Equine Cushing’s disease is a complex progressive disease of the pituitary gland of middle aged to older horses. This condition occurs when the production of dopamine (a neurotransmitter that normally controls the function of a specific portion of the pituitary gland) decreases. The deficiency in dopamine results in an increase in the size of the pituitary gland, subsequently resulting in an increase in the production of adrenocorticotropic hormone (ACTH) and other proteins from cells of the affected pituitary. Following this, elevated levels of ACTH cause overproduction of the hormone cortisol from the adrenal gland.

Signs associated with pituitary disease (Equine Cushing’s disease) in horses are generally slow onset in nature, and may include:

• Development of a long, curly coat
• Increased water consumption
• Increased urination
• Excessive sweating
• Lactation¹

Horses suffering from Equine Cushing’s disease are also prone to chronic infections such as sinusitis, dental disease, and sole abscesses. These conditions are caused by immunosuppression that is a result of prolonged exposure to elevated levels of cortisol. Horses with Cushing’s disease may experience recurrent episodes of laminitis (founder) with no other known predisposing causes. Mares with Cushing’s disease often have reproductive problems such as complete failure to cycle, irregular estrous cycles, estrus suppression, and reduced fertility. “The reproductive problems may be due to suppression of follicle stimulating hormone (FSH) and luteinizing hormone (LH) production due to the elevated levels of cortisol and/or androgens secreted by the hyperstimulated adrenal glands. In addition, enlargement of the affected area of the pituitary may lead to compressive destruction of the pituitary cells that produce FSH and LH.”¹ Insufficient FSH and LH would tend to lead to a decrease in follicular development and failure of ovulation in the mare.

The aforementioned hair coat changes usually develop years after the beginning of pituitary dysfunction. Subtle hair coat changes, such as development of patchy areas of long hairs and a tendency for the winter hair coat to come in earlier and shed out later than normal, may precede more profound changes by many years.

Diagnosis

Diagnosis of Cushing’s disease is usually based on clinical signs and blood tests. Affected horses may have elevated levels of glucose, insulin, cortisol and ACTH in their blood. Additional diagnostic tests include evaluation of cortisol levels in blood samples collected 8 to 10 hours apart or measurement of cortisol levels before and after administration of dexamethasone (the dexamethasone suppression test) or other hormones.

The dexamethasone suppression test is considered to be the favored method for diagnosis of Cushing’s disease in horses. Administration of dexamethasone to normal horses causes marked suppression of blood cortisol, whereas horses with Cushing’s disease have little to no change in cortisol levels in response to dexamethasone. “Evaluation of cortisol rhythm is a relatively common screening test for the presence of Cushing’s disease and is often performed as an alternative to the dexamethasone suppression test in horses with a history of laminitis. However, the cortisol rhythm test may yield false positive or false negative results, and one needs to be cautious basing a diagnosis on this test alone.”¹

Treatment With Pergolide

Pergolide (Pergolide mesylate) is a dopamine agonist that is effective in controlling symptoms associated with equine pituitary pars intermedia dysfunction (PPID, equine Cushing’s disease). The primary use for pergolide in veterinary medicine is in treatment of horses with PPID).²

Pergolide is a potent agonist at dopamine receptors (D₁ and D₂) and is 10-1000 times more potent than bromocriptine. It is thought that PPID in horses is a dopaminergic degenerative disease and pergolide (or dopamine) can reduce expression of proopiomelanocortin (POMC) peptides from the pars intermedia.

Pharmacokinetic studies of pergolide in horses are limited and provide varying information. In a study involving six horses, pergolide was rapidly absorbed following oral administration (0.01 mg/kg) with plasma concentrations reaching maximum levels within 1 hour of dosing. Maximum plasma levels ranged from 1.07-3.38 nanograms/mL. Pergolide appears to be rapidly and widely distributed. Elimination half-life averaged 27 hours, but there was high interpatient variation.³

In a study evaluating 6 horses, 2 mg (~0.004 mg/kg) of pergolide was given each day over a period of six months. Pharmacokinetic parameters were measured after the last dose each day during the six month period. Maximum plasma levels were reached on average within 1 hour of dosing at levels ranging from 0-1.38 ng/mL. Average elimination half-life was determined to be 19.7 hours.⁴

In a study evaluating 8 healthy, young horses, pergolide 0.02 mg/kg IV was given. The mean maximum concentration was found to be 15.62 ng/mL, with a mean terminal elimination half-life of 5.14 hours.⁵

Pergolide Contraindications and Other Warnings

Pergolide is contraindicated in patients hypersensitive to it or other ergot derivatives. Pergolide appears to be well tolerated in horses. Decreased appetite is seen during the first week of therapy in ≈10% of horses treated; temporary dose reduction is often beneficial in alleviating this effect. Colic and diarrhea have been reported to occur more rarely. Adverse effects reported in humans include: nervous system complaints (dyskinesia, hallucinations, somnolence, insomnia), gastrointestinal complaints (nausea, vomiting, diarrhea, constipation), transient hypotension, and rhinitis.²

Safety of pergolide in pregnant horses has not been established. In humans, pergolide is designated by the FDA as a Category B drug (Animal studies have not demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus during the first trimester of pregnancy, and there is no evidence of risk in later trimesters).

It is not known if pergolide enters maternal milk; however, like other ergot-derivative dopamine agonists, it may interfere with lactation.²

Canine Cushing's disease (PPD) in dogs is similar in causes to that of equine Cushing's disease, but treatment differs. Pergolide is not typically recommended for the treatment of Cushing's disease in dogs,⁶ despite its success in the treatment of the ailment in equines. Cushing's disease presents differently in dogs and its effects on a dog's body require alternative treatment. Dogs are also reportedly prone to overdose when pergolide is used.²

The following drug interactions have either been reported or are theoretical in humans or animals receiving pergolide and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.

DOPAMINE ANTAGONISTS (eg, phenothiazines): May decrease the effects of pergolide.

METOCLOPRAMIDE: May decrease the effects of pergolide.
(Plumb’s Veterinary Drugs)

Where to buy Pergolide

Pergolide is available in the U.S. through several pharmaceutical manufacturers and through veterinary custom compounding companies. Pergolide 1 mg/scoop powder from NexGen is indicated for the treatment of PPID (Equine Cushing's disease) in horses.

FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.

¹McCue, Patrick. (2003). Equine Cushing's disease. The Veterinary clinics of North America. Equine practice. 18. 533-43, viii. 10.1016/S0749-0739(02)00038-X.

²Plumb’s Veterinary Drugs.

³Gehring R, et al. Single-Dose Oral Pharmacokinetics of Pergolide Mesylate in Healthy Adult Mares. Vet Therapeutics. 2010;11(1):E1-E8.

⁴McFarlane D, et al. Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction. J Vet Pharmacol Ther. 2017;40(2):158-164.

⁵Rendle DI, et al. Pharmacokinetics of pergolide after intravenous administration to horses. Am J Vet Res. 2015;76(2):155-160.

⁶avma.org.