Equine Endocrinology

Front 1

What are the 2 most common endocrine diseases in the horse?

Back 1

Equine cushing's disease
Metabolic disease

Front 2

What is ECD?

Back 2

It is a pituitary dependent hyperA
Common in OLD horses (rare to see if under 10 yrs)
Ponies are over-represented

Pathogenesis
- There is a loss of dopaminergic innervation of the pars intermedia which results in abnormal hormone production
- Normally, pars intermedia cells don't produce much ACTH... they mainly produce alpha-MSH, CLIP and beta-endorphins
- Loss of dopaminergic control leads to excessive production of ACTH
- Normally, hypothalamus induces pituitary gland to release ACTH --> adrenal gland releasing cortisol, then negative feedback
- Negative feedback doesn't exist in ECD

Leads to
- Excessive circulating ACTH
- Loss of circadian rhythm of cortisol
- Excessive exposure to endogenous glucocorticoids

Front 3

What are teh clinical signs associated with ECD?

Back 3

- Hirsutism (shaggy coat) is the only pathognomonic clinical sign (may be initially localised, then generalised)
- Lethargy
- Laminitis (due to glucocorticoid potentiotion of vasoconstrictor catecholamines, chronic glucotoxicity/oxidative stress, hypercoagulability, activation of matrix metalloproteinases)
- PU/PD (due to glucosuria, partial diabetes insipidus due to abnormal ADH production, glucorticoid induction of thirst)
- Hyperhidrosis (increased sweating)
- Weight loss +/- increased appetite
- Decreased muscle mass, muscle weakness, pot belly
- Fat redistribution (around crest of neck, tail, head, sheath, supraorbital fat pads)
- Hyperlipidaemia
- Recurrent infections (skin diseases, subsolar abscesses, sinusitis, dental infections)
- Neuro abnormalities (central blindness, narcolepsy)

Front 4

How do you diagnose ECD?

Back 4

- Signalment and clinical signs
- PM (gold standard) --> look for an enlarged pituitary gland
- Dex suppression test (gold standard)
- Plasma ACTH concentrations (an alternative)

Less useful
- Domperidone response test
- THyrotropin-releasing hormone stimulation test
- Combined TRH stimulation test and DST
- Serum insulin concentration

Not useful
- Serum cortisol concentration
- Routine biochem and haem
- Blood glucose concentration
- ACTH stim test
- Urinary corticoid:creatinine ratio

Front 5

Discuss

Dex suppression test
Plasma ACTH concentration

Back 5

Dex suppression test
- Normal horses have serum cortisol < 27.6nmol/L 17-19hrs after 40ug/kg of dex IM
- In ECD, they do NOT suppress the cortisol levels
- Very specific test
- Problem when it comes to laminitis... may exacerbate the problem

Plasma ACTH concentration (alternative)
- Will see ACTH levels elevated in ECD horses
- Must use plastic EDTA tubes, and promptly separate out plasma... must do the assay quickly
- Some seasonal variability in ACTH possiby?

Front 6

Discuss

Domperidone response test
TRH stim test
Combine TRH stim and DST
Serum insulin test

Back 6

Domperidone response test
- Domperidone is a dopamine antagonist
- This results in an elevation in plasma ACTH concentration 4hrs after oral admin in horses with ECD, but not in normal horses
- Test still being investigated

Thyrotropin-releasing hormone stimulation test
- Not great

Combined TRH stimulation and DST
- Also not great, and complex to perform in field

Serum insulin concentration
- Not specific for ECD
- May be a prognostic indicator

Front 7

How do you manage ECD?

Back 7

- Can't be cured
- Must imrpove overall health
- Some pharmacotherapy

Front 8

What are some ways you can improve the overall health of older horses?

Back 8

- Body clipping for hirsutism
- Routine dental
- Dietary management
- Regular hoof care
- Care for chronic laminitis
- Parasite control
- Manage recurrent infections

Front 9

What pharmcotherapy is useful for managing ECD?

Back 9

- All drugs are life long
- No drug will halt progression of disease
- Need to treat for 2-3 months before you will see any improvements
- Make sure you monitor improvement and DST and/or ACTH concentrations

Front 10

What drugs can be used for management of ECD?

Back 10

Pergolide mesylate
- A dopamine agonist
- Comes in tablets and liquid forms
- Decreases ACTH concentrations and ameliorates clinical signs
- Adverse side effects = anorexia, depression, diarrhoea, colic

Cyproheptadine
- A serotonin antagonist (serotonin stimulates secretion of ACTH too)
- Less efficacious than pergolide
- Adverse side effects = drowsiness and ataxia

Trilostane
- A competitive inhibitor of adrenal cortisol production
- Not currently available in Australia
- Ameliorates clinical signs, except hirsutism
- No reported adverse side effects

Front 11

What is the prognosis for ECD?

Back 11

- Can be successfully managed for years
- They need close monitoring and attention to health
- Drug therapy can improve quality of life and lifespan

Front 12

What is EMS (equine metabolic disease?)

Back 12

It is a syndrome that is associated with the development of laminitis in overweight or obese MIDDLE-AGED ponies and horses

Very common in ponies

Front 13

What are the clinical signs of EMS

Back 13

- Generalised excessive SC fat deposits around the neck, rump and prepuce
- Excessive intra-abdominal fat
- It is difficult to lose weight in these animals by dietary discretion alone
- Laminitis

Front 14

What is the pathogenesis of EMS?

Back 14

- Insulin resistance and hyperglycaemia (secondary to feeding diets with high glycaemic index e.g. grain) which leads to excessive fat accumulation
- Local tissue hypercortisolaemia due to conversion of cortison to cortisol, especially in omental fat
- Insulin resistance leads to chronic glucotoxicity/oxidative stress on vessels in the hoof lamellae and laminitis

- Vasoconstriction
- Activation of matrix metalloproteinases

Front 15

How do you manage EMS?

Back 15

- Increase exercise

- Change diet
- Induce weight loss
- Improve insulin sensitivity (low glycaemic index)
- Avoid aggressive dietary restriction in ponies because i may lead to hyperlipidaemia

- Manage laminitis

Front 16

How do you prevent EMS?

Back 16

Do not feed grain diets to inactive horses or ponies!!