# Equine Cushings Disease PPID: Prascend Dosing and ACTH Testing ## Key Takeaways - Pituitary Pars Intermedia Dysfunction (PPID), commonly known as equine Cushing's disease, is a progressive, age-related neurodegenerative disorder affecting older horses (typically >15 years) due to loss of dopaminergic inhibition of the pars intermedia. - Diagnosis is primarily based on basal plasma ACTH concentration, with interpretation critically dependent on seasonally adjusted reference ranges due to physiological ACTH fluctuations in late summer and autumn. - Pergolide mesylate (Prascend) is the first-line medical therapy, acting as a dopamine agonist to restore inhibition of the pars intermedia and reduce excessive POMC peptide secretion. - Treatment involves initiating pergolide at 1 mg daily (or 0.5 mg for smaller equids/mild cases), with dose adjustments based on clinical signs and recheck ACTH levels 2-4 weeks post-initiation or dose change, aiming for ACTH within seasonal reference ranges. - Common clinical signs include hypertrichosis (long, curly coat), delayed shedding, muscle wastage, recurrent laminitis, polydipsia, and polyuria, necessitating early intervention to prevent painful complications. - Comprehensive management includes regular ACTH monitoring (every 6-12 months once stable), appropriate nutrition, dental care, farriery, and clipping for hypertrichosis, alongside avoiding unproven remedies. --- If your horse is over 15 years old and has a long, curly coat that fails to shed in spring, or if it is drinking and urinating more than usual, the likely diagnosis is pituitary pars intermedia dysfunction (PPID), commonly called equine Cushing's disease. The first step is a simple blood test for adrenocorticotropic hormone (ACTH). If the level is high, your veterinarian will likely prescribe Prascend (pergolide mesylate). This article explains how ACTH testing guides diagnosis and how Prascend dosing is started, adjusted, and monitored. **Owner triage summary:** Do not wait for severe signs. If you notice hypertrichosis (a long, wavy hair coat), delayed shedding, recurrent laminitis, or unexplained weight loss in a senior horse, contact your veterinarian for an ACTH test. Early diagnosis and treatment with pergolide can prevent painful complications and improve quality of life [1][2]. This article is educational and is not a substitute for veterinary diagnosis or treatment. ## At a Glance: PPID Testing and Treatment | Feature | Details | | :--- | :--- | | **Disease** | Pituitary pars intermedia dysfunction (PPID), equine Cushing's disease [1] | | **Typical Patient** | Middle-aged to older horses and ponies (often >15 years) [1][3] | | **Primary Hormone Test** | Basal plasma ACTH concentration [1][4] | | **Seasonal Variation** | ACTH levels rise in late summer and autumn; seasonally adjusted reference ranges are required [3][5] | | **First-Line Medical Therapy** | Pergolide mesylate (Prascend) [6][2] | | **Treatment Goal** | Reduce clinical signs and lower ACTH into the seasonal reference range [1][2] | | **Monitoring** | Recheck ACTH 2 to 4 weeks after a dose change; repeat clinical examination [1][2] | | **Prognosis** | Good with early diagnosis and consistent management; the disease is progressive but manageable [6][2] | ## Understanding Equine Cushing's Disease (PPID) PPID is a progressive, age-related neurodegenerative disorder of the pituitary gland [3][7]. The disease is caused by the loss of dopaminergic neurons in the hypothalamus, which normally inhibit the melanotropes of the pars intermedia [7][8]. Without this inhibition, the pars intermedia enlarges and produces excessive amounts of pro-opiomelanocortin (POMC)-derived peptides, including ACTH and alpha-melanocyte stimulating hormone (alpha-MSH) [7][9]. The term "equine Cushing's disease" is widely used, but PPID differs from Cushing's disease in humans and dogs. In PPID, the primary problem is not a cortisol-secreting tumor of the pars distalis. Instead, it is a loss of dopaminergic inhibition, leading to hyperplasia or adenoma of the pars intermedia [1][10]. This distinction matters because the clinical signs and diagnostic approach differ. For example, while plasma ACTH is elevated, plasma cortisol is often normal in horses with PPID, a paradox explained by increased cortisol clearance and tissue-specific dysregulation of cortisol metabolism [10]. ### The Role of the Pars Intermedia The pituitary gland has three main parts: the pars distalis (anterior), the pars intermedia (intermediate lobe), and the pars nervosa (posterior). In horses with PPID, the pars intermedia is the primary site of pathology. The melanotropes in this region are normally under tonic inhibition by dopamine. When this inhibition is lost, these cells proliferate and secrete excessive POMC peptides [7][8]. This explains why dopamine agonists like pergolide are effective: they replace the missing dopaminergic inhibition [2][8]. ### How PPID Differs from Other Endocrine Diseases PPID is often confused with equine metabolic syndrome (EMS), but they are distinct conditions. EMS is a metabolic disorder characterized by insulin resistance and a high risk of laminitis, typically occurring in younger, overweight horses. PPID is a neurodegenerative disease of older horses. However, the two conditions can coexist, and both increase the risk of laminitis [3][11]. A thorough veterinary examination is essential to differentiate them, as treatment strategies differ. ## Clinical Signs and Risk Factors The clinical signs of PPID are numerous and often develop gradually. Owners may attribute them to normal aging, which can delay diagnosis [3]. ### Common Clinical Signs - **Hypertrichosis (hirsutism):** A long, curly, or wavy hair coat that fails to shed normally. This is the most frequently reported clinical sign [12][11]. - **Delayed or incomplete shedding:** The horse may retain its winter coat well into the summer months [12]. - **Epaxial muscle wastage and muscle atrophy:** Loss of muscle along the topline and a "pot-bellied" appearance due to abdominal muscle weakness and fat redistribution [11]. - **Laminitis:** A painful and potentially debilitating condition of the hoof lamellae. It is a common and serious complication of PPID [1][11]. - **Polydipsia and polyuria:** Increased thirst and urination, often due to secondary diabetes insipidus or hyperglycemia [12]. - **Weight loss:** Despite a normal or increased appetite, the horse may lose condition [1][12]. - **Chronic infections:** Recurrent or non-healing infections, such as sinusitis or skin infections, may occur due to immunosuppression [1]. - **Lethargy and behavioral changes:** The horse may appear dull, depressed, or less willing to work. - **Reproductive disorders:** In broodmares, PPID can cause irregular estrous cycles or prolonged anestrus. A case report in a stallion found no impairment of reproductive activity [12]. ### Risk Factors - **Age:** The most significant risk factor. The prevalence of PPID increases markedly with age. A study of horses aged 15 years and older found a prevalence of 21.2% [3]. - **Breed:** Ponies and certain breeds may be overrepresented, but PPID can affect any equid [1][3]. - **Sex:** Both males and females are affected. The condition has been reported in mares, geldings, and stallions [12][3]. ## The Importance of ACTH Testing ACTH testing is the cornerstone of PPID diagnosis and monitoring [1][4]. ACTH is a POMC-derived peptide secreted by the pars intermedia in excess in horses with PPID [10]. ### Basal ACTH Measurement A single blood sample for basal plasma ACTH concentration is the most common and practical diagnostic test [1][3]. The test is simple and requires minimal stress to the horse. However, the interpretation of results is highly dependent on the time of year. ### Seasonal Variation in ACTH In normal horses, ACTH levels naturally rise in the late summer and autumn (August to October in the Northern Hemisphere). This is a normal physiological response related to photoperiod, likely mediated by melatonin and dopamine [5]. Horses with PPID often show an exaggerated rise during this period. Therefore, seasonally adjusted reference ranges are essential for accurate diagnosis [3][5]. A study on seasonal changes in aged horses with Cushing's disease found that dopamine output was significantly lower in the affected group in summer and autumn, correlating with the seasonal exacerbation of the disease [5]. This highlights the need for clinicians to use reference ranges specific to the time of year. ### How to Perform an ACTH Test - **Sample Collection:** Blood is collected into a chilled EDTA tube (purple top). - **Handling:** The sample must be centrifuged and the plasma separated promptly, then frozen or shipped on ice to the laboratory. ACTH is unstable at room temperature. - **Laboratory Analysis:** The sample is analyzed using a chemiluminescence immunoassay [4]. - **Reproducibility:** A study evaluating the reproducibility of ACTH concentrations across four different laboratories in Germany found significant variability between laboratories, as well as within the same laboratory on repeated samples. The standard deviation for duplicate samples from the same horse ranged from +/- 6 to +/- 27 pg/ml [4]. This means that a single mildly elevated result should be interpreted with caution and may warrant confirmation, especially if clinical signs are equivocal. ### Interpreting ACTH Results - **Elevated ACTH:** A basal ACTH concentration above the seasonally adjusted reference range is strongly supportive of PPID [3]. - **Normal ACTH:** A normal ACTH in a horse with classic clinical signs (e.g., severe hypertrichosis) does not rule out PPID. In these cases, a TRH stimulation test or a dexamethasone suppression test may be considered [6][12]. - **Equivocal Results:** If the ACTH is borderline, your veterinarian may recommend repeating the test in a few weeks or performing a dynamic test. ### Other Diagnostic Tests - **Dexamethasone Suppression Test (DST):** This test involves administering dexamethasone and measuring cortisol levels after a set period. In normal horses, dexamethasone suppresses cortisol; in horses with PPID, this suppression is blunted [6][12]. This test is useful but is more labor-intensive and requires multiple blood samples. It is also contraindicated in horses with laminitis. - **TRH Stimulation Test:** This test measures the increase in ACTH or alpha-MSH after administration of thyrotropin-releasing hormone (TRH). Horses with PPID have an exaggerated response [9]. - **Alpha-MSH:** This is another POMC-derived peptide that can be measured. It may be useful in some cases, but ACTH is the most widely used and validated marker [3][9]. ## Prascend (Pergolide Mesylate) for PPID Pergolide mesylate is a dopamine agonist that is the first-line medical treatment for PPID [6][2]. It works by mimicking the action of dopamine, thereby restoring inhibition of the pars intermedia and reducing the secretion of POMC peptides [2][8]. ### Efficacy of Pergolide A systematic review of the literature on pergolide efficacy concluded that treatment with pergolide is associated with improvement in clinical signs and a reduction in plasma ACTH concentration compared to no treatment [2]. While the quality of evidence was variable, the review supported the use of pergolide as the standard of care. Most studies showed that pergolide effectively reduced ACTH levels and improved signs such as hypertrichosis and lethargy [2]. The same review noted that a significant proportion of horses may require higher doses than initially prescribed to achieve adequate control [2]. This underscores the need for regular monitoring and dose adjustment. ### Prascend Dosing Protocols Prascend is the brand name for pergolide mesylate. It is available as 1 mg tablets. **Starting Dose:** - The standard starting dose is 1 mg (one tablet) administered orally once daily. - For some horses, particularly ponies or those with mild disease, a lower starting dose of 0.5 mg (half a tablet) may be considered to reduce the risk of side effects. **Dose Adjustment:** - The dose should be titrated based on clinical response and ACTH levels. - The goal is to find the lowest effective dose that controls clinical signs and brings ACTH into the seasonal reference range. - If there is no improvement after 4 to 6 weeks, the dose may be increased by 0.5 to 1 mg increments. - Many horses require 2 mg or more per day to achieve adequate control [2]. **Administration Tips:** - Prascend is a small tablet that can be given directly in the mouth, hidden in a small amount of feed, or dissolved in water and syringed. - It is important to give the medication at the same time each day. - Wear gloves when handling the tablets, as pergolide can be absorbed through the skin. ### Monitoring and Follow-up - **Initial Recheck:** A recheck ACTH level is recommended 2 to 4 weeks after starting treatment or after any dose change [1]. - **Clinical Assessment:** Your veterinarian will also assess clinical signs, such as hair coat quality, muscle mass, and energy levels. - **Long-term Monitoring:** Once a stable dose is achieved, ACTH should be rechecked every 6 to 12 months, or more frequently if clinical signs recur. It is also important to monitor for laminitis and other complications. ### Side Effects of Pergolide Pergolide is generally well-tolerated, but some horses may experience side effects, especially when starting treatment or after a dose increase. Common side effects include: - Decreased appetite - Lethargy or depression - Mild diarrhea (or diarrhoea) - Weight loss These side effects are often transient and may resolve within a few days. If they are severe or persistent, contact your veterinarian. In some cases, a temporary dose reduction or a slower titration schedule may be helpful. ### Pergolide and Nondomestic Equids The use of pergolide is not limited to domestic horses. A case series reported the successful use of pergolide mesylate to reduce basal ACTH concentrations and clinical signs in nondomestic equids, including Chapman's zebras and Przewalski's horses [1]. This suggests that the same principles of diagnosis and treatment apply across equid species. ## Evidence-Based Management of PPID Managing PPID involves more than just medication. A comprehensive approach that addresses the horse's overall health and environment is essential for a good outcome [6]. ### Nutrition and Body Condition - **Weight Management:** Many horses with PPID lose weight, especially in advanced stages. A study of 36 PPID patients under pergolide treatment found that large horses were often underfed relative to their estimated energy requirements [13]. Ensure your horse receives a balanced diet with adequate calories to maintain a healthy body condition score (BCS). - **Dietary Adjustments:** For horses with concurrent EMS or insulin dysregulation, a diet low in non-structural carbohydrates (sugars and starches) is recommended. - **Supplements:** The same study found that requirements for zinc, copper, selenium, and vitamins A and E were often not met [13]. A balanced vitamin and mineral supplement may be beneficial, but always consult your veterinarian first. ### Routine Health Care - **Dental Care:** Regular dental check-ups and floating are crucial, as dental problems can contribute to weight loss and poor condition [6]. - **Farriery:** Regular hoof care is essential, especially for horses with a history of laminitis. A therapeutic farrier can help manage hoof health and prevent complications. - **Parasite Control:** Implement a targeted deworming program based on fecal egg counts. - **Clipping:** Horses with hypertrichosis may benefit from clipping in the spring to help them thermoregulate and reduce the risk of skin infections [6]. - **Vaccinations:** Keep vaccinations current, as PPID can compromise the immune system. ### Environmental Management - **Shelter:** Provide adequate shelter from extreme weather conditions. - **Pasture:** Manage pasture access to prevent excessive weight gain in horses with EMS. For horses prone to laminitis, restrict grazing during times of high non-structural carbohydrate content (spring and autumn). ## Unsafe Home Remedies and Unproven Treatments The internet is full of unproven and potentially harmful "cures" for equine Cushing's disease. It is critical to avoid these and stick to evidence-based treatments. - **Unlicensed Supplements:** Many supplements claim to support pituitary function, but there is no scientific evidence to support their use as a replacement for pergolide. - **Herbal Remedies:** Some herbs, such as chasteberry (Vitex agnus-castus), have been proposed as treatments, but there is no evidence of their efficacy. They should not be used instead of pergolide. - **Iodine:** High doses of iodine are toxic and should never be given. - **Over-the-Counter "Cushing's" Formulas:** These products are not regulated and may contain ingredients that are harmful or interact with other medications. Always consult your veterinarian before giving your horse any supplement or medication, including over-the-counter products. ## Prevention and Early Intervention PPID is a progressive, age-related disease, and it may not be entirely preventable [3][7]. However, early detection and treatment can slow the progression and prevent the development of severe clinical signs and complications [1]. - **Regular Screening:** Consider annual ACTH testing for all horses over 15 years of age, even if they appear healthy. This is especially important in the autumn when ACTH levels are naturally higher [3]. - **Early Treatment:** Starting pergolide early, when clinical signs are mild, may be more effective in managing the disease and preventing complications like laminitis [1][2]. ## Prognosis The prognosis for a horse with PPID is generally good with appropriate management. While the disease is progressive and not curable, it is manageable. With consistent treatment and monitoring, many horses with PPID can live comfortable, active lives for many years [6][2]. The key to a good prognosis is early diagnosis, consistent medication, and regular veterinary check-ups. The goal of treatment is to improve quality of life, not just to normalize blood test results. ## Limitations and When to Contact a Veterinarian This article provides general information about PPID, but it cannot predict the outcome for any individual horse. Every horse is different, and the response to treatment can vary. Breed-specific information is limited, and the disease can manifest differently in different animals. **Contact your veterinarian immediately if you observe any of the following:** - **Signs of laminitis:** Lameness, increased digital pulses, heat in the hooves, or a "sawhorse" stance. - **Severe lethargy or depression:** Your horse is unusually dull or difficult to rouse. - **Loss of appetite:** Your horse is not eating or drinking normally. - **Difficulty breathing:** Any signs of respiratory distress. - **Colic:** Signs of abdominal pain, such as pawing, rolling, or looking at the flank. - **Any new or worsening clinical signs.** Early intervention is critical for managing complications and ensuring the best possible outcome for your horse. Always work closely with your veterinarian to develop a tailored treatment and monitoring plan. ## Frequently Asked Questions ### 1. What is the difference between equine Cushing's disease and equine metabolic syndrome? Equine Cushing's disease (PPID) is a neurodegenerative disease of the pituitary gland, most common in older horses, characterized by high ACTH and clinical signs like hypertrichosis. Equine metabolic syndrome (EMS) is a metabolic disorder of younger, often overweight horses, characterized by insulin resistance and a high risk of laminitis, without the characteristic hair coat changes. ### 2. How is ACTH testing performed in horses? ACTH testing is a simple blood test. Blood is drawn into a chilled EDTA tube, centrifuged, and the plasma is frozen and sent to a laboratory for analysis using a chemiluminescence immunoassay. ### 3. Why does my horse need a seasonal reference range for ACTH? Normal horses have a natural rise in ACTH in the late summer and autumn. Using a seasonal reference range prevents misdiagnosis of normal horses as having PPID and ensures accurate interpretation of test results during these periods. ### 4. What is the starting dose of Prascend for a horse with PPID? The standard starting dose is 1 mg (one 1 mg tablet) administered orally once daily. Your veterinarian may recommend a lower starting dose of 0.5 mg for some horses, particularly ponies. ### 5. How quickly will I see improvement after starting Prascend? Some improvement in clinical signs, such as energy levels, may be seen within a few weeks. However, hair coat changes can take several months to become apparent. ACTH levels should be rechecked 2 to 4 weeks after starting treatment to assess the response. ### 6. What should I do if my horse stops eating after starting Prascend? Decreased appetite is a common side effect when starting pergolide. It is often transient. You can try hiding the tablet in a small amount of feed, or ask your veterinarian about a temporary dose reduction or a slower titration schedule. If the horse refuses to eat entirely, contact your veterinarian. ### 7. Can PPID be cured? No, PPID is a progressive, degenerative disease that cannot be cured. However, it can be effectively managed with medication and supportive care, allowing many horses to live comfortable lives for years. ### 8. Is Prascend safe for all horses and ponies? Prascend is generally safe, but it should be used with caution in horses with certain conditions. It is important to discuss your horse's full medical history with your veterinarian before starting treatment. It has also been used safely in nondomestic equids under veterinary supervision. ## Sources [1] [PITUITARY PARS INTERMEDIA DYSFUNCTION (EQUINE CUSHING'S DISEASE) IN NONDOMESTIC EQUIDS AT MARWELL WILDLIFE: A CASE SERIES. ONE CHAPMAN'S ZEBRA ( EQUUS QUAGGA CHAPMANI) AND FIVE PRZEWALSKI's HORSES ( EQUUS FERUS PRZEWALSKII).](https://pubmed.ncbi.nlm.nih.gov/29900762/) [2] [Efficacy of pergolide for the management of equine pituitary pars intermedia dysfunction: A systematic review.](https://pubmed.ncbi.nlm.nih.gov/33323174/) [3] [Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses.](https://pubmed.ncbi.nlm.nih.gov/22594955/) [4] [[Study on the reproducibility of ACTH concentrations in plasma of horses with and without equine Cushing syndrome].](https://pubmed.ncbi.nlm.nih.gov/23901591/) [5] [Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod.](https://pubmed.ncbi.nlm.nih.gov/18540997/) [6] [Pituitary pars intermedia dysfunction: equine Cushing's disease.](https://pubmed.ncbi.nlm.nih.gov/15635907/) [7] [Equine pituitary pars intermedia dysfunction.](https://pubmed.ncbi.nlm.nih.gov/21392656/) [8] [Nitration and increased alpha-synuclein expression associated with dopaminergic neurodegeneration in equine pituitary pars intermedia dysfunction.](https://pubmed.ncbi.nlm.nih.gov/15796757/) [9] [Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.](https://pubmed.ncbi.nlm.nih.gov/16115743/) [10] [Dysregulation of Cortisol Metabolism in Equine Pituitary Pars Intermedia Dysfunction.](https://pubmed.ncbi.nlm.nih.gov/30289445/) [11] [Epidemiology of pituitary pars intermedia dysfunction: A systematic literature review of clinical presentation, disease prevalence and risk factors.](https://pubmed.ncbi.nlm.nih.gov/29704935/) [12] [Pituitary pars intermedia dysfunction (equine Cushing's disease) in a Thoroughbred stallion: a single report.](https://pubmed.ncbi.nlm.nih.gov/26858577/) [13] [[Nutrition of horses with equine pituitary pars intermedia dysfunction ("Cushing's syndrome") treated with pergolid - A field study].](https://pubmed.ncbi.nlm.nih.gov/30142655/) [14] [Pituitary pars intermedia dysfunction (Equine Cushing's disease) in an onager (Equus hemionus onager).](https://pubmed.ncbi.nlm.nih.gov/20063825/) [15] [Design of an endovascular morcellator for the surgical treatment of equine Cushing's disease.](https://pubmed.ncbi.nlm.nih.gov/25946649/) [16] [Equine pituitary pars intermedia dysfunction: An international survey of veterinarians' approach to diagnosis, management, and estimated prevalence.](https://pubmed.ncbi.nlm.nih.gov/29081583/) ## Related Clinical & Scientific Guides * [Equine Hematologic Disorders: Anemia and Coagulopathies](/knowledge/veterinary-medicine/equine-care/equine-hematologic-disorders-anemia-coagulopathies) * [Equine Lifespan: Factors Influencing Longevity in Horses](/knowledge/veterinary-medicine/equine-care/equine-lifespan-factors-influencing-longevity-in-horses) * [Miniature Horse Care Guide](/knowledge/veterinary-medicine/equine-care/miniature-horse-care)