Equine Pituitary Pars Intermedia Dysfunction

Also known as: PPID — EPPID — Equine Cushing's Disease — Equine Cushing's-like Disease — Equine Cushings Syndrome — Pituitary-dependent Hyperadrenocorticism — Pituitary Adenoma

Introduction

PPID is a slowly-progressive disorder of the horse with a characteristic clinical picture. It is associated with functional adenomas or adenomatous hyperplasia of the pars intermedia of the pituitary gland.

It affects all breeds of horses but is more common in ponies and Morgans. It occurs in older horses, between 10 and 30 years with a mean of 20 years. There are no sex predilections.

Pathophysiology

There is hypertrophy and hyperplasia of the pars intermedia of the pituitary gland due to a decrease or loss of the neurotransmitter dopamine in the innervation of the pars intermedia. The melanotropes located there secrete markedly increased levels of propiomelanocortin (POMC), which releases large amounts of Melanocyte Stimulating Hormone (α-MSH) and β-endorphin as well as smaller but increased amounts of ACTH.

α-MSH and β-endorphin both enhance the action of ACTH, which leads to an increase in adrenocortical steroidogenesis and an increase in plasma cortisol levels. There is also loss of the circadian pattern of cortisol secretion.

The complex array of clinical signs arises as a sequela to excess circulating α-MSH, β-endorphin and ACTH, the metabolic changes associated with increased glucocorticoid concentrations, and physical destruction of the posterior lobe of the pituitary, the hypothalamus or the optic chiasma. These latter signs are very rare.

Clinical Signs

Presenting signs include: weight loss or muscle wasting, decreased muscle tone, abnormal bulging of supraorbital fat pads.

A thick, long and wavy hair coat with an abnormal shedding pattern is evident in 85% of affected horses. This sign is often preceded by months to years of subtle coat variations, such as patchy slow shedding during late spring or delayed shedding with alopecia.

Polyuria and polydipsia: due to insulin antagonism, hyperglycaemia and osmotic diuresis, and ADH antagonism

Lethargy

Persistent sweating

Chronic recurrent laminitis: due to digital vasoconstrictive effects of catecholamines

Chronic recurrent skin, pulmonary, urinary, or sinus infections: due to immunosuppression

Vision disturbances: due to pressure of the expanding pituitary mass on the optic nerve.

Diagnosis

Plasma cortisol concentration can be measured but there is a wide variation in normal values and it is not useful in diagnosing the condition.

outdated/no longer recommended --> The dexamethasone suppression test is the gold standard for diagnosis of the disease. Plasma cortisol samples are taken before and after dexamethasone administration. Normal horses will show a level of cortisol below 1 μg/dL 19 hours after dexamethasone administration, whereas affected horses will show a small degree of suppression in cortisol levels, but not to the level of normal horses, and levels also rebound more quickly.

A variety of other tests exist to evaluate horses for PPID:

ACTH stimulation test, resting ACTH level, TRH stimulation test, glucose tolerance test, insulin levels and insulin tolerance test

None of these are of greater sensitivity or specificity than the dexamethasone suppression test and are frequently less convenient to perform and more expensive.

The only disadvantage of the dexamethasone suppression test is the reported increased risk of laminitis. In at risk cases, ACTH levels are nearly as sensitive in diagnosing the condition.

Haematology and biochemistry may reveal hyperglycaemia and hyperlipidaemia. Liver enzymes may be elevated due to hepatic lipidosis secondary to the lipolysis. There may be a stress leukogram.

Post mortem examination usually reveals an enlarged pituitary gland. Tumours are composed of large columnal or polyhedral cells with hyperchromatic nuclei. There are no metastases. There will be enlargement of the adrenal glands and usually multiple sites of infection.

Treatment

Treatment can be difficult due to the age of the animal and the multiple problems which can occur in a given individual.

In some animals, there may be unacceptable pain from laminitis, or marked debilitation from the muscle wasting and euthanasia may be the humane decision.

Other cases may be managed by supportive therapy:

Treating any infections (skin and respiratory)

Maintaining a high plane of nutrition

Hoof care for mild laminitis, or NSAIDs if needed

Clipping to remove long hair

These cases may have an acceptable quality of life for several years.

Medical therapy is aimed at modifying the secretion of the active peptide substances by the pituitary tumour:

Cyproheptadine: a serotonin antagonist, was one of the first drugs used for the disease. The response is variable

Bromocriptine: dopaminergic agonist, to replace loss of dopaminergic innervation. The bioavailability of the drug is low.

Pergolide: dopaminergic agonist, therapy of choice. Clinical improvement occurs in a few weeks in approximately 80% of cases. Doses can be increased if signs are still apparent, but treatment should be stopped if diarrhoea, anorexia and worsening laminitis occur.

Trilostane: inhibits 3-beta-hydroxysteroid dehydrogenase. It is used in Canine Cushing's but gives variable results in horses.

Prognosis

Management changes, routine health care and pain relief can lead to marked improvement in signs, and horses can be managed for several years.

Medical therapy is also effective.

Prognosis depends on the severity of the clinical signs and the financial and time commitment by the owners.

Equine Pituitary Pars Intermedia Dysfunction Learning Resources
Flashcards Test your knowledge using flashcard type questions	Equine Internal Medicine Q&A 04

References

Snyder, J. (2006) The Equine Manual Elsevier Health Sciences

Bertone, J. (2006) Equine geriatric medicine and surgery Elsevier Health Sciences

Rose, R. (2000) Manual of equine practice Elsevier Health Sciences

Lavoie, J-P. (2009) Blackwell's Five Minute Veterinary Consult: Equine John Wiley and Sons

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