Cushing’s, aka PPID, versus Insulin Resistance (IR) in equines
True Cushing’s in the horse, aka PPID (Pituitary Pars Intermediare Dysfunction) is due to a loss of the descending inhibitory neurons from the hypothalmus into the pars intermediare of the pituitary.
These neurons are dopaminergic – i.e. they use a neurotransmitter in the dopamine family, and their function is to inhibit growth of the pars intermediare. Their loss is currently thought to be due to aging of the brain (loss of dopaminergic neurons in the substantia nigra in humans results in Parkinsons disease). This is why you use a dopinergic precursor, Pergolide (originally developed to treat human Parkinsons) to combat the neuron loss in Cushing’s horses.
The death of the inhibitory neurons results in overgrowth of the PPI and thus an excess output of the hormones that the PPI produces (ACTH and a couple of others). So it isn't a tumor in the sense of cancer, it's an overgrowth of the tissue due to loss of inhibitory controls, which in a loose sense can be called a tumor.
The excess output of ACTH (Adrenal-Cortical Stimulating Hormone) causes the adrenal (the little gland just above the kidney) to put out too much cortisol and other steroids. That is why you measure the ACTH in the equine’s blood to see if it too high - to check for Cushing’s.
Thus the symptoms of Cushing’s are those of chronic steroidism, excess hair growth, loss of active muscle due to the Cori cycle, impairment of glucose uptake from the blood by the muscle cells, fatty liver from the impairment of glucose to fat metabolism, inhibition of the immune system, a slow down in protein synthesis and a thus a slowing of tissue repair and regeneration, etc.
This means you have, as a result of the chronic steroidism, a secondary insulin resistance that is due to the high cortisol levels. However, you also get a host of other problems.
The big pot belly and sway back is due to the weight of the GI tract and other organs of the abdomen pulling down on the back muscles. These back muscles are slowly being lost due to effect of the cortisol delaying their regeneration and repair, and the cycling of essential amino-acids into gluco-neogenesis.
Because Cortisol is a stress hormone, it has the effect of glucose sparing, causing it to be generated in the liver and inhibiting its uptake by muscles. The theory is that this spares the glucose for the tissues that really need it, such as red blood cells and kidney medulla, and lets the muscles and brain use the ketones instead.
So for true Cushing’s, aka PPID, you have the following symptoms:
1) Excess hair growth, as seen in delayed loss of winter coat, and finally hirsutism.
2) Loss of active back muscle, as seen as a sway back and pot belly.
3) Delayed hoof growth, and intermittent growth as seen as hoof rings.
4) Development of insulin resistance, seen as high circulating blood glucose and delayed clearing of glucose from blood following a meal. These can lead to metabolic crises such as laminitis and eventually full blown founder.
5) Impaired tissue repair following injury, and/or impairment of the immune system.
This leads to a lot of minor infections from opportunistic bacteria and viruses, etc. Equine Metabolic syndrome, aka Insulin Resistance, can have some of the same symptoms, since PPID horses have a secondary IR, due to the effect of cortisol inhibiting glucose uptake by muscle tissue. BUT EMS/IR horses won't have the other symptoms and should not have high ACTH, except in the fall when ACTH levels go up naturally to cause the growth of the winter coat. Just why horses become insulin resistant without having PPID we really don't know.
It might be due to:
1) Chronically high levels of simple carbs (sugar/starch) in the diet, leading to constantly high blood glucose, which overloads the glucose uptake mechanisms. There may be a genetic component to this inability to handle chronically high glucose, since 'easy keeper' horses appear to be more prone. This is similar to the theory of development of Type 2 diabetes in humans.
2) Low intake of either a mineral or some other factor which is needed for the glucose uptake mechanisms.
3) Some other reason we don't know about yet. But in general, chronically high blood sugar in horses does seem to cause impairment of peripheral circulation, as it does in humans with Type 2 diabetes.
So the EMS/IR horse will have the symptoms of:
1. Chronic low level laminitis, seen as white line disease, hoof rings and/or strange growth patterns in the foot. This chronic laminitis can result in shortening of stride length, abnormal foot shape and eventually in founder.
2. Development of abnormal fat pads in places such as the neck, shoulders and around the tail head. This fat is not the normal adipose tissue, but is highly vascularised, has very high levels of collagen and is very hard and non flexible when palpated.
It might be similar to the adipose tissue seen in some diabetic humans around the belly and in the abdomen. In horses it develops on the neck and the tail head. These horses generally do not have the excess hair growth, nor the loss of back muscle, nor the impaired healing and immune system problems of the PPID horse.
A paper at this year’s Equine Science Society by a grad student at VA Tech showed that the probability of founder was predictable by a ratio of the neck thickness to the overall body length of the horse. E.g. Horses with thick, cresty necks were more likely to founder!
So where does this leave us?
Right now we really don't understand just why horses get EMS/IR, but we have dietary tools to manage it with. If the diet is changed and the management suitable, IR horses can go on with their lives and seem to fully 'recover'. The same dietary changes help with Cushing’s/PPID horses, however the PPID horse will probably need drug (Pergolide) interventions as well.
As this is not a 'curable' condition, it is always a just a case of keeping their condition from worsening.
The best you can do for a PPID horse is buy some time. What can you do to help them with diet?
MOST IMPORTANT - get them onto a low-glycemic diet. That is a diet low in simple carbs or NSC (non-structural carbohydrates). Depending on how bad the horse is, from
So if you have a really sensitive horse, you will need to have the hay tested for NSC and adjust the diet accordingly. Other things to help are soaking the hay to remove carbs and adding a little fat to slow glucose absorption. Less sensitive horses can have a normal hay diet, with just a few other changes, but will most probably not be able to eat cereal grains. Grass can be high in sugar at certain times in its growth cycle or under drought stress or frost, so monitoring the grazing conditions and altering turnout accordingly is going to be important.
E.g. At high risk times don't let them have access to the grass! Increase certain minerals, most notably Magnesium: Mg affects peripheral circulation - in human diabetics, Mg is used to support peripheral circulation and it seems to have the same effect in horses. Increasing the Mg appears to give a little protection against the loss of circulation into the foot that results in the chronic laminitis. I usually recommend 4-8g per day for a 1,000lb horse. One positive thing is that it is almost impossible to overdose Mg by mouth. If you give too much Mg orally, all you get is diarrhea, thus it is self-limiting, so feel free to give plenty of Mg.
If you are trying to get rid of abnormal fat pads, 20g per day might be needed to reduce them. Then you can drop to the 4-8g/day. Chromium - Cr is a necessary cofactor in the glucose uptake enzymes of the muscle cell wall, so increasing the Cr in the diet helps to clear blood glucose. All the research for this was done in pigs, not horses, so the dosage needed for horses is still not clear yet.
Right now I recommend a minimum of 14mg per day for a 1,000lb horse but that is derived from the pig data, it might be still be too low we really don't know.
Other things that affect glucose uptake:
There are several that have some kind of anecdotal evidence from human data. They are sometimes used in the various mixes, results vary.
Cinnamon - 2-5 grams per day. Cinnamon has anecdotal evidence it can help with glucose clearance.
Bitter Melon - 0.5-1 gram per day, also has some anecdotal evidence it can help with glucose regulation. Jiagoluan - 0.5 grams per day may help with glucose clearance.
Chasteberry - 0.5-1 gram per day may help with regulation of hormones from the pituitary.
Then there are the two latest ones just coming up with some good results.
Acetyl-L-Carnitine - 2-10 grams per day, this amino acid really does seem to help prevent the foot soreness and prevent founder.
Rhodiola rosea - 1-2 grams per day. Rhodiola has a reputation in human nutrition of helping to combat the results of chronic hypersteroidism. With PPID horses, it helps to feed them some essential amino-acids to slow the loss of back muscle and to enhance tissue healing. The essential amino acids won't hurt the IR horse, and might well be useful.
My experience with feeding these horses is that it is a balancing act, but getting too concerned about testing hays and tiny adjustments to mineral balances is not that effective. It is more important in the PPID horse than the IR horse, as they are more fragile and are on a downward spiral anyway.
Yes, you need to keep an eye on the overall NSC intake, keep the Mg & Cr intake up, and watch the Mg:Ca ratio - make sure the horse does get enough Ca as well as Mg. Try the various herbals and amino-acids, but realize that with PPID, you are only buying time and that the next crisis can tip the horse over into problems that he might not recover from, so don't expect miracles.
Horses don't live into their 30s in the wild. If your horse is 25 years plus, you have already had a number of extra years. Just do your best to keep them happy and comfortable, but realize that is a progressive, incurable disease in the long run.
The IR horse should go on and do fine with just the diet changes, HOWEVER don't get complacent and relax standards too much. A true EMS/IR horse will go on to live a full and active life if properly managed. It will be really interesting to see if the IR horses are more prone to developing PPID as they age - we just don't have the data on that yet.
Melyni Worth, PhD, PAS, works as a consultant and writer in equine nutrition and exercise physiology. Her company, Foxden Equine, specializes in products that assist horses and riders to attain and maintain athletic performance. firstname.lastname@example.org , www.foxdenequine.com