, but where it's not due to pituitary adenoma, and more about disregulated adrenal glands that are releasing too much cortisol. Worse - youngstock as young as 2yo are now being diagnosed with Cushing's. Two year olds! I mean - how??? How are they presenting? I'm going to stick my neck out here and say ... they're not. But an ACTH blood test shows otherwise.

So, here's my take on it all, and a quick heads-up, alongside an equally quick disclaimer that the following (apart from where I've quoted sources) is all My Own Opinion, although obviously based on all my own research/studies/training/experience over the last decade-plus.

The ACTH test

So here we go, and personally I have a bit of an issue - well, a Big Issue - with the whole ACTH testing thing. Being where I'm sat I hear so many client stories of truly miserable side-effects courtesy of the eye-wateringly expensive Prascend (the conventional Cushing's drug of choice), as well as seeing very early-onset horses barely presenting with Cushing's associated misery, being immediately prescribed with Prascend based on a higher-than-normal ACTH test.

Am eye-wateringly expensive vet med - and remember, Prascend is presribed for life - all on the basis of a quick ACTH test, a hormone that is scientifically known to go up and down very naturally, depending on so many factors.

There's no welfare issue with a curly coat (hirsutism) - you can clip as and when required. There's also no evidence that Prascend reduces the lami risk - a Cushing's horse with lami is no different to a regular horse getting lami. Getting beloved Ned on Prascend doesn't mean they can now turn into a couch potato on lush grass and sugarlumps. Unless you're going to change how you do things, there is absolutely zero point in putting your Cushing's pony on Prascend.

Prascend also has side effects - around 30% of horses/ponies develop inappetence, lethargy and/or diarrhoea. And let's not forget, there's always the risk of false-positive ACTH results if you're testing in Autumn. One controlled study (Ed Knowles et al, 2018) shows that there's a 70% chance that if the result is incorrect, it will also show negative the following Spring. This study looked at 88 ponies, 56 of who tested positive in the Autumn. Of these 56, 39 again tested negative the following Spring, having received no treatment.

Thoughts and advice move on, as more research is done. Discuss, analyse, retest … we can’t just continue to do something because it’s how it's been done for the last decade.

If there are no clinical signs, then retest in Spring when the coat starts to change. Lots of 'positive' tested horses oddly have perfectly normal ACTH levels when they're retested.

I have to ask, does a higher-than-normal ACTH test always mean an actual pituitary tumour? I mean, Cushing's is a Big Deal, as is the health of a Cushing's horse/pony's owner's bank account - surely something as big a deal as a tumour in the brain should at the very least be confirmed with some kind of CT/MRI scans?

So, is it Cushing's, or not?

The endocrine system

The endocrine system, aka the 'hormone' system, is basically a network of glands and organs located throughout the body, with the pituitary gland the Grand Master of all the glands in the endocrine system because it tells the other glands what to do. They all work together to secrete hormones, aka neurotransmitters - chemical messengers - that travel around the body in the blood, transmitting brain signals that play a vital role in controlling/regulating many of the body’s functions, by stimulating specific cells or tissues into action.

Cushing's Disease, aka PPID, results from a benign tumor on the pituitary gland. Which means, if the pituitary gland's function's gone wonky, this disrupts the entire hormone signalling which then disrupts many of the body's functions. This has a profoundly negative effect on the body with many spin-off syndromes, i.e. the non-shedding of the coat and the eventual - and guaranteed - IR.

However, the biggest change comes from an excess of the adrenal gland hormones, adrenalin and cortisol, the two survival hormones; adrenalin prepares the body for 'fight/flight' so puts the body in a 'wired' state, while cortisol, the stress hormone, starts to shut down the energy-sapping systems in the body, i.e. digestion, in order to direct all the body's blood to the muscles so that the body is prepared for fight or flight. When these two hormones are permanently in control of the cockpit, the horse feels both wired and exhausted at the same time, which eventually leads to abject misery and chronic stress.

Introducing the ACTH hormone

ACTH (Adrenocorticotropic) hormone is secreted by the pituitary gland and has a variety of effects in the body, including ensuring that the adrenal glands are stimulated to produce cortisol.

Meanwhile, as horses age, and as with us humans, the decrease in dopamine - the reward hormone (how we feel after eating chocolate 😉) occurs naturally. As the older horse becomes susceptible to the loss of dopamine, the Pars intermedia produce an excess of hormones, including ACTH, which is why focusing on improving dopamine levels should be part of the protocol (more on this below).

Testing ACTH levels in the blood is the recognised conventional standard for diagnosing Cushings. However, it's now also recognised that a high ACTH value doesn't necessarily mean Cushing's (PPID), giving what's known as a 'false positive' result. It's well known that the ACTH value fluctuates over the day, even in healthy horses, so testing via blood values only shows a snapshot at the exact moment when the blood is drawn.

On the one hand, there are natural circadian fluctuations depending on the time of day - the circadian rhythm being the 24-hr cycle in the physiological process of all us living beings; on the other hand ACTH is also released whenever the horse is under stress, anything as simple as a herd squabble to more serious stressors such as hunger or chronic pain. Equally, some horses stress as soon as they see the vet's car pull in. All examples which can record an increased ACTH value.

In a normal functioning body, when a certain level of ACTH is reached, cortisol feeds this information back to the pituitary gland and the release of ACTH is reduced. However, in the case of a pituitary tumour, this feedback mechanism is disrupted. No matter how much cortisol is produced, the pituitary gland keeps releasing ACTH, so the Cushing's horse has will have a permanently elevated ACTH level.

Which means we now have depression, exhaustion, brain fog, anxiety and stress, on top of everything else including imminent insulin-resistance, because ...

And so begins the metabolic effect

... as if managing all-things-PPID isn't a juggling act enough, cortisol also increases blood sugar levels and enhances the brain’s use of glucose.

When the horse is anxious, signals are sent to the adrenal glands to release adrenalin and cortisol, which as we know triggers the fight/flight syndrome. As long as this fight/flight reaction in the body stays active, cortisol continues to release sugars into the bloodstream, and here comes the side effects of high cortisol levels.

We're looking at abnormal glucose metabolism leading to weight gain, typically cresty necks, rear/belly fat pads, and ... insulin resistance (IR), all the precursors to metabolic laminitis. It’s a vicious cycle - as cortisol levels increase, so insulin levels must then increase to try and keep glucose within what the body thinks are ‘normal’ levels. In humans, we call chronic, unregulated levels of insulin Diabetes Type 2.

Getting the PPID/IR controlled and managed is essential in order to minimise the associated laminitis risk, and keeping anxiety at bay controls the cortisol levels which restores the insulin response in the hooves.

Meanwhile, the natural circadium rhythm is busy determining sleeping/feeding patterns, brainwave activity, hormone production, cell regeneration and other biological activities. Come autumn and the days becoming shorter with a drop in temperatures, it's normal for ACTH levels to increase when the body’s natural hormone levels tell the winter coat to start growing. So now we're getting higher cortisol levels on top of already high cortisol levels.

What is absolute cast-iron knowledge with PPID is that the endocrine system needs stabilising with hormonal - and adrenal - support. Then when the IR kicks in, there's the absolute need to manage the IR, blood glucose levels, and the ever-present lami risk. Some of the symptoms of both PPID and IR will overlap despite the two being kind of mutually exclusive, but as Dr Eleanor Kellon (head of the ECIR group) says, “Every Cushing's horse will get IR.

As if PPID wasn’t challenging enough with the stress and lami risk, PPID and IR can also lead to immune system overreactions like allergies, weight gain/weight loss, runny eyes, swollen sheaths/udders, excessive drinking/peeing, muscle loss, depressed immune system, and slow wound healing.

So what the heck can we do?

Prascend/Pergolide

Convention these days says that PPID should be managed with one particular drug, Prascend, this being the gold standard drug of choice (Prascend is the brand name of the active ingredient Pergolide), and the IR managed with diet as per the typical 'metabolic'/EMS protocol (see our Metabolic Horse page.

However, the renowned ECIR group (Dr Kellon - reminder, Dr Kellon is a vet) takes a slightly different stance, in that:

"Prascend should be the first line treatment for obviously advanced and/or laminitic horses with PPID". If it's an early case, feeding Agnus castus is "a reasonable first step as long as the owner and veterinarian realise it may lose effectiveness."

See the ECIR extract here - https://equinatural.co.uk/i/ecir-extract.

However ...

"There is hardly a drug that is currently as controversial in equine therapy as Prascend. For some it is the magic bullet that should be given to every horse with metabolic problems, because it magically removes all worries such as laminitis and the like.

On the other hand, there are just as many horse owners and therapists who demonize it because more than one horse has had to struggle with serious side effects or simply did not respond to the administration of the (very expensive) drug at all.

It is therefore urgent to take a closer look at what we are actually dealing with here."

Dr Christina Fritz, Sanoanimal

A quick intro, Dr Christina Fritz, Biologist with a PhD in Animal Physiology/Neurobiology, treating horses since 2006 focusing on metabolic therapy using holistic feeding methods via healthy, natural horse nutrition. Christina publishes in German, but thanks to Google Translate (hence the americanisms), the following is a basic translated snapshot of a valuable study she's done on Prascend. See her post in full here - https://wissen.sanoanimal.de/2021/02/03/wie-wirkt-prascent/?fbclid=IwAR2dGnRpDRhUelCrkDPhyoX8xcnNXNXCEWkSg_G8iksDRiJw3GP6fwXj_pM.

Meanwhile, here are some salient pointers from her article:

  • Shortly after the market launch of Prascend, the manufacturer (Boehringer Ingelheim Vetmedica GmbH) began not only with the targeted training of vets on Equine Cushing Syndrome and everyday diagnostics about the ACTH value, but also with offering a free ACTH test for horse owners. This has massively fueled the number of Cushings' diagnoses, despite perfectly healthy horses being diagnosed via the ACTH test for Cushing's, and subsequently been prescribed Prascend.
  • There is no basis for this diagnosis, as a healthy horse can also show increased ACTH levels, both circadian and over the course of the seasons as well as when under stress. To infer the presence of a pituitary adenoma from an increased ACTH level is scientifically simply wrong.
  • A pituitary adenoma leads to a permanently elevated ACTH level, but an elevated ACTH level does not always indicate the presence of a pituitary adenoma.
  • However, the free Cushing Test from Boehringer has proven to be the best marketing measure, since sales have soared since then for a disease that until then had justifiably been a specific niche condition in veterinary medicine.

Natural plant therapy

With it being known that plant extracts have less side effects, natural therapy may well be safer for long term use.

Dr Kellon posts against feeding Agnus castus berry with Pergolide/Prascend in Cushing’s Horses : https://drkhorsesense.wordpress.com/2021/05/18/mixing-chastetree-berries-with-pergolide-in-cushings-horses/, hence why we have two versions of our CushTonic blend - our CushTonic Mk.I with Agnus castus, and our CushTonic Mk.II which excludes it. The remaining proprietary composition is a blend of appropriate 'adaptogen' herbs, which can help 'normalise' the adrenal response and hormone imbalance of PPID, while supporting the endocrine system and immunity.

  • First up, the revered Agnus Castus berry (Vitex agnus castus) which is renowned for helping Cushings/PPID horses. Used for its gentle, tonic action on the anterior pituitary, Ag.castus is an amphoteric herb, meaning it helps maintain normal hormonal levels, rather than cause them to go up or down. We include Ag.castus for its effect on the pituitary's action in adrenal hormone regulation. NB - While it can certainly help with the visible presentations, it won't necessarily control the ACTH levels. (Not wishing to fly in the face of science, personally we've had remarkable success with our Cookie - alongside the amino acid Tyrosine - since her original 'diagnosis' in 2014). TopTip - don't feed Agnus castus if you're horse is on Pergolide/Prascend.
  • Another renowned plant, Milk Thistle seeds (Silybum marianum) are a highly effective herb for liver function, supporting the liver's metabolisation of drugs and toxins for excretion. Another function of the liver is to denature circulating hormones, thereby helping to keep the balance of hormones in the body.
  • Ashwagandha (Withania somniferum), probably my favourite adaptogen herb featuring in both our CushTonic and StressTonic formulas. Adaptogens literally do what it says on the tin - they help the body 'adapt', and Ashwagandha is no exception, being a renowned herb for helping the adrenal glands 'normalise' their response to stress levels, resulting in rebalancing cortisol levels.
  • Astragalus (Astragalus membranaceous) is another popular stress-normalising adaptogen. In particular, Astragalus is high in polysaccharides, constituents that assist the body's normal immune response, hence why its known as an 'immunostimulant'.
  • Sarsaparilla root (Smilax officinalis) has a long-standing reputation for helping the body excrete toxins via the lymphatic system, as well as being a beneficial liver supporter.
  • I also love Brahmi (Bacopa monnieri), taking it myelf in tincture form to support my cognition. Brahmi is both an adaptogen and an antioxidant, helping to counter stress and contribute to healthy mood and cognitive function.
  • Holy Basil (Ocimum sanctum), aka Tulsi, is another gentle adaptogen for supporting the adrenal glands.

When the IR sets in, our CushTonic blends are best fed in synergy with our MetaTonic, each blend fed at opposite ends of the day.

What I can also absolutely guarantee you is that the right nutrition goes a huge way to help. Cushings/PPID is a degenerative condition that requires the whole system needing ultra-nutrition for health and wellness - see our Feeding our Horses/Why what we feed has to be right page.

For hooves, the trim should aim for toes backed and heels low so that the hoof capsule tightly hugs and supports the internal structures. This is one of the most common missing links when soundness is an issue. If there are any lameness issues, boots and pads can help enormously for comfort.

And finally, movement is key! It’s the best IR-buster there is, but it goes without saying that we never force a sore equine to move.

Sadly we know there's no cure for PPID, but the good news is that once it's been diagnosed, management is fairly straightforward and can help a horse return to a comfortable lifestyle.

Top Tips

  • Lower cortisol and increase dopamine levels naturally. Keep levels balanced by maintaining a happy equilibrium; exercising and allowing quality rest, alongside feeding a natural, species-appropriate diet and balancing forage chemistry with an appropriate mineral supplement.
  • Exercise is really important, not just to rid the body of fat cells, but it also increases dopamine levels - remind yourself how you feel after a great ride or a gym session. Regular exercise also helps to burn the extra blood sugar made available through elevated cortisol levels.
  • In addition to the countless physical benefits, exercise can also have psychological benefits. Studies show that exercise can increase the amounts of both dopamine and serotonin neurotransmitters in the brain, as well as helping your horse feel more energised overall. In a May 2007 article in the Journal of Neuroscience, it was noted that exercise could cause the brain cells that use dopamine to work more efficiently, and an August 2007 article in the journal Neuroscience Letters noted that continuous exercise also reduced damage to brain cells that release dopamine.
  • Quality rest time helps lower cortisol levels because otherwise the body’s nervous system stays in a state of alertness that requires cortisol. Getting proper rest also increases serotonin and dopamine, which help control feed cravings.
  • Feed omega-3 fats via micronised linseed as they help trigger the production of serotonin, as well as being a good food source of the trace mineral selenium. A low intake of this mineral has been linked with depression.
  • B-vitamins can help lower cortisol levels, with the equine gut microbiome producing them in the active form that the body recognises and knows what to do with, so maintaining a healthy microbiome and feeding plenty of long, stemmy, fibrous hay in the diet for the hindgut microbes is extremely important. If your horse has a disrupted gut function at any time, feed B6 in its activated form, P5P, for a month at least until gut function is restored back to a healthy normal.
  • Turmeric's active ingredient, Curcumin, shines in brain health. A double-blind, placebo-controlled study included 40 adults between the ages of 50 and 90 with reported mild memory lapses but no dementia. Those who received curcumin supplementation saw significant improvements in memory and concentration, while the control group experienced no improvement. https://www.sciencedirect.com/science/article/pii/S1064748117305110?via%3Dihub
  • Add Acetyl-L-carnitine into the feedbowl, as it has many beneficial effects on brain metabolism, protects against neurotoxic insults, and has been shown to benefit certain forms of depression. It's also super-beneficial for leptin-resistance, another detrimentally effected hormone instruction as a result of IR - https://www.ncbi.nlm.nih.gov/pubmed/22549035
  • Finally, to those orbital pads above the eyes - some people think what looks like swollen pads above the eyes are fat; others think it’s Cushing’s. The good news is that they’re not fat – there’s no tissue here for fat cells to grow in; nor are they Cushing’s related. Anatomically there’s a lot of connective tissue and facia here, so it’s more likely lymph, not fat. Long and short, they’re just one of many indicators that the metabolism is out of order. When you get the metabolism back on track (via a good gut restoration and detox programme and relooking at feed), these pads tend to go away.

Steps to lower cortisol and stimulate dopamine levels naturally

  • Follow a daily regime of 20-30 minutes exercise, even if it’s just a brisk walk. The body's reaction to exercise creates brain activity that regulates hormone and brain chemicals.
  • Add a forage-balanced mineral supplement that supports good overall health and balances your forage/grazing. Avoid sugar, grains, bad fats (PUFAs) and processed feeds which can cause dopamine levels to drop.
  • Feed Tyrosine - dopamine is produced by the body from the amino acid tyrosine, which in horses is one of the non-essential amino acids, i.e. those that the organism can produce itself and does not have to get in via food.
  • In addition to supporting overall health, Vitamin C is helpful in supporting dopamine. A horse's liver synthesises its own vitamin C from glucose in the liver, producing about 72-grams each day; however, a PPID horse may have compromised liver function so adding rosehips to the feedbowl can help as they're jam-packed full of vit.C.
  • A calm, happy horse with horse buddies creates positive brain activity, increasing the amount of feel-good substances such as dopamine and seratonin.

Update - January 2019

Our Cookie recently had a worrying seizure episode which I suspected was related to her Cushings. After doing the usual googling, I found the following related notes courtesy of The Chronicle of the Horse forum: www.chronofhorse.com/forum

I should add that the forum post dates back to 2006 so in theory it’s outdated; however, here in 2019 I still found the following info useful. Credit due to poster Melyni (PhD) PAS, Dipl. ACAN, answering a question from poster ‘equineelders’, of Travellers Rest Equine Elders Sanctuary, whose horse had presented similarly to Cookie:

“At AAEP in early Dec I attended a couple of talks on Cushings. The current thinking was that it isn't tumor per se of the anterior pituatary but a loss of the dopaminergic neurons that descend from the hypothalmus into the pars intermediar.

If I understand it correctly these neurons have an inhibitory effect on the cells of the pars intermedia, and thus the loss of the neurons means a loss of the inhibition, thus the pars intermediar cells begin to put out more and more hormones esp ACTH plus others, which leads to a secondary hypocorticoidism.

It's thus more similar to Parkinson's than to a tumour. Patients with Parkinsons suffer from neurolgical symptoms, such as muscle rigidity, spasms and loss of balance. Loss of control of fine motor neurons occurs as well.

So if you think about Parkinsons as the underlying cause (loss of dopaminergic neurons) rather than a cancerous growth, the symptoms make more sense. Not that this helps anyone dealing with a seizuring horse.

There is a theoretical way to modify the intake on amino-acids to enhance the dopaminergic pathways as opposed to the seratonergic, eg don't feed tryptophan; supplements that contain the amino-acids threonine and tyrosine are effective, but this is not scientific only anecdotal.

Seratonin is made from different precursors than dopamine. They are both made from amino-acid precursors but not the same ones, and there is some indication that increasing the seratonin in Parkinsons’ patients exacerbates the symptoms, as the pathway may be competitive.

Dopamine comes from Tyrosine and Threonine, while Seratonin comes from Tryptophan via the 5HT pathway. Arginine may also be involved in the dopamine pathway.

How do chromium and magnesium fit into this? We have a few on supplements per vet's recommendation, but I don't know specifically what they are doing. From what I have read in such literature as exists, the Mg helps with the peripheral circulation, as in it keeps the small arterioles open and maintains the circulation to the extremities (all data from human studies) thus it (may) minimise the loss of blood flow to the feet, and the subsequent laminitis. It also seems (in humans) to have an anti-inflammatory effect, as in, it reduces C reactive proteins from the adipose tissue.

Chromium is part of the enzyme system that picks up the glucose from the blood stream and enters it into the cell. Thus the extra chromium helps to clear the bloodstream of the glucose, and the extra magnesium helps to maintain peripheral circulation.

All this information came from human studies, and thus you cannot be too literal in saying that this is what happens in horses, as these things don't always transfer from species to species, but as there is next to no research in horses, that is all we have.

I do know from what work I have done, that giving the Cr and Mg to pre-Cushings and Cushings horses you get better laminar bloodflow and a reduction in the symptoms, such that the pergolide dosage can be reduced.

We have measured the reduction in neck thickness and in the abnormal fat pockets, and we can show an improved circulation to the foot. But these effects aren't treating the underlying cause.

Giving essential amino-acids to these horses reduces the loss of muscle tissue and the muscle wasting. Again this is treating the symptoms, not the cause, but overall the horses look and feel better, and are more active, which in itself improves their metabolism.”

As a result of this information, I'm now adding L-Tyrosine and extra salt into Cookie's feedbowl.

Update - June'21

A recent 'Dr K's Horse Sense' post shows that onset pain may affect ACTH testing, as it's known that both ACTH and cortisol levels are more likely to be higher than normal ranges in acute illness.

A 2020 German study looked at hospitalised horses in pain from various sources including colic, laminitis and orthopedic presentations, and with no clinical signs of PPID. The study found:

"acute pain resulted in markedly elevated cortisol and insulin resistance."

Since acute stress, wounds etc. can cause the adrenal glands to release cortisol without ACTH increase, it’s unclear from that study if acute pain will influence ACTH – although it certainly increases insulin. The thinking is that testing for both ACTH and insulin levels should be avoided in the first 24-hrs after onset of painful.

See the full article here: https://drkhorsesense.wordpress.com/2021/06/08/insulin-acth-and-pain/