Equine endocrinology

Question 1

What is Equine PPID? Phyisology and pathogenesis?

Answer 1

Pituitary Pars Intermedia Dysfunction
(Cushing’s)
Pars intermedia is poorly vascularised and relies on neurotransmitters released from axons from the hypothalamus to control secretion (esp inhibition by dopamine)
Pathogenesis:
- Neurodegenerative lesion -> loss of dopaminergic function -> excess pars intermedia hormones (B-endorphin, CLIP, a-MSH and ACTH)
- Hyperplasia or adenomatous change to pars intermedia
Rare extension of tumour to brainstem - blindness reported

Question 2

Is insulin resistance related to cortisol in Equine PPID?

Answer 2

Insulin resistance thought related to anatagonism from cortisol but cortisol usually not raised as ACTH is biologically inactive

Question 3

Clinical presentation of Equine PPID - Epidemiology? Signs?

Answer 3

Usually 15yo or older, rarely <10yo - age related neurodegenerative disorder
Prevalent in aged populations (20% of 15yo+)
No sex predilection
Ponies more likely to be diagnosed than horses - hirsutism more apparent, laminitis risk greater
Signs:
- hypertrichosis (hirsutism) varies from delayed/abnormal shedding to thick curly coat
- laminitis in 50-80%
- may also have frequent foot abscesses, white line disease, lamellar rings, seedy toe, dropped sole
- weight loss and weight redistribution
- wasted epaxial muscles and pot belly (muscle catabolism and type II muscle fibre atrophy)
- bulging supraorbital fat
- lethargy/reduced exercise tolerance (B-endorphin effect)
- sweating
- PUPD
- susceptibility to infections

Question 4

Diagnosis of Equine PPID: haematology, biochemistry and basal endocrine test’s?

Answer 4

Routine haematology and biochem - limited value, no stress leucogram, no induction of liver enzymes
Glucorticoid levels usually normal (most of the ACTH is biologically inactive)
Hyperglycaemia
Hyperinsulinaemia (affected by exercise and feeding)
- survival >2y better if insulin <62uU/ml
- poor if >188uU/ml
Basal ACTH:
- special handling requirements
- collect when horse not stressed in EDTA tube
-se and sp up to 90%
-lab correction for season

Question 5

Diagnosis of equine PPID: low dose dexamethasone suppression test (LDDST)?

Answer 5

= a dynamic endocrine test
Varies with season
Laminitis risk: exacerbation of existing insulin resistance (limited effect of one low dose)
Previously considered gold standard but se and sp lower than original research (still both >90%)
Baseline serum cortisol -> 40ug/kg IM dex -> retest [cortisol] 20 hours later
Requires 2 visits but easy and quite cheap
>70% suppression of a normal baseline cortisol of post dex cortisol <40nmol/l

Question 6

Diagnosis of equine PPID: TRH stimulation test (of ACTH)?

Answer 6

= a dynamic endocrine test
TSH normally produced by pars distalis
But non specific TRH receptors on pars intermedia so if PPID get increased ACTH at 10 and 30 mins

Question 7

Diagnosis of equine PPID: which tests would you choose to do?

Answer 7

Tier 1 test = resting ACTH or overnight DST
-positive -> begin treatment
-negative -> no treatment
If inconclusive e.g. clinical signs present:
-repeat tier 1 test (e.g. ACTH in autumn)
-or perform a tier 2 test (TRH stimulation test measuring ACTH)

Question 8

Treatment for equine PPID? When? What?

Answer 8

Medical therapy improves quality of life
Some vets/owners choose to wait until clinical laminitis develops - but risk of euthanasia when first episode occurs
Pergolide
Monitoring:
- obtain basal ACTH, basal insulin and glucose
- document clinical exam findings (appetite, hair coat, water intake, BCS, muscle loss, laminitis etc)
- insulin is good prognostic indicator (more likely to develop laminitis and not survive 2y if high)
- monthly evaluation of ACTH and insulin for 3 months (increase dose if poor response up to 5x starting dose - expect one or more clinical signs to improve and/or basal ACTH to have returned to normal or close to normal)
- if stable 3 monthly evaluation for 9 months
- then every 6 months in well managed cases

Question 9

Problems with equine PPID treatment?

Answer 9

High doses may cause inappetence - reduce/stop treatment for few days and restart with gradual dose increase
If continued inappetence or weight loss:
- dental exam
- blood test for alternative causes
- further clinical investigation
Continued laminitis/high insulin:
- consider careful dietary control by restricting non-structural carbohydrate access (cereals, grass)
- do not severely restrict due to risk of exacerbating catabolism
- increase exercise if possible
- metformin therapy (if concurrent EMS)

Question 10

Prognosis of equine PPID?

Answer 10

Life long treatment and management (diet, anthelmintics, clipping, teeth, health checks)
Up to 85% if horses show clinical improvement with treatment
Can be successful for >7y

Question 11

Hypothyroidism in horses - how common? Testing?

Answer 11

Very rare
Basal T3 and T4 levels frequently low in normal horses esp in training and bute administration
TRH stimulation - measure T3 and T4 4-5h later
TSH unavailable
Can see goitre and secondary hypothyroidism with feeding excess iodine
Problem if fed to pregnant mares - foals develop problems esp DOD
Fad feeding e.g. seaweed and kelp

Question 12

What is Equine Metabolic Syndrome (EMS)?

Answer 12

A syndrome of obesity (general or regional adiposity), laminitis (or predisposition) and insulin resistance/hyperinsulinaemia

Genetic predisposition and obesity -> insulin resistance + CHO (from feed) -> hyperinsulinaemia -> laminitis

Question 13

Signs of EMS?

Answer 13

Obesity
- typical = bulging supraorbital fat, enlarged crests, fat pads
- bit all are fat, especially brutish breeds
Laminitis
- variable
- associated good problems may include frequent foot abscesses, white line disease, lamellar rings, seedy toe, dropped sole

Question 14

Risk factors for EMS?

Answer 14

Obesity

Genetics - familial links in Dartmoor ponies, ponies at increased risk

Question 15

Testing for hyperinsulinaemia for EMS diagnosis?

Answer 15

Diagnosis can be confirmed by resting hyperinsulinaemia (>20uIU/ml)
Lower reference range for fasting
Clinical cases with laminitis may have much higher serum insulin
Hyperglycaemia rarely found (not type II diabetes!)

Question 16

Proxies for EMS diagnosis?

Answer 16

Calculations based on raw insulin and glucose values
May be more reliable indicators of insulin sensitivity/resistance and pancreatic B cell function
Insulin:glucose ratio may be the most practical

Question 17

Dynamic testing for EMS diagnosis?

Answer 17

If hyperinsulinaemia is equivocal, dynamic tests of insulin sensitivity are warranted
Combined IV glucose and insulin test
In feed sugar tests:
- starve for 6-12h
- offer small amount (half scoop) of forage chaff with 1g glucose powder/kg BW
- take blood sample 2h later and measure insulin
- or 0.15ml/kg corn syrup and sample 60-90 mins later
If 1g/kg glucose and insulin is >85mlU/L then at risk of developing laminitis
If corn syrup and insulin is >60 then at risk of developing laminitis

Question 18

Comparison of EMS and PPID?

Answer 18

EMS:

• younger than horses with PPID
• not hirsute
• negative for PPID on dynamic and basal tests (absence of pituitary pathology)

Question 19

Treatment for EMS?

Answer 19

Management of obesity
- strict diet: reduce caloric intake (1.5-2% BW hay, soak to reduce NSC 8-16h by 50%, provide roughage, protein, vitamins and trace minerals if soaking)
- exercise if possible
Management of hyperinsulinaemia
- exercise
- diet
- metformin 
- thyroxine
- nutraceuticals (Sc-FOS)

Exercise is best!! Then diet, then drugs