Cushing’s disease is one of the most common illnesses in horses older than 15, but is your own horse at risk? Gil Riley MRCVS investigates.
Cushing’s disease — also known as pituitary pars intermedia dysfunction (PPID) — is a progressive disorder caused by a dysfunction of the pituitary gland.
This gland is located at the base of the brain and it produces an assortment of hormones.
In a horse with Cushing’s, the middle lobe of his pituitary gland becomes enlarged over time, often referred to as an adenoma, and results in the over-production of these hormones. The growth can compress the adjacent structures in the pituitary and hypothalamus – a region of the brain – resulting in loss of their function.
One of the hormones produced in the pars intermedia is the adrenocorticotropic hormone (ACTH), which stimulates the cortex of the adrenal glands (two glands located close to the kidneys) to produce cortisol. An increase in ACTH production from the dysfunctional pituitary leads directly to an increase of cortisol circulating in the body.
This increased cortisol level can affect the body in many ways, and is largely responsible for the collection of changes that are associated with Cushing’s disease.
So why is Cushing’s so common among our equine populations? The answer is because the network of nerves that are responsible for controlling the activity of the pituitary gland are sensitive to free radicals – damaging chemicals that are normal by-products of the body’s process of metabolism.
As an animal gets older, the continuous exposure to these free radicals causes the nerves to degenerate, and this occurs more quickly in some animals than in others. In those where it is a faster process, the pituitary starts to produce hormones in an uncontrolled fashion, and these are the animals where we see the disease.
As a horse gets older, its likelihood of getting Cushing’s increases – it is one of the most common diseases found in horses older than 15. The average age at which horses are diagnosed is around 20 years, with over 85% of the horses being over 15. However, it has been diagnosed in horses as young as seven.
In one US study, it was shown that horses aged 20 to 25 years were 4.6 times more likely to have Cushing’s than the horses younger than 15, while horses over 25 years of age were 14
times more likely.
All breeds of horses can develop Cushing’s, but ponies have a higher incidence of the disease. It is worth noting that obesity has been associated with a higher production of free radicals and it is therefore possible that since ponies are more prone to being overweight, this may be one reason why the incidence of the disease in ponies is that much greater.
The classic symptoms associated with Cushing’s disease are an excessively hairy coat (hirsutism) and a pot belly. However, these signs are usually seen late in the disease process with a whole host of more subtle signs making their presence felt earlier. These include excessive drinking and urination; laminitis; lethargy; excessive sweating; loss of muscle mass; repeated infections such as foot abscesses, tooth root infections, sinusitis and repeat conjunctivitis (runny eyes); infertility and bulging eyes.
Conscientious owners will pick up on subtle changes in their animal earlier than the vet might. Therefore, those horses belonging to attentive owners tend to have the disease diagnosed at an earlier stage. As for any disease, the earlier it is detected, the better odds of the treatment working.
Diagnosis
There are several tests available which can confirm the presence of Cushing’s disease, but no single test is 100% accurate. The most frequently used tests are the measurement of resting plasma ACTH concentration, the dexamethasone suppression test and the thyrotropin-releasing hormone (TRH) stimulation test.
The ACTH blood test is the most common. It involves a single sample being taken from the patient and analysed for the level of ACTH present. A high level of ACTH suggests an increase in its production consistent with Cushing’s.
This test can be performed on a single visit, which makes it convenient for vets and owners alike. However, there are a few drawbacks.
Firstly, the ACTH levels in a normal animal vary with the time of year, being particularly high between September and December. This seasonal aberration may be due to a normal hormonal process as the body is triggered to prepare itself for winter. This means a positive test result obtained in the months of September to December should be interpreted carefully.
This annual variation is now accounted for by laboratories who have a different normal range for ACTH depending on the month of the year.
ACTH can also vary with environmental factors – it may be higher in horses affected by intense stress (such as during transport), severe illnesses or pain, or recent strenuous exercise. Sedation prior to testing might affect results but feeding does not.
Therefore, if an animal is stressed or in severe pain, this should be addressed and the animal fully recovered before testing to avoid a false positive.
The dexamethasone suppression test is considered by many to be the most reliable diagnostic test for Cushing’s, although it is less useful when the disease is in its early stages. This test involves suppression of cortisol in a normal horse after administration of dexamethasone.
A blood sample is collected for cortisol measurement at around 4pm in the afternoon, dexamethasone is administered and 19 hours post-injection a second blood sample is collected for cortisol measurement.
In horses with Cushing’s, the dexamethasone will not cause the same reduction in serum cortisol production as it will in the normal horse. As for the single measurement for ACTH, false positives occur more commonly in the months of September to December.
The TRH stimulation test is gaining popularity as it is considered the most accurate test for detecting animals in the early stages of Cushing’s disease. Thyrotropin administration causes an exaggerated ACTH response in Cushing’s patients.
Like the dexamethasone suppression test, a blood sample is taken, the agent administered, and then a second sample taken. However, rather than 19 hours later as in the dexamethasone test, the second sample in the TRH test is taken 10 minutes after the administration of the drug so this test can be completed in a single visit.
Treatment
Pergolide is the drug of choice for treatment of Cushing’s disease. While treatment seldom achieves complete resolution remission of the disease, it can greatly improve quality of life.
The dose – administered in tablet form – can be adjusted according to the response. Usually vets will repeat a test around one month after starting on pergolide to assess whether the treatment is having an effect at a hormonal level.
Of course, the presentation of the animal is extremely important. If there are no more bouts of laminitis, the patient starts to put on muscle or is much less prone to infections, then the treatment is clearly being effective. Because pergolide does not prevent the progression of the disease, as time goes on the dosage may need to be increased.
Testing every six to 12 months, or in response to any clinical blip, would help a decision to be taken on whether the dosage should be increased. Supportive care is also very important for enhancing a patient’s quality of life.
Even if pergolide treatment is deemed too expensive, it does not inevitably mean the end of the patient’s life as there is still much that can be done as regards management to improve the welfare of a Cushing’s patient.
Preventative medicine such as regular worming, dental care and routine farriery is important, while in the warmer months, clipping away unnecessary hair will keep the horse more comfortable as Cushing’s patients do struggle with thermoregulation. Rugs may then be required in colder weather or at night.
A diet low in carbohydrate should generally be fed; there are several excellent commercial rations tailored for this that are low in sugar and starch available on the market. The recommendation is that the non-structural carbohydrates (NSC), which are a combination of water-soluble carbohydrates (WSC, or “sugar”) and starch, is less than 10 to 12% of their overall diet when combined.
Access to a wood-chip paddock so that turnout is still possible when the grass paddocks are considered too rich is advised. The diet should be supplemented with vitamin and minerals to ensure the immune system is supported.
It is important the condition score of the patient is monitored closely, as a loss of muscle mass or a tendency to deposit fat would both indicate that repeat testing to fine tune the dosing of pergolide is appropriate.