Technical information for veterinarians

Cushing’s Disease, Cushing’s Syndrome in Horses

What is Cushing’s syndrome?

A small benign tumour in the pituitary gland causes equine Cushing’s syndrome. Since the pituitary governs the entire endocrine system, a number of conditions are associated with the disease. Cushing’s disease is also referred to as hyperadrenocorticism.

A horse with Cushing’s usually develops the condition in the mid to late years of life (average age, 20 years), although it is sometimes diagnosed in horses as young as seven.

Symptoms/diagnosis of Cushing’s syndrome

Cushing’s syndrome is the term used to define the clinical effects of enhanced glucocorticoid action on the body. While equine Cushing’s syndrome has been associated with both the exogenous administration of potent glucocorticoids (e.g. corticosteroids) and with endogenous glucocorticoid substances produced by the pituitary tumour, there are other potential mechanisms that could explain the increased glucocorticoid effect.

The concentration of cortisol is also controlled locally within the tissues of the horse’s body. Cortisol exerts its effect on the functioning of the cell by entering the cell and interacting with a receptor. The precise concentration of cortisol within the body’s cells is critical to their normal functioning. An enzyme called 11-beta hydroxysteroid dehydrogenase (HSD) is responsible for maintaining the local concentration of cortisol within the optimal limit.

Under normal circumstances, the concentration of cortisol within the cell is adjusted by HSD within the cell itself. This ensures that the requirements of the cell at any given time are met. It has been suggested that Cushing’s syndrome may sometimes be attributed to abnormal HSD activity within the cells. (Human beings whose cellular cortisol concentration is increased due to abnormal HSD activity, develop symptoms that are similar to Cushing’s syndrome.)

Increased HSD activity in the cells leads to increased cortisol within the tissues. This increase is believed to give rise to clinical signs of Cushing’s syndrome. In an attempt to determine if laminitis associated with obesity can be a manifestation of abnormal HSD activity in the peripheral tissues of affected horses, Dr. Philip Johnson at the University of Missouri at Columbia developed a test for HSD in the tissues of horses. Dr. Johnson then compared the level of HSD in the tissues of the skin and hoof of normal healthy adult horses with the level found in horses with laminitis. He was able to show that HSD could be identified both in the skin and hoof tissues and that the level of HSD was substantially elevated in the tissues of horses with laminitis.

The etiology of Cushing’s syndrome

The most common symptoms of Cushing’s syndrome are:

  • Sudden-onset polydipsia. An affected horse may drink as much as 80 litres of water a day (as opposed to an average 20 – 30 litres). This condition is usually accompanied by polyuria.
  • Abnormal hair growth and shedding. Affected horses may develop a growth of heavy, coarse, often curly hair, which does not shed in the summer. This may be accompanied by sweating and seborrhea.
  • Development of a swayback stance and a pot belly.
  • Filling above the eyes caused by the deposition of fat.
  • A general appearance of malaise, with dull eyes and drab coat.
  • Increased appetite (usually with no accompanying weight gain).
  • Chronic laminitis.
  • Loss of muscle over the topline.
  • Compromised immune system. This gives rise to a host of conditions/diseases which are often passed off as old age. These include respiratory disease, skin infections, abscesses of the foot, buccal ulcers, and periodontal disease.

In order to confirm a diagnosis of Cushing’s disease, specific hormone tests are normally undertaken. While the symptoms of Cushing’s syndrome are attributed to excessive production of cortisol by the adrenal glands, the level of cortisol in the blood varies throughout the day. This makes it difficult to differentiate between levels of cortisone concentration in the normal horse and a horse with Cushing’s syndrome.

The most widely used test for classic equine Cushing’s syndrome associated with a pituitary tumor is the dexamethasone suppression test (DST). This test determines the effect of dexamethasone on the blood cortisol concentration. Dexamethasone blocks ACTH secretion by the healthy pituitary gland and significantly reduces circulating cortisol. Since dexamethasone is unable to block ACTH production by the pituitary tumor, it does not suppress blood cortisol levels in the horses affected with classic Cushing’s syndrome.

High cortisol levels interfere with the action of insulin, causing elevated insulin levels in horses with Cushing’s syndrome. Some veterinarians therefore also measure insulin to support their diagnosis.

Treatments for Cushing’s syndrome

Blood and urine tests are normally employed to diagnose Cushing’s disease. Repeat testing may be necessary, as preliminary tests do not always produce conclusive results. Some cases of Cushing’s syndrome are so obvious (polydipsia, dense hair growth, etc.), that treatment is prescribed in advance of testing.

Once a positive diagnosis has been reached, appropriate treatment can begin. When symptoms are caught early, treatment can be extremely successful, returning the horse to normal health for many more years.

MEDICATIONS

When deciding whether to medicate a horse with Cushing’s, the cost of treatment and the condition of the horse in question should first be considered. Horses with relatively mild symptoms generally respond best to medication, which may extend their useful lives by a number of years. However, a horse that is already suffering from chronic founder/laminitis and recurrent infections as a result of immune system failure will likely derive very little benefit. While the drugs listed below treat the symptoms of Cushing’s syndrome, they do not treat the pituitary tumor itself. The tumour will continue to grow until it compromises the horse’s quality of life. There are currently no methods of removing or curbing the growth of equine pituitary adenomas.

Cyproheptadine (Periactin®).

This seratonin blocker is available in tablet form, which is easily absorbed into the horse’s system. Horses are normally started at about 0.13 mg/kg (or about 58 mg for an average 440 kg horse). The dosage should be until the clinical signs of Cushing’s begin to improve.

The simplest way to gauge improvement is to have the owner monitor the horse’s water intake over a 24-hour period. This is best achieved by keeping the horse stabled and provided with water in a bucket. The dosage of medication is slowly increased until the horse’s water intake returns to normal levels (usually taking about six to eight weeks). During this time, other symptoms of Cushing’s syndrome, such as the heavy coat and pot belly, also disappear, and the horse regains vigour and muscle tone. After this level of improvement has continued for a month, the dosage of cyproheptadine is gradually reduced until a maintenance level is reached.

Cyproheptadine is effective in about 75 – 80 percent of cases.

Pergolide mesylate (Permax®)

This drug was originally used to treat human Parkinson’s disease. At the doses considered successful in treating Cushing’s, however, pergolide mesylate had a severe vasoconstricting effect that served to worsen the chronic laminitis that frequently accompanies Cushing’s. In the early ‘90s, Montana equine veterinarian, Dr. Duncan Peters, decided to give a very small dose of the drug to a horse suffering from Cushing’s. This dose was roughly equivalent to one-sixth of the amount considered appropriate for a human. The horse responded positively. In a further study, Dr. Peters was able to duplicate the positive results in eight of nine horses/ponies with no negative side effects.

The average response time was close to three weeks, and improvement continued until the horses stabilized at an average 21 weeks. Since these results were published, pergolide mesylate has become an acceptable treatment option for Cushing’s syndrome.

Pergolide mesylate is usually administered orally, in tablet form. (Crushing the tablets with a little molasses is an effective way for the owner to dose the horse.)

Bromocriptine mesylate (Parlodel®)

A less popular drug used to treat equine Cushing’s disease, although still used by some veterinarians. Problems in absorption are often documented and the drug purportedly produces a number of side effects.

Herbal treatments.

While the jury is still out of the efficacy of herbal treatments for Cushing’s syndrome, there is indication that chaste berry (Vitex agnus castus) may be effective for early stage cases of Cushing’s syndrome. The UK Horse Journal ran a field trial of Vitex including 10 horses and ponies. The subjects were aged between 13 and 25 years, and were either diagnosed with Cushing’s or demonstrating the classical Cushing’s symptoms.

The Journal reported that typical response was “rapid and dramatic.” Shedding would typically begin within three weeks, and energy level quickly increased. High blood glucose and insulin levels dropped in some cases within four to six weeks. (The results of a later study at the University of Pennsylvania’s New Bolton Center repudiated these claims. Nonetheless, some horse owners feel that their horse was helped through use of the herb.)

Helping the horse with Cushing’s syndrome

No treatment for Cushing’s will cure the disease. Therefore, the owner’s role will be to focus on careful health management and preventive treatment as follows:

  • Avoiding stressing the horse. The hormonal profile of many horses with Cushing’s already indicates high stress levels, so reducing stress is critical.
  • Providing a safe, comfortable “sanctuary” for the horse.
  • Sticking to a strict routine, which will help minimize stress.
  • Keeping water and feed conveniently located and in the same place.
  • Clipping the horse in warm weather; using blankets when it is cold.
  • Keeping up grooming to minimize skin diseases.
  • Keeping hooves in good shape.
  • Checking teeth regularly and having them checked by a professional twice a year.
  • Avoiding turning the horse out with aggressive horses.
  • Avoiding contact with horses from a new location.
  • Keeping immunizations to a minimum/ making sure all necessary shots are given.
  • Deworming regularly (usually every 30 – 45 days).
  • Providing an appropriate diet for the horse. This will usually involve elimination of simple carbohydrates.

Equine health options

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