overview of PPID Flashcards
What normaly occurs with the hypothalmic-pituitary-adrenal axis?
Corticotropin releasing hormone (CRH) and Thyrotropin releasing Hormone (TRH) are produced and cause the release of POMC, which causes the release of ACTH and beta endorphins
Normally only a small amount of ACTH makes it to the peripheral circulation which then goes to the adrenal gland for glucocorticoid stimulation.
In the Pars Intermedia TRH is stimulatory and increases the amount of POMC and therefore ACTH produced where as dopamine is inhibitory and reduces the amount of POMC and therefore ACTH produced.
What is the signalment of PPID?
- Affects 20-25% of horses >15 years old
- No sex predilection
- No breed predisposition
What occurs to the hypothalmic-pituitary-adrenal axis during PPID?
pituitary pars intermedia dysfunction, a neurodegenerative disease due to a loss of inhibitory dopamine input from the hypothalamus. This leads to hyperplasia, adenoma formation and overproduction of POMC and and POMC derived peptides including ACTH.
What is seen on histology of a brain with PPID?
- Oxidative damage
- Accumulation of α-synuclein
- Accumulation of lipofuscin
What are the eary clinical signs of PPID?
- Muscle atrophy (epaxial) and pendulous abdomen
- Atrophy of type 2 muscle fibres
- Hair abnormalities - long hair, lack of sheding
- More hair in anagen phase –> increased α-MSH?
- Hypertrichosis –> PATHOGNOMONIC
- Lethargy –> increased B-endorphins (sedative effect)
- Regional adiposity –> α-MSH (affects appetite)
what clinical sign of PPID is this horse showing?
Hypertrichiosis
What are the uncommon signs of PPID in horses?
- Hyperhidrosis leads to anhidrosis
- Pseudo-lactation –> lack of dopaminergic control
- Suspensory ligament breakdown –> collagen disruption
- Blindness –> compression of optic chiasm
- Keratitis –> decreased corneal sensation
- Low fertility, irregular cycling –> adenoma compression
What are the later signs of PPID?
- Laminitis
- PPID exacerbates ID
- Often presenting complaint!
- Recurrent infections due to immune dysfunction
- Eg sinusitis, skin, foot abscess, bronchopneumonia and increased parasite burden
- –> α-MSH affects neutrophil function
- PUPD
- Compression of PN–> decreased ADH?
What is the diagnostic process for PPID?
Depends on level of clinical susspision, as to how to pick and interpret clinical tests
often test for Equine Metabolic Syndrome in cases that have signs of laminitis
What are the key charateristics of baseline ACTH testing for diagnosis of PPID?
- EDTA blood tube
- Ice packs or refrigerated in the car
- Centrifugation within 4h: plasma separation
- Less sensitive in early stages- can get false positives
- High suspicion based on clinical signs then more likely to correctly identify positives
Higher sensitivity in the autumn
What are the key charateristics of TRH stimulation testing for diagnosis of PPID?
Collect baseline
Inject 0.5mg (< 250kg) or 1mg (> 250kg) IV TRH
Collect second sample 10 min later (+/-30min later)
Handle samples as for baseline ACTH (chilled EDTA blood)
- More accurate in horses with a lower clinical suspicion than baseline ACTH
What is the seasonality of ACTH hormone in horses?
What is the significance of this?
There is significant seasonality with hormone production from the PI. The output of the PI increases with shorter day length therefore plasma concentrations of the hormones produced by the PI are greatest in the autumn (Aug-Oct)
This has clinical relevance as it alters the ranges depending on the season for our diagnostic tests which measures blood ACTH and we see more variation in results in the autumn
When should you test a horse for PPID?
- Stress, excitement, trailering: transient increase in ACTH
- ACTH should not be collected within 30 minutes of trailering
- ACTH should not be collected if horse is visibly excited
- Pain
- Low to moderate pain: no effect
- Severe can affect results
- Active laminitic horses CANNOT be tested: postpone until severe pain controlled
- Sedation (xylazine/detomidine +/-butorphanol)
- Can test immediately (within 5-10 minutes) after sedation
- Do not test during 24-48h after sedation
What is can you do if you get an equivocal result on baseline ACTH?
,
What is the treatment and plan for PPID?
- Pergolide administered at initial dose 2μg/kg
- recheck baseline ACTH in 4-6 weeks
- if normal ACTH then Continue with initial dose and recheck in 6 months
- if the same of higher ACTH increase dose by 1-2μg/kg, Recheck in 4-6 weeks
- Once appropriate dose established… recheck baseline ACTH every 6-12months - does will need to be increased as the horse gets older as neurodegenerative disease
What concurrent disease do 33% of PPID cases have?
What other conditions can they have?
33% have - Equine metabolic syndrome
can also have Laminitis and secondary infections
How is PPID different to cushings in dogs?
Horses have high ACTH bu variable cortisol, dogs have high cortisol (which gives them there clinical signs)
In Horses they think that cortisol doesn’t increase due to:
* Downregulation due to excessive prolonged ACTH exposure
* Biologically inert ACTH
* Change in the free cortisol level but not the total cortisol level
