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Pituitary pars intermedia dysfunction (PPID) in horses (equine cushing’s disease) – 2023

Last updated 05/2023

Pituitary pars intermedia dysfunction (PPID) was formerly known as Equine Cushing’s disease, and horse owner awareness of the disease has grown over the last decade. Here we will cover the basics of PPID as a quick refresher and link to our other educational content on this topic.

What is PPID (cushing’s disease in horses)?

PPID is a progressive, life-long neurodegenerative disease and is the most common endocrine disorder of older horses. It affects up to 25% of horses over the age of 15 [1]  years and can impact their quality of life, performance and immunocompetence. It can occur in any breed or sex, although some studies do suggest that ponies may be more at risk than horses [2]. 

What causes PPID (cushing’s disease in horses)?

While PPID is one of the most common endocrine disorders seen in horses, its pathophysiology is still not completely understood.

The disease is caused by loss of inhibitory dopaminergic input to the melanotropes of the pituitary pars intermedia. This appears to be caused by oxidative stress, abnormal protein accumulation and subsequent degeneration of the dopaminergic neurons within the hypothalamus [3].

The loss of dopaminergic inhibition of the pars intermedia results in continuous stimulation of the par intermedia melanotropes resulting in overproduction of their hormones, including adrenocorticotropic hormone (ACTH). Over time, hyperplasia and eventually adenomatous change (microadenoma or macroadenoma) of this area of the gland occurs.

What are the clinical signs of PPID (cushing’s disease in horses)?

Clinical signs depend on the stage of the disease, with more subtle signs occurring early on:

Early PPID signs:

  • Decreased athletic performance
  • Lethargy
  • Behavioural changes
  • Delayed coat shedding
  • Regional hypertrichosis
  • Change in body conformation
  • Regional adiposity
  • Laminitis

Advanced PPID signs:

  • Generalised hypertrichosis
  • Lethargy
  • Loss of seasonal coat shedding
  • Skeletal muscle atrophy (loss of topline)
  • Regional adiposity
  • Pendulous abdomen
  • Hyperhidrosis
  • Polyuria/polydipsia
  • Recurrent infections
  • Infertility
  • Laminitis
  • Hyperglycaemia
  • Neurological deficits/blindness

Some of these signs may be mistaken by owners as signs of general ageing. Therefore, while they recognise the signs, they do not seek veterinary advice and so cases of PPID may remain undiagnosed [4]. It is important for the early and subtle signs of PPID to be recognised to allow for prompt diagnosis and treatment so quality of life can be restored for these animals.

The most commonly recognised clinical signs include:

Hypertrichosis

This is pathognomonic of the disease, and the most recognised clinical sign. It occurs in 69.9% of horses with PPID [5]. 

Laminitis

The prevalence of laminitis in horses with PPID is 48.9%, and it is often the first presenting complaint of horse owners seeking veterinary advice [6]. The cause of laminitis in horses with PPID is unclear but can occur due to hyperinsulinemia. Nearly a third (32%) of horses with PPID have hyperinsulinemia, and of those two-thirds (66%) have laminitis. It is unknown whether, and how insulin dysregulation (ID) and PPID are related. Read more about laminitis in horses.

How is PPID (cushing’s disease in horses) diagnosed?

Diagnosis is based on clinical signs, signalment and further laboratory testing.  It is important to remember that PPID is a disease of older horses, so age, together with clinical signs should be considered before undertaking further diagnostic testing. It is generally not recommended to test horses under the age of 10 years [7] unless hypertrichosis is present.

Basal ACTH concentration is recommended for horses showing obvious clinical signs, using seasonally adjusted thresholds and ‘grey zones’ or equivocal zones. This is to account for the natural seasonal fluctuation in ACTH levels, leading to elevated levels during the late summer and autumn. Results with equivocal results warrant further testing.  To diagnose early cases, those with mild clinical signs, or cases with equivocal results, the thyrotropin-releasing hormone (TRH) stimulation test, which measures ACTH concentrations in response to TRH, should be used.

In acute laminitis cases, ACTH testing should ideally be delayed until it has resolved, as ACTH levels naturally increase during this time. This also applies to other acute and chronic diseases [8].

As a third of horses with PPID also have hyperinsulinemia, and this is a risk factor for laminitis, and a worse prognosis[9] [10], it is recommended to also assess for insulin dysregulation (ID). This can be done with basal insulin concentration, an oral glucose test/oral sugar test, or an insulin response test.

What is the treatment for PPID (cushing’s disease in horses)?

It is not possible to ‘cure’ PPID, and so the goal of treatment is to improve the quality of life of affected animals by reducing the associated clinical signs. View our webinar on the health and welfare of horses and ponies with PPID to learn more. This is done through optimal husbandry and preventative healthcare, together with medical treatment using a dopamine agonist. Pergolide is the licensed active for treatment and is reported to be effective in 65% to 80% of cases. Treatment is life-long and regular ACTH testing is generally advised.

While anecdotally pergolide seems to reduce the risk of laminitis, recent research indicates that pergolide does not have an effect on insulin concentration [11] or laminitis risk [12]. Management of this should therefore be through diet – following the same principles as horses with equine metabolic syndrome (EMS).[SS20] 

Potential adverse side effects of pergolide include anorexia, diarrhoea, depression and colic. Compliance can be a limiting factor of treatment – the licensed form is a tablet, which some horses are reluctant to ingest, and accurate dosing of smaller ponies can be challenging. A study found that only 48 % of horses receive the correct amount of pergolide [13]. Non-licensed preparations exist in the form of a pergolide paste, and a long-acting cabergoline (another dopamine agonist) injection, which could be alternative options in cases where there is compromised welfare due to poor compliance.

Abbreviations

PPID – Pituitary pars intermedia dysfunction

References:

 [1] Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022; 9(10):556. https://doi.org/10.3390/vetsci9100556

 [2] Van der Kolk JH et al (1993). Equine pituitary neoplasia: a clinical report of 21 cases (1990-1992), Vet Rec 133(24): 594-597.

Couëtil L et al (1996). Plasma adrenocorticotropin concentration in healthy horses and in horses with clinical signs of hyperadrenocorticism, J Vet Intern Med 10(1): 1-6.

Donaldson MT et al (2002). Treatment with pergolide or cyproheptadine of pituitary pars intermedia dysfunction (equine Cushing’s disease), J Vet Intern Med 16(6): 742-746.

 [3] Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022; 9(10):556. https://doi.org/10.3390/vetsci9100556

 [4] McGowan TW et al (2013). Prevalence, risk factors and clinical signs predictive for equine pituitary pars intermedia dysfunction in aged horses, Equine Vet J 45(1): 74-79

 [5] Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022; 9(10):556. https://doi.org/10.3390/vetsci9100556

 [6] Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022; 9(10):556. https://doi.org/10.3390/vetsci9100556

 [7] Kirkwood NC, Hughes KJ, Stewart AJ. Pituitary Pars Intermedia Dysfunction (PPID) in Horses. Veterinary Sciences. 2022; 9(10):556. https://doi.org/10.3390/vetsci9100556

 [8] Ayala I et al (2012). Cortisol, adrenocorticotropic hormone, serotonin, adrenaline and noradrenaline serum concentrations in relation to disease and stress in the horse, Res Vet Sci 93(1): 103-107.

 [9] McGowan CM, Frost R, Pfeiffer DU and Neiger R (2004). Serum insulin concentrations in horses with equine Cushing’s syndrome: response to a cortisol inhibitor and prognostic value, Equine Vet J 36(3): 295-298.

 [10] Karikoski NP et al (2016). Lamellar pathology in horses with pituitary pars intermedia dysfunction, Equine Vet J 48(4): 472-478

 [11] Valencia NA, Thompson DL and Oberhaus EL (2017). Long‑term and short-term dopaminergic (cabergoline) and antidopaminergic (sulpiride) effects on insulin response to glucose, glucose response to insulin, or both in horses, J Equine Vet Sci 59: 95-103.

 [12] Knowles EJ (2018). Does pergolide therapy prevent laminitis in horses diagnosed with pituitary pars intermedia dysfunction?, Equine Vet Educ 31(5).

 [13] Hague N et al (2021). Pergolide dosing compliance and factors affecting the laboratory control of equine pituitary pars intermedia dysfunction, Vet Rec 189(1): e142.