Endocrine disease Flashcards by Josie Campbell

What does PPID stand for?

Pituitary pars intermedia dysfunction

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PPID - what is it?

Slowly progressive, degenerative disease of the hypothalamic dopaminergic neurons

Loss of dopaminergic control of the pars intermedia melanotropes causes hyperplasia and formation of adenoma of the PI

POMC -> loss of peptides abnormally elevated

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PPID - risk factors

Age related neuro-degeneration, advancing age is the only known risk factor

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Clinical signs of PPID

Varies and changes over time if untreated

Hypertrichosis (pathognomic)

Coat retention/patchy shedding and coat colour changes (suggestive)

Chronic laminitis may be a feature

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Early clinical findings in PPID

Regional hypertrichosis/delayed shedding (strongly suggestive)

Loss of topline muscle, change in attitude/lethargy, decreased performance, abnormal sweating (suggestive)

Infertility, tendon or ligament laxity, desmitis/tendonitis, regional adiposity, laminitis (possible comorbidities)

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Advanced clinical findings of PPID

Generalised hypertrichosis (strongly suggestive)

Abnormal sweating, topline muscle atrophy, altered mentation, exercise intolerance, rounded abdomen, PU/PD, recurrent infection (suggestive)

Recurrent corneal ulcers, infertility, increased mammary gland secretions, tendon/ligament laxity, desmitis/tendonitis, regional adiposity, laminitis (possible comorbidities)

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Which horses should be tested for PPID?

Don’t just test without justification

PPID could be a contributing factor for many disorders

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Simple tests for PPID

ACTH ***

a MSH
b endorphin
cortisol
glucose
insulin
urine cortisol:creatinine

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Dynamic tests for PPID

TRH stim test (ACTH) **
Overnight dexamethasone suppression test

ACTH stim test
combined ODST/TRH
domperidone stim test
8hr cortisol difference
TRH stim test (cortisol)

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Basal ACTH concentration

Variation with time of year

Variation with individuals

Labs have ‘seasonally adjusted reference intervals’

Increase in autumn in normal horses and ponies AND those with PPID

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How to interpret basal ACTH

Interpret with context (clin signs, age)

Up to 25% with PPID have a grey zone result - positive diagnosis justified if strong clinical suspicion

Up to 30% of non-PPID horses fall in grey zone for other reasons so ignore if nothing else to support diagnosis

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When not to test basal ACTH

Pain - severe pain for at least 24hrs (elevates ACTH - false positive)

Travelled in past 12hrs (elevated due to stress)

Testing in laminitic horses only a problem if severe pain

If negative results after these situations that is still helpful.

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Treatment for PPID

Pergolide (Prascend) - only licensed medicine

Replace dopaminergic control of the pars intermedia

Good response in the majority of cases

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Negative effects of pergolide

Sometimes transient inappetance - stop and restart at a lower dose after a week or two

Can be more fatal in shetlands or donkeys - can cause hyperlipaemia (can be fatal)

Reduces milk production (not often an issue)

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What to expect after pergolide treatment for PPID

Normalised in 37%
>50% inprovement in 38%
<50% improvement in 25%

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Monitoring PPID

Checking insulin (risk of laminitis) and clinical improvement

If ACTH conc is still a bit high but doing well otherwise don’t chase numerical ACTH conc with increasing pergolide dose - instead split the dose into BID

Management for PPID cases

Low starch and sugar feeding

Regular foog trimming to keep feet balanced

Make sure dentistry problems are detected and treated early - enamel points, loose molars

Parasite control

What % of laminitis cases have underlying endocrinopathy?

90%

What is EMS characterised by?

Insulin dysregulation

Obesity (generalised or regional)

Increased (high) risk of laminits

Altered adipokines

Dyslipidaemia

Breeds overepresented in EMS studies

Native ponies
PRE (spanish/portuguese horses)
Morgan horses
Warmbloods (arabs, thoroughbreds)
Paso finos
Saddlebreds
Miniature horses

BUT can happen in any breed

How to recognise adiposity

Generalised obesity

Regional fat deposits
- rump
- cresty neck
- sheath/mammary gland
- intra-abdominal

Signs of subclinical laminitis

Divergent rings (growth ring wider at heel than toes)

Footsore after trimming

‘Doesn’t like hard ground’

Flat soles
Dropped soles
Widening white line

How long do divergent growth rings on hooves take to appear?

> 3 months

How to diagnose insulin dysregulation

Simple unfasted resting basal samples:
- glucose
- insulin
- triglycerides

Post feeding samples (corn syrup) - take sample 45-60 mins later

Adiponectin

Associated not with the anount of fat but with the negative consequences of body fat present. Adipokines are peptides produced by adipose tissue that act locally and systemically.

What does low adiponectin correspond to?

Metabolic obesity and insulin dysregulation - increased risk of laminitis

EMS management recommendations

If only a few regional fat deposits then tight calorie control not as relevant. Do not recommend exercise until laminitis has resolved and foot capsule is stable.

Diet for PPID

Make sure starcha nd sugar component of diet is ALWAYS <10% Fibre and oil doesn't impact insulin dysregulation and laminitis even if making them overweight Cannot be <1% BWT as DM intake per day

What does soaking foarge do?

Takes out some water osluble sugars Longer its soaked for, the more sugars taken up In summer the warmth can make it foul In winter the wet hay can be very unappetising Try low starch/sugar haylage instead

Medicines used for PPID

Metformin Levothyroxine Gliflozins (velag, cannag, ertug)

What is the MoA of the gliflozins?

SGLT2 inhibitors

DOes metformin help PPID?

First pass effect in liver Really safe but likely makes little difference Impairs glucose absorption in horses Reduces insulin response to glucose ingestion Cannot replace diet and management changes May aid weight loss and protect against diet-induced hyperinsulinaemia

Levothyroxine

Speeds up metabolism When on it they become hyperthyroid as they weren't hypothyroid in the first place Makes them restless and hungry

Indications for high dose levothyroxine

For cases with weight loss resistance (no response in a minimum of 30 days) or for accelerated management of obesity in acute laminitis cases. Gradually reduce dose and discontinue treatment after weight loss achieved or after 3-6 months of therapy

Indications for glifozin use

When horses are severely affected by laminitis and severe insulin dysregulation that is not responding to other measures. Horses with marked hypertriglyceridaemia should not be treated with these drugs.

What do gliflozins do?

Spill glucose from the kidneys Massively lowers insulin in most patients Risk of TGs elevation is high and sometimes to a clinically important/life threatening level Some adverse events/idiosyncratic events of liver disease reported