What is Equine PPID (Cushing’s syndrome)?
Cushing’s syndrome in horses was first reported in the literature by Pallaske in 1932 yet it has received little study in terms of its causes and the disease process. The condition is now called equine pituitary pars intermedia dysfunction (PPID), because it is quite different from the human condition of hyperadrenocorticism, previously thought to be the equivalent. For example it doesn’t involve raised blood cortisol levels (McFarlane, 2014).
PPID is a progressive disease of the endocrine system which seems to occur naturally in the aged equine population, but can occur in younger animals (McFarlane, 2014, Sojka-Kritchevsky & Johnson, 2014). It may affect greater than 20% of horses of age 15 years or over (Durham et al, 2014).
Current thinking is that PPID is primarily a dopaminergic neurodegenerative disease of the brain, more specifically the hypothalamus, and pars intermedia of the pituitary gland, similar to Parkinson’s disease in humans (McFarlane, 2007). What this means is that there is a degeneration of the nerve cells running from the hypothalamus to the pituitary, which respond to the brain signalling chemical dopamine, so that their function of inhibiting the production of other hormones declines, and these hormone levels – including ACTH – therefore increase.
The cause of this neurodegeneration is unknown, and it is thought to be a ‘multifactorial and complex condition’ that is linked to both genetics and environmental influences (McFarlane, 2014). Damage as a result of oxidative stress is thought to be involved, which could explain the age-related risk. There is also clumping of a protein called α-synuclein, which disrupts cell function and could contribute to cell death (McFarlane, 2014).
What goes wrong and how it affects the horse’s health
A variety of chemicals regulate pituitary function, including GABA, serotonin and norepinephrine, but little is known about their function in the horse. What is known is that a lack of dopamine to inhibit the production of these regulators causes a host of metabolic problems.
The hormone changes that take place in PPID are similar – but on a much bigger scale – to those that naturally happen in a normal horse in response to shortening day length. The healthy horse will grow a hairy coat and adapt their metabolism in preparation for winter and reduced feed supply.
PPID is most commonly recognised by a long hairy coat (hypertrichosis) which is not shed normally in the spring, but it can also be associated with other coat abnormalities including complete coat retention, coat lightening, and retention of guard hairs (McFarlane, 2014). However, the actual number of cases that show these coat abnormalities in the early stages is unknown, with one study of an unbiased sample of horses affected by PPID, showing that only 33% had coat abnormalities (by veterinary examination) (McFarlane, 2014). So, in many at least in the early stages, no coat signs are present. Other signs which may be present (but are not always) include:
- Weight loss
- Suppressed immune function (slow wound healing, increased susceptibility to infections and parasites)
- Muscle atrophy (withering)
- Excessive urination and drinking
- Abnormal fat distribution, including fat pads on body and fat bulges above the eyes
- Pot belly
- Increased risk of laminitis
- Lethargy (lack of energy)
(McFarlane, 2014; Durham et al, 2014).
The immunosuppression in PPID is probably caused by increases in specific (as yet unknown) pituitary hormones rather than ACTH or cortisol levels, since researchers have found that the increased ACTH is mostly inactive and cortisol is not significantly raised in affected horses (McFarlane, 2014).
Not all PPID- affected horses or ponies develop insulin resistance, or laminitis. Those who do suffer from laminitis tend to have elevated blood insulin levels, now described as insulin dysregulation (Sojka-Kritchevsky & Johnson, 2014). Raised insulin rather than increased cortisol is now thought to be associated with PPID- linked laminitis, but exactly why has yet to be determined (Spelta, 2015). A prevalence of between 50 and 80% of cases of PPID with laminitis has been reported and vets have termed laminitis associated with PPID as ‘endocrinopathic laminitis’ (Geor & Harris, 2013).
The excess hairiness (hypertrichosis) could be due to increased prolactin levels, as a result of lack of inhibition by dopamine (McFarlane, 2014).
Diagnosis and treatment
Diagnosis of equine PPID is complicated, and there has been much debate about how it is carried out. Simply testing ACTH levels is not ideal due to individual and seasonal fluctuations, although research work has been done looking at normal variations with the seasons. A TRH stimulation test that causes in increase in ACTH is believed to be the most reliable test currently available since PPID- affected horses have an exaggerated response (Spelta, 2015; Durham et al, 2014). There is no reliable diagnostic technique of early cases, although very advanced cases can be diagnosed fairly reliably with a physical examination (Sojka-Kritchevsky & Johnson, 2014).
Equine PPID usually responds well to the dopamine antagonist pergolide and a licensed drug is now available for horses (Prascend, Boehringer Ingelheim) (Durham et al, 2014). Monitoring the medicated horse is important and again, not straightforward. Improvement in the horse’s physical symptoms, changes in plasma ACTH levels (ideally via TRH stimulation tests) and measurements of insulin dysregulation (in laminitis-affected cases) are recommended (Sojka-Kritchevsky & Johnson, 2014).
The fruit of the herb Vitex agnus castus, also called chasteberry, agnus castus , and Monk’s pepper is commonly used for PPID cases, probably due to its activity as a dopamine agonist. It contains a number of active compounds, including antioxidants, essential oils and diterpenes. The diterpenes are believed to be component with dopaminergic activity (Bradaric et al, 2013). Very little research has been done investigating the effects of treatment, with Beech and colleagues (2002) reporting no benefits, and Bradaric and colleagues (2013) reporting good results feeding a combination herbal product containing chasteberry both alone, and with pergolide.
Other compounds that have been used to support health in PPID are cinnamon and magnesium, possibly due to their potential balancing effects on insulin levels – but more research is required to investigate the results (Geor & Harris, 2013).
Effects of the diet
Horses and ponies with PPID need a good quality diet, but with controlled intake of non-structural carbohydrates (NSC) such as sugar, starch and fructan (Ralston & Harris, 2013). For affected animals that are also obese, an effective weight loss programme should be implemented, but care should be taken to ensure adequate intake of good quality protein, vitamins and minerals.
For affected animals that are too slim, feed a quality diet that provides extra energy for weight gain from digestible fibre and oil, rather than starch and sugar. Ad lib grass is not ideal since it can be rich in NSC, and neither are traditional conditioning compound feeds, which tend to be rich in starch.
Good quality forage with minimal dust and mould spores, a good protein level (of at least 8%) and a relatively low water soluble carbohydrate (sugar and fructan, or WSC) of under 15% should be sourced (and under 10% if the animal is obese or has laminitis). This should be fed ad lib to slim animals, and at a rate of no less than 1.8% bodyweight in dry matter per 24 hours to overweight animals or those with laminitis.
Well-made haylage can be a good choice for PPID-affected horses and ponies because it tends to be palatable, high quality but relatively low in NSC compared with good quality hays. Soaking hay to reduce NSC is not ideal because it leaches out other essential nutrients as well. Ideally have the forage analysed to check that it is suitable.
If the forage is under 8% crude protein, then a source of good quality protein should be fed, e.g. soy bean meal or flakes to ensure the horse receives enough essential amino acids. Soy beans are the richest vegetable source of the most important essential amino acid, lysine.
Good quality forage will reduce reliance on concentrate feed, but the affected horse or pony might still need some concentrate feed to help them maintain weight e.g. over winter. Choose a low starch, high digestible energy compound with medium energy content, or low starch straights e.g. unmolassed sugar beet, micronized linseed, with cooked soy bean flakes for extra good quality protein.
If straights are fed, or less than the full recommended amount of compound feed, a multi-vitamin and mineral supplement must be fed. Affected horses and ponies that are also suffering from laminitis, need to be fed as a laminitic, with restricted NSC and restricted grass but a well-balanced diet.
PPID-affected horses and ponies benefit from extra dietary antioxidants, especially since they will normally have their grass intake restricted to some degree. Ralston and colleagues (1988) reported low plasma vitamin C levels in PPID-affected horses. Feeding extra vitamin C and vitamin E daily is worthwhile. Do not suddenly stop feeding vitamin C because this is harmful and if stocks run low then the daily amount must be gradually decreased.
Feeding practices that help maintain health
Feeding strategies should help to maintain good health without exacerbating any of the metabolic disturbances:
- Feed plenty of forage, aiming to fulfil as much of the horse’s dietary requirements as possible from fibrous forage (thus reducing reliance on concentrate feed)
- Select appropriate forage, e.g. low energy and NSC for overweight or laminitic animals, and ideally a WSC (sugar and fructan) content of 10% or under for all
- Feed ground-forage replacement feeds to affected horses with diminished chewing ability e.g. soaked high fibre nuts, unmolassed sugar beet, and alfalfa nuts
- Avoid fasting periods of over 4 hours to ensure digestive health and comfort and avoid mental and metabolic stress
- Do not overfeed dietary energy and ensure a healthy condition is maintained
- Monitor body fat levels regularly and adjust the diet accordingly
- Keep dietary starch and sugar low, and feed less than the recommended maximum of 1 g per kilo bodyweight per meal of starch
- Use the ‘safe’ energy from vegetable oil to help meet high energy requirements
- Restrict grass intake in order to maintain a low NSC intake
- Feed a well-formulated vitamin and mineral supplement if less than the full recommended mount of compound feed is given
- If dietary protein quality is questionable e.g. little or no grass intake and late-cut or soaked hay then add a source of good quality protein e.g. soy bean flakes
- Consider feeding chasteberry and extra antioxidants, especially vitamins C and E
Can management help?
Good management can make all the difference to the health and comfort of PPID-affected horses and ponies, particularly in advanced stages of the condition.
Stable hygiene is important, since the immune system can be suppressed, and care should be taken with bedding and forage. Avoid deep littering. Clipping is advisable for horses or ponies with hypertrichosis, especially in spring and autumn when the coat might be very thick but the temperature not particularly low. Parasite control is important (as it is in all horses and ponies) and testing for internal parasites should be done to enable correct treatment. Dental care is also even more important than usual, especially for advanced cases who are too slim. Regular hoof care from a professional knowledgeable and experienced in rehabilitating laminitis cases is important if the PPID-affected horse or pony also suffers from laminitis (Spelta, 2015; Durham et al, 2014; Ralston & Harris, 2013)
Appropriate levels of exercise will help general health and musculature and, providing the laminitis-prone horse or pony is comfortable, will help insulin dysregulation.
PPID (Equine Cushing’s syndrome) is a complex and not well 3understood condition that affects mostly aged, but also some younger horses and ponies. Careful veterinary attention including diagnosis and medical treatment are required, along with careful management and feeding to ensure that the condition is managed in such a way as to optimize health and comfort.
Beech, J. et al (2002) Comparison of Vitex agnus castus extract and pergolide in treatment of equine Cushing’s syndrome. AAEP Proceedings 48: 175-177
Bradaric, Z. et al (2013) Use of the chasteberry preparation Corticosal® for the treatment of pituitary pars intermedia dysfunction in horses. Pferdeheilkunde, 29(6): 721-728.
Durham, A. E. et al (2014) Pituitary pars intermedia dysfunction: Diagnosis and treatment. Equine Veterinary Education, 26(4): 216-223.
Geor, R. J. & Harris, P. A. (2013) Laminitis. In Geor, R. J. et al, Eds, Equine Applied and Clinical Nutrition. Saunders Elsevier, Edinburgh.
McFarlane, D. (2007) Advantages and limitations of the equine disease, pituitary pars intermedia dysfunction as a model of spontaneous dopaminergic neurodegenerative disease. Ageing Research Reviews, 6: 54-63.
McFarlane, D. (2011) The effect of geographic location, breed, and pituitary dysfunction on seasonal adrenocorticotropin and α-melanocyte-stimulating hormone plasma concentrations in horses. Journal of Veterinary Internal Medicine, 25: 872-881.
McFarlane, D. (2014) Pathophysiology and clinical features of pituitary pars intermedia dysfunction. Equine Veterinary Education, 26(11): 592-598.
Ralston, S.L. et al (1988) Differences in diagnostic test results and hematologic date between aged and young horses. Americal Journal of Veterinary Research, 49:1387-1392.
Ralston, S. L. & Harris, P. A. (2013) Nutritional considerations for aged horses. In Geor, R. J. et al, Eds, Equine Applied and Clinical Nutrition. Saunders Elsevier, Edinburgh.
Sojka-Kritchevsky, J. E. & Johnson, P. J. (2014) Current status and future directions: Equine pituitary pars intermedia dysfunction and equine metabolic syndrome. Equine Veterinary Journal, 46: 99-102.
Spelta, C. W. (2015) Equine pituitary pars intermedia dysfunction: current perspectives on diagnosis and management. Veterinary Medicine: Research and Reports, 6: 293-300. Accessed on 04.01.16 at http://dx.doi.org/10.2147/VMRR…